Chronic graft-versus-host-disease treatment in Brazil: analyses of failure-free survival.

Failure-free survival (FFS), defined as the absence of new systemic treatment, recurrence of original malignancy and mortality not associated with recurrence after allogeneic hematopoietic stem cell transplantation (HCT), is a robust clinical measure to interpret results of initial systemic treatment of chronic graft-versus-host disease (cGVHD). We evaluate FFS after initial treatment of cGVHD in a mixed-race cohort from a resource-constrained country. This retrospective study included 354 consecutive patients after their first HCT between January 2014 and August 2020, who received initial systemic treatment for moderate or severe cGVHD at 13 Brazilian centers. Cox regression models were used to identify risk factors for treatment failure. The overall median follow-up among survivors was 28 months (range 1-71) after initial treatment. FFS was 89% at 6 months, 71% at 1 year and 52% at 2 years. New systemic treatment was the major cause of failure. In multivariable models, prior grades II-IV acute GVHD, a National Institutes of Health severity score of 3 in liver, gastrointestinal tract or lung involvement, and onset of initial treatment of cGVHD within 12 months after transplantation were all associated with an increased risk of treatment failure. Our results could serve as a benchmark for the design of future clinical trials evaluating initial treatment of cGVHD in resource-constrained locations.

The challenges of handling deferasirox in sickle cell disease patients older than 40 years.

OBJECTIVES: Deferasirox is an oral iron chelator with established dose-dependent efficacy for the treatment of iron overload secondary to transfusion. However, there is few data reporting the use of Desferasirox in adult patients with sickle cell disease (SCD) and transfusional iron overload. METHODS: We conducted a prospective, single center, nonrandomized study from January 2014 to March 2015 in Campinas, Brazil. Seven patients (five women, median age 50 y.o.) who were followed up on regular transfusion program were treated with a single daily dose of deferasirox (median dose 20 mg/kg). They were monitored for clinical symptoms, renal function and hepatotoxicity. RESULTS: One patient discontinued the study due to lack of compliance. Two patients reported mild to moderate adverse events (gastrointestinal disturbances). Five patients had the drug discontinued due to worsening of renal function. One patient had the drug discontinued due to severe hepatotoxicity that evolved to death; no patient finished the study. Discussion and conclusions: Deferasirox does not appear to be well tolerated in SCD patients older than 40 years, in which complications of the underlying disease are already fully installed. The choice of the ideal iron chelator for this population should include an evaluation of comorbidities and organic dysfunctions, as well as the need to find pharmacogenetic safety markers in this group of patients.