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Allogeneic transplantation for CML in the TKI era: striking the right balance

Nature Reviews Clinical Oncology volume 13, pages 79–91 (2016)Cite this article

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Key Points

  • While TKIs have revolutionised the treatment of CML, allogeneic HSCT remains the only treatment capable of curing CML

  • For the 10–15% of patients with chronic phase CML unable to achieve an adequate response with a tolerable dose of TKI, allogeneic HSCT offers a feasible alternative strategy

  • Early assessment strategies should be used to identify those destined to fail to respond to TKIs, allowing rapid transition through multiple TKIs and on to, if necessary, HSCT before disease progression occurs

  • The mechanisms of disease control from TKI and HSCT are independent, therefore, poor response to TKI does not per se predict poor response to HSCT

  • Allogeneic HSCT remains the standard of care for patients with accelerated phase or blast crisis CML

Abstract

The management of chronic myeloid leukaemia (CML) has changed extensively over the past 15 years. Prior to the development of targeted therapies and in the absence of allogeneic haematopoetic stem-cell transplantation (HSCT), the median survival was 5–7 years. HSCT was quickly established as the standard of care for eligible patients through the 1980s and 1990s, when considerable advances were made in the optimization of conditioning regimens and supportive care. Exploiting a deeper understanding of the molecular basis of CML, the development of tyrosine kinase inhibitors (TKIs) in the late 1990s revolutionized the management of the disease. TKIs offer the prospect of long-term disease control with a simple oral therapy, and are the first-line treatment in the 21st century. The majority of patients treated with TKIs achieve excellent responses with sustained treatment, and some even continue to have undetectable or exceptionally low level disease upon TKI withdrawal; however, for an almost equal number of patients, an adequate response cannot be achieved with any of the currently available TKIs. For those patients who fail to respond adequately to TKIs, HSCT offers the best prospect of long-term survival.

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Figure 1: Overall response rates to TKIs in chronic phase disease.
Figure 2: The number of HSCTs carried out for CML by disease phase from 1990–2013.

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Acknowledgements

J.F.A. and D.M. acknowledge the support of the NIHR Biomedical Research Centre. A.J.I. acknowledges the support of an MRC and NIHR Chain-Florey Clinical Research Fellowship. We are extremely grateful to the EBMT Transplant activity survey office, and in particular to Helen Baldomero and Alois Gratwohl, for the data in Fig. 2.

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  1. Centre for Haematology, Faculty of Medicine, Imperial College London, Hammersmith Campus, W12 0NN, London, UK

    Andrew J. Innes, Dragana Milojkovic & Jane F. Apperley

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A.J.I., D.M. and J.F.A. contributed equally to researching data for article, discussing its content, writing the article, and reviewing and/or editing the manuscript before submission.

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Correspondence to Jane F. Apperley.

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J.F.A. and D.M have received honouraria from, and serve on advisory boards for, Ariad, Bristol–Myers Squibb, Novartis and Pfizer. A.J.I. declares no competing interests.

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Innes, A., Milojkovic, D. & Apperley, J. Allogeneic transplantation for CML in the TKI era: striking the right balance. Nat Rev Clin Oncol 13, 79–91 (2016). https://doi.org/10.1038/nrclinonc.2015.193

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