Ropeginterferon alfa-2b (ropegIFN) is an approved cytoreductive therapy for polycythemia vera (PV). While the current drug label supports a low initial dose with slow titration ("Slow Titration") regimen starting at 50-100 μg with gradual escalation, there is increasing adoption of a high initial dose and accelerated titration (HIDAT) regimen, starting at 250 μg with rapid escalation to 500 μg in 4 weeks. We conducted a systematic review and meta-analysis of ropegIFN studies to derive pooled estimates of efficacy and safety outcomes across HIDAT and Slow Titration studies. We searched MEDLINE, Embase, Web of Science, and ClinicalTrials.gov for literature published up until 3/15/2026. Study selection, data extraction, and risk of bias assessment (ROB2, MINORS, Newcastle-Ottawa Scale) was performed with otto-SR, an AI-powered systematic review platform, with independent human validation. HIDAT achieved significantly higher complete hematologic response (CHR) rates at 3, 6, and 12 months, relative to Slow Titration. Molecular response rates and reductions of JAK2V617F VAF were similarly superior with HIDAT at 6 and 12 months. No significant differences in safety outcomes (adverse events, serious adverse events, trial discontinuations) were observed. These findings support the clinical rationale for HIDAT as a strategy to accelerate hematologic and molecular disease control in PV, while prospective randomized trials are needed to confirm the results.
Umbilical cord blood transplantation (UCBT) is an important alternative donor strategy for patients with high-risk hematologic malignancies. While myeloablative conditioning (MAC) is associated with superior disease control following UCBT compared to reduced-intensity conditioning (RIC), its benefits can be offset by non-relapse mortality (NRM). Intermediate-intensity MAC may preserve the anti-leukemic effects of historically high-intensity MAC while reducing NRM. We conducted a prospective phase 2 trial evaluating outcomes of patients undergoing UCBT following either high-intensity or intermediate-intensity MAC. A total of 132 patients were enrolled between 2006 and 2022, with acute leukemia being the predominant indication. The primary endpoint was overall survival (OS), with secondary endpoints including relapse-free survival (RFS), relapse and NRM. For the overall study population at 1 year, OS was 78% (95% CI, 70-85%) and RFS was 72% (95% CI, 64-79%). Outcomes were comparable between conditioning regimens, with encouragingly low NRM observed in patients receiving intermediate-intensity conditioning, including in the pediatric cohort. Among patients with acute leukemia, measurable residual disease (MRD) positivity at transplant was not associated with an increase in relapse, supporting enhanced GVL following UCBT. These findings were particularly notable in patients with AML. These data demonstrate that UCBT following intermediate intensity MAC is a viable strategy that may reduce toxicity while preserving disease control in selected patients. Collectively, these findings support the unique anti-leukemic properties of UCBT and reinforce its role as a highly effective donor platform for high-risk leukemia in children and adults. This trial was registered at ClinicalTrials.gov as NCT00719888.
Donor types influence outcomes after allogeneic hematopoietic cell transplantation (HCT), but their relative impact in the post-transplant cyclophosphamide (PTCy) era is uncertain. We performed a multicenter retrospective cohort study using Center for International Blood and Marrow Transplant Research data for adults with acute leukemia or myelodysplastic syndromes undergoing first HCT from matched sibling donors (MSD), 8/8 matched unrelated donors (MUD), 7/8 mismatched unrelated donors (MMUD), or haploidentical donors between 2017 and 2023 with PTCy-based graft-versus-host disease (GVHD) prophylaxis. The primary cohort included 12,617 patients: 1,263 MSD, 4,117 MUD, 1,426 MMUD, and 5,811 haploidentical recipients. In multivariable models adjusted for donor age and clinical covariates, overall survival (OS) was lower with MUD (hazard ratio [HR], 1.16; 95% CI, 1.00-1.34, p=0.004), MMUD (HR, 1.32; 95% CI, 1.12-1.55, p<0.001), and haploidentical donors (HR, 1.43; 95% CI, 1.24-1.64, p<0.001) compared with MSD. GVHD-free, relapse-free survival (GRFS) was similar for MUD and MSD (reference) but lower with MMUD and haploidentical donors. Compared to MSD, all other donor groups had lower relapse risk but higher non-relapse mortality and acute GVHD, with similar chronic GVHD. In sensitivity analyses excluding donor-age adjustment, compared to MSD, OS was similar for MUD and MMUD, and GRFS was improved with MUD and similar for MMUD and haploidentical donors. These findings suggest that PTCy narrows outcome differences across donor types, shifting donor selection from rigid hierarchies and supporting timely HCT using the best available donor.
