Tahereh Rostami

Background: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplant cyclophosphamide (PTCy) has expanded donor availability for acute leukemia, yet the clinical relevance of emerging immunogenetic markers remains uncertain. This study investigated whether donor–recipient human leukocyte antigen (HLA)-B leader matching influences transplantation outcomes in adults with acute leukemia undergoing haplo-HSCT. Methods: This retrospective analytical cohort included consecutive adults (18–65 years) with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) who underwent their first haplo-HSCT at one of the most prominent referral hospitals between January 2008 and December 2022. HLA-B leader status was determined by exon 1 sequencing and classified as matched or mismatched between donor and recipient. Outcomes included overall survival (OS), disease-free survival, relapse incidence (RI), non-relapse mortality (NRM), engraftment, acute and chronic graft-versus-host disease (GVHD), and GVHD-free/relapse-free survival (GRFS). Kaplan–Meier methods, Cox regression, and competing-risk models were applied. Results: A total of 140 patients were analyzed (AML 67.9% and ALL 32.1%); 106 (75.7%) were HLA-B leader matched and 34 (24.3%) mismatched, with a median follow-up of 68 months among survivors. HLA-B leader mismatching was not associated with OS [multivariable hazard ratio (HR) = 1.02, 95% confidence interval (CI): 0.65–1.60; P = 0.937] or with NRM (HR 1.28; P = 0.34), and rates of acute GVHD (42.5% vs. 50.0%; P = 0.441) and chronic GVHD (25.5% vs. 29.4%; P = 0.65) were comparable between groups. Relapse was numerically lower in the mismatched group (11.8% vs. 24.5%; HR = 0.49, 95% CI: 0.17–1.41; P = 0.184). In multivariable analysis, age 25–40 years (HR = 1.67, 95% CI: 1.04–2.68; P = 0.034) and transplantation in CR2 or beyond (HR = 1.52, 95% CI: 1.01–2.84; P = 0.045) independently predicted inferior OS; acute GVHD was associated with reduced relapse risk (HR = 0.37, 95% CI: 0.16–0.86; P = 0.021). GRFS did not differ significantly by leader status (HR = 0.85; P = 0.47). Conclusion: In adults with acute leukemia undergoing PTCy-based haplo-HSCT, HLA-B leader matching was not associated with survival or GVHD. However, the observed trend toward lower relapse with leader mismatching, together with the protective association between acute GVHD and relapse, suggests a potential graft-versus-leukemia signal that warrants validation in larger cohorts.

Regulatory T cells (Tregs), winners of the 2025 Nobel Prize in Physiology or Medicine, emerged as an unsung giant of peripheral immune tolerance after allo

Circulating tumor DNA (ctDNA) provides a minimally invasive tool for assessing tumor burden and genetic evolution in diffuse large B-cell lymphoma (DLBCL). This systematic review and meta-analysis evaluated 53 studies reporting the association of ctDNA and survival outcomes. High ctDNA concentration at baseline was associated with increased progression risk (hazard ratio (HR): 2.50, 95% confidence interval (CI) 2.15–2.9). The prognostic power of ctDNA intensified during treatment, with end of treatment (EOT) positivity showing the strongest association (HR: 13.69, 8.37–22.39). In patients with a negative EOT positron emission tomography (PET) scan, positive ctDNA was highly specific (90.8%) for subsequent relapse. Critically, in patients with a positive EOT PET scan, a negative ctDNA result decreased the risk of relapse (negative likelihood ratio 0.15, 0.06–0.3). ctDNA concentration reliably reflects tumor burden and treatment response, refining PET findings. Future studies should standardize ctDNA protocols and assess the feasibility of ctDNA-based DLBCL management.

Allogeneic hematopoietic stem cell transplantation (HSCT) for pediatric acute leukemia is limited by non-relapse mortality (NRM) and relapse. This study evaluated whether the endothelial activation and stress index (EASIX) score—calculated with the formula [lactate dehydrogenase (LDH; U/L) × serum creatinine (mg/dL)]/platelets (10⁹/L)]—could be associated with NRM and overall survival (OS). We analyzed 195 patients (< 25 years) with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) who underwent first-time peripheral blood HSCT at a single center between 2014 and 2022. The EASIX score was assessed pre-transplant (EASIX.PRE) and on day + 7 post-transplant (EASIX.POST). Cutoff values for EASIX.PRE (0.836) and EASIX.POST (1.632) were established using receiver operating characteristic (ROC) curves. Patients with EASIX.PRE scores below the cutoff exhibited significantly improved 12-month OS (84.67% vs. 66.12%, P = 0.028). Multivariable analysis confirmed that an EASIX.PRE score above the cutoff was an independent prognostic factor for inferior OS (HR = 1.83, P = 0.039). Similarly, patients with an EASIX.POST score below the cutoff showed a higher 12-month OS rate (87.78% vs. 72.65%, P = 0.046). However, in multivariable analysis, an EASIX.POST score above the cutoff did not demonstrate a significant relationship with reduced OS. Neither EASIX.PRE nor EASIX.POST score was independently associated with NRM, relapse, graft-versus-host disease (GvHD), leukemia-free survival (LFS), or GvHD-free, relapse-free survival (GRFS). This study highlights the prognostic utility of EASIX.PRE for OS in pediatric HSCT recipients but underscores its limited role in predicting NRM or GvHD. Further studies with larger cohorts and dynamic EASIX assessments are required to confirm these findings and refine risk stratification in pediatric HSCT.