Outcomes After a Sequential Clofarabine/Arac-C Chemotherapy Followed By Reduced-Intensity Conditioning (RIC) and Allogeneic Stem Cell Transplantation (allo-SCT) In Pediatrics Patients With JMML Or Primary/Relapsed Refractory AML: A Pilot Study

The FLAMSA sequential treatment with chemotherapy followed by reduced-intensity conditioning (RIC) for allogeneic stem cell transplantation (allo-SCT) has been introduced few years ago for adult refractory acute myeloid leukemia (AML) showing high activity and relatively good survivals in this particular setting (Schmid, Blood, 2006). There is no study at our knowledge reporting the results of the sequential approach in pediatric refractory AML patients. Here we report our own experience in 6 children using a debulking chemotherapy combining clofarabine and Ara-C followed by RIC before allo-SCT.

These preliminary results included 3 males and 3 females with a median age of 7 years (range: 4-11). All cases had received a sequential regimen before allo-SCT at the CHU of Nantes (n=5) or at the CHU of Montpellier (n=1) for primary refractory AML (n=1), refractory relapsed AML (n=3), slow responder relapsed AML (n=1) and blastic JMML (n=1). Sequential regimen consisted of 1) clofarabine 30 mg/m²/d days-13 to -9, Ara-C 1g/m²/d days-13 to-9 followed by RIC combining cyclophosphamide 60 mg/kg/d day-5, iv Busulfan 3.2 mg/Kg/d days -4 to -3 and ATG 2.5 mg/Kg/d days -3 to -2 in 5 patients and 2) clofarabine 30 mg/m²/d days-13 to -9, Ara-C 1g/m²/d days-13 to-9 followed by RIC total body irradiation 4 grays day-5, cyclophosphamide 40 mg/Kg/d days -4 to -3, and ATG 2.5 mg/Kg/d days -3 to -2 in 1 patient. One patient received a graft from a sibling donor while the five other patients received a graft from an unrelated donor (10/10 n=3; 9/10 n=2). All patients received PBSC as stem cells graft. Ciclosporine alone was used in case of related donor while ciclosporin+MMF were used in case of an unrelated donor.

Engraftment was observed in 4 patients (67%) and 3 patients out of the 5 refractory cases achieved complete remission (CR) after transplant. The 2 patients who had an autologous reconstitution, relapsed and died rapidly. Considering the 4 patients achieving full engraftment and CR, only one relapsed at day+60 and died of relapse. The three other patients are alive in CR at +12, +35 and +51 months post-transplant.

To our knowledge, this is the first report of a sequential allo-SCT approach for refractory pediatric AML patients. Although the number of patients is limited in our cohort, the results showed here are very encouraging as half of the patients are alive in CR with full engraftment. These results have to be confirmed prospectively.

No relevant conflicts of interest to declare.