INFORMATION ON STEM CELLS/BONE MARROW AND REINFUSION/TRANSPLANTATION SUR703.002



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INFORMATION ON STEM CELLS/BONE MARROW AND REINFUSION/TRANSPLANTATION SUR703.002 COVERAGE: SPECIAL COMMENT ON POLICY REVIEW: Due to the complexity of the Peripheral and Bone Marrow Stem Cell Transplantation policies, the patient's treatment history and diagnosis documentation should be reviewed by a Nurse Reviewer or Case Manager who has been specially trained in transplantation and oncology. If there is uncertainty regarding coverage, the case should be referred to a physician reviewer. For individual policy description and coverage information, please refer to the Medical Policies listed in the RELATED POLICIES section. RELATED POLICIES: Colony Stimulating Factors G-CSF (Filgrastim, Neupogen) OR GM-CSF (Sargramostim, Prokine) - RX502.017 Information on Organ and Tissue Transplantation - SUR703.001 Peripheral/Bone Marrow Stem Cell Transplantation (PSCT/BMT) for Non- Malignancies - SUR703.017 Peripheral/Bone Marrow Stem Cell Transplantation (PSCT/BMT) for Malignancies - SUR703.018 Cord Blood as a Source of Stem Cells (CBSC) - SUR703.022 Donor Leukocyte Infusion - SUR703.023 Tandem/Triple High-Dose Chemoradiotherapy with Autologous Stem Cell Support for Malignancies - SUR703.024 DESCRIPTION: Human blood contains a remarkable variety of cells, each precisely tailored to its own vital function. Erythrocytes, or red blood cells, transport life-sustaining oxygen throughout the body. Tiny platelets stop bleeding by promoting clotting. White blood cells (eg. lymphocytes, monocytes, and neutrophils) form the immune system that guards against attack by foreign tissue, viruses, and various other microorganisms. All of these cells develop from master cells or blood cell progenitors (the Hematopoietic [blood-forming or blood-parent] Stem Cell [HSC]) which reside primarily in bone marrow. Injury to the stem cells, from chemotherapy, radiation, or disease, can cripple the immune and blood production systems. Stem cells can be harvested from three sources: the bone marrow, peripheral blood, or umbilical cord blood. When stem cells are harvested from and infused back into the same individual, the procedure is referred to as Autologous (Au). When stem cells from a healthy antigen compatible (histocompatible) donor are harvested and then infused into a different recipient, the

procedure is referred to as Allogeneic (Allo). Syngeneic stem cels refer to genetically identical bone marrow or peripheral stem cells harvested from an identical twin. Syngeneic transplants are obviously limited by the rarity of identical twins. These procedures are, also known as: Hematopoietic Stem Cell Support (HSCS or SCS), Peripheral Stem Cell Transplantation (PSCT), Stem Cell Rescue (previously referred to as Transplant), or Bone Marrow Transplantation (BMT). Stem cells are the main ingredient in BMTs. The stem cells in the transplanted marrow can reestablish the patient's blood-producing and immune systems, which have been devastated by leukemia, cancer, chemotherapy, radiation therapy, or unknown causes. The transplant procedure itself is simple. If the patient is not self-donating his/her bone marrow, it is obtained from a donor individual and is known as Allogeneic Bone Marrow Transplantation (AlloBMT). The bone marrow is aspirated from the iliac crests of the pelvis of: a related or unrelated donor who is human lymphocyte antigen (HLA) compatible (allogeneic), or a related donor who is HLA-identical (syngeneic). If the patient is self-donating his/her bone marrow, known as Autologous Bone Marrow Transplantation (AuBMT), the bone marrow is removed from the iliac crests of the pelvis when a complete remission has been induced. The patient is then given High Dose Chemotherapy (HDC) with the hope of destroying any residual tumor. HDC is a regimen of cytoxic agents that are several times higher than the standard therapeutic dose. This is done to treat malignancy but it may also ablate the patient's bone marrow. The rationale for HDC is that many cytotoxic agents act according to a steep dose-response curve. Therefore, small, increasing doses of the cytotoxic agent will result in large increases of the tumor cell kill. In addition, the increasing doses increase the incidence and severity of adverse effects, such as opportunistic infections, hemorrhage, and organ failure. Since the life-threatening toxicity is so high, patients are usually hospitalized for the HDC regimen and may require further hospitalization to treat the drug toxicity effects. In some regimens to eradicate the tumor cells, whole body or localized radiotherapy may be given with the HDC agents, known as chemoradiotherapy. A subsequent rescue with the patient's own bone marrow or the donated allogeneic or syngeneic bone marrow follows the HDC. BMTs present numerous medical hurdles. The patient must receive a steady supply of fresh red cells, platelets, and antibiotics for several weeks until the transplanted stem cells begin producing large quantities of mature blood elements. In an AlloBMT, the patient's immune system must be sufficiently suppressed so that it will not reject the transplanted stem cells. At the same time, the immune system cells produced by the donor stem cells may recognize their new host as foreign, a reaction known as Graft Versus Host Disease (GVHD), in which case they may cause organ damage and/or death. AuBMT eliminates the need to find a compatible marrow donor and bypasses the risk of GVHD.

Patients treated with HDC regimens that ablate their own bone marrow function are increasingly being reinfused with autologous Peripheral Blood Stem Cells rather than with bone marrow cells. After several cycles of conventional doses of chemotherapy and stimulation with Colony Stimulating Factors (CSFs), the number of hematopoietic stem cells in the peripheral circulation rises. The patient may be subjected to a leukapheresis process several times where peripheral blood is removed and undergoes repeated selective separation and removal of leukocytes. After the patient receives HDC, the patient's bone marrow is reconstituted by the reinfusion of the stem cell population. Characteristics unique to either type of transplant or rescue make one preferable to the other in certain clinical situations. When marrow metastases preclude AuBMT, peripheral blood provides a suitable source of progenitor or stem cells for autografting. The most appropriate stem cell source for a particular patient depends upon his or her disease, treatment history, and the availability of a compatible donor. The most appropriate source of stem cells for each patient must be balanced by: 1. the risks of graft failure and reinfusion of malignant cells in autologous procedures, or 2. the risks of graft rejections and graft-versus-host disease in allogeneic procedures. This becomes critical with the advent of a mismatched or an unrelated donor pool. Umbilical Cord Blood (UCB) or Cord Blood (CB) contains blood cell progenitors and could become a source of stem cells. Stem cells and lymphocytes from cord blood lack the infectious disease resistance that mature blood cells possess by virtue of their prior exposure to various infectious diseases. Umbilical Cord Blood Transplantation (UCBT) or Cord Blood Stem Cells (CBSC) represents a major advance in providing HSCS to patients needing transplantation. Colony Stimulating Factors (CSF) are hematopoietic growth factors that stimulate the growth and maturation of bone marrow stem cells. Two of these CSFs are currently available: Granulocyte Colony Stimulating Factor (G-CSF) or Granulocyte Macrophage Colony Stimulating Factor (GM-CSF). Oncologists have identified that the functional status of the patient can be correlated with the outcome of the underlying disease. The following Karnofsky Performance Status Index (Scale) has been the most widely used measure of the functional status of cancer patients. GENERAL CATEGORY INDEX SPECIFIC CRITERIA Able to carry on normal activity, no special care needed 100 Normal, no complaints, no evidence of disease (same) 90 Able to carry on normal activity,

minor signs or symptoms of disease (same) 80 Normal activity with effort, some signs or symptoms of disease Unable to work, able to live at home and care for most personal needs, varying amount of assistance needed 70 Cares for self, unable to carry on normal activity or to do work (same) 60 Requires occasional assistance from others, but able to care for most needs (same) 50 Requires considerable assistance from others and frequent medical care Unable to care for self, requires institutional or hospital care or equivalent, disease may be rapidly progressing 40 Disabled, requires special care and assistance (same) 30 Severely disabled, hospitalization indicated, death not imminent (same) 20 Very sick, hospitalization necessary, active supportive treatment necessary (same) 10 Moribund (a dying state) N/A 0 Death RATIONALE: None DISCLAIMER:

State and federal law, as well as contract language, including definitions and specific inclusions/exclusions, takes precedence over Medical Policy and must be considered first in determining coverage. The member s contract benefits in effect on the date that services are rendered must be used. Any benefits are subject to the payment of premiums for the date on which services are rendered. Medical technology is constantly evolving, and we reserve the right to review and update Medical Policy periodically. HMO Blue Texas physicians who are contracted/affiliated with a capitated IPA/medical group must contact the IPA/medical group for information regarding HMO claims/reimbursement information and other general polices and procedures. Blue Cross and Blue Shield of Texas, a Division of Health Care Service Corporation, a Mutual Legal Reserve Company* Southwest Texas HMO, Inc.* d/b/a HMO Blue Texas * Independent Licensees of the Blue Cross and Blue Shield Association Posted Jan. 7, 2003