Imatinib mesylate efficacy in 72 previously treated Philadelphia-positive chronic myeloid leukemia patients with and without additional chromosomal changes: single-center results.

Reported here are 72 previously treated Philadelphia chromosome-positive (Ph+) CML patients on imatinib (IM) therapy, with a focus on patients with additional chromosomal aberrations (CAs). At the start of IM treatment, 49 patients exhibited only the Ph chromosome (68%) and 23 patients (32%) had one or more additional CAs. The most frequent additional changes were deletions on the der(9q) (8 of 23), trisomy 8 (3 of 23), and an extra copy of the Ph chromosome (2 of 23). Five patients had a complex karyotype. At the latest follow-up, 49 of the 72 patients (68%) were alive, including 15 of the 23 patients with additional CAs (65%). Median follow-up was 6.6 years; median duration of IM treatment was 4.4 years. In all, 35 of the 49 patients with Ph only (71%) and 10 of the 23 patients with additional CAs (43%) achieved complete cytogenetic response. All patients with deletion on der(9q) achieved complete cytogenetic response. There was no statistically significant difference in the overall survival of patients with additional CAs and patients with Ph as the sole abnormality. Patients in accelerated phase had significantly worse overall survival on IM, regardless of additional CAs. The present results confirm that the majority of previously treated Ph+ CML patients benefit from starting IM therapy, including patients with defined additional changes. In contrast, patients with complex karyotypes have poor prognosis, even with IM.

Most pediatric patients with essential thrombocythemia show hypersensitivity to erythropoietin in vitro, with rare JAK2 V617F-positive erythroid colonies.

Essential thrombocythemia (ET), a Philadelphia (Ph) chromosome negative chronic myeloproliferative disorder, is usually a disease of middle age and it is extremely rare in pediatric patients. In this report we studied 12 children diagnosed with ET and one child with thrombocytosis and family history of ET. We failed to detect JAK2 V617F mutation either in peripheral blood leukocytes or in separated platelets and granulocytes. Monoclonal hematopoiesis was noted in only one female patient. Erythroid progenitors of most of the patients displayed hypersensitivity to erythropoietin (Epo) in vitro; Epo-independent erythroid colonies (EECs) were detected in seven patients. Among EECs of three patients we observed rare colonies heterozygous or homozygous for the JAK2 V617F mutation. Our data suggest that childhood ET patients could bear minor JAK2 V617F-positive subclones.