Transplant Outcomes Using Older Matched Sibling Donors Compared to Young Alternative Donors: A CIBMTR Analysis.

Whether younger donors should be prioritized over HLA-matching for allogeneic hematopoietic cell transplantation (allo-HCT) when using post-transplant cyclophosphamide (PTCy)-based graft versus host disease (GvHD) prophylaxis is unclear. To address this, we compared outcomes of allo-HCT recipients aged ≥50-years using PTCy-based GvHD prophylaxis from an older (≥50-years) matched sibling donor (MSD) to those of younger alternative donors ≤35-years: HLA-matched unrelated donors (MUD), HLA-mismatched unrelated donors (MMUD), and haploidentical (haplo)-related donors reported to the Center for International Blood & Marrow Transplant Research between 2014-2021. Young MUD and older MSD receiving calcineurin inhibitor (CNI)-based allo-HCT that met study criteria were concurrently examined.

Novel Scoring System for Ranking Hematopoietic Stem Cell Transplantation.

Background: When human leukocyte antigen (HLA)-matched donors are not available for hematopoietic stem cell transplants (HSCT), there are no well-accepted guidelines for ranking 7/8 HLA-matched unrelated donors to achieve optimal transplant outcomes. A novel scoring system for ranking HLA mismatches for these donors was investigated.

Methods: High-resolution HLA types were used to determine amino acid mismatches located in the HLA antigen-recognition domain.

JAK2/mTOR inhibition fails to prevent acute GVHD despite reduced Th1/Th17 cells: final phase 2 trial results.

Our phase 1 graft-versus-host disease (GVHD) prevention trial of JAK2 inhibitor, pacritinib (PAC; recommended phase 2 dose: 100 mg orally twice a day on day 0 to +70) plus sirolimus and tacrolimus (SIR/TAC) demonstrated the regimen was safe and free of pan-JAK myelosuppression after allogeneic hematopoietic cell transplantation (alloHCT). PAC inhibits interleukin 6 (IL-6) receptor activity and pathogenic T helper cell 1 (Th1)/Th17 differentiation in preclinical models and the phase 1 trial. Herein, we report on our completed phase 2 trial of PAC/SIR/TAC after 8/8 human leukocyte antigen matched alloHCT.

Outcomes of Human Leukocyte Antigen-Matched Related Donor and Haploidentical Allogeneic Hematopoietic Cell Transplantation Recipients by Immune Profiles of Recipients and Donors.

Haploidentical (Haplo) allogeneic HCTs (alloHCT) have been used more frequently over the last decade as survival is similar to HLA-matched related donor (MRD) alloHCTs. We aimed to identify donor and recipient immune signatures before alloHCT that are associated with clinically meaningful outcomes in MRD vs Haplo alloHCT recipients. This retrospective cohort study of 165 MRD (n = 132) and Haplo (n = 33) alloHCT recipients and their related donors between 2007-2019 with paired peripheral blood samples immunophenotyped for T-cell, B-cell, NK cell and dendritic cell (DC) subsets.

Amphiregulin, ST2, and REG3α biomarker risk algorithms as predictors of nonrelapse mortality in patients with acute GVHD.

Graft-versus-host disease (GVHD) is a major cause of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation. Algorithms containing either the gastrointestinal (GI) GVHD biomarker amphiregulin (AREG) or a combination of 2 GI GVHD biomarkers (suppressor of tumorigenicity-2 [ST2] + regenerating family member 3 alpha [REG3α]) when measured at GVHD diagnosis are validated predictors of NRM risk but have never been assessed in the same patients using identical statistical methods. We measured the serum concentrations of ST2, REG3α, and AREG by enzyme-linked immunosorbent assay at the time of GVHD diagnosis in 715 patients divided by the date of transplantation into training (2004-2015) and validation (2015-2017) cohorts.