Who Is a Better Donor for Recipients of Allogeneic Hematopoietic Cell Transplantation: A Young HLA-Mismatched Haploidentical Relative or an Older Fully HLA-Matched Sibling or Unrelated Donor?

Abstract

replete HLA-mismatched haploidentical transplantation (HIDT) with post-transplant cyclophosphamide is increasingly becoming an acceptable treatment approach for patients lacking timely access to a suitably matched related donor transplant (MRDT) or matched unrelated donor transplant (MUDT). Multiple recent registry and single-center studies have shown comparable overall survival (OS) and disease-free survival (DFS) rates among HIDT, MRDT, and MUDT with a significantly lower risk of acute and chronic graft-versus-host disease (GVHD) among HIDT recipients. Candidates for allogeneic hematopoietic stem cell transplantation (HSCT) often have access to multiple donor sources, and a relevant question is whether outcomes can be improved with a younger HLA-mismatched haploidentical donor (35 years) rather than an older matched related donor (35 years) or matched unrelated donor (35 years). We analyzed 406 consecutive allogenic HSCT recipients, with a median age of 54 years (range, 19 to 77), after a MRDT with a donor age of 35 years (n = 222), MUDT with a donor age of 35 years (n = 91), and HIDT with a donor age of 35 years (n = 93). Median follow-up time for survivors was 51.5 months. Compared with MRDT and MUDT, HIDT recipients had a similar median age at time of HSCT, hematopoietic cell transplant comorbidity index, disease risk index distribution, and donor recipient sex matching. The survival estimates and relapse incidence at 3 years post-HSCT were OS (64% for MRDT, 54% for MUDT, and 62% for HIDT), DFS (55% for MRDT, 44% for MUDT, and 58% for HIDT), Transplant related mortality (TRM) (19% for MRDT, 16% for MUDT, and 18% for HIDT), and relapse (26% for MRDT, 37% for MUDT, and 24% for HIDT). HIDT recipients had better 3-year relapse rates compared with MUDT recipients (24% versus 37%, P= .048), with similar DFS and OS in a univariate analysis. MRDT recipients had a better relapse rate (26% versus 37%, P = .042) compared with MUDT recipients. Recipients of HIDT also had significantly lower rates of moderate to severe chronic GVHD compared with MRDT and MUDT recipients (P = .01). Multivariable analysis showed no effect of donor on OS, DFS, relapse, and TRM. Recipients of HIDT from a young donor 35 years had similar OS, lower rates of chronic GVHD, and better chronic GVHD-free, relapse-free survival compared with patients undergoing transplantation with an MRD or a MUD donor 35 years. This study suggests that given a situation where a choice between a young haploidentical relative and an older matched unrelated donor is to be made, one can achieve similar survival with a haploidentical donor and significantly lower rates of chronic GVHD.

Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide

“…This may have implications on donor selection when there is more than 1 haploidentical donor available (eg, older sibling versus younger offspring). Other studies have also shown donor age to be a factor in outcomes after haploidentical transplant, and our findings support this as a recommended consideration in donor selection [38][39][40].…”

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

“…There is only one published study involving donor selection for old patients among URDs, MRDs, and HIDs, in which the outcomes of 406 allo‐HSCT recipients with a median age of 54 years after MRD‐HSCT with a donor age ≥ 35 years, URD‐HSCT with a donor age ≥ 35 years, and HID‐HSCT with a donor age ≤ 35 years were compared. The results showed that recipients of HID‐HSCT from a young donor ≤ 35 years of age had a similar OS rate, lower rates of cGVHD, and better GRFSs compared with patients undergoing transplantation with a MRD or URD donor ≥ 35 years of age 7 . Hence, for old patients receiving allo‐HSCT, the donor age may be more important to transplantation outcomes than HLA disparity, which need to be confirmed in more homogeneous cohort of old patients.…”

“…Furthermore, there are few studies that have compared the outcomes of patients with acute leukemia receiving allo‐HSCT from a specific type of HIDs with conventional MSDs or URDs. 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.…”

“…Furthermore, there are few studies that have compared the outcomes of patients with acute leukemia receiving allo-HSCT from a specific type of HIDs with conventional MSDs or URDs. 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.…”

Is Haploidentical HCT Better Than…? A Wrong Question for Future Studies

“…The Northside Group, one of the first institutions to perform haploidentical hematopoietic cell transplantation (HCT) in the United States, has published a well-written retrospective analysis addressing the optimal donor type for patients with a hematologic malignancy undergoing first allogeneic HCT performed between 2005 and 2016 [1]. The donor types compared in the study were haploidentical family members age <35 years, matched sibling donors (MRDs), and matched unrelated donors (MUDs) age >35 years.…”