Clinical Policy Title: Bone marrow transplants

Transcription

1 Clinical Policy Title: Bone marrow transplants Clinical Policy Number: Effective Date: January 1, 2016 Initial Review Date: November 18, 2015 Most Recent Review Date: November 16, 2016 Next Review Date: November 2017 Related policies: CP# CP# CP# CP# CP# CP# CP# Corneal transplants (keratoplasty) Heart valves transplants Kidney transplants Heart transplants Liver transplants Pancreas transplants Lung transplants Policy contains: Bone marrow transplant. Hematopoietic stem cell transplant (HSCT). Autologous bone marrow transplant. Allogeneic bone marrow transplant. ABOUT THIS POLICY: AmeriHealth Car has developed clinical policies to assist with making coverage determinations. AmeriHealth Caritas Pensylvania s clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peer-reviewed professional literature. These clinical policies along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state- or plan-specific definition of medically necessary, and the specific facts of the particular situation are considered by AmeriHealth Caritas Pensylvania when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. AmeriHealth Caritas Pensylvania s clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the treatment decisions for their patients. AmeriHealth Caritas Pensylvania s clinical policies are reflective of evidence-based medicine at the time of review. As medical science evolves, AmeriHealth Caritas Pensylvania will update its clinical policies as necessary. AmeriHealth Caritas Pensylvania s clinical policies are not guarantees of payment. Coverage policy AmeriHealth Caritas Pensylvania considers the use of bone marrow transplants and stem cell transplants to be clinically proven and, therefore, medically necessary for the following diseases and conditions with related services and supplies: 1. Autologous bone marrow transplants are allowed for the following diagnoses: a. Non-Hodgkin lymphoma (NHL), stage III or IV. Hodgkin's disease (lymphoma), stage III or IV. b. Neuroblastoma, stage III or IV. c. Acute lymphocytic or non-lymphocytic leukemia and first or subsequent remission. 0

2 2. Allogeneic bone marrow transplants are allowed for the following diagnoses: a. NHL, stage III or IV. b. Hodgkin's disease (lymphoma), stage III or IV. c. Neuroblastoma, stage III or IV. d. Chronic myelogenous leukemia in blast crisis or chronic phase. e. Acute lymphocytic or non-lymphocytic leukemia, acute myelocytic leukemia, in first or subsequent remission, but at high risk for relapse. f. Amylodoisis, stages I and II. g. Multiple myeloma (MM). h. Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. 3. Allogeneic bone marrow transplants for non-malignancies are allowed for the following diagnoses: a. Severe aplastic anemia. b. Homozygous beta-thalassanemia. c. Wiskott-Aldrich syndrome. d. Severe combined immunodeficiencies. e. Infantile malignant osteopetrosis. f. Mucopolysaccharidoses. g. Mucolipidoses. h. Myelodysplastic syndrome (MDS). i. MM. j. POEMS syndrome. Limitations: AmeriHealth Caritas Pensylvania considers all other uses of bone marrow and stem cell transplants to be investigational and, therefore, not medically necessary. 1. An autologous or allogeneic (ablative and non-myeloablative [mini-transplant]) hematopoietic stem cell transplantation (HSCT), single or planned tandem is considered investigational and not medically necessary as a treatment of autoimmune diseases including, but not limited to: a. Juvenile idiopathic arthritis (JIA). b. Rheumatoid arthritis (RA). c. Multiple sclerosis (MS). d. Systemic lupus erythematosus (SLE). e. Systemic sclerosis (SSc; that is, scleroderma). 2. An autologous or allogeneic (ablative and non-myeloablative [mini-transplant]) HSCT, single or planned tandem is considered investigational, and not medically necessary as a treatment for the following diseases and conditions: a. Epithelial ovarian cancer. 1

3 b. Breast cancer. c. Malignant astrocytomas and gliomas, including both glioblastoma multiforme, and oligodendroglioma. d. Adult miscellaneous solid tumors, including, but not limited to: Cancer of the bile duct. Cancer of the fallopian tubes. Cervical cancer. Colon cancer. Esophageal cancer. Gallbladder cancer. Lung cancer, any histology. Malignant melanoma. Nasopharyngeal cancer. Neuroendocrine tumors. Pancreas cancer. Paranasal sinus cancer. Prostate cancer. Rectal cancer. Renal cell cancer. Soft tissue sarcoma. Stomach cancer. Thyroid tumors. Tumors of the thymus. Uterine cancer. Undifferentiated tumors and tumors of unknown primary origin. 3. Required documentation for members: a. Medical records, physical exam, medical, and family history. b. History of current medication. c. Active smoking, alcohol, and drug abuse. d. Summary of the course of illness. e. Laboratory assessments, including serologies. f. Psychosocial concerns. g. All other information requested by the plan. Alternative covered services: Maximum medical management by treating physician to determine the best health decision for the member s individual needs. Note: See Appendix A and B for National Comprehensive Cancer Network (NCCN) Categories of Evidence 2

4 and Consensus for additional resources. Background Bone marrow and stem cell transplant: Blood cells, along with skin cells, have the greatest powers of self-renewal of any adult tissue. They are responsible for the constant maintenance and immune protection of every cell type in the body. This relentless and brutal work requires that blood cells, along with skin cells, have the greatest powers of self-renewal of any adult tissue. The stem cells that form blood and immune cells are known as hematopoietic stem cells (HSCs). They are ultimately responsible for the constant renewal of blood, which involves the production of billions of new blood cells each day. Physicians and basic researchers have known and capitalized on this fact for more than 50 years in treating many diseases. The first evidence and definition of blood-forming stem cells came from studies of people exposed to lethal doses of radiation in A bone marrow transplant, also called stem cells, transplant, is a procedure that replaces damaged or destroyed bone marrow with healthy bone marrow stem cells. Bone marrow is the soft, fatty tissue inside the bones. Stem cells are immature cells in the bone marrow that give rise to all blood cells. There are three basic kinds of bone marrow transplants. Autologous bone marrow transplant: The term auto means self. Stem cells are removed from a patient prior to receiving high-dose chemotherapy (HDC), or radiation treatment. The stem cells are stored in a freezer (cryopreservation). After HDC or radiation treatments, stem cells are put back in the body to regenerate normal blood cells. This is called a rescue transplant. Allogeneic bone marrow transplant: The term allo means other. Stem cells are removed from another person, called a donor. Most times, the donor's genes must at least partly match the member s genes. Special blood tests are done to see if a donor is a good match for the member. A brother or sister is most likely to be a good match. Sometimes parents, children, and other relatives are good matches. Donors who are not related to members may be found through national bone marrow registries. Syngeneic stem cell transplants: This is a special kind of allogenic transplant that can only be used when the recipient has an identical sibling (twin or triplet) who can donate someone who has the same tissue type. An advantage of syngeneic stem cell transplant is that graft-versus-host disease will not be a problem. No cancer cells 3

5 should be in a transplant, either, as there would be no cancer cells in an autologous transplant. Some people may have a stem cell transplant using stem cells from umbilical cord blood. There are cord blood banks that store blood taken from the umbilical cord. After the baby is born and the umbilical cord has been cut, a doctor takes blood from the umbilical cord and placenta. The blood bank may then give the donated stem cells to a person whose blood cells closely match the donated cells. These transplants are mostly used for children because of the lower volume of cells collected. It may be possible for adults to have an HSCT from two different umbilical cords (double-cord transplant). HSCT refers to a procedure in which HSCs are infused to restore bone marrow function in cancer patients who receive bone marrow toxic doses of cytotoxic drugs, with or without whole-body radiation therapy. Bone marrow stem cells may be obtained from the transplant recipient (i.e., autologous HSCT) or from a donor (i.e., allogeneic HSCT). They can be harvested from bone marrow, peripheral blood, or umbilical cord blood and placenta shortly after delivery of neonates. Although cord blood is an allogeneic source, the stem cells in it are antigenically naïve and thus are associated with a lower incidence of rejection, or graft-versus-host disease (GVHD). Sources of HSCs: Bone marrow: The classic source of HSCs is bone marrow. For more than 40 years, doctors performed bone marrow transplants by anesthetizing the stem cell donor, puncturing a bone typically a hipbone and drawing out the bone marrow cells with a syringe. About one in every 100,000 cells in the marrow is a long-term, blood-forming stem cell; other cells present include stromal cells, stromal stem cells, blood progenitor cells, and mature and maturing white and red blood cells. Peripheral blood: As a source of HSCs for medical treatments, bone marrow retrieval directly from bone is quickly fading into history. For clinical transplantation of human HSCs, doctors now prefer to harvest donor cells from peripheral, circulating blood. It has been known for decades that a small number of stem and progenitor cells circulate in the bloodstream, but in the past 10 years, researchers have found they can coax the cells to migrate from marrow to blood in greater numbers by injecting the donor with a cytokine, such as granulocyte-colony stimulating factor (GCSF). Donor stem cells can be collected in two ways: Bone marrow harvest: This minor surgery is done under general anesthesia. This means the donor will be asleep and pain free during the procedure. The bone marrow is removed from the back of both hip bones. The amount of 4

6 marrow removed depends on the weight of the person who is receiving it. Leukapheresis: First, the donor is given five days of shots to help stem cells move from the bone marrow into the blood. During leukapheresis, blood is removed from the donor through an IV line in a vein. The part of white blood cells that contains stem cells is then separated in a machine, removed and later given to the recipient. The red blood cells are returned to the donor. Autoimmune diseases: The use of HDC with autologous stem cell transplantation (ASCT) has demonstrated improved outcomes for specific oncologic indications, such as leukemia and lymphoma. Based on the experiences in these historic applications, the use of autologous and allogeneic stem cell transplantations continues to be studied in other oncologic and non-oncologic indications, such as autoimmune diseases and miscellaneous solid tumors. However, in a position statement from a National Institute of Allergy and Infectious Diseases (NIAID) and National Cancer Institute-Sponsored International Workshop on the "Feasibility of Allogeneic HSCT for Autoimmune Diseases," the authors concluded "Although safer allogeneic transplantation strategies have become available, experience is currently insufficient to allow reliable extrapolation of data on safety and risks from patients with malignancies to patients with autoimmune diseases" (Griffith, 2005). HSCs collected from peripheral blood stem cells (PBSCs) have been successfully used for transplantation. Originally, these cells, collected from patients with chronic myelogenous leukemia, were used to restore the chronic phase of the disease. More recently, PBSCs have been used principally for autologous transplantation for non-hematologic malignancies, although there are a few recorded cases of allogeneic transplantation with PBSCs. The process of obtaining PBSCs is tedious in comparison to the process of harvesting bone marrow for transplantation, requiring multiple lengthy apheresis procedures to collect sufficient cells for transplant. Moreover, the risks associated with PBSC collection (anesthesia risk for catheter placement, risk of introducing infection during collection) are just as great as those associated with marrow harvesting. However, for the patient whose bone marrow is unharvestable due to hypocellularity or fibrosis, PBSC transplantation may reopen the option of treatment by high-dose cytotoxic therapy and autologous HSC rescue. Peripheral blood stem cell transplantation (PBSCT) may also afford the transplant option to the patient whose marrow has been infiltrated with disease. While it has not been demonstrated, it is hypothetically likely that the probability of tumor cell contamination of circulating blood is quite low, due to the lack of adherence necessary for colonization. Recent reports have indicated that autologous transplantation with PBSCs may result in more rapid engraftment, relative to autologous transplantation with bone marrow. This has only been reported in programs wherein PBSCs are collected under mobilizing conditions. If it is the case that PBSCs produce more rapid engraftment, however, then the additional effort and cost associated with PBSC collection might be outweighed by the reduced 5

7 morbidity, mortality, and cost associated with the early return of granulocytes in the transplant patient. The biology of the early engraftment phenomenon should be studied, as it might relate to the mobilizing conditions under which the cells are collected, and not be due to an intrinsic quality of PBSCs (Janssen, 1993). Stem cell transplant for MM: The patient receives HDC sometimes with full-body radiation to the whole body) to kill the cells in the bone marrow, including the myeloma cells. The patient then receives new, healthy blood-forming stem cells. When stem cell transplants were first developed, the new stem cells came from bone marrow. This procedure came to be known as a bone marrow transplant. Now, stem cells are more often gathered from the blood (a PBSCT). Stem cell transplants are commonly used to treat MM. Before the transplant, drug treatment is used to reduce the number of myeloma cells in the patient s body. Searches AmeriHealth Caritas Pensylvania searched PubMed and the databases of: UK National Health Services Centre for Reviews and Dissemination. Agency for Healthcare Research and Quality s National Guideline Clearinghouse and other evidence-based practice centers. The Centers for Medicare & Medicaid Services (CMS). We conducted searches on October 17, Search terms were bone marrow, bone marrow transplantation, HSCs, stem cell transplantation (MeSH), and the free text term transplants. We included: Systematic reviews, which pool results from multiple studies to achieve larger sample sizes and greater precision of effect estimation than in smaller primary studies. Systematic reviews use predetermined transparent methods to minimize bias, effectively treating the review as a scientific endeavor, and are thus rated highest in evidence-grading hierarchies. Guidelines based on systematic reviews. Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not simple cost studies), reporting both costs and outcomes sometimes referred to as efficiency studies which also rank near the top of evidence hierarchies. Findings Currently, there are multiple ongoing clinical trials using autologous and allogeneic stem cell transplants, following high-dose immunotherapies for the treatment of autoimmune diseases. Burt and colleagues 6

8 (2006) described lymphoablation, or the removal of "autoreactive lymphocytes" through the process of ASCT, to promote the generation of new self-tolerant lymphocytes. Examples of autoimmune disorders being studied in this manner include MS, SSc, RA, Crohn's disease, and lupus. These authors have identified the need for further research with randomized controlled trials (RCTs) to verify the benefit and safety of this therapy. Despite the vast experience with HSCs, scientists face major roadblocks in expanding their use beyond the replacement of blood and immune cells. First, HSCs are unable to proliferate (replicate themselves) and differentiate (become specialized to other cell types) in vitro (in the test tube or culture dish). Second, scientists do not yet have an accurate method to distinguish stem cells from other cells, recovered from the blood or bone marrow. Until scientists overcome these technical barriers, they believe it is unlikely that HSCs will be applied as cell replacement therapy in diseases such as diabetes, Parkinson's disease, spinal cord injury, and many others. Compared with chemotherapy alone, HSC transplantation improves survival of patients with MM. Success rates are low for patients with more advanced disease or with responsive solid cancers (e.g., breast cancer or germ cell tumors). Relapse rates are reduced in patients with GVHD, but overall mortality rates are increased if GVHD is severe. Intensive conditioning regimens, effective GVHD prophylaxis, cyclosporine-based regimens, and improved supportive care (e.g., antibiotics as needed, herpes virus and cytomegalovirus prophylaxis) have increased long-term disease-free survival after HSC transplantation. A number of clinical trials studying the efficacy and safety of high-dose immunosuppressive therapy (HDIT) with HCT in various autoimmune disorders are in progress (clinicaltrials.gov). One study underway, the Scleroderma: Cyclophosphamide or Transplantation Trial (SCOT), is a randomized, openlabel, active control trial comparing the efficacy and safety of HDIT followed by HCT and high-dose pulse IV cyclophosphamide. This is a multi-center study with an anticipated enrollment of 114 subjects and study completion date of Policy updates: 2016 Updated National Coverage Determinations (NCDs) and reference information, and deleted old information. Summary of clinical evidence: Citation Reston (2011) Content, Methods, Recommendations Key points: Autologous hematopoietic cell transplantation for multiple sclerosis A systematic review published by evaluated the safety and efficacy of autologous HSCT in participants with progressive MS, refractive to conventional treatment. A total of 10 full-text articles were reviewed, and eight case series with 161 enrolled 7

9 Citation Lenarsky (1990). Bone marrow transplantation for the treatment of immune deficiency states. Atkinson (1997) Hemopoietic stem cell transplant in Australia, : a report from the Australian Bone Marrow Transplant Recipient Registry. Content, Methods, Recommendations participants and median two-year follow-up were included, meeting the inclusion criteria for primary outcome of progression-free survival. An additional six studies were included for a summary of mortality and morbidity. Analysis from the eight case series found there was substantial heterogeneity across studies. Secondary progressive MS was reported in 77% of participants, but studies also included those with primary progressive, progressive-relapsing, and relapse-remitting disease. The studies used varied conditioning regimens prior to HSCT. Five of the studies used intermediate-intensity regimens and the remaining three used high-intensity regimens. All studies were rated as moderate quality. Among a total of 14 studies, 13 were case series; of which seven treatment-related deaths were reported. Six non-treatment related deaths were reported, and five of these were associated with disease progression. Key points: The successful transplantation of Wiskott-Aldrich syndrome patients demonstrated that agents with adequate anti-lymphoid and HSC activity were necessary to achieve complete donor lymphoid and HSG engraftment. Bone marrow transplants for patients with severe combined Immunodeficiency (SCID) have been in the forefront of clinical bone marrow transplantation, including the first successful use of T lymphocyte-depleted haploidentical bone marrow and matched unrelated donors. Bone marrow transplantation for immune deficiency states continues to be in the forefront of human bone marrow transplantation. Key points: To describe allogeneic and autologous bone marrow and blood stem cell transplantation in Australia during Australia-wide, hemopoietin cell transplants have increased in number from 478 in 1992 to 681 in The number of hospitals contributing registrations to the Australian Bone Marrow Transplant Registry has increased from 20 in 1992 to 25 in Trends in bone marrow and blood stem cell transplantation practice in Australia during have been outlined and both practice and outcome can be compared with that in other countries. The main cause of treatment failure, recurrence of the underlying malignant disease, indicates that this is where current and future research needs to focus. Chen XL (2009). Key points: Autologous peripheral blood stem cell transplantation combined with autologous bone marrow transplantation for treating refractory lymphoma Study to investigate the differences of therapeutic efficiencies, side effects, and recovery rates of immune function in refractory lymphoma patients treated with autologous peripheral blood HSCT (APBHSCT), autologous bone marrow transplantation (ABMT), and combination of APBHSCT with ABMT (APBHSCT + ABMT) by retrospective analysis, and to evaluate the merits and demerits of three kinds of transplantation, for treatment of refractory lymphoma. Out of 68 patients, 10 cases were treated with ABMT, 46 cases were treated with APBHSCT, and 12 cases were treated with APBHSCT + ABMT. The efficacy and side effects of APBHSCT + ABMT as compared with ABMT and APBHSCT are roughly the same, but ABMT + APBHSCT can result in more rapid hematopoietic 8

10 Citation Content, Methods, Recommendations reconstitution and less restrictions, which contributes to a wider choice of transplant regimens for older patients with impaired hematopoietic functions. References Professional society guidelines/other: American Society for Blood and Marrow Transplantation (ASBMT) Biology of blood and marrow transplantation. Indications for autologous and Allogeneic Hematopoietic Cell Transplantation (HCT): Guidelines from ASBMT for Blood and Morrow transplantation. Volume 21, Issue 11, November 2015, pps Website. Accessed October 17, American Cancer Society. Accessed on October 17, Hayes Inc., Hayes Medical Technology Report. Bone marrow transplant. Lansdale, Pa. Hayes Inc.; Month, Year. Lemischka I, et al., The Stem Cell Database, Princeton University, Computational Biology and Informatics Laboratory at the University of Pennsylvania stemcell.htm Accessed on October 22, 2016 Lewis SL, Shaw CA. Genetics, Altered immune responses, and transplantation. In: Lewis S, Heitkemper MM, Dirksen SR, O'Brien PG, Bucher L, editors. Medical Surgical Nursing: Assessment and Management of Clinical Problems. 7th ed. St. Louis, MO: Mosby; 2007: Majhail N, Savani B, Palmer J, et al., Indications for autologous and allogeneic hematopoietic cell transplantation: Guidelines from the American Society for Blood and Marrow Transplantation. Site search , available at: Accessed October 22, NCCN Guidelines and Clinical Resources: NCCN categories of evidence and consensus. Available at Accessed October 22, The National marrow donor program. ( Accessed October 21, National Cancer Institute. Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation: Questions and Answers. Reviewed August 12, Available at: Accessed October 22,

11 National Library of Medicine. Medline Plus. Bone Marrow Transplantation. Available at: Accessed on October 22, Newton S. Management of clients with leukemia and lymphoma. In: Black JM, Hawks JH, editors. Medical-Surgical Nursing: Clinical Management for Positive Outcomes. 8th ed. St. Louis, MO: Saunders Elsevier; 2009: Thomas ED, Clift, RA. Allogenic transplantation for chronic myeloid leukemia. Thomas, E.D., Blume, K.G., and Forman, S.J. eds. Blackwell Sci. 1999: Transfusion therapy and blood and marrow stem cell transplantation. In: Nettina SM, editor. Lippincott Manual of Nursing Practice. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006: Peer-reviewed references: Atkinson K, Nivison-Smith I, Hawkins T. Hematopoietic stem cell transplantation in Australia, : a report from the Australian Bone Marrow Transplant Recipient Registry. Department of Hematology, St Vincent's Hospital, Sydney, NSW. Aust N Z J Med. 1997;27(4): Bittner RE, Schofer C, Weipoltshammer K, et al. (1999). Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anat. Embryol. (Berl). 1999;199(5): Burt RK, Loh Y, Cohen B, et al. Autologous non-myeloablative hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol. 2009;8(3): Chen XL, Su H, Zhong KL, DA Y, Xiao XB, et al. Autologous peripheral blood stem cell transplantation combined with autologous bone marrow transplantation for treating refractory lymphoma. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009;17(1): Chen J, Astle CM, Harrison DE. Development and aging of primitive hematopoietic stem cells in BALB/cBy mice. Exp. Hematol. 1999;27(5): Cutler, C and Antin, JH. Peripheral blood stem cells for allogeneic transplantation: a review. Stem Cells. 2001;19(2): Griffith LM, Pavletic SZ, Tyndall A, et al. Feasibility of allogeneic hematopoietic stem cell transplantation for autoimmune disease: position statement from a National Institute of Allergy and Infectious Diseases and National Cancer Institute-sponsored international workshop, Bethesda, MD, March 12 and 13, Biol Blood Marrow Transplant. 2005; 11(11): Janssen WE. Peripheral blood and bone marrow hematopoietic stem cells: are they the same? Semin 10

12 Oncol. 1993;20(5 Suppl 6): Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, Neutzel S, Sharkis SJ. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell. 2001;105(3): Lenarsky C, Parkman R., Bone marrow transplantation for the treatment of immune deficiency states. Bone Marrow Transplant. 1990;6(6): Lickliter JD, McGlave PB, DeFor TE, et al. Matched-pair analysis of peripheral blood stem cells compared to marrow for allogeneic transplantation). Bone Marrow Transplant. 2000;26(7): Reston JT, Uhl S, Treadwell JR, et al. Autologous hematopoietic cell transplantation for multiple sclerosis: a systematic review. Mult Scler 2011;17(2): Sharp JG, Kessinger A, Lynch JC, Pavletic ZS, Joshi SS. Blood stem cell transplantation: factors influencing cellular immunological reconstitution. J Hematother Stem Cell Res. 2000;9(6): CMS National Coverage Determinations (NCDs): Histocompatibility Testing. CMS website. Accessed October 21, Stem Cell Transplant (formerly ) Effective 10/3/2016, CMS website: Accessed October CMS. Manual System Pub NCD Transmittal 191 rescinded and replaced with transmittal 193. Effective January 27, Stem Cell Transplantation for Multiple Myeloma, Myelofibrosis, Sickle Cell Disease, and Myelodysplastic Syndromes. Guidance/Guidance/Transmittals/Downloads/R193NCD.pdf. Accessed October Local Coverage Determinations (LCDs): No LCDs identified as of the writing of this policy. Commonly submitted codes Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is not an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and bill accordingly. 11

13 CPT Code Description Comments Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor Hematopoietic progenitor cell (HPC); autologous transplantation ICD-10 Code Description Comments C74.10-C74.92 Malignant neoplasm of cortex of adrenal gland C82.00-C96.9 Malignant neoplasm of lymphoid, hematopoietic and related tissue [except Hodgkin's disease] C81.00-C81.99 Hodgkin s lymphoma C82.00-C82.89 Follicular lymphoma C83.00-C83.89 Non-follicular lymphoma C90.00 Multiple myeloma C91.00-C91.Z2 Lymphoid leukemia C92.00-C92.Z2 Myeloid leukemia C93.00-C93.Z2 Monocytic leukemia C94.00-C94.82 Other leukemias of specified cell type C95.00-C95.92 Leukemia of unspecified cell type C96.9 Malignant neoplasm of lymphoid, hematopoietic and related tissue, unspecified C96.Z Other specified malignant neoplasms of lymphoid, hematopoietic and related tissue D46.0-D46.Z Myelodysplastic syndromes D56.1 Beta thalassemia D61.01-D61.9 Other aplastic anemias and other bone marrow failure syndromes D82.0 Wiskott-Aldrich syndrome E76.01-E76.3 Mucopolysaccharidosis E77.0-E77.1 Disorders of glycoprotein metabolism (Mucolipidosis) E85.9 Amyloidosis E88.09 POEM s Syndrome Q78.2 Osteopetrosis HCPCS Level II Code N/A Description Comments Appendix A: NCCN Guidelines & Clinical Resources NCCN Categories of Evidence and Consensus: Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the 12

14 intervention is appropriate. Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate. Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate. All recommendations are category 2A, unless otherwise noted. Definitions for Classifying Indications: The definitions for categorizing indications for transplantation are presented below. Standard of Care (S): This category includes indications that are well defined and are generally supported by evidence in the form of high quality clinical trials and/or observational studies (e.g., through CIBMTR or EBMT). Standard of Care, Clinical Evidence Available (C): This category includes indications for which large clinical trials and observational studies are not available. However, HCT has been shown to be an effective therapy with acceptable risk of morbidity and mortality in sufficiently large single- or multi-center cohort studies. HCT can be considered as a treatment option for individual patients after careful evaluation of risks and benefits. As more evidence becomes available, some indications may be reclassified as Standard of Care. Standard of Care, Rare Indication (R): Indications included in this category are rare diseases for which clinical trials and observational studies with sufficient number of patients are not currently feasible, because of their very low incidence. However, single- or multi-center or registry studies in relatively small cohorts of patients have shown HCT to be effective treatment, with acceptable risks of morbidity and mortality. For patients with diseases in this category, HCT can be considered as a treatment option for individual patients after careful evaluation of risks and benefits. Developmental (D): 13

15 Developmental indications include diseases where pre-clinical and/or early phase clinical studies show HCT to be a promising treatment option. HCT is best pursued for these indications as part of a clinical trial. As more evidence becomes available, some indications may be reclassified as Standard of Care, Clinical Evidence Available, or Standard of Care. Not Generally Recommended (N): Transplantation is not currently recommended for these indications where evidence and clinical practice do not support the routine use of HCT. The effectiveness of non-transplant therapies for an earlier phase of a disease does not justify the risks of HCT. Alternatively, a meaningful benefit is not expected from the procedure in patients with an advanced phase of a disease. However, this recommendation does not preclude investigation of HCT as a potential treatment, and transplantation may be pursued for these indications within the context of a clinical trial. Appendix B: Table 1: Indications for HCT in pediatric patients (generally age <18 years) Acute myeloid leukemia Indication and Disease Status Allogeneic HCT Autologous HCT CR1, low risk N N CR1, intermediate risk C C CR1, high risk S N CR2+ S C Not in remission C N Acute lymphoblastic leukemia CR1, standard risk N N CR1, high risk S N CR2 S N CR3+ C N Not in remission C N Chronic myeloid leukemia Chronic phase C N Accelerated phase C N Blast phase C N Myelodysplastic syndromes Low risk C N High risk S N 14

16 Juvenile myelomonocytic leukemia S N Therapy related S N T-cell NHL CR1, standard risk N N CR1, high risk S N CR2 S N CR3+ C N Not in remission C N Lymphoblastic B-cell NHL (non-burkitt) CR1, standard risk N N CR1, high risk S N CR2 S N CR3+ C N Not in remission C N Burkitt s lymphoma First remission R R First or greater relapse, sensitive R R First or greater relapse, resistant R N Hodgkin lymphoma CR1 N N Primary refractory, sensitive C C Primary refractory, resistant C N First relapse, sensitive C C First relapse, resistant C N Second or greater relapse C C Anaplastic large cell lymphoma CR1 N N Primary refractory, sensitive C C Primary refractory, resistant C N First relapse, sensitive C C First relapse, resistant C N Second or greater relapse C C Solid tumors Germ cell tumor, relapse D C Germ cell tumor, refractory D C Ewing s sarcoma, high risk or relapse D S Soft tissue sarcoma, high risk or relapse D C Neuroblastoma, high risk or relapse D S 15

17 Wilm s tumor, relapse N C Osteosarcoma, high risk N C Medulloblastoma, high risk N C Other malignant brain tumors N C Non-malignant diseases Severe aplastic anemia, new diagnosis S N Severe aplastic anemia, relapse/refractory S N Fanconi s anemia R N Dyskeratosis congenita R N Blackfan-Diamond anemia R N Sickle cell disease C N Thalassemia C N Severe combined immunodeficiency R N T cell immunodeficiency, SCID variants R N Wiskott-Aldrich syndrome R N Hemophagocytic disorders R N Lymphoproliferative disorders R N Severe congenital neutropenia R N Chronic granulomatous disease R N Other phagocytic cell disorders R N IPEX syndrome R N Juvenile RA N D Systemic sclerosis N D Other autoimmune and immune dysregulation disorders R N Mucopolysaccharoidoses (MPS-I and MPS-VI) R N Other metabolic diseases R N Osteopetrosis R N Globoid cell leukodystrophy (Krabbe) R N Metachromatic leukodystrophy R N Cerebral X-linked Adrenoleukodystrophy R N Recommendation categories (see text for definition): Standard of care (S); Standard of care, clinical evidence available (C); Standard of care, rare indication (R); Developmental (D); Not generally recommended (N). Table 2: Indications for HSCT in adults (generally age 18 years) Indication and Disease Status Acute myeloid leukemia Allogeneic HCT Autologous HCT CR1, low risk N C CR1, intermediate risk S C CR1, high risk S C 16

18 CR2 S C CR3+ C C Not in remission C N Acute promyelocytic leukemia CR1 N N CR2, molecular remission C S CR2, not in molecular remission S N CR3+ C N Not in remission C N Relapse after autologous transplant C N Acute lymphoblastic leukemia CR1, standard risk S C CR1, high risk S N CR2 S C CR3+ C N Not in remission C N Chronic myeloid leukemia Chronic phase 1, TKI intolerant C N Chronic phase 1, TKI refractory C N Chronic phase 2+ S N Accelerated phase S N Blast phase S N Myelodysplastic syndromes Low/intermeditate-1 risk C N Intermediate-2/high risk S N Therapy related AML/MDS CR1 S N Myelofibrosis Primary, low risk C N Primary, intermediate/high risk C N Secondary C N Plasma cell disorders Myeloma, initial response D S Myeloma, sensitive relapse C S Myeloma, refractory C C Plasma cell leukemia C C Primary amyloidosis N C POEMS syndrome N R 17

19 Relapse after autologous transplant C C Hodgkin lymphoma CR1 (PET negative) N N CR1 (PET positive) N C Primary refractory, sensitive C S Primary refractory, resistant C N First relapse, sensitive S S First relapse, resistant C N Second or greater relapse C S Relapse after autologous transplant C N Diffuse large B-cell lymphoma CR1 (PET negative) N N CR1 (PET positive) N C Primary refractory, sensitive C S Primary refractory, resistant C N First relapse, sensitive C S First relapse, resistant C N Second or greater relapse C S Relapse after autologous transplant C N Follicular lymphoma CR1 N C Primary refractory, sensitive S S Primary refractory, resistant S N First relapse, sensitive S S First relapse, resistant S N Second or greater relapse S S Transformation to high grade lymphoma C S Relapse after autologous transplant C N Mantle cell lymphoma CR1/PR1 C S Primary refractory, sensitive S S Primary refractory, resistant C N First relapse, sensitive S S First relapse, resistant C N Second or greater relapse C S Relapse after autologous transplant C N T-cell lymphoma CR1 C C Primary refractory, sensitive C S 18

20 Primary refractory, resistant C N First relapse, sensitive C S First relapse, resistant C N Second or greater relapse C C Relapse after autologous transplant C N Lymphoplasmacytic lymphoma CR1 N N Primary refractory, sensitive N C Primary refractory, resistant R N First or greater relapse, sensitive R C First or greater relapse, resistant R N Relapse after autologous transplant C N Burkitt s lymphoma First remission R R First or greater relapse, sensitive R R First or greater relapse, resistant R N Relapse after autologous transplant R N Cutaneous T-cell lymphoma Relapse C C Relapse after autologous transplant C N Plasmablastic lymphoma CR1 R R Relapse R R Chronic lymphocytic leukemia High risk, first or greater remission C N T-cell prolymphocytic leukemia R R B-cell, prolymphocytic leukemia R R Transformation to high grade lymphoma C C Solid tumors Germ cell tumor, relapse N C Germ cell tumor, refractory N C Ewing s sarcoma, high risk N C Breast cancer, adjuvant high risk N D Breast cancer, metastatic D D Renal cancer, metastatic D N Non-malignant diseases Severe aplastic anemia, new diagnosis S N 19

21 Severe aplastic anemia, relapse/refractory S N Fanconi s anemia R N Dyskeratosis congenita R N Sickle cell disease C N Thalassemia D N Hemophagocytic syndromes, refractory R N Mast cell diseases R N Common variable immunodeficiency R N Chronic granulomatous disease R N MS N D Systemic sclerosis N D RA N D SLE N D Crohn s disease N D Polymyositis-dermatomyositis N D Recommendation categories (see text for definition): Standard of care (S); Standard of care, clinical evidence available (C); Standard of care, rare indication (R); Developmental (D); Not generally recommended (N). 20