Approaches to Recurrence After HSCT or Refractory JMML

Disease recurrence is the primary cause of treatment failure for children with JMML after HSCT and occurs in 30% to 40% of cases.[6-8] While the role of donor lymphocyte infusions is uncertain,[19] reports indicate that approximately 50% of patients with relapsed JMML can be successfully treated with a second HSCT.[20]

In a prospective study, four children with relapsed JMML after stem cell transplant were treated with azacitidine. Three patients responded to azacitidine and were able to proceed to a second transplant.[21]

In a prospective study, ten children with relapsed or refractory JMML were treated with oral trametinib (an MEK inhibitor) daily for up to 12 28-day cycles. Five patients had objective responses (three clinical PRs and two clinical CRs) within five cycles. Two patients had stable disease. All seven patients remained alive at a median follow-up of 24 months, including three who continued to receive trametinib off study (for 6, 24, and 24 months, respectively) without proceeding to HSCT. The four patients who underwent HSCT remained in CR at a median of 24 months of follow-up. The RAS pathway variants were no longer detected in the four patients who underwent HSCT, whereas the three other patients continued to have detectable variants without progressive disease while receiving trametinib. No severe adverse events were reported.[22]