Notification



Notification Issue Date:



Medicare Advantage Policy

Title:Hematopoietic Stem Cell Transplantation
Policy #:MA11.002h

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


The Company makes decisions on coverage based on the Centers for Medicare and Medicaid Services (CMS) regulations and guidance, benefit plan documents and contracts, and the member’s medical history and condition. If CMS does not have a position addressing a service, the Company makes decisions based on Company Policy Bulletins. 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. Although the Medicare Advantage Policy Bulletin is consistent with Medicare’s regulations and guidance, the Company’s payment methodology may differ from Medicare.

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 Policy Bulletin document describes the status of CMS coverage, medical terminology, and/or benefit plan documents and contracts at the time the document was developed. This Policy Bulletin will be reviewed regularly and be updated as Medicare changes their regulations and guidance, scientific and medical literature becomes available, and/or the benefit plan documents and/or contracts are changed.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's Evidence of Coverage.

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.

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 member's benefit.

For medical necessity criteria on pegfilgrastim (Neulasta®), refer to Medicare Advantage policy MA08.082 Pegfilgrastim (Neulasta®).

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.

ALLOGENIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT)

Allogeneic stem cell transplantation (HSCT) is considered medically necessary and, therefore, covered for any of the following indications:
  • Treatment of leukemia, leukemia in remission, or aplastic anemia
  • Treatment of severe combined immunodeficiency disease (SCID) and the treatment of Wiskott-Aldrich syndrome
  • Treatment of myelodysplastic syndromes (MDS) pursuant to Coverage with Evidence Development (CED) in the context of a Medicare-approved, prospective clinical study
  • Treatment of individuals with Durie-Salmon Stage II or III multiple myeloma, or International Staging System (ISS) Stage II or Stage III multiple myeloma pursuant to Coverage with Evidence Development (CED) in the context of a Medicare-approved, prospective clinical study
  • Treatment of individuals with Dynamic International Prognostic Scoring System (DIPSSplus) intermediate-2 or High primary or secondary myelofibrosis (MF) pursuant to Coverage with Evidence Development (CED) in the context of a Medicare-approved, prospective clinical study
  • Treatment of individuals with severe, symptomatic sickle cell disease (SCD) pursuant to Coverage with Evidence Development (CED) in the context of a Medicare-approved, prospective clinical study

AUTOLOGOUS STEM CELL TRANSPLANTATION

Autologous stem cell transplantation (AuSCT) is considered medically necessary and, therefore, covered for any of the following indications:
  • Treatment of individuals with acute leukemia in remission who have a high probability of relapse and who have no human leukocyte antigens (HLA)-matched
  • Treatment of individuals with resistant non-Hodgkin's lymphomas or those presenting with poor prognostic features following an initial response
  • Treatment of individuals with recurrent or refractory neuroblastoma
  • Treatment of individuals with advanced Hodgkin's disease who have failed conventional therapy and have no HLA-matched donor

Single autologous stem cell transplantation is considered medically necessary and, therefore, covered for Durie-Salmon Stage II or III individuals when ALL of the following criteria are met:
  • Newly diagnosed or responsive multiple myeloma. This includes those individuals with previously untreated disease, those with at least a partial response to prior chemotherapy (defined as a 50% decrease either in measurable paraprotein [serum and/or urine] or in bone marrow infiltration, sustained for at least 1 month), and those in responsive relapse; and
  • Adequate cardiac, renal, pulmonary, and hepatic function.

High-dose melphalan (HDM) and autologous stem cell transplantation are considered medically necessary and, therefore, covered when used together for the treatment of primary amyloid light chain (AL) amyloidosis when all of the following criteria are met:
  • Amyloid deposition in 2 or fewer organs; and
  • Cardiac left ventricular ejection fraction (EF) greater than 45%.

EXPERIMENTAL/INVESTIGATIONAL

Autologous stem cell transplantation is considered experimental/investigational and, therefore, not covered for the following conditions because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature:
  • Acute leukemia not in remission
  • Chronic granulocytic leukemia
  • Solid tumors (other than neuroblastoma)
  • Tandem transplantation (multiple rounds of autologous stem cell transplantation) for individuals with multiple myeloma
  • Non-primary amyloid light chain (AL) amyloidosis

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.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.
Policy Guidelines

Subject to the terms and conditions of the applicable Evidence of Coverage, stem cell transplantation is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

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

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 rate (IgG value > 7 g/dL; IgA value > 5 g/dL)
  • Urine light chain M-component on electrophoresis > 12 g/24 h

SUBCLASSIFICATION (either A or B)

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

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

MYELOMA: INTERNATIONAL STAGING SYSTEM

STAGE I

  • Serum beta-2 microglobulin is less than 3.5 mg/L, and
  • Albumin level is 3.5 g/dL or greater

STAGE II

Neither stage I or III, meaning that either:

  • Beta-2 microglobulin level is between 3.5 mg/L and 5.5 mg/L (with any albumin level), OR
  • Albumin is below 3.5 g/dL while the beta-2 microglobulin is less than 3.5 mg/L

STAGE III
  • Serum beta-2 microglobulin is 5.5 mg/L or greater

MYELOFIBROSIS: DYNAMIC INTERNATIONAL PROGNOSTIC SCORING SYSTEM (DIPSS)

The DIPSS plus prognostic score is based on eight risk factors (need for red blood cell transfusion, hemoglobin level, platelet count, leukocyte count, circulating blasts in the blood, constitutional symptoms, unfavorable cytogenetic profile, and age). There are four risk categories based on the DIPSS plus score as shown in the following table:

Risk Category
Number of Risk Factors
LowNone
Intermediate - 11
Intermediate - 22 or 3
High4 or more


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.
References

Centers for Medicare & Medicaid Services (CMS). National Coverage Determination (NCD) for Stem Cell Transplantation Formerly 110.8.1 (110.23). [CMS Web site]. 01/27/2016. Available at: https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=366&ncdver=1&DocID=110.23&bc=gAAAAAgAAAAAAA%3d%3d&. Accessed April 2, 2019.

National Cancer Institute (NCI). National Cancer Institute Fact Sheet. Blood-Forming Stem Cell Transplants. [NCI Web site]. 08/12/2013. Available at: http://www.cancer.gov/about-cancer/treatment/types/stem-cell-transplant/stem-cell-fact-sheet. Accessed April 2, 2019.


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






Policy History

Revisions from MA11.002h
09/23/2019The following changes were made to this policy:

POLICY SECTION

The reference to Medicare Advantage policy MA08.039 Plerixafor Injection (Mozobil®) was removed because the policy has been archived.

Policy statements regarding Autologous Stem Cell Transplantation were revised for clarity with no impact on intent.

GUIDELINES SECTION

The following guideline was updated:
  • Myeloma: Durie-Salmon Staging System

Revisions from MA11.002g
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

Revisions from MA11.002f
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

Revisions from MA11.002e
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

Revisions from MA11.002d
08/25/2017This version of the policy will become effective 08/25/2017.

Statements were added to the policy section (under Colony-Stimulating Factors) regarding where to find medically necessary criteria for Mozobil® (plerixafor injection) and Neulasta® (pegfilgrastim).

The following HCPCS code was added to the Coding Table: J2562.

The following Revenue Code was added to the Coding Table: 0815.

Revisions from MA11.002c
09/09/2016The following indications for allogeneic stem cell transplantation were added as Medically Necessary:
  • Treatment of individuals with Durie-Salmon Stage II or III multiple myeloma, or International Staging System (ISS) Stage II or Stage III multiple myeloma pursuant to Coverage with Evidence Development (CED) in the context of a Medicare-approved, prospective clinical study.
  • Treatment of individuals with Dynamic International Prognostic Scoring System (DIPSSplus) intermediate-2 or High primary or secondary myelofibrosis (MF) pursuant to Coverage with Evidence Development (CED) in the context of a Medicare-approved, prospective clinical study.
  • Treatment of individuals with severe, symptomatic sickle cell disease (SCD) pursuant to Coverage with Evidence Development (CED) in the context of a Medicare-approved, prospective clinical study.

Multiple myeloma using allogeneic stem cell transplantation was removed as Experimental/Investigational.

The following indication for autologous stem cell transplantation was added as Experimental/Investigational:
  • Tandem transplantation (multiple rounds of autologous stem cell transplantation) for individuals with multiple myeloma

Information regarding the Durie-Salmon Staging System, the International Staging System, and the Dynamic International Prognostic Scoring System were added to the Policy Guidelines.

CODING

AUTOLOGOUS
    The following CPT code was removed because it does not apply to Autologous Hematopoietic Stem Cell Transplantation: 38230

    The following CPT code was revised: 38241

ALLOGENEIC
    The following CPT codes were revised: 38208, 38209, 38240, 38242

Revisions from MA11.002b
12/30/2015This policy has been reissued in accordance with the Company's annual review process.
01/01/2016This policy has been identified for the HCPCS code update, effective 01/01/2016.

The following HCPCS code has been added to this policy under both Autologous and Allogeneic: J1447

The following HCPCS code has been removed from this policy under both Autologous and Allogeneic: J1446

The following HCPCS narrative has been revised in this policy: J1442

Revisions from MA11.002a
07/01/2015The following HCPCS code has been added to this policy under both Autologous and Allogeneic: Q5101

The following HCPCS codes have been added to this policy under Allogeneic: J1442, J1446

Revisions from MA11.002
01/01/2015This is a new policy.




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