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.