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 following situations have traditionally been considered appropriate for an allogeneic stem cell transplant: Availability of a human leukocyte antigen (HLA)-matched donor (at least five of six HLA-match) AND any ONE of the following: failed induction therapy, first remission for patients with poor prognosis or second or subsequent remission. Autologous HSC transplantation for the treatment of acute lymphocytic/lymphoblastic leukemia is appropriate when the patient is not eligible for allogeneic stem-cell transplantation.
More recently, it became appreciated that with current management methods unrelated donors provide equivalent results as sibling donors, although incidence of GVHD remains higher. NCCN(AKK-6) is less positive in its recommendations.It says: allogeneic HSCT if adonor is available (especially MRD+or poor risk cytogenetics)(this is for PH- disease).
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
, Richards SM
, Lazarus HM
, Tallman MS
, Buck G
, Fielding AK
, Burnett AK
, Chopra R
, Wiernik PH
, Foroni L
, Paietta E
, Litzow MR
, Marks DI
, Durrant J
, McMillan A
, Franklin IM
, Luger S
, Ciobanu N
, Rowe JM
. 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 Feb 15;111(4):1827-33. Epub 2007 Nov 29.
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]
Ashfaq K, Yusuf BJ, Jilani AZ, Owais SS, Yahaya I, Chen Y-F, Kinsey SE. Stem cell transplantation for high risk acute lymphoblastic leukaemia in paediatric patients in first remission. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD010348. DOI: 10.1002/14651858.CD010348 – See more at: http://summaries.cochrane.org/CD010348/stem-cell-transplantation-for-high-risk-acute-lymphoblastic-leukaemia-in-paediatric-patients-in-first-remission#sthash.BjAlEfXA.dpuf
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.