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

Abstract

Summary Donor selection for older leukaemia patients undergoing haematopoietic cell transplant (HCT) is not well defined: outcomes might be improved with a younger offspring donor rather than an older human leukocyte antigen (HLA)‐matched sibling donor (MSD). We extended our multicentre dataset. A total of 185 acute leukaemia patients (≥ 50 years) transplanted in first complete remission who received HCT from offspring (n = 62) or MSD (n = 123) were included. A 1:1 ratio matched‐pair analysis was performed. We were able to match 54 offspring with 54 MSD patients. Outcomes were compared between the two matched‐pair groups. The cumulative incidence of grade II/IV acute graft‐versus‐host disease (GVHD) (26% vs. 35%; P = 0·23) and chronic GVHD (37% vs. 24%; P = 0·19) was comparable between groups (MSD vs. offspring). The lower three‐year transplant‐related mortality (9% vs. 26%; P = 0·023) and relapse incidence (6% vs. 17%; P = 0·066) resulted in higher overall survival (85% vs. 58%; P = 0·003) and leukaemia‐free survival (LFS) (85% vs. 56%; P = 0·001) in offspring HCT compared with that in MSD HCT. These data might favour a young offspring over an older MSD in patients >50 years. The current analyses confirm that non‐HLA donor characteristics, such as kinship and donor age, rather than HLA disparity, predominantly influence survival in older acute leukaemia patients.

Haploidentical donor is preferred over matched sibling donor for pre-transplantation MRD positive ALL: a phase 3 genetically randomized study

“…The criteria for selecting the most appropriate transplant donor remain a topic of ongoing debate [4,5,8,9,11,12,14,15]. This prospective, genetically randomized study provided the most robust evidence thus far that HIDT is superior to MSDT, potentially due to stronger GVL effects in certain patients.…”

“…With the increasingly used haploidentical SCT (HIDT), HLA-identical sibling donors remain the first choice, though a number of studies have shown that treating patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) using haploidentical donors (HIDs) could achieve comparable outcomes to those who undergoing HLA-matched sibling donor transplantation (MSDT) [3,6,7]. On the other hand, using haploidentical transplants, the graft-versus-leukemia (GVL) effect may be stronger, as mismatches for HLA antigens on leukemic cells would provide allo-immune targets [4,5,[8][9][10][11][12][13]. A recent large European Society for Blood and Marrow Transplantation (EBMT) study indicated that HIDT has a lower incidence of relapse than MSDT for low-risk (HR = 0.83, P = 0.011) and intermediate-risk (HR = 0.85, P = 0.033) hematological malignancies [5].…”

“…Our previous studies showed that HIDT is superior to MSDT in terms of a lower relapse rate for patients with high-risk leukemia [11]. Furthermore, for older patients with acute leukemia, offspring donors not only result in lower non-relapse mortality (NRM), but also tended to be associated with a lower risk of relapse than MSDT [12]. Although these reports have effectively proven the potential superiority of HIDT to MSDT in the context of relapse risk in treating patients with some specified subgroups of hematological malignancies [4,5,[8][9][10][11][12], they cannot inform decision-making in choosing one donor type over another for a specific patient due to the retrospective nature of the studies or highly diverse populations and various transplant regimens [4,5,[8][9][10][11][12][13].…”

The consensus from The Chinese Society of Hematology on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation: 2021 update

“…HID-HSCT was associated with lower three-year NRM (9% vs. 26%, p = 0.023), a lower CIR (6% vs. 17%, p = 0.066) and higher OS (85% vs. 58%, p = 0.003) and DFS (85% vs. 56%, p = 0.001) rates than MSD-HSCT. These results might indicate that a young offspring donor is preferred over an older MSD for patients > 50 years old [ 102 ].…”

Improved survival for young acute leukemia patients following a new donor hierarchy for allogeneic hematopoietic stem cell transplantation: A phase III randomized controlled study

“…Recently, Karam et al 7 analyzed 406 older allo‐HSCT recipients with a median age of 54 years in haplo‐HSCT with post‐transplant cyclophosphamide (PT‐Cy) platforms and concluded that patients undergoing transplantation with a younger HID (≤ 35 years) had a similar OS rate, lower rates of chronic GVHD (cGVHD), and better cGVHD‐free, relapse‐free survival compared with a MSD or URD ≥ 35 years of age. Wang et al 8 also suggested that kinship and donor age, rather than HLA disparity, predominantly influence survival in older acute leukemia patients undergoing haplo‐HSCT in an ATG and granulocyte colony‐stimulating factor (G‐CSF)‐based protocol; however, donor selection for young acute leukemia (AL) patients undergoing allo‐HSCT has not been defined. To address this issue, we performed a two‐stage cohort study including a retrospective study followed by an independent prospective randomized controlled study to develop a feasible hierarchy guiding the selection of the best donor in the context of young AL patients (≤ 35 years of age) with multiple donors available, including MSDs, URDs, HPDs, and HSDs.…”