Response to CloEC
All children received the first induction chemotherapy according to the
protocol. No deaths related to the clofarabine-containing induction were
observed. Two of the seven patients (both with BCP- ALL) responded to
the first course of CloEC: one proved to be negative for MRD, and the
other was in morphological remission and highly positive for MRD. The
MRD-negative patient continued the treatment according to the protocol
and was transplanted after the second CloEC. As decided by the treating
physician, the highly MRD-positive patient received treatment that
deviated from the protocol, proceeding directly to transplantation after
the first course of CloEC.
The remaining five children did not respond to the first course of
CloEC. One of those non-responders was diagnosed with possible
cerebro-pulmonary invasive fungal infection and was found to have
leukemic blasts in peripheral blood. The parents declined further
treatment, and the patient died of progressive disease 1 month after the
first CloEC. In one patient with sAML who was recruited to the study in
relapse after previous haploidentical transplantation, there was no
measurable effect of the first course of CloEC on the tumor burden; the
treating physician considered it unreasonable to continue with the
second course stipulated in the protocol. This patient instead received
liposomal daunorubicin, fludarabine, and cytarabine (FLADx), and
achieved MRD-negative remission and could finally proceed to transplant.
Three of the five children who did not achieve remission after the first
course of CloEC received the second course, but none of them responded.
Two of those three continued with only palliative treatment after the
second CloEC and died of progressive disease 57 and 132 days after the
first course. One child was in a very good clinical condition after the
second CloEC, and disease evaluation at this time point showed a
reduction in blasts from 80% to below 30%; as decided by the treating
physician, despite not fulfilling response criteria after the second
course of CloEC, this patient received the third course but without
further decrease in percentage of blasts. Inasmuch as the clinical
condition of this patient was still very good, the fourth course of
chemotherapy (FLADx) was given, after which further reduction in blast
percentage was observed. Despite still not being in morphological
remission after the fourth course of chemotherapy, the patient proceeded
to transplant.
In all, two of the seven enrolled children achieved protocol-defined
response criteria. One additional patient (sAML) who went into remission
after CloEC was changed to FLADx. Re-induction with CloEC and the
patients’ responses are summarized in Table 2.