Search

Introduction Survival rate of patients with chemorefractory acute myeloid leukemia (AML) or myelodysplastic syndrome with excess blasts (MDS-EB) is poor. Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy in these patients. Patients and Methods We report a retrospective analysis of outcomes of therapy of 24 patients with AML or MDS-EB refractory to high-dose salvage chemotherapy or who had failed previous HCT, who received T-cell–replete HLA haploidentical HCT in aplasia after cladribine/cytarabine-based chemotherapy followed by reduced intensity or myeloablative conditioning. All patients had active disease before commencement of the treatment. Results Of the patients, 91.7% achieved complete remission (CR), whereas 2 patients (8.2%) died in aplasia. One-year relapse rate was 49.3%. Cumulative incidence of nonrelapse mortality (NRM) was 25.6%. In a subgroup of patients with HCT–comorbidity index score ≤ 3, NRM was 15.4%. Two-year overall survival and relapse-free survival were 30.6% and 22.6%, respectively. Incidence of grade 3 and 4 acute graft versus host disease was 21.3% and 8.3, respectively. Conclusion We found that sequential therapy with HCT in aplasia after cladribine/cytarabine chemotherapy is feasible, results in high CR rates, and has acceptable toxicity profile; however, posttransplant relapse is common in patients treated with active disease.

This work summarizes our experience with WT1 monitoring before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT).The expression of WT1 gene was measured by real-time polymerase chain reaction in peripheral blood according to the European Leukemia Net recommendations. Between May 2005 and August 2019, we analyzed 147 consecutive patients with acute myeloid leukemia with high WT1 expression at diagnosis, transplanted in first (CR1) or second (CR2) complete remission.At the time of allo-HSCT, 107 patients had WT1-normal expression (WT1 ≤ 50 copies), and 40 patients had WT1-high expression. The median follow-up was 21 months. The estimated 5-year overall survival and event-free survival was significantly better in the WT1-normal cohort (65% and 57% vs. 37% and 25%; P = .0003 and P .0001, respectively) and 5-year cumulative incidence of relapse was significantly lower in the WT1-normal group (19% vs. 53%; P .0001). Five-year non-relapse mortality was not significantly different (20% and 23%). Multivariate analysis revealed WT1-high expression and acute graft-versus-host disease grade 3/4 as significantly negative prognostic factors for OS. Overall, 49 patients developed WT1 molecular relapse in the post-transplant period; in 14 cases, the therapeutic intervention was done. In all but 1 relapsed patient where WT1 minimal residual disease (MRD) was monitored (38 patients), we detected WT1-high levels (sensitivity of 97%).The results of the analysis confirmed our previous experience that WT1 status before allo-HSCT is a strong prognostic factor for both OS and relapse risk. In addition, we confirmed the usefulness of this marker for MRD monitoring after allo-HSCT. The main advantage is the possibility of frequent MRD monitoring in peripheral blood and early bone marrow examination based on WT1-high expression.

Gonadotropin-releasing hormone (GnRH) antagonist combined with the human chorionic gonadotropin hormone (hCG) is commonly used in assisted reproduction techniques (ARTs) to induce controlled ovarian hyperstimulation (COH) and to synchronize oocyte maturation. While hCG is known to have immunomodulatory properties, we aimed to assess its effect on immunological changes, with respect to HLA-G binding receptors and embryo implantation success.The study involved 103 subjects, including patients undergoing COH protocols (n=66), divided on the basis of the pair's fertility disorder (FD) causes (female FD, n=29; male FD, n=37), and age matched healthy women (n=37). The relative distribution of T cell (CD3+/CD4+, CD3+/CD8+) and NK cell (CD56bright/CD16-, CD56dim/CD16+) populations was evaluated together with HLA-G ligands KIR2DL4 and LILRB1 expression by flow cytometry in the peripheral blood of all subjects, as well as in patient follicular fluids.Both groups of patients exhibited a significant decrease of their CD4/CD8 index, a down-modulation of LILRB1-positive CD8 T cells, and increased KIR2DL4-positive NK cell distribution, when compared to the healthy donors. We attribute these changes to the COH protocol, since the only significant change between the patient groups was in the number of cytotoxic CD56dim NK cells (elevated in the female FD group). Patients with male FD causes, having an above-average CD4/CD8 index (≥3.17) and below-average KIR2DL4+/CD56bright NK cell levels(≤13.3%), exhibited higher embryo implantation rates.The GnRH antagonist/hCG protocol promotes CD3+/CD8+ and KIR2DL4+ NK cell levels, more abundant in subjects with lower implantation rates, and thus decreases the embryotransfer success in otherwise fertile women.

The interpretation of the role of HLA-DPB1 in unrelated haematopoietic stem cell transplantation (HSCT) is subject to discussion. We have investigated the role of HLA-DPB1 allele matching in HSCT outcomes in 161 recipients who were HLA-A, -B, -C, -DRB1 and -DQB1-matched with their unrelated donors at the allelic level (10/10). In addition, we analysed the association of polymorphic amino acid mismatches of DPB1 molecule with HSCT end-points, and a previously published permissiveness concept. HLA-DPB1 allele mismatches were significantly associated with an increased incidence of acute graft-versus-host disease (aGvHD) and worse overall survival (OS). The mismatch at amino acid position 69 significantly increased the risk for transplant-related mortality (TRM). Risk factors for aGvHD also included mismatches at positions 8, 9, 35, 76 and 84. This is to our knowledge, the first report of an in vivo effect of single amino acid mismatches on HSCT outcomes. In this study, grouping of allelic mismatches into permissive and non-permissive categories and their association with transplantation end-points was relevant for TRM but not for other clinical end-points.