Background-The success of unrelated hematopoietic-cell transplantation (HCT) is limited by graft-versus-host disease (GVHD). A sequence dimorphism in exon one of HLA-B gives rise to

PURPOSE The main aim of this study was to evaluate the significance of HLA-DPB1 expression in acute graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) from HLA-A, -B, -C, -DRB1, -DQB1–matched and –mismatched unrelated donors. PATIENTS AND METHODS Between January 1, 2017, and January 10, 2019, we assessed 19,136 patients who received HCT from an HLA-A, -B, -C, -DRB1, -DQB1–matched or –mismatched unrelated donor performed in Australia, the European Union, Japan, North America, and the United Kingdom between 1988 and 2016. Among transplant recipients with one HLA-DPB1 mismatch, the patient’s mismatched HLA-DPB1 allotype was defined as low or high expression. Multivariable regression models were used to assess risks of GVHD associated with high expression relative to low expression HLA-DPB1 mismatches. The effect of increasing numbers of HLA-DPB1 mismatches on clinical outcome was assessed in HLA-mismatched transplant recipients. RESULTS In HLA-A, -B, -C, -DRB1,-DQB1–matched transplant recipients, donor mismatching against one high-expression patient HLA-DPB1 increased moderate (odds ratio [OR], 1.36; P = .001) and severe acute GVHD (OR, 1.32; P = .0016) relative to low-expression patient mismatches, regardless of the expression level of the donor’s mismatched HLA-DPB1. Among transplant recipients with one HLA-A, -B, -C, -DRB1, or -DQB1 mismatch, the odds of acute GVHD increased with increasing numbers of HLA-DPB1 mismatches (OR, 1.23 for one; OR, 1.40 for two mismatches relative to zero mismatches for moderate GVHD; OR, 1.19 for one; OR, 1.40 for two mismatches relative to zero for severe GVHD), but not with the level of expression of the patient’s mismatched HLA-DPB1 allotype. CONCLUSION The level of expression of patient HLA-DPB1 mismatches informs the risk of GVHD after HLA-A, -B, -C, -DRB1, -DQB1–matched unrelated HCT, and the total number of HLA-DPB1 mismatches informs the risk of GVHD after HLA-mismatched unrelated HCT. Prospective consideration of HLA-DPB1 may help to lower GVHD risks after transplantation.

Adult HCT recipients have a high risk of decreased eGFR by 1 year after HCT. Although eGFR remains fairly stable thereafter, a decreased eGFR is significantly associated with higher risk of mortality, with a progressively increased risk as eGFR declines.

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The recurrence of malignancy after hematopoietic cell transplantation (HCT) is the primary cause of transplant failure. The NKG2D axis is a powerful pathway for anti-tumor responses, but its role in the control of malignancy after HCT is not well-defined. We tested the hypothesis that gene variation of the NKG2D receptor and its ligands MICA and MICB affect relapse and survival in 1,629 patients who received a haploidentical HCT for the treatment of a malignant blood disorder. Patients and donors were characterized for MICA residue 129 and the exon 5 short tandem repeat (STR), and MICB residues 52, 57, 98, 189. Donors were additionally defined for NKG2D residue 72. Mortality was higher in patients with MICB-52Asn relative to 52Asp (HR 1.83 [95% CI 1.24-2.71; P = 0.002]) and lower with MICA STR-mismatching relative to STR-matching (HR 0.66 [95% CI 0.54-0.79; P = 0.00002]). Relapse was lower with NKG2D-72Thr donors relative to 72Ala (relapse HR 0.57 [95% CI 0.35-0.91; P = 0.02]). The protective effects of patient MICB-52Asp with donor MICA STR-mismatching and NKG2D-72Thr were enhanced when all three features were present. The NKG2D ligand/receptor pathway is a transplantation determinant. The immunobiology of relapse is defined by the concerted effects of MICA, MICB and NKG2D germline variation. Consideration of NKG2D ligand/receptor pairings may improve survival for future patients.

Hematopoietic cell transplantation (HCT) remains the only curative therapy for pediatric myelodysplastic syndrome (MDS) in all but rare cases. While HCT outcomes for pediatric MDS are similar across the largest registry and single center trials, factors identified as contributing to inferior outcomes vary from study to study. We performed an analysis to provide more clarity on the prognostic implications of disease characteristics including blast burden and cytogenetic abnormalities in the current era. We conducted a retrospective analysis of 36 consecutive children (<18 years of age at HCT) who underwent allogeneic HCT for MDS between June 2000 and October 2019 at the Fred Hutchinson Cancer Center. Overall survival (OS) was 77% (95% CI 64-92%) and Relapse-free survival (RFS) was 71% (95% CI 57-88%) at 2-years post-HCT. Patients with < 5% blasts by morphology in the bone marrow at time of HCT showed superior 2-year OS at 87% (95% CI 74-100%) as compared to 54% (95% CI 32-93%) in patients with ≥5% blasts, consistent with an HR of 4.6 (CI 1.14-18.7, p=0.03). The inferior outcomes in patients with ≥ 5% blasts were due to increased relapse incidence (HR 7.6, CI 1.5-39.3) with no difference in NRM or acute GVHD. OS and RFS were comparable to what has been observed in other large, single center studies (OS 77%, RFS 71% at 2 years) and compared favorably to outcomes from the largest multi-center retrospective analyses. The primary disease factors that correlated with inferior OS and/or RFS and relapse were higher disease burden at time of HCT and administration of chemotherapy pre-HCT.