Arsenic trioxide therapy for relapsed acute promyelocytic leukemia: a bridge to transplantation.
OBJECTIVE
Arsenic trioxide (ATO) has been reported to be a safe and effective treatment for relapsed acute promyelocytic leukemia (APL). The aim of this study was to evaluate the efficacy and toxicity as well as the eligibility to stem cell transplantation (SCT) in a series of 7 patients with relapsing APL, managed with ATO.


METHODS
Seven patients with relapsing APL while on maintenance treatment with all-trans-retinoic acid (ATRA) or who were ATRA refractory-received ATO at a dose of 10 mg daily by 2-hour intravenous infusion until complete remission (CR). After consolidation chemotherapy, patients were programmed to receive autologous or allogeneic stem cell transplantation (SCT) according to donor availability. The median age of the patients was 55 (21-71) years: 2 patients presented with concomitant extramedullary relapse.


RESULTS
Six patients (86%) achieved CR after a median of 35 ATO doses (20-49) with negligible toxicity; one patient died from pneumonia. After consolidation with a four-day course of cytarabine at 1 g/m2 and mitoxantrone 6 mg/m2, two patients underwent allogeneic SCT, two received PML/RARa negative autologous peripheral blood stem cells collected after consolidation plus granulocyte colony-stimulating factor, one failed mobilization and received a second consolidation course. One elderly patient refused further treatment and relapsed 6 months later. After a median follow-up of 15 months from CR2 achievement, 5 patients are alive in continuous CR.


CONCLUSIONS
The high CR rate and the mild toxicity confirm that ATO represents a valid alternative to salvage chemotherapy for patients relapsing while on ATRA treatment or who are ATRA-refractory. Allogeneic or autologous SCT after ATO-induced CR is feasible in the majority of patients.
Leoni
Franco
F
Divisione di Ematologia, Policlinico di Careggi, viale Morgagni 85, 50134 Florence, Italy. f.leoni@dfc.unifi.it
Gianfaldoni
Giacomo
G
Annunziata
Mario
M
Fanci
Rosa
R
Ciolli
Stefania
S
Nozzoli
Chiara
C
Ferrara
Felicetto
F
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000633:toxicity; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage* / Q000633:toxicity; D012074:Remission Induction / Q000379:methods; D016879:Salvage Therapy; D033581:Stem Cell Transplantation / Q000379:methods; D015996:Survival Rate; D013810:Therapeutic Equivalency; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide