Stem-Cell Transplant for Acute Lymphocytic Leukemia (ALL)
© Blue Cross and Blue Shield of Montana
Current Effective Date:
December 27, 2013
Original Effective Date:
July 09, 2008
September 27, 2013
March 1, 2010, July 1, 2011, March 22, 2012; September 10, 2013
Acute lymphocytic leukemia (ALL) results from an acquired (not inherited) genetic injury to the DNA (Deoxyribonucleic acid) of a single cell in the bone marrow. The effects are:
- The uncontrolled and exaggerated growth and accumulation of cells called "lymphoblasts" or "leukemic blasts," which fail to function as normal blood cells, and
- The blockade of the production of normal marrow cells, leading to a deficiency of red cells (anemia), platelets (thrombocytopenia), and normal white cells (especially neutrophils, i.e., neutropenia) in the blood.
ALL occurs in multiple forms that vary with regard to cellular morphology, cytochemistry, immunophenotype, cytogenetic abnormalities, and other prognostic features. Although adult and childhood forms of ALL vary in the distribution of these prognostic features, there is considerable overlap, particularly among late adolescents and young adults. Consequently, no clear age demarcation divides the adult and childhood forms.
However, in general, adult ALL is characterized by a predominance of immature and pleomorphic cells, more frequent co-expression of myeloid markers, a greater percentage of leukemias derived from T-cells rather than B-cells, and a higher incidence of cytogenetic abnormalities with negative prognostic implications (such as the Philadelphia chromosome). In contrast, childhood ALL cells usually have a more mature morphology, and infrequently are of T-cell origin or positive for myeloid markers or the Philadelphia chromosome. As a consequence of these differences, the adult and childhood forms of ALL respond differently to treatment and vary in their risk for relapse once remission is achieved. For example, childhood ALL is a highly curable disease, with long-term survival rates ranging from 60%–85%. Similar therapy regimens have had less favorable outcomes in adult ALL. Approximately 65%–90% of those with adult ALL achieve an initial complete remission, but only 20%–30% become long-term survivors.
Risk factors associated with a *high risk of relapse following initial complete remission includes:
- Age greater than 15 years;
- Leukocyte count greater than 10 x 109/L;
- Extramedullary disease, particularly in the central nervous system;
- Chromosomal abnormalities, including Philadelphia chromosome;
- Failure to achieve a complete remission (CR) within six weeks after induction therapy begins.
41.00, 41.01, 41.02, 41.03, 41.04, 41.05, 41.06, 41.07, 41.08, 41.09, 41.91, 99.25, 99.74, 99.79, 204.00, 204.01, 204.02
C91.00-C91.02, 30250G0, 30250X0, 30250Y0, 30250G1, 30250X1, 30250Y1, 30253G0, 30253X0, 30253Y0, 30253G1, 30253X1, 30253Y1, 6A550ZT, 6A550ZV, 6A551ZT, 6A551ZV
36511, 38204, 38205, 38206, 38207, 38208, 38209, 38210, 38211, 38212, 38213, 38214, 38215, 38220, 38221, 38230, 38232, 38240, 38241, 38242, 38243, 81265, 81266, 81267, 81268, 81370, 81371, 81372, 81373, 81374, 81375, 81376, 81377, 81378, 81379, 81380, 81381, 81382, 81383, 86805, 86806, 86807, 86808, 86812, 86813, 86816, 86817, 86821, 86822, 86825, 86826, 86849, 86950, 86985, 88240, 88241, S2140, S2142, S2150
- Autologous Bone Marrow Transplantation in Acute Lymphocytic and Non-Lymphocytic Leukemia Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center (1987 November):243-57.
- High-Dose Chemotherapy with Autologous Bone Marrow Transplantation for Acute Lymphocytic and Non-Lymphocytic Leukemia in the First Remission. Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center (1990 November):264-73.
- Attal, M., Blaise, D., et al. Consolidation treatment of adult acute lymphoblastic leukemia: a prospective, randomized trial comparing allogeneic versus autologous bone marrow transplantation and testing the impact of recombinant interleukin- 2 after autologous bone marrow transplantation. BGMT Group. Blood (1995) 86(4):1619-28.
- High-Dose Chemotherapy with Autologous Stem-Cell Support in the Treatment of Adult Acute Lymphoblastic Leukemia. Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center Assessment Program (1998 January) 12(25):1-25.
- Wheeler, K.A., Richards, S.M., et al. Bone marrow transplantation versus chemotherapy in the treatment of very high-risk childhood acute lymphoblastic leukemia in first remission: results from Medical Research Council UKALL X and XI. Blood (2000) 96(7):2412-8.
- Harrison, G., Richards, S., et al. Comparison of allogeneic transplant versus chemotherapy for relapsed childhood acute lymphoblastic leukaemia in the MRC UKALL R1 trial. Annals of Oncology (2000) 11(8):999-1006.
- Lawson, S.E., Harrison, G., et al. The UK experience in treating relapsed childhood acute lymphoblastic leukaeima: a report on the Medical Research Council UK ALLR1 study. British Journal of Haematology (2000) 108(3):531-43.
- Uderzo, C. Indications and role of allogeneic bone marrow transplantation in childhood very high risk acute lymphoblastic leukemia in first complete remission. Haematologica (2000) 85(11 suppl):9-11.
- Uderzo, C., Dini, G., et al. Treatment of childhood acute lymphoblastic leukemia after the first relapse: curative strategies. Haematologica (2000) 85(11 suppl):47-53.
- Gaynon, P.S., Trigg, M.E., et al. Children’s Cancer Group trials in childhood acute lymphoblastic leukemia: 1983-1995. Leukemia (2000) 14(12):2223-33.
- Blaise, D., Kuentz, M., et al. Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early stage leukemia: a report from the Société Française de Greffe de Moelle. Journal of Clinical Oncology (2000) 18(3):537-46.
- Blaise, D., Attal, M., et al. Randomized study of recombinant interleukin-2 after autologous bone marrow transplantation for acute leukemia in first complete remission. European Cytokine Network (2000) 11(1):91-8.
- Champlin, R.E., Schmitz, N., et al. Blood stem cells compared to bone marrow as a source of hematopoietic cells for allogeneic transplantation. Blood (2000) 95(12):3702-9.
- Salvage HDC/AlloSCS for Relapse or Incomplete Remission Following HDC/AuSCS for Hematologic Malignancies. Chicago, Illinois: Blue Cross Blue Shield Association – Technology Evaluation Center. (2000 August) Tab 9.
- Collins, R.H., Goldstein, S., et al. Donor leukocyte infusions in acute lymphocytic leukemia. Bone Marrow Transplant (2000 September) 26(5):511-6.
- Dombret, H., Gabert, J., et al. Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia–results of the prospective multicenter LALA-94 trial. Blood (2002) 100(7):2357-66.
- Hunault, M., Harousseau, J.L., et al. Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial. Blood (2004) 104(10):3028-37.
- Goldstone, A.H., Lazarus, H.J., et al. The outcome of 551 1st CR transplants in adult ALL from the UKALL XII/ECOG 2993 study [abstract]. Blood (2004) 104:178a.
- Hahn, T., Wall, D., et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in children: an evidence-based review. Biology of Blood and Marrow Transplant (2005) 11(11):823-61.
- Ribera, J.M., Oriol, A., et al. Comparison of intensive chemotherapy, allogeneic or autologous stem cell transplantation as post-remission treatment for adult patients with high-risk acute lymphoblastic leukemia. Results of the PETHEMA ALL-93 trial. Haematologica (2005) 90(10):1346-56.
- Donor Leukocyte Infusion for Hematologic Malignancies that Relapse after Allogeneic Stem Cell Transplant. BCBSA Medical Policy Reference Manual (2005 September) Medicine: 2.03.03.
- Hahn, T., Wall, D., et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in adults: an evidence-based review. Biology of Blood and Marrow Transplant (2006) 12(1):1-30.
- Ribera, J.M., Ortega, J.J., et al. Comparison of intensive chemotherapy, allogeneic, or autologous stem-cell transplantation as postremission treatment for children with very high risk acute lymphoblastic leukemia: PETHEMA ALL-93 trial. Journal of Clinical Oncology (2007) 25(1):16-24.
- Gutierrez-Aguirre, C.H., Gomez-Almaguer, D., et al. Non-myeloablative stem cell transplantation in patients with relapsed acute lymphoblastic leukemia: results of a multicenter study. Bone Marrow Transplant (2007) 40(6):535-9.
- Mohty, M., Labopin, M., et al. Reduced intensity conditioning allogeneic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation. Haematologica (2008) 93(2):303-6.
- Non-Hodgkin’s Lymphoma. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology.v.3. (2008) www.nccn.org.
- Hematopoietic Stem-Cell Transplantation for Acute Lymphocytic Leukemia. Chicago Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (2008 June) Therapy 8.01.32.
||Policy name chaged from general Leukemia SCT to specific Acute Lymphoblastic Leukemia. |
||Policy updated with literature search; references 15 and 23 added, reference 32 updated. No change to policy statements|
||Policy formatting and language revised. Title changed from "Hematopoietic Stem-Cell Transplantation for Acute Lymphoblastic Leukemia" to "Stem-Cell Transplant for Acute Lymphocytic Leukemia (ALL)". Removed from the medically necessary statement "|