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Influence of NPM1 and FLT3-ITD status on outcome in relapsed/refractory AML patients receiving salvage therapy including gemtuzumab ozogamicin

Leukemia volume 24, pages 467–469 (2010)Cite this article

Acute myeloid leukemia (AML) encompasses a group of very heterogeneous diseases both in terms of presentation and outcome. Thus far, cytogenetic abnormalities are widely recognized as the most important prognostic factors and serve as basis for treatment decision algorithms. The AML subgroup without cytogenetic abnormalities accounts for around 40–50% of all AML cases.1 In this subgroup, two particular gene alterations have been shown to confer prognostic relevance. On one hand, internal tandem duplications of the fms-related tyrosine kinase 3 gene (FLT3-ITD+) have been associated with poor outcome. On the other hand, mutations in the nucleophosmin gene (NPM1+) have been associated with a favorable outcome (reviewed in Bacher et al.2). Therefore, assessment of these two factors allowed for identifying a particularly favorable subgroup of patients. Indeed, AML patients presenting with a mutation for NPM1 without concomitant FLT3-ITD can have a better outcome compared with patients presenting with other combinations. Moreover, a recent study from the German–Austrian AML Study Group1 proposed to classify these patients in the favorable risk leukemia group similar to the core-binding factor AML subgroup, in which allogeneic stem cell transplantation in first complete remission (CR) is not recommended anymore. However, all the above-mentioned studies have considered NPM1/FLT3-ITD status at diagnosis and to the best of our knowledge no series has focused on the effect of the NPM1/FLT3-ITD status at the time of disease relapse, especially in terms of response to salvage therapy and overall outcome. We have previously shown that salvage chemotherapy including gemtuzumab ozogamicin (GO) is a valid option for the treatment of relapsed/refractory CD33+ AML patients.3 With this background, the aim of this report was to investigate the influence of the NPM1/FLT3-ITD status on outcome in relapsed/refractory AML patients with normal karyotype who received a salvage regimen using GO as monotherapy or in combination with other agents.

For this purpose, we analyzed the outcome of 57 AML patients with normal karyotype treated in four institutions (Nantes, Marseille, Bordeaux and Angers) in France, between 2001 and 2009. Patients received GO as monotherapy or in combination with other chemotherapeutic agents at time of relapse (n=36) or in the setting of refractory disease (n=21). There were 26 men and 31 women with a median age of 52 (range, 20–70) years at time of leukemia diagnosis. The French–American–British distribution included 2, 13, 15, 11, 12 and 1 AML cases from the M0, M1, M2, M4, M5 and M6 subgroups, respectively. Three cases were considered as unclassified. In addition, five patients had secondary AML. All patients were CD33+ with a median CD33 expression level of 98%. As salvage treatment, 46 patients received the MIDAM regimen (GO: 9 mg/m2 at day 4+cytarabine 1 g/m2 every 12 h for days 1–5+mitoxantrone 12 mg/m2 per day for days 1–3).3 In two patients receiving the MIDAM regimen, mitoxantrone was omitted to avoid cardiac toxicity. Four patients received GO as monotherapy at 9 mg/m2 (n=3) or at 6 mg/m2 (n=1). The five remaining patients received GO 3–9 mg/m2 combined with other chemotherapeutic agents (cytarabine+VP16+GO, n=2; cytarabine+idarubicin+GO, n=2; cytarabine+amsacrine+GO, n=1). After salvage therapy, 25 patients could proceed and receive consolidation with an allogeneic stem cell transplant.

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Authors and Affiliations

  1. Service d’Hématologie Clinique, CHU, Nantes, France

    P Chevallier, J Delaunay, L Lode, S Richebourg, J-L Harousseau & M Mohty

  2. Université de Nantes, INSERM U892, Nantes, France

    P Chevallier, J Delaunay, L Lode, S Richebourg, J-L Harousseau & M Mohty

  3. Département d’Hématologie, Institut Paoli-Calmettes, Marseille, France

    T Prebet, N Vey & D Blaise

  4. Service d’Hématologie Clinique, CHU de Bordeaux, France

    A Pigneux, F Perry & N Milpied

  5. Service d’Hématologie Clinique, CHU d’Angers, France

    M Hunault, O Blanchet & N Ifrah

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  1. P Chevallier
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  2. T Prebet
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  3. A Pigneux
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  7. L Lode
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Correspondence to P Chevallier.

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Chevallier, P., Prebet, T., Pigneux, A. et al. Influence of NPM1 and FLT3-ITD status on outcome in relapsed/refractory AML patients receiving salvage therapy including gemtuzumab ozogamicin. Leukemia 24, 467–469 (2010). https://doi.org/10.1038/leu.2009.214

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