Comparative study of safety and efficacy of imatinib mesylate therapy in pediatric and adult chronic myeloid leukemia

Abstract

20016 Background: Chronic Myeloid Leukemia (CML) is one of the rare pediatric cancers. Imatinib is now the standard of care in adult CML (ACML) with newer compounds being investigated to overcome the burden of Imatinib resistance. Pediatric CML (PCML) has been an area little explored and effective strategies are not yet defined. Although, allogenic hematopoietic stem cell transplantation (HSCT) still remains the gold-standard treatment, the choice of drug in the subset in which HSCT is not a suitable option remains to be determined. Methods: This was a single-institution prospective study conducted from April 2004-March 2006, analyzing and comparing 293 Philadelphia chromosome (PH) positive CML patients in pediatric and adolescent subsets (i.e. age =18 years) not eligible for allogenic HSCT with ACML. After obtaining a written informed consent, a starting dose of 400 mg/m2/d Imatinib mesylate was administered in adults, whereas in pediatric and adolescents it was 400 mg/m2/d if the body surface area (BSA) was <1 m2, or 400 mg/d if BSA was >1m2. Results: 27 patients were in the age group =18 years; male to female ratio was 1.07:1. Gender ratio in 266 ACML patients showed a male preponderance (2.5:1). The mean age in ACML was 37.4 years. In pediatric subsets, a trend toward CML in adolescents was observed with mean age 14.85 years. Majority of the patients were in chronic phase (81.5% PCML and 85.7% ACML) with overall 93% patients receiving prior hydroxyurea as a cytoreductive agent. An unusual finding was higher incidence of Hypodiploidy (significance undetermined) and 5 patients had double PH. 80.1% ACML patients achieved complete hematological response, but it was significantly lower (59.3%) in PCML. 39.5% ACML achieved major cytogenetic response which was less than most published western data. Hematologic and non-hematologic toxicities (GI, dermatological etc) were found to be higher in ACML. Low toxicities in PCML were attributed to good tolerance to Imatinib therapy; however a higher dropout rate in pediatric subsets was possibly due to poor social and parental support. Conclusion: We conclude that imatinib mesylate is both safe and efficacious drug for ACML, however further research is warranted in pediatric and adolescent population to establish its efficacy. No significant financial relationships to disclose.