Unmanipulated haploidentical in comparison with matched unrelated donor stem cell transplantation in patients 60 years and older with acute myeloid leukemia: a comparative study on behalf of the ALWP of the EBMT

Abstract

BackgroundAcute myeloid leukemia (AML) is both more common and with more biologically aggressive phenotype in the elderly. Allogenic stem cell transplantation (allo-SCT) is the best treatment option in fit patients. Either HLA-matched unrelated donor (MUD) or haploidentical (Haplo) donor are possible alternative for patients in need.MethodsWe retrospectively compared non-T-cell-depleted Haplo (n = 250) to 10/10 MUD (n = 2589) in AML patients ≥ 60 years.ResultsMedian follow-up was 23 months. Disease status at transplant differs significantly between the two groups (p < 10−4). Reduced intensity conditioning (RIC) was administrated to 73 and 77% of Haplo and MUD, respectively (p = 0.23). Stem cell source was the bone marrow (BM) in 52% of the Haplo and 6% of MUD (p < 10−4). Anti-thymocyte globulin (ATG) was most frequently used in MUD (p < 10−4) while post-Tx cyclophosphamide (PT-Cy) was given in 62% of Haplo. Engraftment was achieved in 90% of the Haplo vs 97% of MUD (p < 10−4). In multivariate analysis, no significant difference was found between Haplo and MUD for acute (a)graft versus host disease (GVHD) grade II–IV, relapse incidence (RI), non-relapse mortality (NRM), leukemia free survival (LFS), graft-versus-host-free-relapse free survival (GRFS), and overall survival (OS). Extensive chronic (c)GVHD was significantly higher for MUD as compared to Haplo (HR 2, p = 0.01, 95% CI 1.17–3.47). A propensity score analysis confirmed the higher risk of extensive cGVHD for MUD without differences for other outcomes.ConclusionsAllo-SCT from both Haplo and MUD are valid option for AML patients ≥ 60 years of age with similar results. Transplantation from MUD was associated with higher extensive cGVHD. Our findings suggest that Haplo is a suitable and attractive graft source for patients≥ 60 with AML in need of allo-SCT.

Improved survival after offspring donor transplant compared with older aged‐matched siblings for older leukaemia patients

“…The non‐significant trend for lower risk of chronic GVHD after haploidentical HCT as compared with matched HCT is in accordance with other reports (Blaise et al ., ; Devillier et al ., ; Robinson et al ., ; Santoro et al ., ). The possible explanation may be as follows.…”

“…These data suggest donor source and HLA-matching are not significantly correlated with transplant outcomes in these settings. Regardless, these publications have mainly described younger patients and lack data from older populations (Blaise et al, 2016;Devillier et al, 2018;Santoro et al, 2018).…”

Haploidentical Hematopoietic Stem Cell Transplantation Followed by ‘Post-Cyclophosphamide’: The Future of Allogeneic Stem Cell Transplant

“…Others must turn to bone marrow registries in pursuit of a matched-unrelated donor (MUD). Overall survival (OS) between MRD and MUD is similar; however, complications, most significantly graft vs. host disease (GvHD), are higher in the latter [5][6][7]. GvHD is the process by which the newly donated T cells (present in the graft) recognize the recipient (the host) as foreign and attack primarily the skin, gut and liver.…”

Impact of conditioning intensity on outcomes of haploidentical stem cell transplantation for patients with acute myeloid leukemia 45 years of age and over

“…In recent years, most haplo‐SCTs are being performed without T cell depletion (T cell–replete haplo‐SCT) with improving outcomes due to faster immune reconstitution and a lower incidence of nonrelapse mortality (NRM) related to graft‐versus‐host disease (GVHD), graft rejection, and life‐threatening infections . Notably, the results of haplo‐SCT also improved in patients with AML who were ≥60 years of age …”

“…2,3 Notably, the results of haplo-SCT also improved in patients with AML who were ≥60 years of age. 4,5 The optimal conditioning intensity regimen for allogeneic transplantation for patients with AML is a debated topic. Reduced-intensity conditioning (RIC), which is based mainly on the graft-versus-leukemia effect and less on the cytotoxicity of the chemotherapy or radiotherapy was originally developed for older and less-fit patients, those with comorbidities, and those unable to undergo myeloablative conditioning (MAC).…”