Second allogeneic hematopoietic cell transplantation enables long-term disease-free survival in relapsed acute leukemia

Abstract

Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice for high-risk myeloid and lymphoid leukemias. Relapse after allogeneic HCT is associated with a dismal prognosis and further therapeutic options are limited. One potential curative approach is a second allogeneic HCT. However, there is no consensus about optimal transplant modalities, suitable patients, and entities. We performed a retrospective analysis of our institutional database to evaluate risk factors that influence survival after a second allogeneic HCT for the treatment of relapsed acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). We identified 40 patients (AML, n = 29; ALL, n = 11) that received a second allogeneic HCT at our institution. At time of second HCT, 48% of patients were in complete remission (CR). Current overall survival (OS) was 14/40 patients with a median follow-up of 64 months (range 4-140) of patients alive resulting in a Kaplan-Meier estimated 2-year event-free survival (EFS) and OS of 32%, respectively. Cumulative incidence of non-relapse mortality (NRM) and relapse at 2 years was 31 and 37%, respectively. We identified several independent risk factors influencing OS: > 6 months from first to second transplant (p = 0.02), complete remission prior to transplant (p = 0.003), and the subsequent occurrence of chronic graft-versus-host disease (p = 0.003) were associated with a significantly improved OS. In conclusion, our data suggest that a second allogeneic HCT is a curative treatment option for relapsed acute leukemias in selected patients.

Second allogeneic stem cell transplantation in patients with acute lymphoblastic leukaemia: a study on behalf of the Acute Leukaemia Working Party of the European Society for Blood and Marrow Transplantation

“…Outcomes of relapsed ALL after allo-HCT2 were poor compared to relapsed AML (Bosi et al, 1997;Ruutu et al, 2015). A relatively better 2-year OS of 30% in our study compared to similar reports (Ruutu et al, 2015;Schneidawind et al, 2018) may be a result of deeper remissions prior to allo-HCT2 due to advances in salvage treatments (blinatumomab, Inotuzumab ozogamicine) as well as improved post-transplant supportive care. It is important to determine the predictive factors associated with outcomes of allo-HCT2 given the risk of disease relapse and the high NRM.…”

“…Tumour-directed allogeneic immunotherapy in the form of DLI or allo-HCT2 can cure a small subset of patients with this high-risk disease. Previously reported studies on allo-HCT2 in ALL has shown long-term LFS in 10-20% of patients (Table S2) (Bosi et al, 1997(Bosi et al, , 2001Eapen et al, 2004;Poon et al, 2013;Schneidawind et al, 2018). The reliable estimate of factors associated with allo-HCT2 outcomes is difficult due to the limited sample size of these studies.…”

Haploidentical transplants for patients with relapse after the first allograft

“…4,5 Most studies have shown an increased risk for both non-relapse mortality (NRM) and relapse exceeding 40% and 50%, respectively, attributed to lower ability to tolerate a more intense conditioning regimen, short duration of remission after first transplant, high disease risk, and transient remission status after the first transplant. 4,[6][7][8][9] In general, HLA-matched unrelated donor (MUD) is considered the first alternative donor choice for patients without an HLAmatched related donor. 4,5 However, longer time to transplantation using MUDs could impact on ability to take patients rapidly to transplant.…”

G‐CSF administration prior to donor lymphocyte apheresis promotes anti‐leukaemic effects in allogeneic HCT patients

“…In addition, occurrence of chronic GVHD after DLI was associated with a significantly improved survival. We and others found in previous studies that limited forms of GVHD were associated with favourable graft-versus-tumour effects and improved survival, whereas severe GVHD outweighed such benefits by higher GVHDrelated morbidity and mortality (Introna et al, 2017;Miyamoto et al, 2017;Tan et al, 2017;Saillard et al, 2018;Schneidawind et al, 2018). immature myeloid precursor cells with distinct immunoregulatory properties.…”