Experience with ponatinib in paediatric patients with leukaemia.

Ponatinib has proven to be effective in adults with Philadelphia chromosome-positive leukaemias, but data in paediatrics are scarce. Among paediatric patients with chronic myeloid leukaemia (n = 9) or acute lymphoblastic leukaemia (n = 12) treated with varying doses of ponatinib in 13 centres, 71% showed a decrease in disease burden after a median of three months. Ponatinib was well tolerated, with grade 3 toxicities occurring in 29% of patients. Toxicities were similar to those reported in adults, with the exception of arterial thrombotic events, which were not observed. Ponatinib has a favourable safety profile in this paediatric cohort, but dose-finding studies are needed.

Unmasking Hemophilia B After Hip Aspiration: A Case Report.

CASE: A 7-year-old boy presented with excruciating hip pain for 1 day, unable to bear weight. Magnetic resonance imaging (MRI) revealed small hip joint effusion and synovitis, which was treated by urgent operative aspiration to rule out infection. Subsequently, the postoperative site bled continuously, despite compression. The hip wound and blood cultures showed no growth. He was examined by a hematologist and had normal coagulopathy lab results. He was discharged and went home 4 days after aspiration and was scheduled for outpatient hematology work-up. He was readmitted 11 days after aspiration with continued pain and MRI was repeated, showing large hip hemarthrosis. Lab results at that time showed a prolonged partial thromboplastin time of 43.9 seconds. The patient was given fresh frozen plasma. The hip effusion was stable on ultrasound. He was found to have low factor IX <17% consistent with hemophilia B and was given recombinant factor IX (Benefix) of 2,000 units. The following day, his pain was markedly improved and he was discharged. At the 4-month follow-up, the patient was fully ambulatory. CONCLUSIONS: This is a case of unexpected bleeding after hip aspiration which led to the life-changing diagnosis of Hemophilia B in a pediatric patient. Orthopedists should be wary of bleeding dyscrasias and involve consultants as needed.

Arsenic Trioxide Consolidation Allows Anthracycline Dose Reduction for Pediatric Patients With Acute Promyelocytic Leukemia: Report From the Children's Oncology Group Phase III Historically Controlled Trial AAML0631.

Purpose The Children's Oncology Group AAML0631 trial for newly diagnosed pediatric acute promyelocytic leukemia (APL) was a phase III historically controlled trial to determine the survival of patients receiving arsenic trioxide (ATO) consolidation and reduced doses of anthracyclines. Patients and Methods Patients age 2 to 21 years with de novo APL confirmed by PML-RARα polymerase chain reaction were stratified as standard risk (SR) or high risk (HR) on the basis of diagnostic WBC count. All patients received all-trans retinoic acid (ATRA) during induction, each consolidation course, and maintenance. All patients received two cycles of ATO therapy during consolidation 1, an additional two (SR) or three (HR) consolidation courses that included high-dose cytarabine and anthracycline, and maintenance therapy comprising ATRA, oral methotrexate, and mercaptopurine. Results One hundred one patients (66 SR and 35 HR) were evaluable for outcome. The 3-year overall survival was 94%, and event-free survival (EFS) was 91%. For SR and HR patients with APL, the overall survival was 98% versus 86% ( P = .003), and EFS was 95% versus 83% ( P = .03), respectively. The EFS for SR patients in AAML0631 was noninferior to that of patients in the AIDA 0493 historical control, which used a significantly higher anthracycline dose and did not include ATO consolidation. Relapse risk for patients in AAML0631 from end consolidation 1 (after ATO treatment) was only 4% at 3 years and did not differ significantly between SR and HR patients. Conclusion ATO consolidation cycles were well tolerated in pediatric patients with APL and allowed significant reduction in cumulative anthracycline doses while maintaining excellent survival and a low relapse risk for both SR and HR patients with APL.

Hematopoietic stem cell transplant for pediatric acute promyelocytic leukemia.

The optimal form of treatment for children with relapsed or refractory acute promyelocytic leukemia (APL) is unclear. We retrospectively analyzed the results of 32 (11 autologous, 21 allogeneic) hematopoietic stem cell transplants (HSCT) performed for children originally treated on either the Eastern Cooperative Group E2491 Trial or the Cancer and Leukemia Group B C9710 Trial and subsequently diagnosed with relapsed or refractory APL. For autologous HSCT, the incidence of treatment-related mortality (TRM) and relapse was 0% (95% confidence interval [CI], 0%-30%) and 27% (95% CI, 9%-57%), respectively. The 5-year event-free survival (EFS) and overall survival (OS) following autologous HSCT was 73% (95% CI, 43%-91%) and 82% (95% CI, 51%-96%), respectively. For allogeneic HSCT, the incidence of TRM and relapse was 19% (95% CI, 7%-41%) and 10% (95% CI, 2%-30%), respectively. The 5-year EFS and OS following allogeneic HSCT was 71% (95% CI, 50%-86%) and 76% (95% CI, 55%-90%), respectively. There was no significant difference in EFS or OS between autologous and allogeneic HSCT. This data demonstrates that autologous and allogeneic HSCT are both effective therapies for treatment of children with relapsed or refractory APL. Autologous HSCT is associated with a low incidence of TRM, whereas allogeneic HSCT is associated with a low incidence of relapse, suggesting a strong GVL effect against residual APL.