Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Hematopoietic Stem Cell Transplantation (Bone Marrow Transplant)

Policy #:11.07.01t

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract. State mandates do not automatically apply to self-funded groups; therefore, individual group benefits must be verified.

Coverage for hematopoietic stem cell transplantation (also referred to as bone marrow and/or peripheral blood stem cell transplantation) is provided when both the type of transplant and the individual's condition meet the medical necessity criteria outlined below. Please note that this section is organized alphabetically by disease category, followed by type of stem cell transplantation (i.e., autologous or allogeneic), and, finally, by coverage position.

When hematopoietic stem cell transplantation is considered medically necessary, all required procedures for the transplantation are also considered medically necessary and, therefore, covered, subject to the benefit contract.

Collection and storage of stem cells (apheresis therapy) for future stem cell transplantation is considered medically necessary and, therefore, covered for those individuals with an existing condition that meets the medical necessity criteria outlined below.

AMYLOIDOSIS (PRIMARY)

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Medically Necessary

Autologous hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the treatment of primary systemic amyloidosis.

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Experimental/Investigational

Allogeneic hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for the treatment of primary systemic amyloidosis.

AUTOIMMUNE DISEASES

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Medically Necessary

Systemic Sclerosis/Scleroderma

Autologous hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the treatment of individuals with rapidly progressing systemic sclerosis/scleroderma at risk of organ failure if ALL of the following conditions are met:
    • Adult individuals <60 years of age; AND
    • Maximum duration of condition of 5 years; AND
    • Modified Rodnan Scale Scores ≥15; AND
    • Internal organ involvement as indicated by the following measurements:
      • Cardiac
        • abnormal electrocardiogram; OR
      • Pulmonary
        • diffusing capacity of carbon monoxide (DLCo) <80% of predicted value
        • decline of forced vital capacity (FVC) of ≥10% in last 12 months
        • pulmonary fibrosis
        • ground glass appearance on high resolution chest CT; OR
      • Previous scleroderma-related renal disease
    • History of <6 months treatment with cyclophosphamide; AND
    • No active gastric antral vascular ectasia; AND
    • Does not have any of the following exclusion criteria:
      • Cardiac
        • left ventricular ejection fraction <50%
        • tricuspid annular plane systolic excursion <1.8 cm
        • pulmonary artery systolic pressure >40 mm Hg
        • mean pulmonary artery pressure >25 mm Hg
      • Pulmonary
        • DLCo <40% of predicted value
        • FVC <45% of predicted value
      • Renal: creatinine clearance <40 ml/minute

Experimental/Investigational

Other Autoimmune Diseases
Autologous hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for all other autoimmune diseases (e.g., chronic inflammatory demyelinating polyneuropathy, juvenile idiopathic and rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes).

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Experimental/Investigational

Allogeneic hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for autoimmune diseases, including, but not limited to:
    • Chronic inflammatory demyelinating polyneuropathy
    • Juvenile idiopathic and rheumatoid arthritis
    • Multiple sclerosis
    • Systemic lupus erythematosus
    • Systemic sclerosis/scleroderma
    • Type 1 diabetes

BREAST CANCER

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Not Medically Necessary

Autologous hematopoietic stem cell transplantation is considered not medically necessary and, therefore, not covered for the treatment of breast cancer at any stage.

Tandem autologous hematopoietic stem cell transplantation (two or more courses of high-dose chemotherapy scheduled regardless of the response to the first, each followed by stem cell rescue) is considered not medically necessary and, therefore, not covered for the treatment of breast cancer at any stage.

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Experimental/Investigational

Allogeneic hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for the treatment of breast cancer at any stage.

GENETIC DISEASES AND ACQUIRED ANEMIAS

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Medically Necessary

Allogeneic hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the following disorders:

    • Bone Marrow Failure Syndromes
      • Aplastic anemia including hereditary (e.g., Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, Diamond-Blackfan syndrome) or acquired (e.g., secondary to drug or toxin exposure) forms.
    • Genetic Disorders Affecting Skeletal Tissue
      • Infantile malignant osteopetrosis (marble bone disease or Albers-Schonberg disease (autosomal dominant osteopetrosis, type II))
    • Hemoglobinopathies
      • Homozygous beta-thalassemia (i.e., thalassemia major)
      • Sickle cell anemia in children or young adults when one of the following criteria are met:
        • The individual has a haploidentical to HLA-matched donor
        • The individual has either a history of prior stroke or at increased risk of stroke or end-organ damage
    • Inherited Metabolic Diseases
      • Lysosomal and peroxisomal storage disorders including the following:
        • Alpha-mannosidosis
        • Aspartylglucosaminuria
        • Austin's disease (Multiple sulfatase deficiency)
        • Batten disease (Neuronal ceroid lipofuscinosis)
        • Childhood onset cerebral X-linked adrenoleukodystrophy
        • Farber disease (Farber lipogranulomatosis)
        • Fucosidosis
        • Galactosialidosis
        • Gaucher types 1 and 3
        • GM1 gangliosidosis
        • Hurler Syndrome (Mucopolysaccharidosis Type I)
        • Krabbe disease (Globoid cell leukodystrophy or Galactosylceramide lipidosis)
        • Maroteaux-Lamy Syndrome (Mucopolysaccharidosis Type VI)
        • Metachromatic leukodystrophy
        • Mucolipidosis II (I-cell disease)
        • Niemann-Pick disease
        • Sialidosis
        • Sly Syndrome (Mucopolysaccharidosis Type VII)
        • Wolman disease
    • Primary Immunodeficiencies
      • Absent or defective T-cell function (e.g., severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, X-linked lymphoproliferative syndrome)
      • Absent or defective natural killer function (e.g., Chediak-Higashi syndrome)
      • Absent or defective neutrophil function (e.g., Kostmann syndrome [severe congenital neutropenia], chronic granulomatous disease, leukocyte adhesion defect)

Experimental/Investigational

Allogeneic hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for the following disorders:
    • Inherited Metabolic Diseases
      • Lysosomal and peroxisomal storage disorders
        • Hunter Syndrome (Mucopolysaccharidosis Type II)
        • Morquio Syndrome (Mucopolysaccharidosis Type IV)
        • Sanfilippo Syndrome (Mucopolysaccharidosis Type III)

GERM CELL TUMORS

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Medically Necessary

Single autologous hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered as salvage therapy for germ cell tumors:
    • In individuals with favorable prognostic factors that have failed a previous course of conventional-dose salvage chemotherapy
      • Individuals with favorable prognostic factors include those with:
        • a testis or retroperitoneal primary site
        • a complete response to initial chemotherapy
        • low levels of serum markers
        • low-volume disease
    • In individuals with unfavorable prognostic factors as initial treatment of first relapse (i.e., without a course of conventional-dose salvage chemotherapy) and in individuals with platinum-refractory disease
      • Individuals with unfavorable prognostic factors are those with:
        • an extratesticular primary site
        • an incomplete response to initial therapy
        • high levels of serum markers
        • high-volume disease
        • relapsing mediastinal nonseminomatous germ cell tumors
Tandem autologous hematopoietic stem cell transplantation or transplant with sequential high-dose chemotherapy is considered medically necessary and, therefore, covered for the treatment of testicular tumors, either as salvage therapy or with plantinum-refractory disease.

Experimental/Investigational

Autologous hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered as a component of first-line treatment for germ cell tumors.

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Experimental/Investigational

Allogeneic hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered to treat germ cell tumors, including, but not limited to, its use as therapy after a prior failed autologous hematopoietic stem cell transplantation.

HODGKIN'S LYMPHOMA

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Medically Necessary

Autologous hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for individuals with primary refractory or relapsed Hodgkin's lymphoma.

Tandem autologous hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the following indications:

    • Individuals with primary refractory Hodgkin's lymphoma
    • Relapsed disease in individuals with poor risk features who do not attain a complete remission after pre-transplantation cytoreductive chemotherapy

Experimental/Investigational

Autologous hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for the following:
    • A second autologous hematopoietic stem cell transplantation for relapsed lymphoma after a prior autologous hematopoietic stem cell transplantation
All other uses of autologous hematopoietic stem cell transplantation for individuals with Hodgkin's lymphoma are considered experimental/investigational and, therefore, not covered, including, but not limited to, initial or up-front therapy for newly diagnosed disease to consolidate a first complete remission.

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Medically Necessary

Allogeneic hematopoietic stem cell transplantation, using either myeloablative or reduced-intensity conditioning regimens, is considered medically necessary and, therefore, covered for the following:
    • Individuals with primary refractory or relapsed Hodgkin's lymphoma
    • Individuals who relapse after autologous hematopoietic stem cell transplantation that was used to treat primary refractory or relapsed disease
Reduced-intensity allogeneic hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the following:
    • Individuals who have failed prior autologous hematopoietic stem cell transplantation used to treat primary refractory or relapsed disease
    • Individuals who would otherwise qualify for a myeloablative allogeneic transplant, but would be unable to tolerate a standard myeloablative conditioning regimen
    • When insufficient stem cells are collected for an autologous hematopoietic stem cell transplantation

Experimental/Investigational

All other uses of allogeneic hematopoietic stem cell transplantation for individuals with Hodgkin's lymphoma are considered experimental/investigational and, therefore, not covered, including, but not limited to, initial or up-front therapy for newly diagnosed disease to consolidate a first complete remission.

LEUKEMIA
(see Guidelines section of this policy for risk factors)

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Acute Lymphoblastic Leukemia

Medically Necessary

Autologous hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the following:
    • Childhood acute lymphoblastic leukemia in first complete remission when there is a high risk of relapse
    • Childhood acute lymphoblastic leukemia in second or greater remission, or refractory acute lymphoblastic leukemia
    • Adult acute lymphoblastic leukemia in first complete remission when there is a high risk of relapse

Experimental/Investigational

Autologous hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for the following:
    • Adult acute lymphoblastic leukemia in second or greater remission or those individuals with refractory disease
    • Childhood and adult acute lymphoblastic leukemia in individuals not meeting any of the above criteria.

Acute Myeloid Leukemia

Medically Necessary

Autologous hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the following:
    • Acute myeloid leukemia in first complete remission or beyond, or relapsed acute myeloid leukemia, if responsive to intensified induction chemotherapy in individuals who are not candidates for allogeneic hematopoietic stem cell transplantation

Experimental/Investigational

Autologous hematopoietic stem cell transplantation for the treatment of acute myeloid leukemia is considered experimental/investigational and, therefore, not covered for individuals not meeting any of the above criteria.

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Experimental/Investigational

Autologous hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for the following:
    • Chronic lymphocytic leukemia
    • Small lymphocytic lymphoma

Chronic Myeloid Leukemia

Experimental/Investigational

Autologous hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for the treatment of chronic myeloid leukemia.

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Acute Lymphoblastic Leukemia

Medically Necessary

Allogeneic hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the following:
    • Childhood acute lymphoblastic leukemia in first complete remission when there is a high risk of relapse
    • Childhood acute lymphoblastic leukemia in second or greater remission, or refractory acute lymphoblastic leukemia
    • Childhood acute lymphoblastic leukemia in relapse after prior autologous hematopoietic stem cell transplantation
    • Adult acute lymphoblastic leukemia in first complete remission for any risk level
    • Adult acute lymphoblastic leukemia in second or greater remission, or in individuals with relapsed or refractory adult acute lymphoblastic leukemia
    • Adult acute lymphoblastic leukemia in relapse after prior autologous hematopoietic stem cell transplantation
    • Reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation as a treatment for acute lymphoblastic leukemia in individuals who are in complete marrow and extramedullary first or second remission, and who, for medical reasons, would be unable to tolerate a standard myeloablative conditioning regimen.
      • Medical reasons include: individuals whose age (typically >60 years) or comorbidities (e.g., liver or kidney dysfunction, generalized debilitation, prior intensive chemotherapy including autologous or allogeneic hematopoietic stem cell transplantation, low Karnofsky Performance Status score) preclude the use of a standard myeloablative conditioning regimen.

Experimental/Investigational

Allogeneic hematopoietic stem cell transplantation for the treatment of childhood and adult acute lymphoblastic leukemia is considered experimental/investigational and, therefore, not covered in individuals not meeting any of the above criteria.

Acute Myeloid Leukemia

Medically Necessary

Allogeneic hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the following:
    • Acute myeloid leukemia using a myeloablative conditioning regime to treat the following:
      • Poor- to intermediate-risk acute myeloid leukemia in first complete remission
      • Acute myeloid leukemia that is refractory to standard induction chemotherapy but can be brought into complete remission with intensified induction chemotherapy
      • Acute myeloid leukemia that has relapsed following a prior autologous hematopoietic stem cell transplantation, but can be brought into complete remission with intensified induction chemotherapy when the individual is medically able to tolerate the procedure
      • Acute myeloid leukemia that relapses following chemotherapy-induced first complete remission but can be brought into a second complete remission or beyond with intensified induction chemotherapy
    • Reduced-intensity conditioning regimen as a treatment for acute myeloid leukemia in individuals who are in complete marrow and extramedullary remission (first complete remission or beyond), and who, for medical reasons, would be unable to tolerate a myeloablative conditioning regimen
      • Medical reasons include: individuals whose age (typically >60 years) or comorbidities (e.g., liver or kidney dysfunction, generalized debilitation, prior intensive chemotherapy including autologous or allogeneic hematopoietic stem cell transplantation, low Karnofsky Performance Status score) preclude the use of a standard myeloablative conditioning regimen.

Experimental/Investigational

Allogeneic hematopoietic stem cell transplantation for the treatment of acute myeloid leukemia is considered experimental/investigational and, therefore, not covered for individuals not meeting any of the above criteria.

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Medically Necessary

Allogeneic hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the following:
    • Chronic lymphocytic leukemia or small lymphocytic lymphoma in individuals with markers of poor-risk disease
      • Poor-risk disease for transplant is noted as having one of the following:
        • Non-response or early relapse (within 12 months) after purine analogue--containing therapy
        • Relapse (within 24 months) after purine analogue combination therapy or treatment of similar efficacy (i.e., autologous stem cell transplantation)
        • p53 deletion/mutation (del 17p) requiring treatment

Experimental/Investigational

Allogeneic hematopoietic stem cell transplantation for the treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma is considered experimental/investigational and, therefore, not covered for individuals not meeting any of the above criteria.

Chronic Myeloid Leukemia

Medically Necessary

Allogeneic hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the following:
    • Chronic myeloid leukemia using a myeloablative conditioning regimen
    • Reduced-intensity conditioning regimen as a treatment for chronic myeloid leukemia for individuals who meet clinical criteria for an allogeneic hematopoietic stem cell transplant, but who are not considered candidates for a myeloablative conditioning allogeneic stem cell transplantation
Experimental/Investigational

Allogeneic hematopoietic stem cell transplantation for the treatment of chronic myeloid leukemia is considered experimental/investigational and, therefore, not covered for individuals not meeting any of the above criteria.

MULTIPLE MYELOMA

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Medically Necessary

Autologous hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the following:
    • Durie-Salmon Stage II or Stage III multiple myeloma, when both of the following criteria are met:
      • The individual has newly diagnosed or responsive multiple myeloma, with any of the following:
        • Previously untreated disease
        • At least a partial response to prior chemotherapy (defined as a 50 percent decrease in either measurable paraprotein [serum and/or urine] or in bone marrow infiltration sustained for at least 1 month)
        • Responsive relapse
      • The individual has adequate cardiac, renal, pulmonary, and hepatic function.
    • A single or second (salvage) autologous hematopoietic stem cell transplantation to treat multiple myeloma
    • Tandem autologous hematopoietic stem cell transplantation to treat multiple myeloma in individuals who fail to achieve at least a near-complete or very good partial response after the first transplant in the tandem sequence
    • Tandem transplantation with an initial round of autologous hematopoietic stem cell transplantation followed by a non-marrow-ablative conditioning regimen and allogeneic stem cell transplantation (i.e., reduced-intensity conditioning transplant) to treat individuals who are newly diagnosed with multiple myeloma

Experimental/Investigational

Autologous hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for individuals not meeting any of the above criteria, including those with multiple myeloma in refractory relapse (except for those with primary refractive disease).

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Medically Necessary

Allogeneic hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the following:
    • Tandem transplantation with an initial round of autologous hematopoietic stem cell transplantation followed by a non-marrow ablative conditioning regimen and allogeneic stem cell transplantation (i.e., reduced-intensity conditioning transplant) to treat individuals who are newly diagnosed with multiple myeloma

Experimental/Investigational

Allogeneic hematopoietic stem cell transplantation, myeloablative or nonmyeloablative, is considered experimental/investigational and, therefore, not covered for the following:
    • As upfront therapy for newly diagnosed multiple myeloma
    • As salvage therapy for multiple myeloma

MYELODYSPASTIC SYNDROMES (MDS) AND MYELOPROLIFERATIVE NEOPLASMS (MPN)

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Medically Necessary

Myeloablative allogeneic hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the treatment of:
    • Myelodysplastic Syndromes (MDS)
    • Myeloproliferative Neoplasms (MPN) (e.g., myelofibrosis)
Reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation in individuals who for medical reasons would be unable to tolerate a myeloablative conditioning regimen is considered medically necessary and, therefore, covered for the treatment of:
    • Myelodysplastic Syndromes (MDS)
    • Myeloproliferative Neoplasms (MPN) (e.g., myelofibrosis)

NON-HODGKIN'S LYMPHOMA (NHL)

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Medically Necessary

Autologous hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the following:
    • Aggressive non-Hodgkin's lymphoma B-cell subtypes (except mantle cell lymphoma) when transplantation is used for any of the following:
      • As salvage therapy for individuals who do not achieve complete remission after first-line treatment (induction) with a full course of standard-dose chemotherapy
      • To consolidate a first complete remission in individuals with diffuse large B-cell lymphoma, whose age-adjusted International Prognostic Index score predicts a high or high-intermediate risk of relapse
      • To achieve or consolidate a complete remission in individuals in a chemosensitive first or subsequent relapse
    • Indolent non-Hodgkin's lymphoma B-cell subtypes, when transplantation is used for any of the following:
      • As salvage therapy for individuals who do not achieve complete remission after first-line treatment (induction) with a full course of standard-dose chemotherapy
      • To achieve or consolidate complete remission in individuals in a first or subsequent chemosensitive relapse, regardless of whether the lymphoma has progressed to a higher grade
    • Bulky low-grade non-Hodgkin's lymphoma that has relapsed after at least two prior treatment regimens
    • Mantle cell lymphoma (MCL)
      • To consolidate a first remission
    • Mature T-cell or NK-cell (peripheral T-cell) neoplasms
      • To consolidate a first complete remission in high-risk subtypes
      • As salvage therapy
      • To treat peripheral T-cell lymphoma, noncutaneous, first-line consolidation with stem cell rescue and high-dose chemotherapy
        • All individuals, except those with low risk, as determined by the age-adjusted International Prognostic Index
          • Those individuals with a good prognosis do not require consolidative transplant, if the disease is in remission
      • To treat peripheral T-cell lymphoma in individuals with relapsed or refractory disease
A second hematopoietic stem cell transplantation (allogeneic or autologous) is considered medically necessary and, therefore, covered to manage relapsed non-Hodgkin's lymphoma if the initial hematopoietic stem cell transplantation was followed by a disease-free interval of at least 1 year.

Experimental/Investigational

Autologous hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for any of the following:
    • As initial therapy (i.e., without a full course of standard-dose induction chemotherapy) for any non-Hodgkin's lymphoma
    • To consolidate a first complete remission in individuals with diffuse large B-cell lymphoma and an age-adjusted International Prognostic Index score that predicts a low or low-intermediate risk of relapse
    • To consolidate a first complete remission in individuals with indolent (slow-growing) non-Hodgkin's lymphoma B-cell subtypes
    • As salvage therapy for mantle cell lymphoma (MCL)
    • Tandem transplants to treat individuals with any stage, grade, or subtype of non-Hodgkin's lymphoma

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Medically Necessary

Allogeneic hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the following:
    • Aggressive non-Hodgkin's lymphoma B-cell subtypes (except mantle cell lymphoma) using a myeloablative conditioning regimen for any of the following:
      • As salvage therapy for individuals who do not achieve complete remission after first-line treatment (induction) with a full course of standard-dose chemotherapy
      • To consolidate a first complete remission in individuals with diffuse large B-cell lymphoma whose age-adjusted International Prognostic Index score predicts a high or high-intermediate risk of relapse
      • To achieve or consolidate a complete remission in individuals in chemosensitive first or subsequent relapse
    • Indolent non-Hodgkin's lymphoma B-cell subtypes using a myeloablative conditioning regimen for any of the following:
      • As salvage therapy for individuals who do not achieve complete remission after first-line treatment (induction) with a full course of standard-dose chemotherapy
      • To achieve or consolidate complete remission in individuals in a first or subsequent chemosensitive relapse, regardless of whether the lymphoma has progressed to a higher grade
    • Mantle cell lymphoma (MCL)
      • As salvage therapy using myeloablative or reduced-intensity conditioning
    • Mature T-cell or NK-cell (peripheral T-cell) neoplasms
      • As salvage therapy with myeloablative or reduced-intensity conditioning
    • To treat peripheral T-cell lymphoma in individuals with relapsed or refractory disease
Reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the following:
    • Treatment of non-Hodgkin's lymphoma in individuals who meet the criteria for an allogeneic hematopoietic stem cell transplantation but who do not qualify for a myeloablative allogeneic hematopoietic stem cell transplantation
A second hematopoietic stem cell transplantation (allogeneic or autologous) is considered medically necessary and, therefore, covered to manage relapsed non-Hodgkin's lymphoma if the initial hematopoietic stem cell transplantation was followed by a disease-free interval of at least 1 year.

Experimental/Investigational

Allogeneic hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for any of the following:
    • As initial therapy (i.e., without a full course of standard-dose induction chemotherapy) for any non-Hodgkin's lymphoma
    • To consolidate a first complete remission in individuals with diffuse large B-cell lymphoma and an age-adjusted International Prognostic Index score that predicts a low or low-intermediate risk of relapse
    • To consolidate a first complete remission in individuals with indolent (slow growing) non-Hodgkin's lymphoma B-cell subtypes
    • Tandem transplants to treat individuals with any stage, grade, or subtype of non-Hodgkin's lymphoma
    • To consolidate a first remission in individuals with mantle cell lymphoma
    • To consolidate a first remission in individuals with mature T-cell or NK-cell (peripheral T-cell) neoplasms

POEMS SYNDROME

MEDICALLY NECESSARY
Autologous hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the treatment of disseminated POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes) Syndrome.

EXPERIMENTAL/INVESTIGATIONAL
Allogeneic hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for the treatment of POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes) Syndrome.

Tandem hematopoietic stem cell transplantation (either autologous-autologous or autologous-allogeneic) is considered experimental/investigational and, therefore, not covered for the treatment of POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes) Syndrome.

SOLID TUMORS IN ADULTS

EXPERIMENTAL/INVESTIGATIONAL
Autologous and allogeneic hematopoietic stem cell transplantation are considered experimental/investigational and, therefore, not covered, for the following malignancies in adults:

    • Cancer of the bile duct
    • Cancer of the fallopian tubes
    • Cervical cancer
    • Colon cancer
    • Epithelial ovarian cancer
    • Esophageal cancer
    • Gall bladder cancer
    • Lung cancer, any histology
    • Malignant melanoma
    • Nasopharyngeal cancer
    • Neuroendocrine tumors
    • Pancreatic cancer
    • Paranasal sinus cancer
    • Prostate cancer
    • Rectal cancer
    • Renal cell cancer
    • Soft tissue sarcomas
    • Stomach cancer
    • Thyroid tumors
    • Tumors of the thymus
    • Tumors of unknown primary origin
    • Uterine cancer

SOLID TUMORS OF CHILDHOOD

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Medically Necessary

Autologous hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the following:
    • Ewing's sarcoma, for any of the following:
      • Initial treatment of high-risk Ewing's sarcoma
      • Treatment of recurrent or refractory Ewing's sarcoma
    • Neuroblastomas, for any of the following:
      • Initial treatment of high-risk neuroblastomas
      • Treatment of recurrent or refractory neuroblastomas
    • Metastatic retinoblastoma
Tandem autologous hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for:
    • High-risk neuroblastoma

Experimental/Investigational

Autologous hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for the following:
    • Initial treatment of low- or intermediate-risk Ewing's sarcoma
    • Initial treatment of low- or intermediate-risk neuroblastoma
    • Tandem autologous hematopoietic stem cell transplantation for the treatment of all other types of pediatric solid tumors (with the exception of high-risk neuroblastoma)
Autologous hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for the treatment of other solid tumors of childhood such as, but not limited to:
    • Wilms’ tumor
      • With the following exception: for New Jersey members, per New Jersey state mandate/benefits, treatment of Wilms' tumor includes, but is not limited to, autologous bone marrow transplants when standard chemotherapy treatment is unsuccessful
    • Retinoblastoma without metastasis
    • Osteosarcoma
    • Rhabdomyosarcoma

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Experimental/Investigational

Allogeneic hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for the following:
    • Myeloablative or nonmyeloablative allogeneic hematopoietic stem cell transplantation for the treatment of pediatric solid tumors
    • As salvage therapy for pediatric solid tumors that relapse after autologous hematopoietic stem cell transplantation or fail to respond to autologous hematopoietic stem cell transplantation
Allogeneic hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for the treatment of solid tumors of childhood such as, but not limited to:
    • Wilms’ tumor
      • With the following exception: for New Jersey members, per New Jersey state mandate/benefits, treatment of Wilms' tumor includes, but is not limited to, autologous bone marrow transplant when standard chemotherapy is unsuccessful
    • Retinoblastoma
    • Osteosarcoma
    • Rhabdomyosarcoma

TUMORS OF THE CENTRAL NERVOUS SYSTEM

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Embryonal Tumors and Ependymoma

Medically Necessary

Autologous hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered for the following:
    • To treat recurrent embryonal tumors of the central nervous system (e.g., medulloblastoma, neuroblastoma arising in the central nervous system, ependymoblastoma, pineoblastoma)
    • As consolidation therapy for previously untreated embryonal tumors of the central nervous system that show partial or complete response to induction chemotherapy, or stable disease after induction therapy
Experimental/Investigational

Autologous hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for the treatment of ependymoma.

Tandem autologous hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for the following:

    • To treat embryonal tumors of the central nervous system
    • To treat ependymoma

Astrocytomas and Gliomas

Experimental/Investigational

Autologous hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for the treatment of malignant astrocytomas and gliomas (including both glioblastoma multiforme and oligodendroglioma).


ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Embryonal Tumors and Ependymoma

Experimental/Investigational

Allogeneic hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered, for the following:

    • To treat embryonal tumors of the central nervous system
    • To treat ependymoma

WALDENSTROM MACROGLOBULINEMIA

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Medically Necessary

Autologous hematopoietic stem cell transplantation is considered medically necessary and, therefore, covered as salvage therapy of chemosensitive Waldenström macroglobulinemia (lymphoplasmacytic lymphoma).


ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Experimental/Investigational

Allogeneic hematopoietic stem cell transplantation is considered experimental/investigational and, therefore, not covered for the treatment of Waldenström macroglobulinemia (lymphoplasmacytic lymphoma).

SYNGENEIC TRANSPLANTATION

MEDICALLY NECESSARY
Syngeneic hematopoietic stem cell transplantation (transplantation between identical twins) is considered medically necessary and, therefore, covered for the following:

    • When the individual's condition meets the medical necessity criteria for Allogeneic (related donor) Hematopoietic Stem Cell Transplantation.

DONOR LYMPHOCYTE INFUSION

MEDICALLY NECESSARY
Donor lymphocyte infusion is considered medically necessary and, therefore, covered following allogeneic hematopoietic stem cell transplantation (HSCT) that was originally considered medically necessary for the treatment of a hematologic malignancy that has relapsed or is refractory, to prevent relapse in the setting of a high risk of relapse, or to convert an individual from mixed to full donor chimerism.

EXPERIMENTAL/INVESTIGATIONAL
Donor lymphocyte infusion following allogeneic hematopoietic stem cell transplantation (HSCT) that was originally considered experimental/investigational for the treatment of a hematologic malignancy is considered experimental/investigational and, therefore, not covered because its safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.

Donor lymphocyte infusion for the treatment of nonhematologic malignancies following a prior allogeneic hematopoietic stem cell transplantation (HSCT) is considered experimental/investigational and, therefore, not covered because its safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.

Genetic or other modification of donor lymphocytes is considered experimental/investigational and, therefore, not covered because its safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.

UMBILICAL CORD BLOOD

MEDICALLY NECESSARY
The collection and storage of cord blood from a newborn is considered medically necessary and, therefore, covered, when an allogeneic transplant is imminent in an identified recipient with a condition that is medically appropriate for an allogeneic transplant. No other scenarios for cord blood collection and storage are covered by the Company.

For individuals who do not have a hematopoietic stem cell donor, transplantation of cord blood cells from a related or unrelated donor is considered medically necessary and, therefore, covered if the individual meets the medical necessity criteria outlined above for both the medical condition and allogeneic hematopoietic stem cell transplantation.

NOT MEDICALLY NECESSARY
Prophylactic collection and storage of cord blood for future allogeneic or autologous stem cell transplantation is considered not medically necessary and, therefore, not covered when proposed for an unspecified future use as an autologous stem cell transplant in the original donor, or for an unspecified future use as an allogeneic stem cell transplant in a related or unrelated donor.

EXPERIMENTAL/INVESTIGATIONAL
Transplantation of cord blood stem cells from related or unrelated donors in all other situations is considered experimental/investigational and, therefore, not covered because the safety and/or efficacy of this service cannot be established by review of the available published peer-reviewed literature.

COLONY-STIMULATING FACTORS

FDA-approved granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are considered medically necessary and, therefore, covered when used to mobilize hematopoietic stem cells into the peripheral blood for collection and subsequent transplantation in individuals who meet medically necessary criteria for hematopoietic stem cell transplantation.

Colony-stimulating factors (G-CSF or GM-CSF) are considered experimental/investigational and, therefore, not covered for all other indications because their safety and/or effectiveness cannot be established by review of the available published peer-reviewed literature.

FDA-approved colony-stimulating factors (G-CSF or GM-CSF) used to mobilize peripheral blood progenitor cells for hematopoietic stem cell transplantation include:
  • Granix® (tbo-filgrastim)
  • Leukine® (sargramostim)
  • Mozobil® (plerixafor)
  • Neulasta® (pegfilgrastim)
  • Neupogen® (filgrastim)
  • NivestymTM (filgrastim-aafi)
  • Zarxio® (filgrastim-sndz)

For medical necessity criteria on Neulasta® (pegfilgrastim), refer to medical policy 08.01.32 Pegfilgrastim (Neulasta®).

BONE MARROW DONOR SEARCH

Bone marrow donor searches are eligible for reimbursement in increments of five potential donors, in order to avoid screening more potential donors than necessary.
Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, hematopoietic stem cell transplantation is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in the medical policy are met.

However, services that are identified in this policy as experimental/investigational or not medically necessary are not eligible for coverage or reimbursement by the Company.

DEFINITIONS OF TERMS

A near complete response is the disappearance of M protein at routine electrophoresis, but positive immunofixation.

A very good partial response is a 90% decrease in the serum paraprotein level.

Allogeneic stem cell transplantation uses stem cells from a matched related or unrelated donor.

Apheresis (also known as pheresis) is a procedure in which blood is collected, part of the blood (such as platelets or white blood cells) is harvested, and the rest of the blood is returned to the donor.

Autoimmune disease is an illness that occurs when the body tissues are attacked by its own immune system. Individuals with autoimmune diseases frequently have unusual antibodies circulating in their blood that target their own body tissues. Examples of autoimmune diseases include systemic lupus erythematosus, Sjogren syndrome, Hashimoto thyroiditis, rheumatoid arthritis, juvenile (type 1) diabetes, polymyositis, scleroderma, Addison disease, vitiligo, pernicious anemia, glomerulonephritis, and pulmonary fibrosis.

Autologous stem cell transplantation uses stem cells from the same individual who will get the transplant.

Chemosensitive disease tumors are those that respond to standard-dose chemotherapy with a minimum 50 percent reduction in size.

Colony-stimulating factor is a group of proteins that causes blood cells to grow and mature.

Complete response (also known as complete remission) is the disappearance of all signs of cancer in response to treatment; this does not always mean the cancer has been cured.

Donor lymphocyte infusion is a type of therapy in which lymphocytes from the blood of a donor are given to an individual who has already received a stem cell transplant from the same donor. The donor lymphocytes may kill remaining cancer cells. Donor lymphocyte infusion is used to treat conditions that have recurred, such as chronic myeloid leukemia, and myeloma. It is being studied in the treatment of other types of cancer.

Human leukocyte antigen (also known as human lymphocyte antigen) is one of a group of proteins found on the surface of white blood cells and other cells that plays an important part in the body's immune response to foreign substances. These antigens vary from person to person. Human leukocyte antigen tests are done prior to organ transplantation to determine whether the donor and recipient tissues match.

Indolent cancer is a type of cancer that grows slowly.

Myeloablation (also known as severe myelosuppression) is a severe form of myelosuppression. Myelosuppression is a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. It is a side effect of some cancer treatments.

Nonmyeloablative (also known as reduced-intensity or mini-transplant) is a bone marrow transplant in which the individual's marrow is not completely destroyed prior to receiving the donor's marrow or stem cells.

Partial tumor response is defined as at least a 50 percent reduction in tumor burden.

Primary refractory acute myeloid leukemia is leukemia that does not achieve a complete remission after conventionally dosed (non-marrow ablative) chemotherapy.

Primary refractory Hodgkin's lymphoma is, generally, a progression of disease during induction therapy or a partial or transient response (less than 60 days) to induction therapy.

Refractory cancer is cancer that does not respond to treatment. The cancer may be resistant at the beginning of treatment, or it may become resistant during treatment. Also called resistant cancer.

Refractory tumors are tumors that exhibit less than 50 percent reduction in size.

Relapse tumors are tumors that recur after a prior complete response.

Salvage therapy is treatment that is given after the cancer has not responded to other treatments.

Single stem cell transplantation consists of two types: autologous or allogeneic.

Tandem stem cell transplantation consists of two stem cell transplants that are performed within a period time to treat a condition. Tandem stem cell transplants can be autlogous/autologous or autologous/allogeneic.

EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS

Stage
Description
0
Fully active, able to carry on all pre-disease performance without restriction.
1
Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g., light house work, office work).
2
Ambulatory and capable of all selfcare, but unable to carry out any work activities. Up and about more than 50% of waking hours.
3
Capable of only limited selfcare. Confined to bed or chair more than 50% of waking hours.
4
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair.
5
Dead


KARNOFSKY PERFORMANCE STATUS

The Karnofsky Performance Status is a standard way of measuring the ability of individuals with cancer to perform ordinary tasks. The scores on the scale range from 0 to 100. A higher score means the individual is better able to carry out daily activities. The Karnofsky Performance Status may be used to determine an individual's prognosis, to measure changes in an individual's ability to function, or to decide whether an individual could be included in a clinical trial.

ACUTE LYMPHOBLASTIC LEUKEMIA

Adverse prognostic factors in children include:
  • Age younger than 1 year or more than 9 years
  • Male sex
  • White blood cell count at presentation above 50,000/μL
  • Hypodiploidy (<45 chromosomes)
  • Translocation involving chromosomes 9 and 22 (t[9;22]) or BCR-ABL fusion
  • Translocation involving chromosomes 4 and 11 (t[4;11]) or MLL-AF4 fusion
  • ProB or T-lineage immunophenotype

Risk factors associated with a high risk of relapse following initial complete remission of childhood lymphoblastic leukemia include:
  • Poor response to initial therapy including poor response to prednisone prophase defined as an absolute blast count of 1000/μL or greater, or poor treatment response to induction therapy at 6 weeks with high-risk having 1% or higher minimal residual disease measured by flow cytometry
  • All children with T-cell phenotype
  • Individuals with either the t(9;22) or t(4;11) regardless of early response measures

Risk factors associated with a high risk of relapse following initial complete remission of adult lymphoblastic leukemia include:
  • Age greater than 35 years
  • Leukocytosis at presentation of greater than 30,000/µL (B-cell lineage) or greater than 100,000/µL (T-cell lineage)
  • Chromosomal abnormalities, including Philadelphia chromosome (t[9;22])
  • Extramedullary disease, particularly in the central nervous system
  • Failure to achieve a complete remission within 4 weeks after induction therapy begins


ACUTE MYELOID LEUKEMIA: WORLD HEALTH ORGANIZATION

The World Health Organization recognizes five major subcategories of acute myeloid leukemia:
  • Acute myeloid leukemia with recurrent genetic abnormalities
  • Acute myeloid leukemia with multilineage dysplasia
  • Therapy-related acute myeloid leukemia and myelodysplasia
  • Acute myeloid leukemia not otherwise categorized
  • Acute leukemia of ambiguous lineage


MARKERS OF POOR PROGNOSIS IN CHRONIC LYMPHOCYTIC LEUKEMIA AND SMALL LYMPHOCYTIC LEUKEMIA

COMMUNITY CENTER
  • Advanced Rai or Binet stage
  • Male sex
  • Atypical morphology or chronic lymphocytic/small lymphocytic leukemia
  • Peripheral lymphocyte doubling time less than 12 months
  • CD38+
  • Elevated beta2-microglobulin level
  • Diffuse marrow histology
  • Elevated serum lactate dehydrogenase level
  • Fludarabine resistance

SPECIALIZED CENTERS
  • IgVh wild type
  • Expression of ZAP-70 protein
  • del 11q22-q23 (loss of ATM gene)
  • del 17p13/variant TP53
  • Trisomy 12
  • Elevated serum CD23
  • Elevated serum tumor necrosis factor-alpha
  • Elevated serum thymidine kinase

CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LEUKEMIA: CLASSIFICATION (STAGING AND PROGNOSIS)
    Stage 0: Low, Lymphocytosis

    Stage I: Intermediate, Lymphocytosis plus lymphadenopathy

    Stage II: Intermediate, Lymphocytosis plus splenomegaly plus/minus lymphadenopathy

    Stage III: High, Lymphocytosis plus anemia plus/minus lymphadenopathy or splenomegaly

    Stage IV: High, Lymphocytosis plus thrombocytopenia plus/minus anemia, splenomegaly, or lymphadenopathy



CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LEUKEMIA: BINET CLASSIFICATION
    BINET STAGE

    Stage A: ≤3 lymphoid areas, normal hemoglobin and platelets

    Stage B: ≥3 lymphoid areas, normal hemoglobin and platelets

    Stage C: Any number of lymphoid areas, anemia, thrombocytopenia



HODGKIN'S LYMPHOMA: WORLD HEALTH ORGANIZATION

The World Health Organization divides Hodgkin's lymphoma into two main types:
  • Classic Hodgkin's lymphoma
    • Accounts for 95 percent of Hodgkin's lymphoma cases
    • Characterized by the presence of neoplastic Reed-Sternberg cells in a background of numerous non-neoplastic inflammatory cells
  • Nodular lymphocyte-predominant Hodgkin's lymphoma
    • Accounts for 5 percent of Hodgkin's lymphoma cases
    • Characterized by the presence of lymphocytic and histiocytic cells termed "popcorn cells"


LYMPHOMA: ANN ARBOR CLASSIFICATION

The Ann Arbor Staging Classification is commonly used for the staging of lymphomas and is the scheme defined in the American Joint Committee on Cancer Manual for Staging Cancer. Originally developed for Hodgkin's lymphoma, this staging scheme was later expanded to include non-Hodgkin's lymphoma.
    STAGE I
    Single lymph node region (I), or localized involvement of a single extralymphatic organ or site (IE)


    STAGE II
    Two or more lymph node regions on the same side of the diaphragm (II), or localized involvement of a single associated extralymphatic organ or site and its regional lymph node(s) with or without involvement of other lymph node regions on the same side of the diaphragm (IIE).

    STAGE III
    Involvement of lymph node regions or structures on both sides of the diaphragm. These individuals are further subdivided as follows:

    • III-1: disease limited to spleen or upper abdomen
    • III-2: periaortic or pelvic node involvement

    STAGE IV
    Disseminated (multifocal) involvement of 1 or more extralymphatic organs, with or without associated lymph node involvement, or isolated extralymphatic organ involvement with distant (nonregional) nodal
    involvement.


MYELOMA: DURIE-SALMON STAGING SYSTEM

STAGE I: All of the following:
  • Hemoglobin value > 10 g/dL
  • Serum calcium value normal or ≤ 12 mg/dL
  • On bone x-ray, normal bone structure (scale 0) or solitary bone plasmacytoma only
  • Low M-component production rate (IgG value < 5 g/dL; IgA value < 3 g/dL)
  • Urine light chain M-component on electrophoresis < 4 g/24 h

STAGE II
  • Neither stage I nor stage III

STAGE III: One or more of the following:
  • Hemoglobin value < 8.5 g/dL
  • Serum calcium value > 12 mg/dL
  • Advanced lytic bone lesions (scale 3)
  • High M-component production rates (IgG value > 7 g/dL; IgA value > 5 g/dL)
  • Urine light chain M-component on electrophoresis > 12 g/24 h

SUBCLASSIFICATION
    A = Relatively normal renal function (serum creatinine < 2.0 mg/dL)

    B = Abnormal renal function (serum creatinine ≥ 2.0 mg/dL)


NEUROBLASTOMA: INTERNATIONAL NEUROBLASTOMA STAGING SYSTEM

Stage
Description
Stage I Localized tumor with complete gross excision, with or without minimal residual disease; lymph nodes negative for tumor
Stage IIA Localized tumor with incomplete gross excision; lymph nodes negative for tumor
Stage IIB Localized tumor with incomplete gross excision; ipsilateral lymph nodes positive for tumor
Stage III Unresectable unilateral tumor infiltrating across the midline, with or without regional lymph node involvement; or localized unilateral tumor with contralateral regional lymph node involvement; or midline tumor with bilateral extension by infiltration or by lymph node involvement
Stage IV Any primary tumor with dissemination to distant lymph nodes, bone marrow, liver, skin, or other organs (except as defined as Stage IVS)
Stage IVS Localized primary tumor with dissemination limited to skin, liver, or bone marrow, less than 10 percent of cells identified as malignant, limited to infants younger than 1 year of age


NON-HODGKIN'S LYMPHOMA: INTERNATIONAL PROGNOSTIC INDEX SCORE

The International Lymphoma Classification Project identified the most common non-Hodgkin's subtypes as follows: diffuse large B-cell lymphoma, 31 percent; follicular lymphoma, 22 percent; small lymphocytic lymphoma/chronic lymphocytic leukemia, 6 percent; mantle cell lymphoma, 6 percent; peripheral T-cell lymphoma, 6 percent; and marginal zone B-cell lymphoma/mucosa--associated lymphoid tissue lymphoma, 5 percent. All other subtypes each represent less than 2 percent of cases of non-Hodgkin's lymphoma.

Based on the number of risk factors present and adjusted for patient age, the International Prognostic Index defines four risk groups: low, low-intermediate, high-intermediate, and high, based on five significant risk factors prognostic of overall survival:

1.Age older than 60 years
2.Elevated serum lactate dehydrogenase (LDH) level
3.Ann Arbor Stage III or IV disease
4.Eastern Cooperative Oncology Group Performance Status of 2, 3, or 4
5.Involvement of more than one extranodal site

Risk groups are stratified according to the number of adverse factors as follows: 0 or 1 is low risk, 2 is low-intermediate risk, 3 is high-intermediate risk, and 4 or 5 is high risk.

Individuals with two or more risk factors have a less than 50 percent chance of relapse-free survival and overall survival at 5 years. Age-adjusted International Prognostic Index and stage-adjusted modifications of this index are used for younger individuals with localized disease.

Adverse risk factors for age-adjusted International Prognostic Index include Stage III or IV disease, elevated lactate dehydrogenase level, and Eastern Cooperative Oncology Group Performance Status greater than or equal to 2, and can be calculated as follows: 0 is low risk, 1 is low-intermediate risk, 2 is high-intermediate risk, and 3 is high risk.

BILLING FOR COLLECTION AND STORAGE OF CORD BLOOD

It is inappropriate to report the collection and storage of cord blood when it does not meet the medical necessity requirements listed in the Policy section above.

Description

Traditionally, high-dose chemotherapy, also known as myeloablative therapy, and extensive radiation therapy have been used to treat certain drug-resistant cancers or relapsed diseases. High-dose chemotherapy and radiation generally affect cells that divide rapidly, and cancer cells divide more often than most healthy cells. High-dose chemotherapy involves the administration of cytotoxic agents at doses several times greater than the standard therapeutic dose.

The rationale for high-dose chemotherapy is that many chemotherapeutic agents act according to a steep dose-response curve. Small increments in drug dosage result in relatively large increases in tumor cell destruction. The limiting dynamic of high-dose chemotherapy and radiation therapy is the toxic effect that these treatments have on bone marrow cells. Although high-dose chemotherapy kills the tumor cells, it also increases the incidence and severity of adverse effects associated with chemotherapy, such as bone marrow destruction (myeloablation), opportunistic infection, hemorrhage, and organ failure.

Bone marrow is a soft, spongelike material found inside bones. Bone marrow contains cells known as hematopoietic, or blood-forming, cells. Hematopoietic stem cells either divide to form additional blood-forming stem cells, or they mature to form one of three types of cells: white cells (leukocytes), red blood cells (erythrocytes), or platelets. Most hematopoietic stem cells are found in bone marrow, but some are also found in the bloodstream and are known as peripheral blood stem cells. Blood in the umbilical cord also contains hematopoietic stem cells. In individuals who have undergone high-dose chemotherapy and radiation, hematopoietic stem cell transplantation can be used to regenerate bone marrow and aid in the development of mature blood cell products, thereby decreasing the incidence of life-threatening conditions and aiding in the individual's recovery.

STEM CELL TRANSPLANTATION

Hematopoietic stem cell transplantation (also referred to as bone marrow transplantation) and peripheral
blood stem cell transplantation are used to restore stem cells destroyed by high-dose chemotherapy and radiation therapy. Transplantation is accomplished in the same manner as a blood transfusion.

The transplantation of hematopoietic stem cells is an adjunctive therapy and follows the administration of high-dose chemotherapy and/or whole-body or localized radiotherapy prior to the transplant. The transplantation of hematopoietic stem cells has been found to increase the efficacy of high-dose chemotherapy and/or radiotherapy in the treatment of certain conditions such as leukemia, lymphomas (e.g, Hodgkin's lymphoma), aplastic anemia, and some inherited immune disorders.

TYPES OF STEM CELL TRANSPLANTATION

Transplants are classified as one of three types:
  • Autologous: an individual receives his or her own stem cells
  • Allogeneic: an individual receives stem cells from a related or unrelated donor with a human leukocyte antigen (HLA) match
  • Syngeneic: an individual receives stem cells from his or her identical twin

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
In autologous hematopoietic stem cell transplantation, the individual receives his or her own stem cells, which were harvested prior to myeloablative therapy and are relatively cancer-free. Myeloablative chemotherapy is performed to eradicate cancerous cells from the blood and bone marrow, thereby permitting subsequent engraftment and repopulation of bone marrow space with presumably normal hematopoietic progenitor cells or cells that allow themselves to differentiate from other cells. As a result, autologous stem cell transplantation is typically performed as consolidation therapy when the individual's disease is in complete remission. Individuals who receive autologous stem cell transplantation are susceptible to chemotherapy-related toxicities and opportunistic infections prior to engraftment, but not graft-versus-host disease.


High-dose chemotherapy, in conjunction with autologous hematopoietic stem cell transplantation, is the established standard of therapy for various malignancies such as acute myelogenous leukemia, multiple myeloma, and non-Hodgkin's lymphoma. Autologous hematopoietic stem cell transplantation is also preferred for the elderly, for individuals who have acute lymphocytic leukemia, or for individuals who lack a donor with suitable HLA typing. HLAs are a set of proteins that are found on the surface of cells and are identifiable by a special blood test. The higher the number of matching HLAs between the individuals, the greater the chance that the recipient will accept the donor’s stem cells.

Advantages of autologous transplants include the reduced toxicity that is associated with treatment and an extended, disease-free survival time, most often without the need for additional treatment.

Tandem transplantation is a type of autologous hematopoietic stem cell transplantation in which the individual receives two sequential courses of high-dose chemotherapy that are typically given several weeks to several months apart.

ALLOGENEIC AND SYNGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Allogeneic hematopoietic stem cell transplantation involves using hematopoietic stem cells harvested from a donor. The success of the transplant depends in part on how well the HLAs of the donor’s stem cells match those of the recipient’s stem cells.


Close relatives, especially siblings, are more likely than unrelated individuals to be HLA-matched; however, only 25 to 35 percent of transplant candidates have a sibling who is an HLA match. Identical twins, having identical genes, also have the same HLAs; an individual's body will, therefore, accept a stem cell transplantation from his or her identical twin. However, identical twins represent a small number of all births, so syngeneic transplantation is rare.

STAGES OF TRANSPLANTATION

Hematopoietic stem cell transplantation involves the mobilization, harvesting, and transplantation of hematopoietic stem cells that have been collected from bone marrow or peripheral blood.

MOBILIZATION
Preparing for a hematopoietic stem cell transplantation first requires stem cell mobilization. Mobilization makes harvesting more efficient and occurs when the accumulation of stem cells has reached its highest level.
Prior to harvesting, autologous blood stem cell donors are occasionally given a course of chemotherapy to destroy some of the malignant tumors in their body. This low-dose chemotherapy reduces the risk for tumor contamination and facilitates the filtering of stem cells for collection. Autologous donors may also receive injections of a colony-stimulating factor. Colony-stimulating factors are groups of proteins that cause blood cells to grow and mature, which facilitates mobilization. In some cases, a combination of chemotherapy and colony-stimulating factor is used.

In allogeneic donors, mobilization is accomplished through a series of subcutaneous injections of colony-stimulating factors (i.e., granulocyte colony-stimulating factor [G-CSF] or granulocyte-macrophage colony-stimulating factor [GM-CSF]). Typically, the colony-stimulating factor is administered for 4 to 5 days, followed by apheresis, which generally occurs over the next day or two. Apheresis, also called pheresis, is a procedure in which blood is collected, the stem cells are removed, and the remaining blood is given back to the donor. The stem cells are frozen until they are given to the recipient.

HARVESTING
After mobilization, hematopoietic stem cells can be harvested from bone marrow and/or peripheral blood. Harvesting from bone marrow involves inserting a hollow needle into the pelvic (hip) bone or, in rare cases, the sternum (breastbone), under general or regional anesthesia. The procedure takes about 1 hour. The cells are harvested prior to myeloablative therapy. The harvested cells can sometimes be treated before transplantation in a process known as purging. This process reduces the number of cancer cells, thereby minimizing the likelihood that cancer will recur.

Because purging may damage healthy stem cells, an excess of cells is removed from the individual prior to transplantation so that an adequate supply of healthy stem cells will remain after purging.

In most instances, the harvested marrow is filtered and given to the recipient on the same or next day. If the transplantation cannot occur within that timeframe, the marrow can be combined with a preservative solution and frozen until needed. Known as cryoablation, this technique can preserve the harvested marrow for years. When the recipient is ready to receive the marrow, it is thawed and transfused in a procedure that is similar to a blood transfusion. The hematopoietic stem cells are then drawn to the bone marrow, where they start to grow and produce new blood cells.

In individuals undergoing peripheral blood stem cell transplantation, stem cells are removed from the bloodstream via apheresis. The purpose of therapeutic apheresis is to remove a component of the blood that contributes to an illness. In apheresis, blood is removed through a large vein in the arm or a central venous catheter (a flexible tube that is placed in a large vein in the neck, chest, or groin area) and sent to sterile equipment, where it is separated into various components, such as red cells, white cells, and plasma. Healthy parts of the blood are then returned to the individual. Apheresis typically takes 4 to 6 hours. For 4 or 5 days before apheresis, the donor may be given a medication to increase the number of stem cells released into the bloodstream.

TRANSPLANTATION
Upon entering the bloodstream, the stem cells travel to the bone marrow, where they begin to produce new white blood cells, red blood cells, and platelets in a process known as engraftment. Engraftment typically occurs within 2 to 4 weeks after transplantation, and is monitored by blood counts. Following the transplant, full recovery of the immune system may take several months for autologous transplantation recipients and as much as 1 to 2 years for individuals receiving allogeneic or syngeneic transplantations. A bone marrow aspiration may also be performed to determine the progress of the new marrow.

UMBILICAL CORD STEM CELL TRANSPLANTATION

Umbilical cord hematopoietic stem cells are harvested from the placenta via the umbilical cord, post-delivery. The blood in the placenta is rich in hematopoietic stem cells (commonly known as naive cells), which are easily collected in a process that poses no risk to the donor (the newborn) because the newborn has been separated from the placenta, and the placenta is considered a disposable organ. Cord blood requires no mobilization; once collected, it is mixed in a preservative solution and stored at a very low temperature until needed. Umbilical cord stem cells are typically used for children, future offspring, or adults of small stature.

OTHER TREATMENTS FOR HEMATOLOGIC MALIGNANCY

Treatment options are very limited for individuals with a hematologic malignancy who have experienced a relapse after allogeneic hematopoietic stem cell transplantation. Studies have shown that these individuals may respond to a form of adoptive immunotherapy in which they receive an infusion of lymphocytes that are acquired from the individual's original stem cell donor. To obtain the necessary lymphocytes, the original donor undergoes leukapheresis, which is similar to the apheresis procedure used during stem cell harvesting. The collected lymphocytes are then infused into the recipient. The donor-lymphocyte infusion, also known as a donor-leukocyte or buffy-coat infusion, aims to induce a beneficial graft-versus-tumor response to eradicate the malignant cells without the need for an additional hematopoietic stem cell harvest from the donor or further high-dose chemotherapy for the recipient.

In response to the potential adverse results of high-dose chemotherapy and other myeloablative therapies, new treatment regimens are being investigated in the hopes of reducing treatment-related adverse effects while retaining beneficial graft-versus-tumor effects.
References

See Attachment A in this policy for the full list of references.



Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

38204, 38205, 38206, 38207, 38208, 38209, 38210, 38211, 38212, 38213, 38214, 38215, 38220, 38221, 38222, 38230, 38232, 38240, 38241, 38242, 38243, 81370, 81371, 81372, 81373, 81374, 81375, 81376, 81377, 81378, 81379, 81380, 81381, 81382, 81383, 86812, 86813, 86816, 86817, 86821, 86825, 86826, 86828, 86829, 86830, 86831, 86832, 86833, 86834, 86835, 86849


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

N/A


HCPCS Level II Code Number(s)

C1830 Powered bone marrow biopsy needle


J1442 Injection, filgrastim (g-csf), excludes biosimilars, 1 microgram

J1447 Injection, tbo-filgrastim, 1 microgram

J2505 Injection, pegfilgrastim, 6 mg

J2562 Injection, plerixafor, 1 mg

J2820 Injection, sargramostim (GM-CSF), 50 mcg

Q5101 Injection, filgrastim-sndz, biosimilar, (zarxio), 1 microgram

Q5110 Injection, filgrastim-aafi, biosimilar, (nivestym), 1 microgram

S2140 Cord blood harvesting for transplantation, allogeneic

S2142 Cord blood-derived stem-cell transplantation, allogeneic

S2150 Bone marrow or blood-derived stem cells (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; including pheresis and cell preparation/storage; marrow ablative therapy; drugs, supplies, hospitalization with outpatient follow-up; medical/surgical, diagnostic, emergency, and rehabilitative services; and the number of days of pre- and post-transplant care in the global definition

S9537 Home therapy; hematopoietic hormone injection therapy (e.g., erythropoietin, G-CSF, GM-CSF); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem



Revenue Code Number(s)

0815 Acquisition of body components – stem cells - allogeneic

Coding and Billing Requirements


Cross References

Attachment A: Hematopoietic Stem Cell Transplantation (Bone Marrow Transplant)
Description: References for the hematopoietic stem cell transplantation policy.




Policy History

11.07.01t
09/23/2019The following revisions were made to this policy:

POLICY SECTION

The following disease categories were created:
  • Amyloidosis (Primary)
  • Genetic Diseases and Acquired Anemias
  • Germ Cell Tumors
  • Myelodyspastic Syndromes (MDS) and Myeloproliferative Neoplasms (MPN)
  • POEMS Syndrome
  • Solid Tumors in Adults
  • Waldenstrom Macroglobulinemia


The following disease categories were revised:
  • AUTOIMMUNE DISEASES
    Autologous Hematopoietic Stem Cell Transplantation is now considered Medically Necessary for the treatment of Systemic sclerosis/scleroderma when the medically necessary criteria in the policy are met.
  • GENETIC DISEASES AND ACQUIRED ANEMIAS
    Criteria was revised for Allogeneic Hematopoietic Stem Cell Transplantation when used to treat Bone Marrow Failure Syndromes and Hemoglobinopathies.

    Under Inherited Metabolic Diseases, a number of Lysosomal and Peroxisomal Storage Disorders were added as Medically Necessary.
  • GERM CELL TUMORS
    Language was added regarding favorable and unfavorable prognostic factors.

    Language regarding Tandem Autologous Hematopoietic Stem Cell Transplantation for Germ-Cell Tumors was revised.
  • LEUKEMIA

    "Acute lymphocytic leukemia" was revised to "acute lymphoblastic leukemia" throughout the policy.

    "Acute myelogenous leukemia" was revised to "acute myeloid leukemia" throughout the policy.

    "Chronic myelogenous leukemia" was revised to "chronic myeloid leukemia" throughout the policy.

    The following sub-categories for leukemia were created:

      • Acute Lymphoblastic Leukemia
      • Acute Myeloid Leukemia
      • Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma
      • Chronic Myeloid Leukemia

    ACUTE LYMPHOBLASTIC LEUKEMIA

    Language has been added indicating that Autologous and Allogeneic hematopoietic stem cell transplantation is considered Experimental/Investigational in individuals not meeting medically necessary criteria.

    Language has been revised for reduced-intensity conditioning allogenic hematopoietic stem cell transplantation.

    ACUTE MYELOID LEUKEMIA

    Language has been added indicating that Autologous and Allogeneic hematopoietic stem cell transplantation is considered Experimental/Investigational in individuals not meeting medically necessary criteria.

    Language has been revised for reduced-intensity conditioning allogenic hematopoietic stem cell transplantation.

    CHRONIC LYMPHOCYTIC LEUKEMIA / SMALL LYMPHOCYTIC LYMPHOMA

    Language has been added indicating that Allogeneic hematopoietic stem cell transplantation is considered Experimental/Investigational in individuals not meeting medically necessary criteria.

    CHRONIC MYELOID LEUKEMIA

    Language has been added indicating that Allogeneic hematopoietic stem cell transplantation is considered Experimental/Investigational in individuals not meeting medically necessary criteria.

  • OTHER MALIGNANCIES AND DISEASES
    All indications under "Other Malignancies and Disease" have been removed from this policy because they are now addressed in other disease categories.
  • COLONY-STIMULATING FACTORS
    The following list FDA-approved colony-stimulating factors (G-CSF or GM-CSF) were added to the policy:
      • Granix® (tbo-filgrastim)
      • Leukine® (sargramostim)
      • Mozobil® (plerixafor)
      • Neulasta® (pegfilgrastim)
      • Neupogen® (filgrastim)
      • NivestymTM (filgrastim-aafi)
      • Zarxio® (filgrastim-sndz)

    The reference to medical policy 08.00.79 Plerixafor Injection (Mozobil®) was removed because the policy has been archived.
    GUIDELINES SECTION
      • Definitions of Allogeneic and Autologous Stem Cell Transplantation, Autoimmune Disease, Single Stem Cell Transplantation, and Tandem Stem Cell Transplantation were added.
    • The following guidelines were updated:
      • Acute Lymphocytic Leukemia
      • Markers of Poor Prognosis in Chronic Lymphocytic Leukemia and Small Lymphocytic Leukemia
      • Lymphoma: Ann Arbor Classification
      • Neuroblastoma: International Neuroblastoma Staging System
    • The following guideline was removed because it is considered to be outdated:
      • Non-Hodgkin's Lymphoma: International Working Formulation Classification

    11.07.01s
    10/01/2018This policy has been identified for the HCPCS code update, effective 10/01/2018.

    The following HCPCS code has been added to this policy: Q5110

    11.07.01r
    04/01/2018This policy has been identified for the HCPCS code update, effective 04/01/2018.

    The following HCPCS narrative has been revised in this policy: Q5101

    11.07.01q:
    01/01/2018This policy has been identified for the CPT code update, effective 01/01/2018.

    The following CPT code has been added to this policy: 38222
    The following CPT code has been termed from this policy: 86822
    The following CPT narratives have been revised in this policy: 38220, 38221


    Effective 10/05/2017 this policy has been updated to the new policy template format.

    Version Effective Date: 09/23/2019
    Version Issued Date: 09/23/2019
    Version Reissued Date: N/A

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