BlueCross BlueShield of Tennessee Medical Policy Manual

Nonmyeloablative Allogeneic Stem Cell Transplantation (Reduced Intensity Stem Cell Transplant) for Treatment of Malignancy


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.


See also:


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.



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.




American Cancer Society. (2009). Issues related to stem cell transplants. Retrieved May 20, 2010 from


American Cancer Society. (2009). Types of stem cell transplants. Retrieved May 20, 2010 from


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]. (2012, July) Stem cell transplantation (NCD 110.8.1, p. 2-53 to 2-55). Ingenix.


Harousseau, J. L. (2007). Role of stem cell transplantation. Hematology/Oncology Clinics of North America, 21 (6), 1157-1174.


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


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)


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)




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