Clinical Policy Title: Histocompatibility testing of potential hematopoietic stem cell donors

Transcription

1 Clinical Policy Title: Histocompatibility testing of potential hematopoietic stem cell donors Clinical Policy Number: CCP.1402 Effective Date: November 1, 2018 Initial Review Date: August 30, 2018 Most Recent Review Date: October 2, 2018 Next Review Date: October 2019 Policy contains: Allogenic transplantation of progenitor hematopoietic cells. Human leukocyte antigen testing. Related policies: CCP.1209 CCP.1286 CCP.1226 CCP.1367 Bone marrow transplants for cancer other than breast cancer Hematopoietic stem cell transplant for thalassemia major and sickle cell anemia Bone marrow transplant for children with hyper IgM disorder Hematopoietic stem cell transplant for leukemias ABOUT THIS POLICY: Prestige Health Choice has developed clinical policies to assist with making coverage determinations. Prestige Health Choice 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 Prestige Health Choice 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. Prestige Health Choice 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. Prestige Health Choice s clinical policies are reflective of evidence-based medicine at the time of review. As medical science evolves, Prestige Health Choice will update its clinical policies as necessary. Prestige Health Choice s clinical policies are not guarantees of payment. Coverage policy Prestige Health Choice considers the compatibility testing of potential family donors of stem cells and bone marrow tissue to be clinically proven and, therefore, medically necessary under the following conditions (Centers for Medicare & Medicaid Services [CMS] National Coverage Determination , 2016): The individual in need of the transplant is a covered member. The individual in need of the transplant has been medically approved for transplantation. The facility where the transplantation will take place is in agreement with the procedure. The individual to be tested for compatibility is related to the member and consents to be tested. 1

2 Prestige Health Choice considers the harvesting and storage of stem cells and bone marrow tissue to be clinically proven and, therefore, medically necessary when the donation is extracted from a compatible related donor and all of the above criteria are met. Limitations: Coverage determinations are subject to benefit limitations and exclusions as delineated by the state Medicaid authority. The Florida Medicaid website may be accessed at Pre-transplantation medical regimen requirements that optimize efficacy of transplantation must be met. Prestige Health Choice does not cover the costs associated with compatibility testing of unrelated donors, as these are typically covered by donor registries. Related potential donors should not be screened by the patient s own clinician due to a potential conflict of interest. Alternative covered services: None. Background Bone marrow or stem cell transplantation with hematopoietic cells has been shown to be effective in numerous diseases and diagnoses, including several types of leukemias, lymphomas, bone and blood disorders (including various types of anemia), inherited immune disorders, hemoglobinopathies (sickle cell disease and thalassemia major), and a few rare metabolic disorders. In some conditions, it is the sole method of cure. There are three possible sources for progenitor cells for hematopoietic stem cell transplant: mobilized peripheral blood stem cells, bone marrow, and umbilical cord blood. Mobilized peripheral blood stem cells are extracted during a non-surgical procedure following four to five daily injections of filgrastim, a drug that increases blood-forming cells. See Appendix. Bone marrow donations are obtained during a surgical procedure. Donors are given anesthesia, and bone marrow is extracted through a needle in the pelvic bone. Pregnant women may register to donate umbilical cord blood between the 28th and 34th week of pregnancy through the website of the National Marrow Donor Program (2018). 2

3 Autologous transplantation occurs when a person s cells are stored for future transplantation, and can only be used to treat certain diseases. Allogeneic donations must come from a human leukocyte antigen-matched donor, who may be a matched related donor (a family member) or an unrelated person. Of transplants received in the United States during , 14 percent came from a matched sibling, less than 1 percent were from an identical twin, 4 percent were from another related donor, 25 percent were from an unrelated donor, and 58 percent were autologous (Center for International Blood and Marrow Transplant, 2017). The National Marrow Donor Program (2018) estimates that about 70 percent of people who need a bone marrow transplant cannot identify a matched related donor and must seek a donor through a registry. Searches Prestige Health Choice searched PubMed and the databases of: UK National Health Services Centre for Reviews and Dissemination. Guidelines International Network, the National Institute for Health and Care Evidence, and other evidence-based practice centers. The Centers for Medicare & Medicaid Services. We conducted searches on August 2, Search terms were: stem cell transplantation, hematopoietic, related, family, donor, and donation. 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 The Centers for Medicare & Medicaid Services National Coverage Determination for Stem Cell Transplantation specifies the following: The Centers for Medicare & Medicaid Services (CMS) is clarifying that bone marrow and peripheral blood stem cell transplantation is a process which includes mobilization, harvesting, and transplant of bone marrow or peripheral blood stem cells and the administration of high dose chemotherapy or radiotherapy prior to the actual 3

4 transplant. When bone marrow or peripheral blood stem cell transplantation is covered, all necessary steps are included in coverage. When bone marrow or peripheral blood stem cell transplantation is non-covered, none of the steps are covered. Recommendations regarding family donor care management on behalf of the World Marrow Donor Association focus on the following areas (van Walraven, 2010): A practitioner who is not the provider for the potential transplant recipient should assess the potential donor. This may be within the same institution. The assessing practitioner should have a comprehensive understanding of donor rights. The potential donor should receive counseling before tissue typing. During this counseling, potential medical problems which could prevent transplantation may be identified, and potential donors who are unwilling may be screened out before any procedure begins. Consider independent counseling with a psychologist or donor advocate to ensure that the potential donor does not feel coerced. There should be an effort to balance the benefits to the potential recipient with the risks and benefits to the potential donor. These concerns are particularly important when screening potential child donors and those who are intellectually challenged. Fully informed consent should be obtained before laboratory screening and cell extraction. The American Academy of Pediatrics Committee on Bioethics (2010) describes five conditions under which a minor may be asked to donate stem cells: No compatible adult relation is physically able and willing to donate. The relationship between the potential minor donor and the recipient is both strong and positive. The recipient is likely to benefit from the transplantation. The risks to the donor (clinical, emotional, and psychosocial) are all minimized and are reasonable when compared with the anticipated benefits to both the donor and the recipient. Permission of the parents or guardians and, when appropriate, the child, have been granted. Barriers to hematopoietic stem cell transplantation among African Americans have been identified, as this population has low participation rates in clinical trials and reduced access to the most current medical therapies. Omondi (2013) postulates that these barriers occur due to gaps in knowledge of sickle cell disease, limited access to trial information, and mistrust of medical professionals. Providers can reach out to sickle cell camps to improve access to these needed services. Policy updates: None. Summary of clinical evidence: 4

5 Citation Billen (2014 ) Content, Methods, Recommendations Key points: A review of the haematopoietic stem cell donation experience: Is there room for improvement? Due to a relatively small body of literature, adverse events are not as well understood in related donors as they are in unrelated donors. It is conjectured that some risks that appear to be higher may be due to the same provider caring for the transplant patient as well as screening the donor, or to related donors being screened with less stringent criteria. Screening should include a full medical and psychological evaluation, including history, clinical examination, electrocardiogram, chest X-ray, and often a urine dip, as well as informed consent. Common side effects of peripheral blood and bone marrow donation include bone pain or harvest site pain, fatigue, headache, joint pain, insomnia, myalgia, anorexia, and nausea. Solely in bone marrow donation, donors may experience throat pain and harvest site reactions. Factors associated with adverse reactions in donors of both peripheral blood stem cells and bone marrow include female gender and older age (although one study found donors < 35 more likely to have headache). Factors associated with higher rates of reactions in peripheral blood stem cell donors include overweight and obesity, having less total blood volume, having lower net fluid balance, receiving higher doses of granulocyte colony stimulating factor, elevated white blood cell count after third dose of stimulating factor, and elevated baseline mononuclear cell count. Factors associated with higher rates of adverse reactions in bone marrow donors include being related to the recipient, having an active job, a longer duration of harvest, and average blood volume depletion in females. One study found more reactions associated with regional anesthesia, while three studies did not. Psychological outcomes in family donors are affected by death of the recipient (although bereaved donors later experience psychological gains), more physical difficulty with donation, longer collection times and greater volumes of collected material, and greater ambivalence. Related donors appear to have higher depression scores both before and after donation. Adequate preparation for donation; emotional support from family, friends, and hospital staff; and empathy motives are associated with improved psychological outcomes. References Professional society guidelines/other: American Academy of Pediatrics Committee on Bioethics. Policy statement children as hematopoietic stem cell donors. Pediatrics Doi: /peds Angelucci E, Matthes-Martin S, Baronciani D, et al. Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel. Haematologica. 2014;99(5): Doi: /haematol

6 Being a related donor. BMT Infonet. Accessed August 24, Center for International Blood and Marrow Transplant, a contractor for the C.W. Bill Young Cell Transplantation Program operated through the U.S. Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau. U.S. Transplant Data by Center Report, Table 2. Number of HCTs performed in the United States and reported to CIBMTR by donor type (autologous, related, unrelated). Last Updated: April 15, Accessed August 21, Learn if you can donate cord blood. Be the Match Registry. National Marrow Donor Program. Accessed August 21, National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Acute lymphoblastic leukemia. Version March 12, Accessed August 21, National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Acute myeloid leukemia. Version August 1, Accessed August 21, National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Chronic myeloid leukemia. Version August 1, Accessed August 21, National Comprehensive Cancer Network (NCCN). NCCN Clinical Guidelines in Oncology. Myelodysplastic syndromes. Version August 29, 2017d. Accessed August 21, van Walraven SM, Nicoloso-de Faveri G, Axdorph-Nygell UA, et al. Family donor care management: principles and recommendations. Bone marrow transplantation. 2010;45(8): Doi: /bmt Peer-reviewed references: Billen A, Madrigal JA, Shaw BE. A review of the haematopoietic stem cell donation experience: is there room for improvement? Bone marrow transplantation. 2014;49(6): De la Morena MT, Leonard D, Torgerson TR, et al. Long-term outcomes of 176 patients with X-linked hyper-igm syndrome treated with or without hematopoietic cell transplantation. J Allergy Clin Immunol. 6

7 2017;139(4): Doi: /j.jaci Latham K, Little AM, Madrigal JA. An overview of HLA typing for hematopoietic stem cell transplantation. Methods Mol Biol. 2014;1109: Doi: / _5. Omondi NA, Ferguson SE, Majhail NS, et al. Barriers to hematopoietic cell transplantation clinical trial participation of African American and black youth with sickle cell disease and their parents. J Pediatr Hematol Oncol. 2013;35(4): Doi: /MPH.0b013e31828d5e6a. Riezzo I, Pascale N, La Russa R, Liso A, Salerno M, Turillazzi E. Donor Selection for Allogenic Hemopoietic Stem Cell Transplantation: Clinical and Ethical Considerations. Stem cells international. 2017;2017: Doi: /2017/ Seber A. The cost of hematopoietic stem cell transplantation in the real world. Hematology. 2012;17 Suppl 1:S Doi: / x Centers for Medicare & Medicaid Services National Coverage Determinations: National Coverage Determination for Stem Cell Transplantation (formerly ) (110.3) National Coverage Analysis for Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Myelodysplastic Syndrome (CAG-00415N) National Coverage Analysis for Stem Cell Transplantation (CAG-00287R) National Coverage Analysis for Stem Cell Transplantation (Removal of Coding Information from NCD)(CAG-00193N) Local Coverage Determinations: Stem Cell Transplantation Medical Policy Article (A52879) 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. CPT Code Description Comments Management of recipient hematopoietic progenitor cell donor search and cell acquisition 7

8 CPT Code Description Comments Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; allogeneic Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; autologous 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 depletion 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 Cordocentesis (intrauterine), any method HLA typing; A, B, or C, multiple antigens HLA typing; DR/DQ, multiple antigens HLA typing; lymphocyte culture, mixed (MLC) Compatibility test each unit; immediate spin technique Compatibility test each unit; incubation technique Compatibility test each unit; antiglobulin technique Compatibility test each unit; electronic ICD-10 Code Description Comments Z Unspecified donor, stem cells Z52.3 Bone marrow donor HCPCS Level II Code S2150 Description 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 Comments Appendix Prior Authorization Group Description: White Blood Cell Stimulators 8

9 Drugs: Formulary status: Specialty tier (PA required) Zarxio (filgrastim-sndz) Neupogen (filgrastim) Neulasta (pegfilgrastim) Mozobil (plerixafor) Leukine (sargramostim) Covered uses: Medically accepted indications are defined using the following sources: the Food and Drug Administration (FDA), Micromedex, American Hospital Formulary Service (AHFS), United States Pharmacopeia Drug Information for the Healthcare Professional (USP DI), the Drug Package Insert (PPI), or disease state-specific standard of care guidelines. Exclusion criteria: N/A Required medical information: See other criteria Age restrictions: N/A Prescriber restrictions: N/A Coverage duration: The request will be approved for up to 12 weeks. If all of the above criteria are not met, the request will be referred to a Medical Director/clinical reviewer for medical necessity review. Other criteria: For Leukine requests only: Documentation is submitted of the patient s current diagnosis, current body weight, body surface area, and absolute neutrophil count (within 30 days of the request). For Neulasta requests only: If the medication request is being ordered for a patient requiring dosedense chemotherapy (e.g., for a documented diagnosis of breast cancer), no prior trials of any other white blood cell stimulator are needed for that patient. For Neupogen requests that are less than 180 mcg, Neupogen can be approved. For all other requests for Neupogen or Neulasta: The patient has a documented treatment failure (e.g., failure to reach or maintain target absolute neutrophil count [ANC], prolonged febrile neutropenia, unplanned hospitalization, infection requiring prolonged anti-infectives) that is consistent with pharmacy claims data, with an adequate trial (including dates and doses of therapy) of Zarxio, or another documented medical reason (e.g., intolerance, hypersensitivity, dose-dense chemotherapy, stem cell collection) for not using Zarxio to treat their medical condition. For Mozobil requests only: Documentation must be submitted that the patient is using Mozobil in combination with a granulocyte-colony stimulating factor (G-CSF) agent (e.g., Zarxio) Patient s ANC (absolute neutrophil count) has been submitted with request, and prescribed dosing of medication is within FDA-approved dosing. Medical Director or clinical reviewer must override criteria when, in his or her professional judgment, the requested item is medically necessary. Revision/review date: 7/2017 9

10 PARP approved: 8/2017 \\kmhp.com\mercycorpdata\public (Non-PHI)\Formulary Files for Insight\KMHP-AMHP\Prior Authorization Criteria Published August 2, Accessed August 22,