Imatinib mesylate (IM) is the standard therapy in adult patients with chronic myeloid leukemia (CML). In children, the superiority of Imatinib over allogenic transplantation is not well established. Concerns exist about the long term effects of Imatinib in this population.
Outcomes of children (≤18 years) diagnosed with chronic phase CML from 2002 to 2008 were retrospectively analysed. All received Imatinib at a dose of 260–300mg/m2/day. Progression free survival (PFS- time from starting treatment till loss of complete hematologic response (CHR), or disease acceleration), ad Overall survival (OS) were estimated by the Kaplan Meier method. Those who progressed received higher doses of Imatinb or were changed to hydroxyurea. No patient had access to second line tyrosine kinase inhibitors or to allogenic stem cell transplant.
31 patients, median age 13 (6–18)years, Males-17 (48.6%), were treated. The presenting complaints over a median symptom duration of 1 month (10 days to 12 months) were abdominal distension and/or pain (68%), fever (38%), weight loss (13%), bone pains (10%), anemic symptoms (16%). Examination revealed splenomegaly (100%), heptomegaly (47%) and lymphadenopathy (6%). Laboratory: Hemoglobin (9.3g/dL;4.2–10.9), White cell count (228,000/mm3;10,000–800,000), Platelet count (412,000/mm3, 120,000–12,80,000), peripheral eosinophilia (2%;0–10), basophilia (2%; 0–7). CHR was seen in 30/31 (97%) at a median of 2 months (1.5–8). Sokal risk category was low in 13 (41%), intermediate in 15 (48.4%) and high in 3 (9.7%). The cumulative incidence of Major and Complete cytogenetic response (MCR and CCR) among those who had not progressed by 2 years (n=23) was 82% and 70% respectively. Molecular assessment done in 11 patients who had achieved CCR by 2 years showed MMR in 6/11 (55%). After a median follow up of 49.2 months (4.4 – 86.4) disease progression occurred in 8 patients (5-year PFS 68%-median not reached) which led to death in 6 patients (5-year OS 75.8%). Among those with cytogenetic data, the PFS for those with CCR vs those without was 93.8% and 53.6 % respectively at 5 years (p=0.048). The drug was well tolerated with no discontinuation because of toxicity.
Imatinib is a reasonable option in the first line therapy of pediatric CML and gives 5 year PFS and OS rates comparable to the results of upfront allogenic transplant. It is to be considered as an alternative especially in resource constrained settings where options for transplant are limited.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.