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TKI's before, after transplantation feasible in advanced pediatric CML


J Pediatr Hematol Oncol 2016;advance online publication


medwireNews: Treatment with tyrosine kinase inhibitors (TKIs) prior to and after allogeneic haematopoietic stem cell transplantation (HSCT) may improve outcomes in children presenting with an advanced stage of chronic myeloid leukaemia (CML), suggests a case series.

The team from Boston Children’s Hospital in Massachusetts, USA, identified five patients aged 12–18 years who underwent allogeneic HSCT for advanced stage disease between 2010 and 2013. Three patients presented in lymphoid blast crisis and one in accelerated phase, while the remaining patient presented in chronic phase but developed blast crisis during pretransplantation TKI treatment.

Imatinib was the physician’s choice of initial pretransplantation TKI in four cases, while one patient was started on dasatinib. One imatinib-treated patient needed further lines of treatment as a result of disease progression, and was given dasatinib, followed by nilotinib briefly (discontinued due to QT prolongation) and finally ponatinib. The four patients in blast crisis also received acute lymphoblastic leukaemia-directed induction and consolidation chemotherapy prior to HSCT.

TKI therapy was stopped before the initiation of pretransplantation conditioning, at which point all patients were in haematological and cytogenetic remission; two patients still had disease detectable by fluorescence in situ hybridisation, but less than 5% of cells were positive for the Philadelphia chromosome. One patient had achieved molecular remission, three had a molecular response without meeting criteria for remission and the final patient did not undergo testing directly before HSCT.

Four of the five patients were restarted on TKIs – three on imatinib and one on dasatinib – at an average of 129 days after transplantation, and treatment continued for a mean of 598 days. One patient was not given post-transplantation TKI therapy due to a risk of thrombosis.

At the time of analysis, all patients were alive and in molecular remission, with undetectable BCR–ABL transcripts as evaluated by polymerase chain reaction, for an average of 38 months, report David Shulman and co-researchers.

They add that the TKIs were well tolerated, with pre- and post-transplantation adverse events generally manageable with dose reductions and interruptions. Moreover, patients received TKIs for a mean of 20 months post-transplantation “without demonstrating irreversible myelosuppression or graft failure”, the researchers say in the Journal of Pediatric Hematology/Oncology.

Shulman et al believe that pre- and post-transplantation TKI therapy “may have contributed to the excellent outcomes in these patients”. But given the small sample size, they highlight the need for larger, multicentre studies to evaluate the optimal use of TKIs as an adjunct to HSCT in this patient population.


By Shreeya Nanda, Senior medwireNews Reporter

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