Clinical Efficacy of Mitoxantrone-Based Salvage Chemotherapy in Adult Patients with Relapsed or Refractory All; Retrospective Multicenter Study of Korean Adult ALL Working Party

Although intensified chemotherapy plus stem cell transplantation improves treatment result in adult acute lymphoblastic leukemia (ALL), leukemic relapse in adult ALL remains a major therapeutic problem. Still, most adults with ALL will die from disease progression. Several study reported the result as patients with primary refractory disease or in first recurrence have CR rates to 31%-45% with salvage chemotherapy and the median survival was about 5 months. Mitoxantrone is an anthracenadione, acts on topoisomerase II isoforms and it also has the ability to create DNA adducts, stimulating binding of nuclear factor κB, and potentiate immune-based cell kill by tagging leukemic cells with calcireticulin. However, the effective combination with mitoxantrone and feasible dosage was not identified in relapsed or refractoryadult ALL.

Total forty-six patients with relapsed and/or refractory ALL previously unexposed to the mitoxantrone combined chemotherapy were enrolled from five centers, retrospectively. We analyzed the complete remission rates, toxicities, and percent of receiving transplantation after mitoxantrone based chemotherapy.

Thirty-one of relapsed and fifteen of refractory patients for previous treatment were enrolled. Median duration from diagnosis to mitoxantrone salvage therapy was 7.9 months (range, 0.8–151.7) and the median number of previous induction therapy was one (1st: 36, 2nd: 6, 3rd: 2 and 4th: 2). Twelve (26%) patients were previously received stem cell transplantation (SCT) (10: allogeneic, 2: autologous). The 27 patients received the double chemotherapeutic agent combination (mitoxantrone + Ara-C ± TKI) and 19 patients received the triple combination (mitoxantrone + Ara-C + VP16). After mitoxantrone based chemotherapy, 20 (43.5%) patients achieved complete remission (CR, 32.6%) or CR without platelet recovery (10.9%) and, 8 out of 20 responder received SCT. The median overall survival in all patients was 6.2 months (95% CI 3.5–8.8). The achievement of CR (p=0.09) after mitoxantrone-based chemotherapy or double vs triple combination treatment (p=0.869) did not show the statistical prognostic significance. After CR achievement, median overall survival of the patients received SCT was 11.6 months (95% CI: 1.6–21.6) and non-transplant patients was 6.9 months (95% CI: 0.6–13.2) (p=0.017). Treatment related mortality was observed in 7 patients (15.2%). Five patients died of infection and other two patients did not recover from cytopenia.

Mitoxantrone-based chemotherapy for relapsed or refractory adult ALL is feasible salvage regimen and treatment related mortality is tolerable. SCT after CR achievement is the only prognostic marker to improve the survival in our study. Therefore, immediate SCT or new innovative treatment after post-remission will be considered for improvement of the survival.

No relevant conflicts of interest to declare.