Cancer Treatment Today

Lay Summary: The accepted situations that warrant allogeneic transplants for ALL are discussed.

Most current induction regimens for adult acute lymphoblastic leukemia (ALL) include prednisone, vincristine, and an anthracycline. Some regimens also add other drugs, such as asparaginase or cyclophosphamide. Current multiagent induction regimens result in complete response rates that range from 60% to 90%. However some patients relapse and salvage therapy is inadequate for cure. Poor risk ALL is also considered  appropriate for consolidation allogeneic transplantation, but NCCN recommends it only when a donor is available (ALL-6).

The goal of stem cell transplantation is to cure the patient’s cancer by destroying the cancer cells in the bone marrow with high doses of chemotherapy and then replacing them with new, healthy blood-forming stem cells.

The accepted benefits of allogeneic hematopoietic cell transplantation (HCT) are due to both the myeloablative chemoradiotherapy and the immune-mediated reaction of donor lymphocytes directed against residual ALL cells in the recipient (ie, the graft-versus-leukemia reaction). To be effective, the survival benefit should outweigh the greater expense and higher risk of early toxicity and death, and late complications such as graft-versus-host disease (GVHD) and sterility. Allogeneic HCT is commonly used as part of the post-remission therapy of patients with ALL demonstrating high-risk features, such as the presence of the Philadelphia (Ph) chromosome or a Ph-like molecular signature [3]. Results have been best when allogeneic HCT is performed in first CR, but allogeneic HCT can also cure some patients in second CR.Franco J. et al, How I treat relapsed childhood acute lymphoblastic leukemia Blood October 4, 2012 vol. 120 no. 14 2807-2816

L.S Muffly et al, Management of Acute Lymphoblastic Leukemia in Young Adults. Clinical Advances in Hematology & Oncology
February 2018 – Volume 16, Issue 2

Goldstone AH, Richards SM, Lazarus HM, et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: Final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008; 111(4): 1827-1833The goal of stem cell transplantation is to cure the patient’s cancer by destroying the cancer cells in the bone marrow with high doses of chemotherapy and then replacing them with new, healthy blood-forming stem cells.

The accepted benefits of allogeneic hematopoietic cell transplantation (HCT) are due to both the myeloablative chemoradiotherapy and the immune-mediated reaction of donor lymphocytes directed against residual ALL cells in the recipient (ie, the graft-versus-leukemia reaction). To be effective, the survival benefit should outweigh the greater expense and higher risk of early toxicity and death, and late complications such as graft-versus-host disease (GVHD) and sterility. Allogeneic HCT is commonly used as part of the post-remission therapy of patients with ALL demonstrating high-risk features, such as the presence of the Philadelphia (Ph) chromosome or a Ph-like molecular signature [3]. Results have been best when allogeneic HCT is performed in first CR, but allogeneic HCT can also cure some patients in second CR.Franco J. et al, How I treat relapsed childhood acute lymphoblastic leukemia Blood October 4, 2012 vol. 120 no. 14 2807-2816

L.S Muffly et al, Management of Acute Lymphoblastic Leukemia in Young Adults. Clinical Advances in Hematology & Oncology February 2018 – Volume 16, Issue 2

Goldstone AH, Richards SM, Lazarus HM, et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: Final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008; 111(4): 1827-1833

A 2009(Imrie et al) guideline considers allogenec transplantation appropriate for:

Acute Lymphoblastic Leukemia (ALL) (including lymphoblastic lymphoma)

First complete remission:
Allogeneic stem cell transplantation is an option for patients with ALL with poor prognostic features such as Philadelphia chromosome or t(4;11) positivity or delayed time to first complete remission.
Autologous stem cell transplantation is not recommended for patients with ALL in first complete remission.
Beyond first complete remission:
Allogeneic transplantation is the recommended treatment option for eligible patients with ALL who achieve a second remission.

A 2012 review presented retrospective reviewes and reports that suggest that umbilical cord is as effective as a sibling donor for children with ALL treated with stem cell transplantation but there remain no comparative studies.

There is insufficient evidence to support or refute the use of autologous stem cell transplantation beyond first remission for patients with ALL.

Franco J. et al, How I treat relapsed childhood acute lymphoblastic leukemia Blood October 4, 2012 vol. 120 no. 14 2807-2816
Stem cell transplant for acute lymphocytic/lymphoblastic leukemia (adult). Philadelphia (PA): Intracorp; 2005. Various p. [47 references]

Evidence-based Reviews, American Society of Blood and Marrow Transplantation. 2004. Published in Biology of Blood and Marrow Transplantation and available online at: http://www.asbmt.org/policystat/policy.html

S. Giebel, Hematopoietic Stem Cell Transplantation for Adults With Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia in First Remission: A Position Statement of the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL) and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2019 Jun;54(6):798-809

L.S Muffly et al, Management of Acute Lymphoblastic Leukemia in Young Adults. Clinical Advances in Hematology & Oncology
February 2018 – Volume 16, Issue 2

Imrie K, Rumble RB, Crump M, Advisory Panel on Bone Marrow and Stem Cell Transplantation, Hematology Disease Site Group. Stem cell transplantation in adults: recommendations. Toronto (ON): Cancer Care Ontario Program in Evidence-based Care; 2009 Jan 30. 78 p. (Recommendation report; no. 1). [66 references]

EJohn Moore,et al,Equivalent Survival for Sibling and Unrelated Donor
Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia, Biology of Blood and Marrow Transplantation 13:601-607 (2007)

Russell JA, Savoie ML, Balogh A, et al. Allogeneic transplantation for adult acute leukemia in first and second remission with a novel regimen incorporating daily intravenous busulfan, fludarabine, 400 cGy total-body irradiation, and thymoglobulin. Biol Blood Marrow Transplant. 2007; 13(7):814-821.

Schetelig J, Bornhäuser M, Schmid C, et al. Matched unrelated or matched sibling donors result in comparable survival after allogeneic stem-cell transplantation in elderly patients with acute myeloid leukemia: a report from the cooperative German transplant study group. J Clin Oncol. 2008; 26(32):5183-5191.

Kiehl MG, Kraut L, Schwerdtfeger R, et al. Outcome of allogeneic hematopoietic stem-cell transplantation in adult patients with acute lymphoblastic leukemia: No difference in related compared with unrelated transplant in first complete remission. J Clin Oncol. 2004; 22(14):2816-2825.

Revised: 8/22/11