The role of stem cells in post-remission treatment of acute myeloid leukaemia

Richard Heywood, University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0SP

The treatment for acute myeloid leukaemia (AML) is in two parts: patients receive chemotherapy until complete remission is achieved, and then receive post-remission therapy to minimise the risk of recurrence. This can consist of further chemotherapy with cytarabine, or transplant of allogeneic or autologous haematopoietic stem cells (HSCs) to replace the abnormal HSC population.

Due to the risk of disease recurrence with autologous HSCs (HSCs removed from the patient before chemotherapy begins), patients with high-risk cytogenetic abnormalities receive allogeneic HSC transplants, whereas low- and intermediate-risk patients generally receive cytarabine. These low- and intermediate- risk patients may benefit from autologous HSC transplants as they reduce the toxicity associated with cytarabine. However, it was unknown which patients would benefit from autologous HSC transplants. Pfirmann et al. writing in Lancet Oncology[1], report the findings of a post-hoc analysis of a large trial looking at post-remission therapies (PRT)[2], and report a new PRT score which predicts survival and identifies patients who will benefit from the different therapy options.

The authors looked at 586 patients who achieved complete remission in the previous trial. They identified the main variables which predicted survival after remission:

  • Age (worse prognosis with higher age)
  • Type of cytogenetic abnormality (for example t(8:21) translocations are considered low risk, t(9:22) and others are considered high risk)
  • The ratio of cells with internal tandem duplications (exon duplications) of the FLT-3 tyrosine kinase gene (a ratio of >0.8:1 abnormal: wild type is prognostically unfavourable)
  • The proportion of CD34+ blasts (a higher proportion is prognostically unfavourable)

The authors assigned each variable a score based on the presence or absence of the prognostic factors, and combined these values to give a “PRT score”. Using this score they identified 3 groups, “favourable”, “intermediate” and “unfavourable”, with differences in overall survival which were validated in 2 large datasets.

They then looked at patients in the different groups who received the various therapies. In the “favourable” group and “unfavourable” group, allogeneic stem cell therapy gave the best survival outcomes, whereas in the intermediate group autologous stem cells were most favourable. In all groups, chemotherapy was the least beneficial treatment.

This study provides physicians treating AML patients with a new, easy to calculate score to predict prognosis in their patients. However, more importantly, it allows them to identify which patients will benefit from autologous or allogeneic stem cell transplants, whilst suggesting that cytarabine chemotherapy, a previous mainstay of AML post-remission therapy, is not beneficial. Therefore treatment can be tailored to the individual patient to improve survival outcomes whilst minimising toxicity.

References: 

1. Pfirrmann M, Ehninger G, Thiede C, Bornhäuser M, Kramer M, Röllig C, Hasford J, Schaich M. Prediction of post-remission survival in acute myeloid leukaemia: a post-hoc analysis of the AML96 trial. Lancet Oncology. 2012 Feb; 13(2):207-14.
doi:10.1016/S1470-2045(11)70326-6

2. Röllig C, Thiede C, Gramatzki M, Aulitzky W, Bodenstein H, Bornhäuser M, Platzbecker U, Stuhlmann R, Schuler U, Soucek S, Kramer M, Mohr B, Oelschlaegel U, Stölzel F, von Bonin M, Wermke M, Wandt H, Ehninger G, Schaich M. A novel prognostic model in elderly patients with acute myeloid leukemia: results of 909 patients entered into the prospective AML96 trial. Blood. 2010 Aug 12;116(6):971-8.
doi:10.1182/blood-2010-01-267302

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