Management of relapse in acute promyelocytic leukaemia treated with up‐front arsenic trioxide‐based regimens

Abstract

The standard of care for patients with acute promyelocytic leukaemia (APL) relapsing after front-line treatment with arsenic trioxide (ATO)based regimens remains to be defined. A total of 67 patients who relapsed after receiving ATO-based up-front therapy and were also salvaged using an ATO-based regimen were evaluated. The median (range) age of patients was 28 (4-54) years. While 63/67 (94%) achieved a second molecular remission (MR) after salvage therapy, three (4Á5%) died during salvage therapy. An autologous stem cell transplant (auto-SCT) was offered to all patients who achieved MR, 35/63 (55Á6%) opted for auto-SCT the rest were administered an ATO + all-trans retinoic acid maintenance regimen. The mean (SD) 5-year Kaplan-Meier estimate of overall survival and event-free survival of those who received auto-SCT versus those who did not was 90Á3 (5Á3)% versus 58Á6 (10Á4)% (P = 0Á004), and 87Á1 (6Á0)% versus 47Á7 (10Á3)% (P = 0Á001) respectively. On multivariate analysis, failure to consolidate MR with an auto-SCT was associated with a significantly increased risk of relapse [hazard ratio (HR) 4Á91, 95% confidence interval (CI) 1Á56-15Á41; P = 0Á006]. MR induction with ATO-based regimens followed by an auto-SCT in children and young adults with relapsed APL who were treated with front-line ATO-based regimens was associated with excellent longterm survival.

Autologous stem cell transplantation finds a place in acute promyelocytic leukaemia

“…Contrary to what is suggested by a European LeukemiaNet panel, 3 these data supported the possible reinduction with the same ATObased regimens, as already previously reported, but only in selected small cohorts of patients. 4,7 The important finding reported in the study by Fouzia et al 10 is the outcome of achieving post-molecular remission. Autologous transplant was proposed to all patients, but only 35 patients (55Á6%) underwent this procedure due to personal financial resources, and the estimated five-year OS and event-free survival (EFS) were 90Á3% and 87Á1% respectively in this subset.…”

“…The important finding reported in the study by Fouzia et al 10 . is the outcome of achieving post‐molecular remission.…”

“…[8][9] In their paper, Fouzia et al reported 67 younger APL patients (median age 28 years, range 4-54) who relapsed after front-line ATO. 10 The majority of patients presented a morphological relapse and only one patient an isolated molecular relapse. As demonstrated in the past, pre-emptive treatment intervention in patients with isolated molecular relapse is associated with an advantage in overall survival (OS) compared to treatment for overt haematologic relapse, 11,12 suggesting the importance of monitoring for bone marrow molecular residual disease (MRD) in clinical practice.…”

“…Some questions remain to be solved: (i) how to mobilize and harvest CD34 positive stem cells and what is the best moment to do it. In 13 patients (37%) reported by Fouzia et al 10 . a second day was needed to harvest the required number of CD34 cells, which probably means a prolonged exposure to granulocyte colony‐stimulating factor.…”

“…In their paper, Fouzia et al . reported 67 younger APL patients (median age 28 years, range 4–54) who relapsed after front‐line ATO 10 . The majority of patients presented a morphological relapse and only one patient an isolated molecular relapse.…”