Favorable Outcome in Patients with Acute Myelogenous Leukemia with the Nucleophosmin Gene Mutation Autografted after Conditioning with High-Dose Continuous Infusion of Idarubicin and Busulfan

Abstract

Mutations of the nucleophosmin gene (NPM1), in the absence of concurrent FLT3-internal tandem duplication (FLT3-ITD) have impressive prognostic value in patients with acute myelogenous leukemia (AML), carrying normal karyotype (NK). In this study we describe treatment results from a series of 19 patients with NPM+/FLT3- autografted in first complete remission (CR) after conditioning with a regimen, named BuI, based on high-dose continuous infusion of idarubicin and Busulfan. Ninety-nine consecutive patients (median age of 54 years) with NK AML autografted in first CR were analyzed. Nineteen of 99 patients (19%) had NPM1 mutation in the absence of FLT3 mutations. The control group, accounting for 80 patients, included 16 cases (15%) with both mutations, 10 (12%) with FLT3/ITD mutation and no NPM mutation, and 54 (68%) in whom neither NPM1 nor FLT3 mutations were detectable. The median overall survival (OS) for the whole patient population was 34 months, the median disease-free survival (DFS) was 22 months. Median OS and DFS were significantly longer for patients with isolated NPM1 mutation as opposed to controls (OS: not reached versus 25 months, P = .02; DFS: not reached versus 16 months, P = .007, respectively). Of interest, patients with isolated NPM1 mutation had a better outcome in terms of either OS or DFS compared to the group of 16 NMP1+/FLT3+ patients. In conclusion, our study suggest that BuI regimen results in favorable clinical outcome in patients with isolated NPM1 mutation, and could be investigated in a randomized study versus other regimes or repeated courses of high dose cytosine-arabinoside.

Hematopoietic stem cell transplantation for adult patients with isolated NPM1 mutated acute myeloid leukemia in first remission

“…However, we showed excellent results with MSD‐SCT in CR1, which are similar to the ones presented in the study from Rollig et al, and in which MSD were applied, with a 3‐year LFS of 83% in the 43 patients with i NPM1 m AML . On the contrary, auto‐SCT and MUD‐SCT resulted in the same 2‐year LFS of about 65%, which is similar to the figures in previous studies performed in NPM1 mutated AML, as well as in the allo‐ versus auto‐SCT studies performed in good‐risk AML . The similar outcomes observed in both auto‐SCT and MUD‐SCT do not support the existence of an allogeneic effect in this population, but as previously discussed the worst results obtained after MUD‐SCT are not fully understood within our study.…”

“…Because of its intrinsic chemosensitivity, the same benefit might be expected for i NPM1 m AML. Indeed, Ferrara et al showed a significant advantage of high dose chemotherapy and auto‐SCT in 35 AML patients with NPM1 mutations . In another French study of 46 AML patients with i NPM1 m, the authors did not find significant difference in terms of survival between patients who received allo‐SCT or auto‐SCT as consolidation therapy .…”

Role of autologous hematopoietic stem cell transplantation according to the NPM1/FLT3‐ITD molecular status for cytogenetically normal AML patients: A GOELAMS study

“…Indeed, the impact of the NPM1/FLT3 ‐ITD molecular status is now well established [1–5, 8]. It was recently evaluated in 99 autografted NK‐AML patients showing significantly longer OS and LFS in the subgroup of 19 patients with a favorable molecular status (OS: not reached vs. 25 months, P = 0.02; LFS: not reached vs. 16 months, P = 0.007) [13].…”

Day 15 bone marrow driven double induction in young adult patients with acute myeloid leukemia: Feasibility, toxicity, and therapeutic results

“…The analysis of FLT3 mutation was performed as previously described [22]. Analysis of nucleophosmin gene (NPM1) mutations in AML cells was performed by fragment analysis according to molecular assay as previously published [23]. Patients aged up to 60 years with de novo AML were given induction treatment consisting of idarubicin 10 mg/m 2 on days 1, 3, and 5; cytarabine (ARA-C) 100 mg/m 2 as c.i.…”