Alternative donor transplants for adult acute lymphoblastic leukaemia: a comparison of the three major options

Abstract

Myeloablative sibling-matched allogeneic transplantation for adult acute lymphoblastic leukaemia provides the best outcome, but most patients lack a suitable, related histocompatible donor. We reviewed three haematopoietic stem cell donor sources used for alternative donor transplantation pointing out drawbacks of these approaches including inherent selection bias. Matched unrelated donor allografts most often are performed in Philadelphia chromosome-positive disease and in second complete remission (CR2); a nearly 30% event-free survival (EFS) can be anticipated in select patients. Transplants using haploidentical donors are most successful if undertaken in CR1 and CR2 and appear to produce EFS rates of about 25%. Limited umbilical cord blood transplant data suggest efficacy, but marked patient and treatment heterogeneity hamper conclusions. Each of these three strategies has unique potential benefits and disadvantages. The growing use of minimal residual disease detection may identify subgroups of patients unlikely to be cured by chemotherapy alone; these patients are candidates for upfront high-dose chemoradiotherapy and cellular immunotherapy. These three approaches are plagued by treatment-related mortality and relapse rates as high as 40%, but advances in technology and supportive care may make each stem cell source more feasible and efficacious.

Long-term outcomes of adults with acute lymphoblastic leukemia after autologous or unrelated donor bone marrow transplantation: a comparative analysis by the National Marrow Donor Program and Center for International Blood and Marrow Transplant Research

“…In this situation, the question is further complicated by choice and availability of donor cells, extreme variations in toxicities relative to the specific type and timing of transplantation. 24 The final and most important question is whether either of these treatments potentially result in superior long-term LFS recurrence. This analysis directly addresses these questions and, in particular, provides important information on long-term leukemia-free and OS.…”

Philadelphia Chromosome–Positive Acute Lymphocytic Leukemia: A New Era of Challenges

“…Advances in SCT such as the application of nonmyeloablative reduced intensity conditioning regimens to older patients or those with comorbidities prohibiting traditional myeloablative regimens, in addition to increased availability of umbilical cord blood as a source of stem cells, have allowed this modality to be applied in a more systematic fashion. 20 Several studies have reported an improvement in the rate of allogeneic SCT in first CR after imatinib-based therapy compared with the prior experience. 28,31,32,35 This success is in part related to (1) an increase in the proportion of sustained remissions, offering additional time for identification of a suitable donor, and to (2) an improvement in the quality of the remissions (e.g., lower levels of BCR-ABL transcripts after imatinib-based therapy), resulting in a lower pretransplantation tumor burden.…”

Reduced-intensity vs myeloablative conditioning allogeneic hematopoietic SCT for patients aged over 45 years with ALL in remission: a study from the Adult ALL Working Group of the Japan Society for Hematopoietic Cell Transplantation (JSHCT)

“…[7][8][9] Most conditioning regimens have included TBI, sometimes exceeding 13 Gy for patients in CR2. 10,11 We have reported excellent outcomes of allo-SCT using a conditioning regimen with medium-dose VP-16, CY and TBI (12 Gy) for adult patients with ALL. 12,13 However, non-relapse mortality (NRM) may cause a worse overall outcome of MAC allo-SCT for elderly patients and patients with comorbidities.…”