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Measurable residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an independent risk factor for relapse in patients with acute lymphoblastic leukemia (ALL). This study aimed to assess the efficacy, safety, and immune reconstitution of chimeric antigen receptor T-cell (CAR-T) therapy in patients with molecular relapse after allo-HSCT. Eleven patients with molecular relapse of B-cell-ALL who underwent CAR-T therapy after allo-HSCT were enrolled. The rate of MRD negativity after a month of CAR-T infusion was 81.8%. Patients who bridged to second-HSCT after CAR-T therapy (n = 3) showed a trend of higher 3-year leukemia-free survival and 3-year overall survival than those who did not (n = 8; 100% vs. 75.0%; 95% CI, 45.0–104.9%; p = 0.370). No treatment-related mortalities were observed. Among patients who did not bridge to second-HSCT and remained in complete remission until the last follow-up (n = 6), five of them had not recovered normal immunoglobulin concentrations with a median follow-up of 43 months. CAR-T therapy may be a safe and effective treatment strategy to improve survival after allo-HSCT; however, the problem of prolonged hypogammaglobulinemia in patients who do not bridge to second-HSCT is worth noting. [ABSTRACT FROM AUTHOR]

Introduction: The role of haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) in pediatric patients with relapsed or refractory (R/R) ETV6/RUNX1-positive acute lymphoblastic leukemia (ALL) is unclear. This study aimed to identify prognostic factors and explore the role of haplo-HSCT in the treatment of ETV6/RUNX1-positive ALL. Methods: We analyzed the clinical characteristics and treatment outcomes of 20 pediatric patients who were diagnosed with ETV6/RUNX1-positive ALL and received chemotherapy/chimeric antigen receptor T-cell bridged to haplo-HSCT between 2016 and 2021 at our institution. Results: With a median follow-up time of 47 months, the 3-year cumulative incidence of relapse, disease-free survival, and overall survival were 35.9% (95% confidence interval (CI): 15.3–57.1%), 59.1% (95% CI: 37.2–81.0%), and 75.0% (95% CI: 56.0–94.0%), respectively. Multivariate analysis revealed that pre-HSCT measurable residual disease (MRD) positivity (hazard ratio, 13.275; 95% CI: 2.406–73.243; p = 0.003) had a significant negative impact on relapse. A total of 7 patients experienced positive ETV6/RUNX1 gene expression at a median of 7.2 months after haplo-HSCT, and 5 of them experienced relapse at a median time of 12.1 months after haplo-HSCT. ROC curve analysis was performed to analyze the significance of pre-HSCT and post-HSCT ETV6/RUNX1 transcripts for predicting relapse; the AUC were 0.798 (95% CI: 0.567–1.0, p = 0.035) and 0.875 (95% CI: 0.690–1.0, p = 0.008), respectively. The optimal cut-off points to predict an inevitable relapse were 0.011% and 0.0019%, respectively. Conclusion: Patients with R/R ETV6/RUNX1-positive ALL may benefit from haplo-HSCT. Deeply eliminating pre-HSCT MRD and preemptive treatment for post-HSCT MRD may be crucial to further improving the prognosis. [ABSTRACT FROM AUTHOR]

This letter to the editor discusses the outcomes of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with the "Beijing protocol" in pediatric myeloid neoplasms post cytotoxic therapy (MN-pCT). MN-pCT is a rare complication in pediatric cancer survivors, and research on this population is limited. The study reports the outcomes of pediatric patients with MN-pCT who underwent haplo-HSCT, which is the only treatment providing long-term survival. The study found that haplo-HSCT using the Beijing protocol resulted in long-term survival with low treatment-related mortality. The authors suggest that haplo-HSCT may be a suitable alternative when matched sibling or unrelated donors are unavailable. [Extracted from the article]

Summary: Data from 200 children with high‐risk acute myeloid leukaemia who underwent their first haploidentical haematopoietic stem cell transplantation (haplo‐HSCT) between 2015 and 2021 at our institution were analysed. The 4‐year overall survival (OS), event‐free survival (EFS) and cumulative incidence of relapse (CIR) were 71.9%, 62.3% and 32.4% respectively. The 100‐day cumulative incidences of grade II–IV and III–IV acute graft‐versus‐host disease (aGVHD) were 41.1% and 9.5% respectively. The 4‐year cumulative incidence of chronic GVHD (cGVHD) was 56.1%, and that of moderate‐to‐severe cGVHD was 27.3%. Minimal residual disease (MRD)‐positive (MRD+) status pre‐HSCT was significantly associated with lower survival and a higher risk of relapse. The 4‐year OS, EFS and CIR differed significantly between patients with MRD+ pre‐HSCT (n = 97; 63.4%, 51.4% and 41.0% respectively) and those with MRD‐negative (MRD‐) pre‐HSCT (n = 103; 80.5%, 73.3% and 23.8% respectively). Multivariate analysis also revealed that acute megakaryoblastic leukaemia without Down syndrome (non‐DS‐AMKL) was associated with extremely poor outcomes (hazard ratios and 95% CIs for OS, EFS and CIR: 3.110 (1.430–6.763), 3.145 (1.628–6.074) and 3.250 (1.529–6.910) respectively; p‐values were 0.004, 0.001 and 0.002 respectively). Thus, haplo‐HSCT can be a therapy option for these patients, and MRD status pre‐HSCT significantly affects the outcomes. As patients with non‐DS‐AMKL have extremely poor outcomes, even with haplo‐HSCT, a combination of novel therapies is urgently needed. [ABSTRACT FROM AUTHOR]

This study investigates the influence of donor‐specific anti‐HLA antibodies (DSA) levels on primary poor graft function (PGF) and graft rejection (GR) after haploidentical stem cell transplantation (haplo‐SCT) with rituximab desensitization. A total of 155 DSA‐positive haplo‐SCT candidates with mean fluorescence intensity (MFI) between 2000 and 10,000 were enrolled in this prospective clinical trial. Receiver operating characteristic (ROC) curves determined the optimal DSA MFI cutoff for identifying high‐risk patients. Patients were categorized into two groups: DSA low‐level group (2000 ≤ DSA MFI < 5000, Group A) and high‐level group (5000 ≤ DSA MFI ≤ 10,000, Group B). The incidence of primary PGF was 6.5% (2.6%–10.3%), while GR incidence was 0.6% (0.0%–1.9%). Group A had significantly lower primary PGF rates than Group B (2.3% [0.0%–5.7%] vs. 12.9% [4.8%–21.0%], p = 0.017). Only one patient in Group B experienced GR. High DSA levels (5000 ≤ MFI ≤ 10,000) were identified as the sole independent risk factor for primary PGF and GR after haplo‐SCT with rituximab desensitization (HR = 7.282, 95% CI 1.517–34.953, p = 0.013). The 4‐year cumulative incidence of relapse, non‐relapse mortality, disease‐free survival, and overall survival were 14.7% (11.6%–17.8%), 16.3% (13.1%–19.4%), 69.0% (65.9%–76.2%), and 70.6% (66.4%–74.8%), respectively. DSA levels have an impact on efficiency of rituximab desensitization, and a DSA MFI threshold is provided for predicting primary PGF and GR. [ABSTRACT FROM AUTHOR]