Hematology

400 cGy TBI haplo-BMT with PTCy yields high survival and low toxicity in severe sickle cell disease

Forty-three severe SCD patients aged 2–70 received reduced-intensity haploidentical BMT with ATG, fludarabine, cyclophosphamide, and single-fraction 400 cGy TBI plus PTCy-based GVHD prophylaxis. Five-year overall survival was 95.5%, and 2-year disease-free survival was 94.5%, with only 5% graft failure. Rates of grade 3–4 acute GVHD and moderate–severe chronic GVHD were low, and median time to stopping immunosuppression was about one year. Among transplanted women, many had return of menses or normalized gonadal function, suggesting fertility preservation with this regimen. 1

Post-IST failure HSCT in pediatric SAA now approaches upfront transplant survival

This study followed 179 pediatric severe aplastic anemia patients undergoing upfront HSCT (n=87) or HSCT after IST failure (n=92). Overall, 5-year OS and GRFS were 89% and 79%, with 10% graft failure and low rates of significant acute and chronic GVHD. Upfront HSCT had higher OS than post-IST HSCT overall, but outcomes for post-IST failure transplants improved substantially after 2015. From 2015 onward, OS for upfront versus post-IST HSCT became comparable, particularly with matched sibling or ≥9/10 unrelated donors. 2

Imetelstat improves fatigue and quality of life alongside transfusion independence in lower-risk MDS

In the phase III IMerge trial, imetelstat improved ≥8-week red-cell transfusion independence versus placebo in LR-MDS with transfusion-dependent anemia after ESA failure or ineligibility. Exploratory analyses using multiple validated instruments showed fewer imetelstat-treated patients had deterioration in fatigue versus placebo. More imetelstat recipients achieved sustained improvements in fatigue and broader quality-of-life domains than placebo-treated patients. Within the imetelstat arm, transfusion-independence responders had markedly higher rates of sustained fatigue and QoL improvement than nonresponders. 3

HCT Frailty Scale independently stratifies outcomes in allo-HCT candidates

In this prospective cohort of 1,077 adult allo-HCT candidates across 16 programs, frailty was assessed using the Hematopoietic Cell Transplantation Frailty Scale. Patients were classified as fit (33.4%), pre-frail (53.7%), or frail (12.8%) based on eight routinely collected variables. Increasing frailty correlated with longer hospital stays and higher 180-day ICU admission rates in a graded fashion. Two-year overall survival declined from 77.2% in fit to 65.7% in pre-frail and 52.8% in frail patients, with corresponding NRM increases. 4