Sunflower Health Plan Non-Myeloablative Allogeneic Stem Cell Transplants (PDF) Form

Allogeneic hematopoietic stem cell transplants that do not destroy all of the hematopoietic cells in the bone marrow are termed reduced-intensity or nonmyeloablative conditioning regimens. Although there are no clear definitions, reduced-intensity conditioning (RIC) generally destroys more hematopoietic cells and is more toxic than nonmyeloablative conditioning, but less so than myeloablative conditioning. Both nonmyeloablative and RIC regimens are categorized as non- fully ablative regimens, and are used interchangeably in this policy, unless otherwise noted. RIC/nonmyeloablative approaches can circumvent the need for high-dose conditioning regimens that are associated with organ toxicity and mortality depending on graft vs. tumor and immunosuppressive mechanisms. Note: Please refer to CP.MP.108 for requests for Allogeneic Hematopoietic Cell Transplants for Sickle Cell Anemia and β-Thalassemia. Please refer to CP.MP.162 Tandem Transplant if request is for an allogeneic reduced conditioning transplant for multiple myeloma in a tandem transplant. Policy/Criteria I. It is the policy of health plans affiliated with Centene Corporation® that nonmyeloablative/reduced-intensity conditioning (RIC) allogeneic transplants are medically necessary for members/enrollees who meet all of the following criteria: A. Candidate for allogeneic stem cell transplantation for any of the following diagnoses: 1. Acute lymphoblastic leukemia; 2. Acute myelogenous leukemia; 3. Acquired bone marrow failure such as severe aplastic anemia; 4. Familial bone marrow failure syndromes such as, but not limited to, one of the following: a. Dyskeratosis congenita; b. Shwachman-Diamond syndrome; c. Diamond-Blackfan anemia; d. Kostmann syndrome; e. Fanconi anemia; 5. Paroxysmal nocturnal hemoglobinuria; 6. Chronic lymphocytic leukemias; 7. Chronic myelogenous leukemia; 8. Congenital immunodeficiency syndromes: 9. Hodgkin’s lymphoma: primary refractory or relapsed, including those who have relapsed after an autologous bone marrow transplant; 10. Non-Hodgkin’s lymphoma, any of the following: Page 1 of 10 CLINICAL POLICY Non-Myeloablative Allogeneic Stem Cell Transplants a. Primary refractory or relapsed, including those who have relapsed after having an autologous bone marrow transplant (excluding diffuse large B-cell lymphoma); b. Follicular lymphomas; c. Mantle cell lymphoma; d. Diffuse large B-cell lymphoma that is in remission following second-line therapy for relapsed or refractory disease; 11. Myelodysplastic syndromes; 12. Lysosomal storage disorders types IH/IS (Hurler/Hurler-Scheie), VI (maroteaux), VII (Sly); 13. Macrophage discords such as hemophagocytic lymphohistiocytosis (HLH); 14. Myeloproliferative neoplasms such as, but not limited to: a. Chronic myeloid leukemia; b. Juvenile myelomonocytic leukemia; c. Primary myelofibrosis; d. Essential thrombocytosis; B. Unsuitable for conventional high-dose myeloablative allografting because of untreatable significant dysfunction of another major organ system and/or severe comorbidities, including, but not limited to, any of the following: 1. Bilirubin > 2 mg/dL; 2. Hemostasis: international normalized ratio (INR) > 1.6 (unless on oral anticoagulants); 3. Cardiac function: multigated acquisition (MUGA) scan or echocardiogram with ejection fraction (EF) < 45%; 4. Pulmonary function, one of the following: a. Forced expiratory volume in 1 second (FEV1) ≤ 50% of predicted value; b. Diffusing capacity of the lung for carbon monoxide (DLCO ) ≤ 50% of predicted value; 5. Performance scale index, one of the following: a. Karnofsky or Lansky score < 70%; b. Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2; C. Does not have ANY of the following absolute contraindications: 1. Infections with highly virulent and/or resistant microbes that are poorly controlled pre-transplant; 2. Inability to adhere to the regimen necessary to preserve the transplant, even with caregiver support; 3. Absence of an adequate or reliable social support system; 4. Active substance use or dependence including current tobacco use, vaping, marijuana use (unless prescribed by a licensed practitioner), or intravenous drug use without convincing evidence of risk reduction behaviors (unless urgent transplant timelines are present, in which case a commitment to reducing behaviors is acceptable). Serial blood and urine testing may be used to verify abstinence from substances. II. It is the policy of health plans affiliated with Centene Corporation that current evidence does not support the use of nonmyeloablative/RIC allogeneic transplants for any of the following indications: A. Solid tumors including, but not limited to: Page 2 of 10 CLINICAL POLICY Non-Myeloablative Allogeneic Stem Cell Transplants 1. Brain tumors; 2. Ovarian epithelia and mixed epithelial/germ cell cancers; 3. Primitive neuroectodermal tumors (PNET), including medulloblastoma and ependymoma; 4. Renal cell carcinoma; 5. Testicular cancer; 6. Wilms tumor; 7. Ewing sarcoma; 8. Melanoma; 9. Osteosarcoma; 10. Rhabdomyosarcoma; 11. Retinoblastoma; 12. Germ cell tumors; 13. Neuroblastoma; 14. Multiple myeloma (except in tandem transplant- refer to CP.MP.162); B. Autoimmune disorders including, but not limited to: 1. Multiple sclerosis; 2. Rheumatoid arthritis; 3. Juvenile idiopathic arthritis; 4. Systemic lupus erythematosus; 5. Systemic sclerosis; 6. Dermatomyositis; 7. Polymyositis; 8. Scleroderma; C. Hemoglobinopathies including, but not limited to: 1. Thalassemias; 2. Sickle cell anemia. Background Allogeneic hematopoietic cell transplantation (HCT) has been used as a treatment for cancer and diseases of the blood system for decades. For this treatment, stem cells are collected from either related or unrelated donors.1 During the conditioning phase, high doses of chemotherapy (HDC), with or without radiation therapy, are used to eradicate the disease and this is followed by infusion of stem cells to rescue bone marrow and restore normal immune function. Major limitations of this technique include the increased risk of high morbidity and mortality related to increased age, relapsed or refractory disease or disease with an elevated risk of relapse following HCT, a history of aggressive chemotherapy, and comorbidities.7 All stem cell transplants (SCTs) preparative regimens have the potential for extensive toxicity. Loss of appetite and energy, alopecia, and nausea/vomiting occur frequently and contribute to poor physical and emotional tolerance of the transplant procedure. In addition, mucositis, diarrhea, and transient pancytopenia are inevitable side effects of most preparative regimens, and these complications are synergistic in dramatically increasing the risk of infections during and post-transplant.21 Any decrease in toxicity, without concomitant loss of efficacy, would be desirable. Myeloablative means that the treatment kills (ablates) the stem cells in the bone marrow; the cells that produce new blood cells. Several less intense conditioning regimens have been Page 3 of 10 CLINICAL POLICY Non-Myeloablative Allogeneic Stem Cell Transplants developed and rely more on immuno-suppression than cytotoxic effects to permit engraftment of donor cells. These regimens are collectively termed nonmyeloablative. Studies have shown that donor allogeneic stem cells can engraft in recipients using less-intensive conditioning regimens that are sufficiently immunosuppressive to permit graft-host tolerance. This manifests as a stable mixed donor-host hematopoietic chimerism, a term which means coexistence of donor and recipient cells. Nonmyeloablative allogeneic transplants, also referred to as “mini-transplant” or “transplant lite”, are thought to be potentially as effective as conventional HDC followed by an allogeneic stem cell transplantation, but with decreased morbidity and mortality related to the less intense, nonmyeloablative chemotherapy conditioning regimen.1,22 Coding Implications This clinical policy references Current Procedural Terminology (CPT®). CPT® is a registered trademark of the American Medical Association. All CPT codes and descriptions are copyrighted 2022, American Medical Association. All rights reserved. CPT codes and CPT descriptions are from the current manuals and those included herein are not intended to be all-inclusive and are included for informational purposes only. Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services. CPT® Codes 38204 38205 38207 38208 38209 38210 38211 38212 38213 38214 38215 38230 38240 HCPCS Codes S2142 Management of recipient hematopoietic progenitor cell donor search and cell acquisition Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; allogeneic Transplant preparation of hematopoietic progenitor cells; cryopreservation and storage Transplant preparation of hematopoietic progenitor cells; thawing of previously frozen harvest, without washing, per donor Transplant preparation of hematopoietic progenitor cells; thawing of previously frozen harvest, with washing, per donor Transplant preparation of hematopoietic progenitor cells; specific cell deletion within harvest. T-cell depletion Transplant preparation of hematopoietic progenitor cells; tumor cell depletion Transplant preparation of hematopoietic progenitor cells; red blood cell removal Transplant preparation of hematopoietic progenitor cells; platelet depletion Transplant preparation of hematopoietic progenitor cells; plasma (volume) depletion Transplant preparation of hematopoietic progenitor cells; cell concentration in plasma, mononuclear, or buffy coat layer Bone marrow harvesting for transplantation; allogeneic Hematopoietic progenitor cell (HPC), allogeneic transplantation per donor Cord blood-derived stem cell transplantation, allogeneic Page 4 of 10 CLINICAL POLICY Non-Myeloablative Allogeneic Stem Cell Transplants HCPCS Codes 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 Reviews, Revisions, and Approvals Policy adopted from HN version Clarified in I. that policy statements applied to RIC and nonmyeloablative regimens. Removed criteria in I.A. that patient be a candidate for conventional allogeneic transplantation. Added paroxysmal nocturnal hemoglobinuria as an indication. Changed chronic lymphoblastic leukemia to chronic lymphocytic leukemia. Added criteria to multiple myeloma requiring that it be responsive to primary treatment. For myelodysplastic syndromes, restricted indication to adults. Added myelofibrosis as an indication. Edited comorbidity in criteria I.B. to include the listed comorbidities as well as others not mentioned – “including but not limited to.” Removed contraindication in II.A. of ineligibility for conventional high-dose chemotherapy/myeloablation, as well as restriction for members/enrollees under 3 years of age. Updated description. Moved beta thalassemia and sickle cell anemia from the list of approved indications to the list of E/I indications. Removed age restriction from myelodysplastic syndromes. Added to the multiple myeloma indication that an RIC/NMA approach is appropriate post – autologous or fully myeloablative stem cell transplant. Removed diffuse large b-cell lymphoma from E/I list. Clarified that diffuse large cell lymphoma is diffuse large b-cell lymphoma, and added requirement that the patient is in remission following second-line therapy for relapsed or refractory disease. Specialist reviewed. Added note to refer to CP.MP.108 for requests for Allogeneic HCT’s for Sickle Cell Anemia and β-Thalassemia and CP.MP.162 if request is for a tandem transplant for multiple myeloma. Clarified in I.A.8. that Hodgkin’s disease is now referred to as Hodgkin’s lymphoma. Moved multiple myeloma and neuroblastoma from list of approved indications to the list of E/I indications. Removed sickle cell anemia from list of E/I indications. Removed CPT 38206 as code is for autologous transplant. Added ICD-10 Codes: D59.5, D75.81 Annual review completed. References reviewed. Codes checked. Changed “members/enrollee” to members/enrollee.” Specialty review completed with no updates. Review Date 03/17 02/18 Approval Date 4/17 02/18 02/19 02/19 02/20 02/20 02/21 02/21 Page 5 of 10 CLINICAL POLICY Non-Myeloablative Allogeneic Stem Cell Transplants Reviews, Revisions, and Approvals Annual review. Rephrased criteria I.A.3. from “aplastic anemia” to “acquired bone marrow failure such as severe aplastic anemia.” Added new indication I.A.4., “Familial bone marrow syndromes such as….” Removed “molecular remissions induced by Gleevec” from I.A.8.” Added criteria points 13. and 14. to criteria I.A. “Experimental/investigational” verbiage in criteria II. replaced with descriptive language. Sorted list of non-supported indications in criteria II. into 3 subcategories, solid tumors, autoimmune disorders and hemoglobinopathies. In criteria I.C., combined and rephrased contraindications 2. and 3. and updated verbiage regarding substance abuse and dependence in 4. Minor rewording in description and background with no impact on criteria. Removed ICD-10 codes D57.00- D57.819 for sickle-cell disorders from ICD-10 table of codes to support coverage. References reviewed and updated. Changed “review date” in the header to “date of last revision” and “date” in the revision log header to “revision date." Reviewed by specialist. Annual review completed. Criteria I.C.4. updated to exclude marijuana use when prescribed by a licensed practitioner and include required commitment to reducing substance use behaviors if urgent transplant timelines are present. Background updated; minor rewording with no clinical significance. ICD-10 diagnosis code table removed. References reviewed and updated. Review Date 02/22 Approval Date 02/22 02/23 02/23