Post-remission treatment with allogeneic stem cell transplantation in patients aged 60 years and older with acute myeloid leukaemia: a time-dependent analysis

Jurjen Versluis, Carin L. E. Hazenberg, Jakob R. Passweg, Wim L. J. van Putten, Johan Maertens, Bart J. Biemond, Matthias Theobald, Carlos Graux, Jurgen Kuball, Harry C. Schouten, Thomas Pabst, Bob Lowenberg, Gert Ossenkoppele, Edo Vellenga, Jan J. Cornelissen*, HOVON Leukemia Grp, SAKK Leukemia Grp

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background Acute myeloid leukaemia mainly affects elderly people, with a median age at diagnosis of around 70 years. Although about 50-60% of patients enter first complete remission upon intensive induction chemotherapy, relapse remains high and overall outcomes are disappointing. Therefore, effective post-remission therapy is urgently needed. Although often no post-remission therapy is given to elderly patients, it might include chemotherapy or allogeneic haemopoietic stem cell transplantation (HSCT) following reduced-intensity conditioning. We aimed to assess the comparative value of allogeneic HSCT with other approaches, including no post-remission therapy, in patients with acute myeloid leukaemia aged 60 years and older.

Methods For this time-dependent analysis, we used the results from four successive prospective HOVON-SAKK acute myeloid leukaemia trials. Between May 3, 2001, and Feb 5, 2010, a total of 1155 patients aged 60 years and older were entered into these trials, of whom 640 obtained a first complete remission after induction chemotherapy and were included in the analysis. Post-remission therapy consisted of allogeneic HSCT following reduced-intensity conditioning (n=97), gemtuzumab ozogamicin (n=110), chemotherapy (n=44), autologous HSCT (n=23), or no further treatment (n=366). Reduced-intensity conditioning regimens consisted of fludarabine combined with 2 Gy of total body irradiation (n=71), fludarabine with busulfan (n=10), or other regimens (n=16). A time-dependent analysis was done, in which allogeneic HSCT was compared with other types of post-remission therapy. The primary endpoint of the study was 5-year overall survival for all treatment groups, analysed by a time-dependent analysis.

Findings 5-year overall survival was 35% (95% CI 25-44) for patients who received an allogeneic HSCT, 21% (17-26) for those who received no additional post-remission therapy, and 26% (19-33) for patients who received either additional chemotherapy or autologous HSCT. Overall survival at 5 years was strongly affected by the European LeukemiaNET acute myeloid leukaemia risk score, with patients in the favourable risk group (n=65) having better 5-year overall survival (56% [95% CI 43-67]) than those with intermediate-risk (n=131; 23% [19-27]) or adverse-risk (n=444; 13% [8-20]) acute myeloid leukaemia. Multivariable analysis with allogeneic HSCT as a time-dependent variable showed that allogeneic HSCT was associated with better 5-year overall survival (HR 0.71 [95% CI 0.53-0.95], p=0.017) compared with non-allogeneic HSCT post-remission therapies or no post-remission therapy, especially in patients with intermediate-risk (0.82 [0.58-1.15]) or adverse-risk (0.39 [0.21-0.73]) acute myeloid leukaemia.

Interpretation Collectively, the results from these four trials suggest that allogeneic HSCT might be the preferred treatment approach in patients 60 years of age and older with intermediate-risk and adverse-risk acute myeloid leukaemia in first complete remission, but the comparative value should ideally be shown in a prospective randomised study.

Original languageEnglish
Pages (from-to)E427-E436
Number of pages10
JournalLancet Haematology
Volume2
Issue number10
DOIs
Publication statusPublished - Oct-2015

Keywords

  • 1ST COMPLETE REMISSION
  • RISK-ADAPTED APPROACH
  • COUNCIL AML11 TRIAL
  • GEMTUZUMAB OZOGAMICIN
  • EUROPEAN LEUKEMIANET
  • MYELODYSPLASTIC SYNDROME
  • INDUCTION CHEMOTHERAPY
  • ADULT PATIENTS
  • SURVIVAL
  • METAANALYSIS

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