Genotoxicity associated with hydroxyurea exposure in infants with sickle cell anemia: Results from the BABY‐HUG phase III clinical trial

Abstract

Background The laboratory and clinical benefits of hydroxyurea therapy for children with sickle cell anemia (SCA) are well recognized, but treatment in young patients is limited in part by concerns about long-term genotoxicity, and specifically possible carcinogenicity. Procedure The Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) was a multi-center double-blinded placebo-controlled randomized clinical trial (NCT00006400) testing whether hydroxyurea could prevent chronic organ damage in very young patients with SCA. An important secondary objective was the measurement of acquired genotoxicity using 3 laboratory assays: chromosomal karyotype, illegitimate VDJ recombination events, and micronucleated reticulocyte formation. Results Our data indicate that hydroxyurea treatment was not associated with any significant increases in genotoxicity compared to placebo treatment. Conclusions These data provide additional support to the safety profile of hydroxyurea for young patients with SCA, and suggest that genotoxicity in this patient population is low.

Increased serum baseline tryptase levels and extensive skin involvement are predictors for the severity of mast cell activation episodes in children with mastocytosis

“…Consequently, early intensive antimediator therapy should probably be given as soon as possible to children identified to be at risk for severe mastocytosis-related anaphylaxis on the basis of the extent of cutaneous involvement and a sbT >16 µg/l. In the only nonresponding case, corresponding to the patient with WDSM, cytoreductive therapy with hydroxyurea was added based on a good response achieved in an adult with progressing WDSM (Escribano L, personal observation) and the safety profile of hydroxyurea in children with sickle cell anemia (31–33). Interestingly, a dramatic response was obtained in this patient with a progressive decrease in clinical symptoms, skin lesions, and the need for intensive antimediator therapy.…”

Risk of individual malignant neoplasms in patients with sickle cell disease: English national record linkage study

“…However, findings from clinical trials do not support this. 27,28 Strengths and weaknesses This is a large population-based study, using a linked database containing all admissions to NHS hospitals in England. Its use of rates, i.e.…”

Optimal therapy for polycythemia vera and essential thrombocythemia can only be determined by the completion of randomized clinical trials

“…In fact, in a phase III randomized trial comparing HU to placebo in infants with sickle cell disease, evidence of HUinduced genotoxicity was not detected. 18 However, others have reported that the type of PV-directed therapy that individual patients receive may influence the pattern of karyotypic abnormalities observed in PV-related AL. 19 Hydroxyurea has, for the last 30 years, been adopted as the myelosuppressive agent of choice for patients with high-risk ET/PV.…”