Haploidentical transplantation outcomes for secondary acute myeloid leukemia: Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) study

Abstract

Secondary acute myeloid leukemia (sAML) traditionally has inferior outcomes compared to de novo AML. Allogeneic hematopoietic cell transplantation (HCT) is the sole potentially curative therapy. This study analyzes the outcomes for unmanipulated haploidentical HCT (haploHCT) for sAML using the Acute Leukemia Working Party (ALWP) registry of the European Society for Blood and Marrow Transplantation (EBMT). We identified 154 patients with sAML who underwent haploHCT from 2006 to 2016. Median age at HCT was 60 years with time from diagnosis to HCT 5 months. At transplantation, 69 patients were in first CR and 85 had active disease. Fifty-seven (38.0%) patients underwent myeloablative conditioning and 97 (62.0%) reduced intensity conditioning (RIC) conditioning. Multivariate analysis showed that there was no difference in RI, nonrelapse mortality (NRM), leukemia free survival (LFS), overall survival (OS), or GVHD-free/relapse free survival (GRFS) for conditioning intensity, age, performance status, or graft source. Active disease was associated with higher RI and inferior LFS, OS, and GRFS compared with patients in CR at time of transplant. T-cell depletion with anti-thymoglobulin resulted in higher NRM and inferior LFS, OS, and GRFS compared to post-transplant cyclophosphamide (PTCy) (HR 2.25, 2.01, 2.16, and 1.73, respectively with P values <.05). Our data shows that haploHCT is a feasible alternative for sAML when matched transplantation is unavailable.

Comparative outcomes of myeloablative and reduced‐intensity conditioning allogeneic hematopoietic cell transplantation for therapy‐related acute myeloid leukemia with prior solid tumor: A report from the acute leukemia working party of the European society for blood and bone marrow transplantation

“…Furthermore, transplantation with myeloablative conditioning conferred a superior 3‐year LFS and OS of approximately 50% with a trend toward a decreased relapse incidence and no significant difference in NRM compared to RIC. The results reported here are consistent with other studies showing a 2‐year OS of approximately 50% following allogeneic HCT for patients with secondary AML with prior solid tumor . Additional factors significant for survival included having active disease at the time of transplantation and having a latency interval of more than 45 months from diagnosis of the primary solid tumor to diagnosis of t‐AML.…”

Cord blood transplantation is associated with good outcomes in secondary Acute Myeloid Leukaemia in first remission

“…The aim of this manuscript is to describe the outcomes of sAML patients given CBT and thus formal comparison with other stem cell sources is out of the scope of the current manuscript. Nevertheless, results of CBT for sAML in CR1 in the current survey seems in the range to what has been recently observed in sAML patients given grafts from HLA-haploidentical donors where 2-year OS and LFS were 57% and 49%, respectively, in patients receiving posttransplant cyclophosphamide as GVHD prophylaxis, and 44% and 39%, respectively, in those given ATG as GVHD prophylaxis [27]. In contrast, patients with active disease at transplantation seem to have worst OS with CBT (19% OS at 2-year in the current study) than with HLA-haploidentical donors (35% at 2-years in the above-mentioned study by Li et al [27]).…”

“…Two-year incidences of relapse and of NRM were 29% (95% CI, [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] and 39% (95% CI, 31-48), respectively. The figures were 25% (95% CI, [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] and 35% (95% CI, 25-45), respectively, in patients in CR1, versus 36% (95% CI, 22-49, P = 0.06) and 49% (95% CI, 33-62, P = 0.03), respectively, in patients with active disease at transplantation ( Fig. 1).…”

“…Two-year cumulative incidences of chronic and extensive chronic GVHD were 25% (95% CI, [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] and 12% (95% CI, 7-19), respectively. In multivariate analysis, female recipient (HR = 0.36, 95% CI 0.17-0.78, P = 0.01) and higher TNC infused (HR = 0.69, 95% CI 0.49-0.96, P = 0.03) were each associated with a lower incidence chronic GVHD.…”

Inferior outcome of allogeneic stem cell transplantation for secondary acute myeloid leukemia in first complete remission as compared to de novo acute myeloid leukemia

“…Allogeneic stem cell transplantation (alloSCT) is regarded as the treatment option for sAML with the best chance of achieving a long-term remission. Considering the transplant setting 8,9 , patients with sAML tend to have less available HLA identical siblings, and the majority receive reduced intensity conditioning (RIC) 10,11 . However, it is not clear whether having sAML per se is a risk factor for outcome after alloSCT, when all wellknown risk factors are controlled for 8 .…”