A novel GMP-manufactured medicinal product candidate composed of NK and γδ T cells as adjunct immunotherapy for hematopoietic stem cell transplantation.

Analysis of the Impact of KIR B Haplotype Donors on Outcomes after Haploidentical (HI) and Matched Related (MR) Hematopoietic Stem Cell Transplantation (HSCT)

Little is known regarding the effect of KIR/HLA incompatibilities (inc.) in the setting of T-replete haploidentical allogeneic hematopoietic stem cell transplantation using posttransplant cyclophosphamide (PTCy). In this retrospective study, the impact of KIR/HLA inc. on clinical outcomes and NK cell reconstitution was studied in a cohort of 51 consecutive patients receiving a T cell-replete haploidentical allogeneic hematopoietic stem cell transplantation after a reduced-intensity conditioning using peripheral blood stem cells as the source of the graft and PTCy as graft-versus-host disease (GvHD) prophylaxis. The NK cell repertoire reconstitution was examined by multiparameter flow cytometry in 34 of these 51 patients from day 0 to day 100 posttransplant. Genetic KIR2DL/HLA inc. were found to be significantly associated with more GvHD (81.2 versus 45.7%, p = 0.01) and less relapse (6.2 versus 42.8%, p = 0.008) in this context. GvHD is associated with increased levels of differentiated and activated NK cells. A significant loss of KIR2DL2/3+ NK cells was observed at day 30 in patients with inhibitory KIR/HLA inc., suggesting that responsive KIR NK cells are particularly targeted by the immunosuppressive PTCy treatment. Further investigations are needed from a larger cohort with an identical clinical approach to consolidate these results and to identify the NK cell subsets that may be beneficial for the graft-versus-leukemia effect observed. Because many haploidentical donors can be identified in a family, the prediction of KIR NK cell alloreactivity could be of crucial importance for donor selection and patient outcome.

An Examination of Cytomegalovirus, Socioeconomic Status, Race, and Ethnicity on Outcomes after Haploidentical Hematopoietic Transplantation

Introduction. Hematopoietic stem cell transplantation (HSCT) from an alternative donor is the main treatment option for patients with severe acquired aplastic anemia (AAA) refractory to combined immunosuppressive therapy with anti-thymocyte globulin and cyclosporine A. Although the outcomes of unrelated and haploidentical HSCTs have improved over the years, graft-versus-host disease (GVHD) continues to pose a major clinical challenge associated with significant morbidity and mortality. Aim: to present the outcomes of unrelated and haploidentical HSCTs with TCRαβ-depleted grafts in patients with AAA. Materials and methods. Eighty patients (42 males and 38 females) with AAA underwent HSCT between September 2012 and February 2022. The median age at transplantation was 10 (2.3–22.7) years. Seventy-eight patients received HSCT after relapse or refractory disease after one (n = 14) or two (n = 18) courses of immunosuppressive therapy. Two patients underwent HSCT as first-line treatment. The median time from diagnosis to transplantation was 1 (0.1–11.8) year. Conditioning regimen included cyclophosphamide (100–150 mg/kg), fludarabine (150 mg/kg), antithymocyte globulin (ATGAM (100 mg/kg) or thymoglobulin (5–10 mg/kg)), and thoracoabdominal irradiation (2–6 Gy). In some cases, additional medications such as melphalan (140 mg/m2), thiophosphamide (5–10 mg/kg), and rituximab (200 mg/m2) were used. Patients with paroxysmal nocturnal hemoglobinuria (n = 6) received eculizumab at a dose of 600 mg from day –7 to day +14 (every 7 days). Post-transplant GVHD prophylaxis included calcineurin inhibitors. TCRαβ/CD19 depletion was performed using a CliniMACS Plus system (Miltenyi Biotec, Bergish Gladbach, Germany). The median CD34+ cell dose in the graft was 10 (2.7–23.0) × 10⁶/kg, and the median TCRαβ+ cell dose was 26.6 (0.85–316.00) × 10³/kg. Results. The cumulative incidence of engraftment was 0,95 (95% confidence interval (CI) 0.9–1.0) with the median time to neutrophil recovery being 13 (9–24) days and to platelet recovery – 12 (7–25) days. Graft rejection occurred in 9 patients, the cumulative incidence of rejection was 0,11 (95% CI 0.06–0.20). Three of these patients underwent successful retransplantation. The cumulative incidence of grade II–III acute GVHD was 0,12 (95% CI 0.05–0.27) in the patients who had undergone unrelated donor HSCT versus 0,42 (95% CI 0.29–0.61) in the haploidentical HSCT recipients (p = 0.003). The cumulative incidence of chronic GVHD was 0,5 (95% CI 0.01–0.20) in the unrelated donor HSCT group and 0,21 (95% CI 0.12–0.38) in the haploidentical HSCT group (p = 0.02). The median follow-up was 6.4 years. Twenty-two (27.5%) patients died. Sixteen of them died of complications after the first HSCT; 4 deaths occurred due to complications associated with repeat HSCT. Two patients died after graft rejection due to infectious complications. The overall survival was 0,79 (95% CI 66–91) in the unrelated donor HSCT group and 0,66 (95% CI 51–81) in the haploidentical donor HSCT group. Conclusion. The use of TCRαβ/CD19-depleted HSCT from alternative donors ensured high engraftment rates and reduced the incidence of severe GVHD. However, there were no significant improvements in graft rejection or mortality.

Selective Photodepletion of Recipient-Alloreactive T-Cells Enables Safe and Efficacious Haploidentical HSCT: Initial Results from a Phase 2 Trial in Patients with AML, ALL, and MDS

Current practices, organizational structures, technologies and challenges in developing atmps: A survey by dare-NL, nxtgen hightech, T2EVOLVE and ctiwp of EBMT - a gocart-coalition initiative

Haploidentical Transplantation for DOCK8 Deficiency

Profile of Thrombosis Distribution Following Haploidentical and Identical-Sibling Transplantation: A 15-Year Experience at a Single Center in China

Objective To compare the efficacy of haploidentical hematopoietic stem cell transplantation (HSCT) and HLA-identical transplantation for hematologic diseases, and analyze risk factors related to overall survival (OS). Methods There were 81 patients with hematological malignancies receiving Allo-HSCT from October, 2011 to July, 2017. The patients were divided into two groups: 30 patients undergoing haploidentical HSCT and 51 cases undergoing matched sibling donor HSCT (MSD-HSCT). Implantations of hematopoietie stem cells, incidence of graft versus host disease (GVHD), OS rate, disease free survival (DFS) rate, incidence of relapse and non-relapse-mortality were analyzed statistically. Multivariate analysis was used to analyze the risk factors related to OS. Results All patients achieved sustained engraftment. 100 days after Allo-HSCT, the cumulative incidence for Ⅱ-Ⅳ aGVHD had no significant difference between haplo-HSCT and MSD-HSCT (56.7% versus 11.8%, P=0.000). There was no significant difference in the 1-year cumulative incidence for cGVHD between haplo-HSCT and MSD-HSCT (20.6% versus 45%, P=0.341). The 2-year OS rate in patients receiving haplo-HSCT and MSD-HSCT was 63.2% and 78.4% respectively (P=0.078). The 2-year DFS rate in patients receiving haplo-HSCT and MSD-HSCT was 54.8% and 66.9% respectively (P=0.159). The 2-year relapse and non-relapse-mortality rate in patients receiving haplo-HSCT and MSD-HSCT was 25.9% and 24%, and 22.9% and 9.5% respectively. There were no statistically significant differences in relapse rate and mortality between two groups (P=0.465, 0.118). Multivariate analysis showed that relapse and Ⅱ-Ⅳ aGVHD were independent prognostic indictors for OS with relative risk 6.671 (95% CI 2.791-15.946) and 3.073 (95% CI 1.296~7.284) (P<0.05). Conclusion The therapeutic effects of haploidentical transplantation were similar to those of HLA-identical sibling transplantation. Relapse and Ⅱ-Ⅳ aGVHD after transplantation have prognostic significance for the long-term survival of transplant patients. Key words: hematopoietic stem cell transplantation; Hematopathy; Prognosis

Allogeneic Blood and Marrow Transplantation for Pediatric Patients with Sickle Cell Anemia: An Institutional Experience

Bloodstream infection (BSI) is a common and serious complication after hematopoietic stem cell transplantation (HSCT). An investigation of the characteristics of pre-engraftment BSI after haploidentical HSCT compared with human leukocyte antigen (HLA)-identical sibling HSCT has not been conducted. A single-center cohort representing 1847 consecutive patients undergoing haploidentical or HLA-identical sibling HSCT from 2013 to 2016 was selected. We investigated the characteristics of pre-engraftment BSI after haploidentical HSCT and its impact on patient outcome, and we compared it with HLA-identical sibling HSCT. After haploidentical HSCT, the cumulative incidence of pre-engraftment BSI was higher (30-day: 9.2% [7.6, 10.8] vs 1.7% [0.5, 2.9], P < .0001) and median onset of BSI was earlier (day +3 vs day +9, P = .001) than HLA-identical sibling HSCT. Escherichia coli, Klebsiella pneumoniae, and coagulase-negative staphylococci were the most common isolates after haploidentical HSCT. However, Enterococcus faecium was the most common isolate after HLA-identical sibling HSCT. A multivariate analysis suggested that variables associated with BSI after haploidentical HSCT included a diagnosis of myelodysplastic syndrome (MDS), an interval from diagnosis to HSCT ≥190 days, carbapenem therapy, and grade 3-4 intestinal mucositis. The same variables, except MDS, were also associated with BSI after HLA-identical sibling HSCT. The multivariate analysis also suggested that BSI was a risk factor for increased all-cause mortality at 3 months after haploidentical HSCT (hazard ratio = 2.281; 95% confidence interval: 1.334, 3.900; P = .003). Pre-engraftment BSI was more common after haploidentical HSCT than HLA-identical sibling HSCT. It was an independent factor associated with increased all-cause mortality at 3 months after haploidentical HSCT.

Increase In NK Cell Lysis of Leukemic Blasts Due to Loss of Mismatched HLA Haplotype After Haplo-Identical Stem Cell Transplantation

BackgroundSince the introduction of tyrosine kinase inhibitors (TKIs) into combination chemotherapy regimens, the majority of newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) patients have achieved complete remission (CR). However, without allogeneic hematopoietic stem cell transplantation (HSCT), long-term outcomes in adults remain unsatisfactory. Indeed, haploidentical HSCT has become a common treatment for adult patients who lack an HLA-matched donor, though limited data are available on the efficacy of haploidentical HSCT in Ph+ ALL patients.MethodsWe analyzed the clinical outcomes of 82 Ph+ ALL patients who underwent haploidentical HSCT (n = 47) or HLA-matched HSCT (n = 35). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to assess BCR-ABL expression. All of the patients were treated with an imatinib-based regimen before undergoing HSCT. Imatinib treatment was resumed in the patients’ posttransplantation following detection of BCR-ABL transcripts.ResultsAll of the patients achieved neutrophil and platelet engraftment, with the exception of five patients who died prior to engraftment. Haploidentical HSCT was associated with higher incidences of acute graft-versus-host disease (GVHD) (51.1 vs. 25.7 %, p < 0.05) and chronic GVHD (48.9 vs. 25.7 %, p < 0.05) compared with HLA-matched HSCT, but there was no difference in the incidence of either grades III–IV acute GVHD or extensive chronic GVHD. The incidence of cytomegalovirus (CMV) infection was significantly higher in the patients treated with haploidentical HSCT than in those treated with HLA-matched HSCT (38.3 vs. 14.3 %, p < 0.05). Haploidentical HSCT was associated with a significantly lower relapse rate compared with HLA-matched HSCT (44.8 vs. 19.1 %, p < 0.05). There were no differences in non-relapse mortality (NRM), leukemia-free survival (LFS), or overall survival (OS) between the patients who received HLA-matched HSCT and those who underwent haploidentical HSCT.ConclusionsOur data indicate that the incidence of NRM after HSCT is similar between the patients who receive HLA-matched donor cells and those who receive haploidentical donor cells and that haploidentical HSCT reduces the relapse rate. Haploidentical HSCT represents an encouraging treatment option for Ph+ ALL patients who lack a suitable HLA-matched donor.

Higher Graft Failure after Haploidentical in Comparison to Matched Related and Unrelated Stem Cell Transplantation for Severe Aplastic Anemia: A Single-Center Retrospective Study

Haploidentical Transplantation with Post-Transplant Cyclophosphamide versus Unrelated Donor Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.