Nonmyeloablative Allogeneic Stem Cell Transplantation (Reduced Intensity Stem Cell Transplant) for Treatment of Malignancy
DESCRIPTION
Transplantation of allogeneic hematopoietic stem cells derived from bone marrow or peripheral blood, in conjunction with myeloablative chemotherapy, is an established therapy for various malignancies, including acute and chronic leukemias, Hodgkin’s disease, and non-Hodgkin’s lymphomas. The treatment effect results from chemotherapeutic ablation of malignant cells, as well as an associated immune-mediated graft versus malignancy effect. The conventional practice of allogeneic stem-cell transplants (allo-SCT) involves administration of myelotoxic agents (e.g., cyclophosphamide, busulfan) with or without total body irradiation at high enough doses to cause bone marrow failure in most patients. While such treatment may eradicate the malignant cells, patients are as likely to die from opportunistic infections, graft-versus-host disease, and organ failure as from the underlying malignancy.
Recently, regimens have been developed that seek to reduce treatment-related adverse effects while retaining beneficial (i.e., graft versus malignancy) effects. So-called nonmyeloablative regimens have been tentatively defined as those that do not eradicate the patient’s hematopoietic ability, allowing for relatively prompt hematopoietic recovery (e.g., 28 days or less) without a transplant. Examples of such regimens include fludarabine-cyclophosphamide and fludarabine-idarubicin-cytarabine combinations. On engraftment, patients treated with nonmyeloablative regimens will demonstrate mixed chimerism initially. Most will subsequently convert to full-donor chimerism and may be supplemented with donor lymphocyte infusions to further eradicate malignant cells. Nonmyeloablative chemotherapy is now commonly referred to as reduced-intensity conditioning (RIC), with patients also receiving allogeneic stem-cell support. This procedure also has been called “mini-transplant”.
Two general categories of individuals have been considered to determine who is a candidate for nonmyeloablative transplants. One category includes individuals who are considered candidates for a conventional, myeloablative transplant. For these individuals, conditioning with milder nonmyeloablative regimens represents a technical modification of an established procedure. The other category includes individuals who would not be considered candidates for a conventional, myeloablative transplant. For these individuals, nonmyeloablative transplants would be considered a novel approach. This is because co-morbidities preclude a standard myeloablative-conditioning regimen, or studies have not shown that conventional myeloablative allogeneic transplants have effectively treated malignancies.
POLICY
Nonmyeloablative allogeneic stem cell transplantation for individuals who are candidates for conventional high dose chemotherapy with allogenic stem cell transplantation for the treatment of malignancy is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Repeated labs and procedures to address changes in condition and for continued transplant listing are considered medically necessary.
Multiple labs and work-up procedures for the sole purpose of repeat evaluation at multiple transplant centers are considered not medically necessary.
Nonmyeloablative allogeneic stem cell transplantation for individuals who are not candidates for conventional high dose chemotherapy with allogeneic stem cell transplantation as treatment of malignancy is considered investigational.
Other applications of nonmyeloablative allogeneic stem-cell transplantation are considered investigational, including its use in patients who do not meet criteria for high-dose chemotherapy and allogenic stem-cell transplantation due to either age or comorbidities, or as treatment of other malignancies, including, but not limited to, multiple myeloma, renal cell carcinoma, other solid tumors, or autoimmune disease.
See also:
MEDICAL APPROPRIATENESS
Please refer to the Milliman Care Guidelines - Bone Marrow and Peripheral Blood Stem Cell Transplantations for specific disease guidelines.
Nonmyeloablative allogeneic stem cell transplantation (reduced intensity stem cell transplant) for the treatment of malignancy is considered medically appropriate if ALL of the following criteria are met:
Clinical information submitted for determination of medical appropriateness criteria is dated within the last 7 months
Presence of a disease or condition where hematopoietic stem cell transplant provides improved outcomes over standard therapy
Presence of a good performance status based on the Karnofsky Performance Scale or equivalent measurement scale
Have no serious, uncontrolled psychiatric illness that would hinder compliance with any stage of the transplant process
Have no neurologic illness independent of the disease process being treated
Have completed a full psychosocial evaluation including evaluation of support systems, etc.
Have no active drug or alcohol abuse (documented six month abstinence from drug or alcohol use and ongoing participation in a formal treatment program)
Documentation of the current status for the following: Hepatitis, Cytomegalovirus (CMV), Herpes Simplex Virus (HSV) profiling
Have no active infection (must be afebrile for greater than 48 hours and off antibiotics)
Pulmonary function tests: FVC, FEV1, DLco must all be greater than or equal to 60% of predicted (Young children may be unable to comply and may be evaluated using age appropriate testing)
Left ventricular (LV) ejection fraction must be greater than or equal to 50% of the institutional lower limit of normal
Estimated creatinine clearance must be greater than or equal to 60 ml/min
Serum bilirubin and SGOT must be less than or equal to 1.5 times the institutional upper limit of normal
If hepatitis C RNA positive, individual is ineligible for transplant if liver function tests are elevated
Willingness and ability of the individual or legal guardian to give signed consent and to comply with regular follow-up requirements
Note: Medical Appropriateness Criteria above is to match that contained in the medical policy entitled High Dose (Myeloablative) Chemotherapy with Bone Marrow, Peripheral Stem Cell, or Cord Blood Transplant for Hematopoietic Stem Cell Support.
IMPORTANT REMINDER
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
ADDITIONAL INFORMATION
Reduced intensity conditioning regimes with allogeneic stem-cell support are increasingly being used in many centers, and it is clear they will continue to evolve and will likely supplant myeloablative condition regimens for select patients. However, the scientific evidence available to date does not provide direct comparison of health outcomes with sufficiently long follow-up in similar patient groups to draw sound conclusions about the net health benefit of this therapeutic approach.
Published data in peer-reviewed literature is insufficient to permit scientific conclusions regarding the use of nonmyeloablative allogeneic stem cell transplantation for individuals who are not candidates for conventional high dose chemotherapy with allogeneic stem cell transplantation as treatment of malignancy.
SOURCES
American Cancer Society. (2009). Issues related to stem cell transplants. Retrieved May 20, 2010 from http://www.acsevents.org/docroot/ETO/content/ETO_1_4X_Issues_Related_to_Stem_Cell_Transplants.asp.
American Cancer Society. (2009). Types of stem cell transplants. Retrieved May 20, 2010 from http://www.acsevents.org/docroot/ETO/content/ETO_1_4X_Stem_Cell_Transplant_Basics.asp.
BlueCross BlueShield Association. Medical Policy Reference Manual. (5:2008). Nonmyeloablative allogeneic transplants of hematopoietic stem cells for treatment of malignancy (8.01.38). Retrieved May 18, 2010 from BlueWeb. (24 articles and/or guidelines reviewed)
Complete Guide to Medicare Coverage Issues [Computer software]. (2009, November). Stem cell transplantation (NCD 110.8.1, p. 2-54, 2-55). The Ingenix Complete Guide to Medicare Coverage Issues.
Harousseau, J. L. (2007). Role of stem cell transplantation. Hematology/Oncology Clinics of North America, 21 (6), 1157-1174.
Hayes. Medical Technology Directory. (2006, February). Nonmyeloablative transplantation for hematological malignancies. Retrieved May 18, 2010 from www.Hayesinc.com/subscribers. (77 articles and/or guidelines reviewed)
Laport, G. G., Sandmaier, B. M., Storer, B. E., Scott, B. L., Stuart, M. J., Lange, T., et al. (2008). Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation for adult patients with myelodysplastic syndrome and myeloproliferative disorders. Biology of Blood and Marrow Transplantation, 14 (2), 246-255. (Level 1 Evidence - Independent study)
National Cancer Institute. (2008, October). Bone marrow transplantation and peripheral blood stem cell transplantation. Retrieved May 20, 2010 from http://www.cancer.gov/cancertopics/factsheet/Therapy/bone-marrow-transplant/print?page=&keyword=.
Pollack, S. M., Steinberg, S. M., Odom, J., Dean, R. M., Fowler, D. H., & Bishop, M. R. (2009). Assessment of the hematopoietic cell transplantation comorbidity index in non-Hodgkin lymphoma patients receiving reduced-intensity allogeneic hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation, 15 (2), 223-230. (Level 2 Evidence - Independent study)
Rotta, M., Storer, B. E., Sahebi, J. A., Bruno, B., Lange, T., et al. (2009). Long-term outcome of patients with multiple myeloma after autologous hematopoietic cell transplantation and nonmyeloablative allografting. Blood, 113 (14), 3383-3391. (Level 1 Evidence - Independent study)
Sandmaier, B. M., Mackinnon, S., & Childs, R. W. (2007). Reduced intensity conditioning for allogeneic hematopoietic cell transplantation: Current perspectives. Biology of Blood and Marrow Transplantation, 13 (1), 87-97.
Sorror, M. L., Storer, B. E., Sandmaier, B. M., Maris, M., Shizuru, J., Maziarz, R., et al. (2008). Five-year follow-up of patients with advanced chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. American Journal of Clinical Oncology, 26 (30), 4912-4920. (Level 1 Evidence - Industry sponsored)
Technology Evaluation Center. (2001, May). Nonmyeloablative allogeneic stem-cell transplantation for malignancy (Vol.16, No. 3). Chicago: BlueCross BlueShield Association. (106 articles and/or guidelines reviewed)
Vigouroux, S., Michallet, M., Porcher, R., Attal, M., Ades, L., Bernard, M., et al. (2007). Long-term outcomes after reduced-intensity conditioning allogeneic stem cell transplantation for low-grade lymphoma: A survey by the French Society of Bone Marrow Graft Transplantation and Cellular Therapy (SFGM-TC). Haematologica, 92 (5), 627-634. (Level 1 Evidence - Independent study)
ORIGINAL EFFECTIVE DATE: 1/1/2002
MOST RECENT REVIEW DATE: 6/10/2010
ID_BT
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