Outcome of treatment after first relapse in younger adults with acute myeloid leukemia initially treated by the ALFA-9802 trial

Department of Hematology, Hôpital Edouard Herriot, Lyon, France.
Leukemia research (Impact Factor: 2.35). 05/2012; 36(9):1112-8. DOI: 10.1016/j.leukres.2012.04.020
Source: PubMed


Forty-seven percent of adults with acute myeloid leukemia (AML) who entered the ALFA-9802 trial and achieved a first complete remission (CR) experienced a first relapse. We examined the outcome of these 190 adult patients. Eighty-four patients (44%) achieved a second CR. The median overall survival (OS) after relapse was 8.9 months with a 2-year OS at 25%. Factors predicting a better outcome after relapse were stem cell transplant (SCT) performed in second CR and a first CR duration >1 year. Risk groups defined at the time of diagnosis and treatment received in first CR also influenced the outcome after relapse. The best results were obtained in patients with core binding factor (CBF)-AML, while patients initially defined as favorable intermediate risk showed a similar outcome after relapse than those initially entering the poor risk group. We conclude that most adult patients with recurring AML could not be rescued using current available therapies, although allogeneic SCT remains the best therapeutic option at this stage of the disease.

7 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Inhibition of cholesterol synthesis and uptake sensitizes acute myeloid leukaemia (AML) blasts to chemotherapy. A Phase 1 study demonstrated the safety of high dose pravastatin given with idarubicin and cytarabine in patients with AML and also demonstrated an encouraging response rate. The Southwestern Oncology Group (SWOG) trial, SWOG S0919, was a Phase 2 trial evaluating the complete remission (CR) rate in a larger number of patients with relapsed AML treated with idarubicin, cytarabine and pravastatin. This study closed to accrual after meeting the defined criterion for a positive study. Thirty-six patients with a median age of 59 years (range 23–78) were enrolled. The median time from diagnosis to registration was 18 months. Relapse status was first relapse, 17 patients (47%); second relapse, 15 patients (42%); third relapse, two patients (5·5%) and fourth relapse, two patients (5·5%). The response rate was 75% [95% confidence interval: 58–88%; 20 CRs, 7 CR with incomplete count recovery (CRi)], and the median overall survival was 12 months. The P-value comparing 75–30% (the null response rate based on prior SWOG experience) was 3·356 × 10−4. Given the encouraging CR/CRi rate, this regimen should be considered for testing in a prospective randomized trial against best conventional therapy.
    British Journal of Haematology 07/2014; 167(2). DOI:10.1111/bjh.13035 · 4.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Allogeneic stem cell transplantation (SCT) is an increasingly important therapeutic option for the treatment of adult patients with acute myeloid leukemia. Here we review the current indications of SCT in this disease. While patients with favorable cytogenetics should receive consolidation chemotherapy, patients with unfavorable karyotype are prime candidates for SCT or new approaches to SCT (which should be done in first complete remission). Patients with intermediate prognoses should also receive SCT in first complete remission. In the absence of a suitable matched related donor, most patients will be able to find an alternative donor to proceed to a potentially curative allogeneic transplantation. The use of reduced-intensity conditioning regimens before SCT has allowed patients in the sixth or seventh decades of life to be routinely transplanted. Despite major differences among transplant centers in the intensity and composition of the conditioning regimen and immunosuppression, choice of graft source, postgraft immune-modulation, and supportive care, there has been a dramatic improvement in terms of tolerance. Although it is presumed to be a curative strategy, major complications of SCT remain graft-versus-host disease, delayed immune recovery, multiple comorbidities, and relapse after transplant.
    Bulletin du cancer 10/2014; 101(9). DOI:10.1684/bdc.2014.1944 · 0.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this Phase 1b study, the safety and tolerability of maintenance therapy, comprising lenalidomide (0–25 mg, days 5–25) in combination with azacitidine (50–75 mg/m2, days 1–5) every 28 d, was explored in 40 patients with acute myeloid leukaemia (AML) in complete remission after chemotherapy. Eligibility included AML in first complete remission (CR1) with adverse risk karyotype (n = 8), fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) (n = 5), age ≥60 years (n = 31) or AML in second remission (CR2) (n = 14). Dose-limiting toxicity was not reached. Common toxicities were haematological, infection, injection pain, constipation, fatigue and diarrhoea. In CR1, median relapse-free (RFS) and overall survival (OS) was 12 and 20 months, respectively. In CR2, median RFS was 11 months, with median OS not yet reached. Among 29 patients with intermediate cytogenetic risk, RFS was 50% at 24 months. There were five patients with concomitant FLT3-ITD and nucleophosmin (NPM1) mutation; none have relapsed and all are still alive after 17–39 months. Maintenance lenalidomide/azacitidine augmented the function of cytotoxic T lymphocytes, particularly in patients with NPM1 mutation. The lenalidomide/azacitidine maintenance combination was effective in suppressing residual DNA (cytosine-5-)-methyltransferase 3 alpha (DNMT3A)-positive disease, resulting in sustained remission in patients with concurrent NPM1 mutation. Azacitidine/lenalidomide as maintenance therapy for high-risk AML warrants further exploration.
    British Journal of Haematology 02/2015; 169(2). DOI:10.1111/bjh.13281 · 4.71 Impact Factor