TRANSMITTAL #: 129

DATE:  12/23/2011

TRICARE CHANGE #: C-121

CHAMPVA POLICY MANUAL

CHAPTER: 2

SECTION: 31.10

TITLE: HDC (HIGH DOSE CHEMOTHERAPY) AND STEM CELL TRANSPLANTATION

AUTHORITY: 38 CFR 17.270(a), 17.272(a), and 17.273

RELATED AUTHORITY:  32 CFR 199.4(e)(5) and (g)(15)

I. EFFECTIVE DATE(S)

November 1, 1983

II. PROCEDURE CODE(S)

CPT Codes: 38205-38206, 38230-38241, 86812-86822, and 88240-88241

III. DESCRIPTION(S)

A.      HDC (High Dose Chemotherapy) is the use of cytotoxic therapeutic agents (that are otherwise approved for general use in humans) by the FDA (Food and Drug Administration) in dosages and/or frequencies of dosage that exceed the FDA labeling for the agent.  HDC is generally considered when conventional regimens of chemo-therapeutic agents have failed to arrest disease progression.  One of the major adverse effects of HDC occurs when bone marrow suppression occurs and it can be a lethal process.

B.      Stem cells are multi-potential, blood cell producing agents important in immune defenses against disease. Stem cell "transplantation" or "rescue" is defined as a technique for collecting stem cells from a donor (either from the bone marrow or from the bloodstream), preparing and storing the collected stem cells, then reinfusing the prepared stem cells into the bloodstream of a patient in the treatment of oncologic, hematologic or lymphoproliferative disease with curative potential.  The goal of stem cell "transplantation" or "rescue" is to reverse the bone marrow suppression caused by either HDC or by a primary bone marrow disease process, that is, aplastic anemia.

C.      There are five general types of stem cell “transplantation” or “rescue”:

1.       Allogeneic bone marrow transplantation, where stem cells from a histocompatible donor (other than the patient) are harvested from the bone marrow, then later infused into the bloodstream of the patient.  With allogeneic bone marrow transplantation, the patient may have either a related or unrelated donor who has the same or closely matched HLA (Human Leukocyte Antigen) typing necessary for successful transplantation.

2.       Allogeneic PSCT (Peripheral Stem Cell Transplantation) where stem cells are harvested from the bloodstream of a histocompatible donor (other than the patient) then later infused into the bloodstream of the patient.

3.       ABMT (Autologous Bone Marrow Transplant), where the patient is both donor and recipient of stem cells harvested from the bone marrow.

4.       Autologous PSCT (Peripheral Stem Cell Transplantation), where the patient is both donor and recipient of stem cells harvested from the bloodstream using the apheresis process.

5.       UCBT (Umbilical Cord Blood Stem Cell Transplantation), where stem cells are harvested from the umbilical cord and placenta, then later infused into the bloodstream of the patient.

IV. POLICY

A.      Benefits are covered for HDC with ABMT or autologous PSCT, allogeneic BMT or allogeneic PSCT, and allogeneic UCBT, with or without HDC.

B.      HDC with ABMT or autologous PSCT is covered in the treatment of the following malignancies.  The list of indications is not all inclusive.  Other indications are covered when documented by reliable evidence as safe, effective and comparable or superior to standard care (proven).

1.       Non-Hodgkin’s lymphoma, follicular, intermediate, or high-grade; when:

a.       Conventional dose chemotherapy has failed.

b.       The patient has relapsed following a course of radiation. therapy.

c.        The patient is in first complete remission with risk factors for relapse.

Note:  For purposes of coverage, mantle cell lymphomas will be considered as intermediate grade, non-Hodgkin’s lymphomas.

2.       Hodgkin’s disease when:

a.       Conventional dose chemotherapy has failed.

b.       The patient has relapsed following a course of radiation therapy, and has also failed at least one course of conventional dose chemotherapy subsequent to the failed radiation therapy.

c.        The patient is in second or third complete remission.

3.       Neuroblastoma.

a.       Stage III or IV, when the patient is one for who further treatment with a conventional dose therapy is not likely to achieve a durable remission.

b.       Tandem autologous PSCT for high-risk neuroblastoma INSS (International Neuroblastoma Staging System) Stage III with either N-MYC (neuroblastoma derived myelocytomatosis) gene amplification or unfavorable Shimada histology or INSS Stage IV).

4.       Acute lymphocytic or nonlymphocytic leukemias, such as, myelocytic, myelogenous, myeloblastic, or myelomonoblastic, chronic myelogenous leukemia, or preleukemic syndromes.

5.       PNET (Primitive Neuroectodermal Tumors)/Ewing's Sarcoma.

6.       Gliofibromas (also known as desmoplastic astrocytoma and desmoplastic glioblastoma).

7.       Glioblastoma multiforme.

8.       Posterior fossa teratoid brain tumors.

9.       Rhabdomyosarcoma and undifferentiated sarcomas.

10.  Multiple myeloma. Tandem autologous stem cell transplantation is covered for the treatment of multiple myeloma.

11.  Chronic myelogenous leukemia.

12.  Waldenstrom’s macroglobulinemia.

13.  AL (Amyloid Light-Chain) Amyloidosis.

14.  Wilms’ tumor.

15.  Trilateral retinoblastoma/pineoblastoma.

16.  Osteosarcoma (osteogenic sarcoma).

17.  Germ cell tumors in a second or subsequent relapse.

18.  HDC with ABMT or PSCT for the treatment of desmoplastic small round cell tumor is covered on a case-by-case basis under the provisions for treatment of rare diseases.

19.  Immunoablative therapy with ABMT or autologous PSCT for the treatment of severe systemic lupus erythematosus refractory to conventional treatment.

C.      Allogeneic BMT or allogeneic PSCT, with or without HDC, is covered in the treatment of the following disease processes when either a related or unrelated donor is used.  The list of indications is not all inclusive.  Other indications are covered when documented by reliable evidence as safe, effective and comparable or superior to standard care (proven).

1.       Aplastic anemia.

2.       Acute lymphocytic or nonlymphocytic leukemias, such as myelocytic, myelogenous, myeloblastic, myelomonoblastic); CML or preleukemic syndromes.

3.       Severe combined immunodeficiency, such as adenosine deaminase deficiency and idiopathic deficiencies.

a.       Partially matched-related donor stem cell transportation (without regard for the number of mismatched antigens in determining histocompatibility) in the treatment of Bare Lymphocyte Syndrome.

b.       Unrelated donor and/or related donor (without regard for mismatched antigens) with or without T-cell lymphocyte depletion in the treatment of FEL (Familial Erythrophagocytic Lymphohistiocytosis), generalized lymphohistiocytic infiltration; familial lymphohistiocytosis; familial reticuloendotheliosis; FHL (Familial Hemophagocytic Lymphohistiocytosis) for patients whose medical records document failure of conventional therapy (etoposide; corticosteroids; intrathecal methotrexate; and cranial irradiation).

c.        Partially matched-related donor stem cell transplantation (without regard for the number of mismatched antigens) in the treatment of X-linked severe combined immunodeficiency syndrome (X-Linked SCID).

4.       Wiskott-Aldrich Syndrome.

5.       Infantile malignant osteopetrosis (Albers-Schonberg syndrome or marble bone disease).

6.       Thalassemia major.

7.       Intermediate and high grade lymphoma.

8.       Myeloproliferative/dysplastic syndromes.

9.       Congenital mucopolysaccharidoses.

10.  Congenital amegakaryocytic thrombocytopenia.

11.  Metachromatic leukodystrophy.

12.  Sickle cell disease.

13.  CLL (Chronic Lymphocytic Leukemia) when previous therapy has failed or when the CLL is refractory to conventional therapy.

14.  Hyperesinophilic Syndrome.

15.  Multiple myeloma when HCD with ABMT or PSCT has failed.

16.  X-linked hyper-IgM Syndrome.

17.  Chediak-Higashi Syndrome.

18.  Langerhans Cell Histiocytosis, refractory to conventional treatment.

19.  Hodgkin’s disease.

D.      Unirradiated donor lymphocyte infusion (donor buffy coat infusion, donor leukocyte infusion or donor mononuclear cell infusion) is covered for patients with AML or CML (Acute Myelogenous/Chronic Myeloid Leukemia), who relapse following their first or subsequent course of HDC with allogeneic stem cell transplantation. The medical record must document that the patient:

1.       Is in relapse following an adequate trial of HDC with allogeneic stem cell transplantation of CML or AML.

2.       Qualified (or would have qualified) for authorization for HDC with allogeneic stem cell transplantation according to the provisions set forth in this policy.

E.       Allogeneic UCBT, with or without HDC, is covered in the treatment of the following disease processes when either a related or unrelated donor is used.  The list of indications is not all inclusive.  Other indications are covered when documented by reliable evidence as safe, effective and comparable or superior to standard care (proven).

1.       Aplastic anemia.

2.       Acute lymphocytic or non-lymphocytic leukemias.

3.       Chronic myelogenous leukemia.

4.       Severe combined immunodeficiency.

5.       Wiskott-Aldrich syndrome.

6.       Infantile malignant osteopetrosis.

7.       Blackfan-Diamond anemia.

8.       Fanconi anemia.

9.       Neuroblastoma.

10.  X-linked lymphoproliferative syndrome.

11.  Hunter syndrome.

12.  Hurler syndrome.

13.  Congenital amegakaryocytic thrombocytopenia.

14.  Sickle cell anemia.

15.  Globoid cell leukodystrophy.

16.  Adrenoleukodystrophy.

17.  Kostmann’s Syndrome.

18.  Lesch-Nyhan disease.

19.  Intermediate and high grade non-Hodgkin’s lymphoma.

20.  Thalassemia major.

21.  Myelodysplastic Syndrome.

22.  X-linked hyper-IgM Syndrome.

23.  Langerhans Cell Histiocytosis, refractory to conventional treatment.

F.       Syngeneic (identical twin donor) stem cell transplantation is covered for the treatment of Hodgkin’s disease.

G.      CHAMPVA will reimburse costs for donor searches.  The patient must use the NMDP (National Marrow Donor Program) for donor searches.  The NMDP is located in Minneapolis, Mn., 1-800-627-7692, and is available to anyone needing assistance in locating a suitable donor for unrelated allogeneic bone marrow transplantation).  Donor searches through foreign registries must first be initiated or coordinated through NMDP. Prior to using NMDP services, pre-authorization for services must be obtained from the HAC.

1.       Charges for donor searches must be fully itemized and billed by the transplant center.

2.       Costs for donor searches are covered in accordance with established reimbursement guidelines for outpatient diagnostic testing.

3.       Donor search costs may be billed at any time.  There is no limit on how many searches a transplant center may request from the search printout.

H.      For the purposes of the NMDP and CHAMPVA coverage, the greatest degree of incompatibility allowed between donor or recipient (for either related or unrelated donors) is a single antigen mismatch at the A, B, or Dr. locus except for:

1.       Patients with undifferentiated leukemia, CML, aplastic anemia, ALL or AML, when histocompatible related or unrelated donors are not available, a 3-antigen mismatch is allowed for related donors.  For patients under 18 years of age with a relapsed leukemia, when histocompatible related or unrelated donors are not available, parental CD34++ stem cell transplantation with 2-3 antigen mismatch is allowed.

I.        Donor costs are covered under the conditions outlined in Chapter 2, Section 31.1, Donor Costs.

J.        BMT, PSCT, and UCBT is a process which includes mobilization, harvesting, and transplant of bone marrow, peripheral blood stem cell, or umbilical cord blood stem cells and the administration of HDC or radiotherapy prior to the actual transplant. When BMT, PSCT, or UCBT is covered, all necessary steps are included in coverage.  When BMT, PSCT, or UCBT is non-covered, none of the steps are covered.  In the event that the patient expires prior to the stem cell reinfusion being completed, benefits for the harvesting may be allowed.

K.      Benefits are allowed for Hepatitis B and pneumococcal vaccines for patients undergoing transplantation.

L.       Benefits may be allowed for Deoxyribonucleic Acid-Human Leucocyte Antigen (DNA-HLA) tissue typing in determining histocompatibility.

M.     Charges for stem cell and umbilical cord blood preparation and storage shall be billed through the transplantation facility in the name of the CHAMPVA patient.

N.      Charges for the umbilical cord blood bank may be allowed only for patients who have undergone a covered transplant.

O.     Preauthorization and retrospective authorization for HDC with allogeneic bone marrow transplants or allogeneic PSCT, or HDC with ABMT and autologous PSCT, or UCBT with HDC must meet the following two criteria:

1.       The patient meets (or as of the date of transplantation, would have met) patient selection criteria.

2.       The transplant facility is (or as of the date of transplantation would have been) Medicare, TRICARE, VA approved.

P.       Claims for services and supplies related to the HDC and transplant for beneficiaries under the age of 18 will be reimbursed based on billed charges.  Claims for HDC and transplant for adult patients, 18 years and older, will be reimbursed under the Diagnostic Related Group (DRG) payment system.  Outpatient institutional facility charges will be paid as billed.  Professional services are reimbursed under the CHAMPVA Maximum Allowable Charge (CMAC) Methodology.

Q.     In those cases where the beneficiary fails to obtain preauthorization, benefits may be extended if the services or supplies otherwise would qualify for benefits except for the failure to obtain preauthorization.  If preauthorization is not received, the HAC will review the claim to determine whether the beneficiary’s condition meets the clinical criteria for the transplant.

R.      Air ambulance is covered when appropriate based on benefit policy (see Chapter 2, Section 32.1, Ambulance Services).

V. EXCLUSION(S)

A.      Allogeneic BMT for treatment of low grade non-Hodgkin’s lymphoma is not a benefit.

B.      Autologous UCBT therapy, as this procedure is considered unproven.

C.      Allogeneic BMT for neuroblastoma, as this procedure is considered unproven.

D.      Allogeneic donor BMT (infusion) performed with or after organ transplants for the purpose of increasing tolerance of the organ transplant is considered unproven.HDC with ABMT or autologous PSCT, allogeneic BMT or allogeneic PSCT, with or without HDC, or allogeneic UCBT, with or without HDC, if the patient has a concurrent condition (other existing illness) that would jeopardize the achievement of successful transplantation.

E.       Administration of an unproven immunosuppressant drug that is not FDA approved.

F.       Donor lymphocyte infusion if not specifically listed as covered in POLICY above.

G.      Expenses waived by the transplant center, that is, beneficiary/sponsor is not financially liable.

H.      HDC with ABMT or PSCT is not covered for treatment of breast cancer.

I.        HDC with allogeneic BMT is not a benefit for treatment of Waldenstrom’s macroglobulinemia.

J.        HDC with stem cell rescue is not a benefit for the treatment of epithelial ovarian cancer.

K.      HDC with allogeneic stem cell transplantation is not covered for the treatment of cold agglutinin disease.

L.       Immunoablative therapy with bone marrow or peripheral stem cell transplantation is not covered for the treatment of multiple sclerosis.

M.     Immunoablative therapy with BMT or PSCT is unproven and not covered for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis.

N.      Immunoablative therapy with allogeneic BMT or allogeneic PSCT is not covered for the treatment of systemic lupus erythematosus not refractory to conventional treatment.

O.     Pre- or post-transplant nonmedical expenses, that is, out-of-hospital living expenses, to include, hotel, meals, and privately owned vehicle for the beneficiary or family members.

P.       Reduced intensity transplants (non-myeloablative allogeneic stem cell transplants, mini transplants, transplant lite) for renal cancer and other solid tumors of solid tissues or organs.

Q.     Salvage HDC/AlloSCS (High Dose Chemotherapy/Allogeneic Stem Cell Support) after HDC/AuSCS (High Dose Chemotherapy/Autologous Stem Cell Support) for patients with recurrent neuroblastoma, breast cancer, germ cell tumors in relapse, or any other solid tumor.

R.      Salvage HDC/AlloSCS for relapse of incomplete remission after HDC/AuSCS for patients with multiple myeloma, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, acute myeloblastic leukemia and acute lymphoblastic leukemia.

S.       Services and supplies not provided in accordance with applicable program criteria, that is, part of a grant, research program or unproven procedure.

T.       Transportation of a donor living or cadaver.

U.      The prophylactic harvesting, cryopreservation and storage of bone marrow, peripheral blood stem cells, or umbilical cord blood stem cells when proposed for possible future use is not covered.

*END OF POLICY*