Impact of postremission consolidation chemotherapy on outcome after reduced‐intensity conditioning allogeneic stem cell transplantation for patients with acute myeloid leukemia in first complete remission: A report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Abstract

BACKGROUND:The objective of the current study was to investigate the role of postremission consolidation chemotherapy before reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (alloSCT) for patients with acute myeloid leukemia (AML) in first complete remission (CR1). METHODS: Of the 789 consecutive patients with AML in CR1 who underwent RIC alloSCT from a human leukocyte antigen-matched sibling or matched unrelated donor peripheral stem cell grafts between 2001 and 2010, 591 patients received at least 1 cycle of consolidation chemotherapy and 198 patients did not receive any consolidation chemotherapy before alloSCT. To minimize inherent survival bias in favor of patients who underwent transplant long after achieving CR1, the study focused on 373 patients who underwent transplant within the median time frame between achievement of CR1 and alloSCT (3 months for patients who underwent alloSCT from matched siblings and 4 months for patients who underwent alloSCT from matched unrelated donors). In this subgroup, 151 patients did not receive any consolidation chemotherapy and 222 patients received 1 consolidation chemotherapy cycle. RESULTS: With a median follow-up of 36 months (range, 2 months-135 months), the 3-year cumulative recurrence incidence (RI) was not significantly different between the groups (36% 6 4% for the group treated without consolidation chemotherapy vs 38% 6 3% for patients who received consolidation chemotherapy; P 5.89). In addition, leukemia-free survival was similar between the groups (45% 6 4% and 47% 6 3%, respectively; P 5.41). Dose intensity of cytarabine given during consolidation chemotherapy appeared to have no influence on RI. On multivariate analysis, pretransplant consolidation ( 1 cycle vs 0 cycles) was found to have no significant impact on RI (hazards ratio, 1.29; 95% confidence interval, 0.84-1.97 [P 5.24]) or leukemia-free survival (hazards ratio, 1.00; 95% confidence interval, 0.71-1.42 [P 5.99]). CONCLUSIONS: The data from the current study suggest no apparent advantage for postremission consolidation chemotherapy before RIC alloSCT, provided a donor is readily available. Cancer 2014;120:855-63.

Sequential Intensified Conditioning Regimen Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Intermediate- or High-Risk Acute Myeloid Leukemia in Complete Remission: A Study from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

“…Notably, the cumulative incidences of relapse and LFS were 22.8% and 52.8%, respectively. These results compare favorably with previous studies evaluating RIC regimens for AML, with relapse incidences up to 41% and LFS below 50% [12][13][14][15][16][17] but with the results of myeloablative conditioning regimens showing relapse incidences ranging from 24% to 29% [12,16]. Our results are also comparable with those of other intermediate conditioning regimens, combining fludarabine, ATG, and 3 days of Bu [4], associated with a cumulative incidence of relapse of 29.1% and an LFS of 57% [5].…”

“…Of note, we reported only 2 deaths related to cardiac toxicity, a known side effect of amsacrine [20], and there was no increase in the mortality related to sinusoidal obstruction syndrome, with only 2 deaths reported. Taken together, the low cumulative incidence of relapse and the NRM led to an OS rate of 56.1% at 2 years, which compared favorably with result of the previously cited studies evaluating both RIC (OS ranged from 36% to 55%) [12][13][14][15][16] and myeloablative regimens (OS ranged from 57% to 53%) [12,16]. The patients' outcome was similar using either the TBI or the Bu-based FLAMSA regimen.…”

Impact of early remission by induction therapy on allogeneic stem cell transplantation for acute myeloid leukemia with an intermediate‐risk karyotype in first complete remission

“…One approach could be to apply repetitive courses of consolidation chemotherapy until MRD negativity is reached. A recently published analysis of EBMT registry data clearly indicates that, at least for patients with AML undergoing RIC‐alloSCT in CR1, consolidation therapy neither reduces the risk of relapse, nor improves overall outcome . One should assume that the results in patients undergoing alloSCT following MAC are similar.…”

Is the D14 bone marrow in acute myeloid leukemia still the gold standard?

“…Other studies showed that patients who received one induction cycle had an identical posttransplant prognosis regardless of the fact if induction was followed by consolidation prior to transplant [25,26]. No firm data exist to support any change in postremission management of AML patients based on day 14 bone marrow results; however, in clinical practice, early bone marrow response may be taken into consideration in debatable cases, such as assignment of patients with intermediate-risk AML with comorbidities to allo-HCT.…”