Long-term clinical outcomes of hematopoietic cell transplantation for intermediate-to-poor-risk acute myeloid leukemia during first remission according to available donor types

Abstract

Standard therapy for acute myeloid leukemia (AML) consists of hematopoietic cell transplantation (HCT) including autologous-HCT (AUTO) and allogeneic-HCT from a matched-sibling donor (MSD) or well-matched unrelated donor (WM-URD). When a conventional donor is not available, HCT from a partially-matched (PM)-URD or familial-mismatched donor (FMMD) is typically considered. We analyzed 561 patients with intermediate to poor-risk molecular cytogenetics who underwent transplant from 2002 to 2013 in their first remission. Engraftment was successful in all donor types except five patients who died in aplasia. Disease-free survival (DFS) at 5 years was 61.4% for MSD, 62.1% for WM-URD, 65.3% for FMMD, 44.7% for AUTO and 36.8% for PM-URD. AUTO showed the highest relapse rate (51.0%) compared to MSD (23.5%) and FMMD (18.5%), but showed the lowest 5-year non-relapse mortality (NRM) rate (3.8%). PM-URD showed the highest NRM (29.3%) with more instances of acute graft-vs.-host disease (GVHD) with grade≥III (29.3%), compared to MSD (15.6%) and FMMD (15.7%). In a poor-risk subgroup, the 5-year DFS for FMMD and MSD was 59.8% and 46.7%, respectively, while for AUTO and PM-URD it was 12.6% and 0.0%, respectively, which was caused by a high relapse rate (87.1% in AUTO, 83.3% in PM-URD). In the intermediate-risk subgroup, the 5-year DFS of AUTO (53.9% was not different from the conventional donors in multivariate analysis, presenting a low NRM rate (5.1%). FMMD should be considered prior to PM-URD in intermediate-to-poor-risk AML and GVHD prophylaxis should be intensified when PM-URD is needed. AUTO might be considered for selected patients in the intermediate-risk group.

Outcomes of hematopoietic stem cell transplantation from unmanipulated haploidentical versus matched sibling donor in patients with acute myeloid leukemia in first complete remission with intermediate or high-risk cytogenetics: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…When looking at cytogenetics groups, this result was confirmed in intermediate risk, but not in high risk, where Haplo and MSD had similar NRM, in line with previous reports. 17 , 19 , 20 Furthermore, female donor to male recipient was associated to a higher NRM in intermediate AML and not in high risk AML. Therefore, one can speculate that the impact of female to male mismatch could depend on the risk of the underlying disease, as previously shown.…”

“…Similarly, Yoon et al . 20 analyzed long-term outcomes of 561 patients with intermediate (n=417) or poor risk (n=144) AML that underwent HSCT in CR1 from various donors including from MSD and Haplo. In poor risk AML, the authors observed a 5-year disease-free survival (DFS) of 47% versus 60% ( P <0.01) for MSD and Haplo, respectively; while in intermediate risk AML, DFS was 66% and 68% ( P =0.08) for MSD and Haplo, respectively.…”

Refined graft-versus-host disease/relapse-free survival in transplant from HLA-identical related or unrelated donors in acute myeloid leukemia

“…In our study we observed that, despite a rather promising OS of 69% and 65% for MSD and MUD recipients, respectively, only 44% of patients survived at 4 years after HSCT without experiencing at least one GRFS event, mainly represented by disease relapse and extensive cGVHD. When comparing outcomes of HSCT in patients with intermediate or poor-risk AML in first CR according to different donor types, Yoon et al [23] found a similar OS of 63% in both MSD and MUD, with no differences in LFS.…”

Comparison of the effects of early intensified induction chemotherapy and standard 3+7 chemotherapy in adult patients with acute myeloid leukemia

“…For patients in CR, we searched for available donors for allogeneic-hematopoietic cell transplantation (HCT) during the consolidation period, giving initial preference to human leukocyte antigen (HLA)-matched sibling donors (MSDs), followed by HLA well-matched unrelated donors (URDs). When conventional donors were not available, we searched for haploidentical familial mismatched donors; if a patient refused allogeneic-HCT, we performed autologous-HCT or completed three cycles of consolidation chemotherapy alone according to the patient's and physician's joint decision [ 16 17 18 ]. If a patient was a candidate for autologous-HCT, CD34+ hematopoietic stem cells were collected for 3 days during consolidation chemotherapy after the neutrophil count had recovered.…”