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The objective is to underscore the significance of pre-existing anti-HLA Abs in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for SAA. A retrospective analysis was conducted using data from 244 SAA patients who underwent allo-HSCT between January 2016 and October 2022. The patient cohort was divided into 2 groups based on the presence of pre-existing anti-HLA Abs. Out of 244 SAA patients, 82 were tested positive for anti-HLA Abs. Seventeen patients were tested with DSA in haplo-HSCT. We found that the presence of pre-existing anti-HLA Abs did not influence neutrophil engraftment (P = .600); however, it resulted in delayed platelet recovery (P = .006). Comparatively, patients with anti-HLA Abs demonstrated lower overall survival (OS) compared to their counter parts without anti-HLA Abs (P = .001), with a correspondingly elevated transplant-related mortality (TRM) in the former group (P = .002). Multivariate analysis established pre-existing anti-HLA Abs as an independent risk factor for impaired platelet recovery (HR 1.67, 95% CI 1.16 to 2.44, P = .006) and OS (HR 2.19, 95% CI 1.03 to 4.67, P = .043). However, there were no differences between DSA and non-DSA patients after desensitization in haplo-HSCT. In summary, the presence of pre-existing anti-HLA Abs in SAA patients undergoing allo-HSCT appears to detrimentally affect platelet recovery and overall prognosis., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The combination of cladribine, cytarabine, and G-CSF (CLAG) has exhibited robust synergistic anti-leukemia activity as an induction therapy (IT) in acute myeloid leukemia (AML). However, the impact of CLAG as a bridging therapy (BT) administered between IT and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with relapsed or refractory (R/R) AML remains uncertain. In this retrospective study, we examined the efficacy of CLAG as a transitional strategy prior to allo-HSCT in R/R AML. We included 234 patients with R/R AML who received the modified busulfan plus cyclophosphamide conditioning regimen for allo-HSCT in our center during the past 6 years, performed a propensity-score matching analysis, partitioned them into four distinct cohorts, and further integrated them into the CLAG group and non-CLAG group based on response to IT and utilization of CLAG. Our cohorts encompassed 12 patients in Cohort A (modified composite complete remission (mCRc) after IT, CLAG), 31 in Cohort B (mCRc after IT, non-CLAG), 35 in Cohort C (non-complete remission (non-CR) after IT, CLAG), and 80 in Cohort D (non-CR after IT, non-CLAG). Intriguingly, among patients with non-CR status, the administration of CLAG correlated with a notably statistically diminished risk of relapse and improved survival at 2-year follow-up (Cohort C vs. Cohort D). Employing CLAG as a BT prior to allo-HSCT demonstrates substantial effectiveness, a relative degree of safety, and manageable toxicity in selected R/R AML cases., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To analyse the effect of HLA-DPA1 and HLA-DPB1 allelic mismatches on the outcomes of unrelated donor haematopoietic stem cell transplantation (URD-HSCT), we collected 258 recipients with haematological disease who underwent HLA-10/10 matched URD-HSCT. HLA-A, -B, -C, -DRB1, -DQB1, -DRB3/4/5, -DQA1, -DPA1 and -DPB1 typing was performed for the donors and recipients using next-generation sequencing (NGS) technology. After excluding 8 cases with DQA1 or DRB3/4/5 mismatches, we included 250 cases with HLA-14/14 matching for further analysis. Our results showed that the proportion of matched DPA1 and DPB1 alleles was only 10.4% (26/250). The remaining 89.6% of donors and recipients demonstrated DPA1 or DPB1 mismatch. In the DPA1 matched and DPB1 mismatched group, accounting for 18.8% (47/250) of the cohort, DPB1*02:01/DPB1*03:01 allelic mismatches were associated with decreased 2-year OS and increased NRM. DPB1*02:02/DPB1*05:01 and DPB1*02:01/DPB1*05:01 mismatches showed no impact on outcomes. Moreover, the specific allelic mismatches observed were consistent with the DPB1 T-cell epitope (TCE) classification as permissive and non-permissive. We innovatively established an analysis method for DPA1 ~ DPB1 linkage mismatch for cases with both DPA1 and DPB1 mismatched, accounting for 70% (175/250) of the total. DPA1*02:02 ~ DPB1*05:01/DPA1*02:01 ~ DPB1*17:01 linkage mismatches were associated with lower 2-year OS, especially among AML/MDS recipients. DPA1*02:02 ~ DPB1*05:01/DPA1*01:03 ~ DPB1*02:01 linkage mismatches showed no impact on outcomes. In conclusion, applying the DPA1 ~ DPB1 linkage mismatch analysis approach can identify different types of mismatches affecting transplant outcomes and provide valuable insight for selecting optimal donors for AML/MDS and ALL recipients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Elderly patients with acute myeloid leukemia or myelodysplastic syndromes (AML/MDS) have historically had poor prognoses. However, there has been a recent increase in the use of allogenic hematopoietic stem cell transplantation (allo-HSCT) are in this patient population. Nevertheless, the optimal choice of donor type for the patients remains an unmet need. Limited data exist on the use of allo-HSCT in elderly patients with AML/MDS from China. To better understand and optimize the selection of donor type for the elderly patients, particularly for those with refractory or relapsed disease, in comparison with the previous studies in the US and Europe., Methods: Our retrospective study enrolled 259 patients aged over 55 years who underwent their first allo-HSCT between April 2015 and August 2022. These patients were divided into three groups based on donor type: haploidentical related donor group (haploidentical related donor transplantation [HID], n = 184), matched sibling donor group (matched sibling donor transplantation [MSD], n = 39), and matched unrelated donor group (matched unrelated donor transplantation [MUD], n = 36). Statistics were performed with the chi-square test, the log-rank and Fine-Gray tests., Results: The median age of the cohort was 57 years (range: 55-75) and 26.25% of patients were over 60 years old. Younger patients had a higher incidence of acute graft-versus-host disease (HR = 1.942, P = 0.035), faster neutrophil recovery (HR = 1.387, P = 0.012), and better overall survival (HR = 0.567, P = 0.043) than patients aged ≥ 60 years across the entire cohort. Patients with refractory or relapsed (R/R) diseases had delayed neutrophil engraftment (P = 0.010, HR = 0.752) and platelet engraftment (P < 0.001, HR = 0.596), higher incidence of relapses (HR = 2.300, P = 0.013), and inferior relapse-free survival (RFS) (HR = 1.740, HR = 0.016) regardless of donor type. When it came to graft-versus-host-disease-free, relapse-free survival (GRFS), MUDs turned out to be superior to HIDs (HR = 0.472, P = 0.026) according to the multivariable analysis. In contrast, we found MSDs had an inferior GRFS to HIDs in parallel (HR = 1.621, P = 0.043)., Conclusion: The choice of donor type did not significantly affect the outcomes of allo-HSCT. However, when considering the quality of post-transplant life, MUDs or HIDs from younger donors may be the optimal choice for elderly patients., (© 2024. The Author(s).)

To examine the production time, type, and MFI of post-transplantation de novo HLA antibodies, and their effects on haplo-HSCT outcomes, we retrospectively included 116 patients who were negative for pre-existing HLA antibodies. In total, 322 serum samples from pre-transplantation to post-transplantation were dynamically tested by Luminex and single-antigen bead reagents. Patients were divided into: HLA antibody persistently negative group (group 1), the de novo HLA antibody transiently positive group (group 2), the de novo HLA antibody non-persistently positive group (group 3), and the de novo HLA antibody persistently positive group (group 4). Group 4 included DSA+non-DSA (NDSA) (group 4a) and NDSA (group 4b) groups. The detection rate of de novo HLA antibodies was 75.9% (88/116). The median MFI for de novo HLA antibodies was 2439 (1033-20162). The incidence of II-IV aGvHD was higher in group 2 than in group 1 (52.6% vs 17.9%, P < 0.01); in group 4a than in group 1 (87.5% vs 17.9%, P < 0.001); and in group 4a than in group 4b (87.5% vs 40.0%, P = 0.001). The DFS (37.5% vs 85.7%, P < 0.01) and OS (37.5% vs 85.7%, P < 0.01) of group 4a were lower than those of group 1. The DFS (48.0% vs 85.7%, P < 0.01) and OS (56.0% vs 85.7%, P = 0.03) of group 4b were lower than those of group 1. Multivariate analysis showed that de novo HLA antibody being transiently positive (HR: 5.30; 95% CI: 1.71-16.42, P = 0.01) and persistently positive (HR: 5.67; 95% CI: 2.00-16.08, P < 0.01) were both associated with a higher incidence of II-IV aGvHD. Persistently positive de novo HLA antibodies were a risk factor for reduced DFS (HR: 6.57; 95% CI: 2.08-20.70, P < 0.01) and OS (HR: 5.51; 95% CI: 1.73-17.53, P < 0.01). DSA and NDSA can be detected since 15 days after haplo-HSCT in patients without pre-existing HLA antibodies, and affect aGvHD, DFS, and OS. Haplo-HSCT patients must be monitored for HLA antibodies changes for appropriate preventive clinical management, and we recommend that 1-month post-transplantation is the best test time point., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Ji, Chen, Li, Zhu, Yuan, Bao, Wu and He.)

The National Marrow Donor Program and Center for International Blood and Marrow Transplant Research provided guidelines for the use of anti-HLA antibodies and HLA-DP–mismatched loci in unrelated donor hematopoietic stem cell transplantation (HSCT). However, a deeper understanding of other potentially useful biomarkers for predicting clinical outcomes in HLA-A, -B, -C, -DRB1, -DQB1, and -DQA1 (12/12)–matched unrelated donor HSCT is needed to further improve clinical outcomes. We tested HLA genotyping for 123 pairs of patients and donors. Anti-HLA antibodies using the Luminex method was applied to 123, 117, and 106 serum samples collected before and 1 month and 3 months after transplantation. The presences of anti-HLA antibodies at the 3 time points were 37.4% (46 of 123), 40.2% (47 of 117), and 22.6% (24 of 106). Mismatch of HLA-DPB1 and/or DPA1 allele between patient-donor pairs was 83.6% (92 of 110). Patients with anti-HLA antibodies had delayed platelet recovery. The presence of anti-HLA antibodies and their dynamic changes after transplantation were associated with increased occurrence of grades II to IV acute and chronic graft-versus-host disease (GVHD), higher treatment-related mortality, and reduced overall survival (OS) and disease-free survival, especially in acute myeloid leukemia and myelodysplastic syndrome patients. Multivariate analysis showed that presence of anti-HLA antibodies before transplantation was a risk factor for GVHD and OS. Furthermore, HLA-DP loci–matched subgroup showed a trend towards a lower rate of acute GVHD and a higher OS in the anti-HLA Abs-negative group. Our results suggest that dynamic changes of anti-HLA antibodies independently predict for a negative outcome of HSCT, independent of HLA-DP loci mismatches. Routine monitoring for anti-HLA antibody dynamics should be conducted before and after HSCT. [ABSTRACT FROM AUTHOR]

Aim To investigate the role of donor killer cell immunoglobulin-like receptor (KIR) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to develop a donor selection strategy for Chinese population. Methods In this 5-year retrospective study, we performed KIR genotyping on a total of 626 donor and recipient pairs by PCR-SSP. All patients underwent HSCT, comprising 219 HLA-identical sibling HSCT, 210 HLA-identical unrelated donor (URD) HSCT, and 197 HLA haplo-identical HSCT, for treatment of myeloid and lymphoid leukemia. Results Donor KIR genotypes and KIR gene motifs influenced transplantation outcomes for AML/MDS but not ALL/NHL patients in 3 models of transplants. In sibling HSCT for AML/MDS patients (n = 128), KIR mismatch between patient and donor had a better overall survival (OS; 87.3% versus 69.3%; P = 0.027) and reduced grade III to IV acute graft-versus-host disease (aGVHD; 4.6% versus 13.6%; P = 0.029). However, the effect was not observed in URD (n = 122) and haplo-identical HSCT (n = 108) for AML/MDS patients. Multivariate analysis indicated that centromeric B motifs contributed to improved survival in all models of transplants: (1) In sibling HSCT, donors’ haplotype cB-tA/tB were associated with improved OS compared with cA-tB (96.6% versus 71.2%; P = 0.021) or cA-tA (96.6% versus 72.1%; P = 0.017); (2) In URD-HSCT, donors with Cen -B were associated with a significantly improved OS (HR = 0.256; 95% CI, 0.084 to 0.774; P = 0.016) and RFS (HR = 0.252; 95% CI, 0.084 to 0.758; P = 0.014); (3) In haplo-identical HSCT, the same effect of Cen -B was observed on OS (HR, 0.335; 95% CI, 0.164 to 0.667; P = 0.002), RFS (HR, 0.331; 95% CI, 0.167 to 0.657; P = 0.002), and NRM (HR, 0.286; 95% CI, 0.120 to 0.683; P = 0.005). Regarding the KIR genotypes, compared with other donor KIR B/x genotypes: (1) In sibling HSCT, genotype Bx1 was a risk factor for lower OS (HR, 8.667; 95% CI, 2.321 to 32.37; P = 0.001) and RFS (HR, 9.207; 95% CI, 2.631 to 32.22; P = 0.001); (2) The same negative effect of Bx1 was also found in URD-HSCT (OS: P = 0.047; RFS: P = 0.041) and haplo-identical HSCT (OS: P = 0.002; RFS: P = 0.002). Conclusions Avoiding the selection of Bx1 donors is strongly advisable for AML/MDS patients undergoing both related and unrelated HSCT whereas the presence of the Cen -B motifs was rather recommended in donor selection. [ABSTRACT FROM AUTHOR]