Journal of Clinical Oncology, Vol 18, Issue 5
(March), 2000: 947
© 2000 American Society for Clinical Oncology
Therapy-Related Myelodysplasia and Secondary Acute Myelogenous Leukemia After High-Dose Therapy With Autologous Hematopoietic Progenitor-Cell Support for Lymphoid Malignancies
By Ivana N. M. Micallef,
Debra M. Lillington,
John Apostolidis,
John A. L. Amess,
Michael Neat,
Janet Matthews,
Taane Clark,
James M. Foran,
Ashiq Salam,
T. Andrew Lister,
Ama Z. S. Rohatiner
From the Imperial Cancer Research Fund Medical Oncology Unit, Departments of Medical Oncology and Haematology, St Bartholomew’s Hospital, London; and Imperial Cancer Research Fund Centre for Statistics in Medicine, Institute of Health Sciences, Oxford, United Kingdom.
Address reprint requests to Ama Z.S. Rohatiner, MD, Imperial Cancer Research Fund Medical Oncology Unit, Department of Medical Oncology, St Bartholomew’s Hospital, 45 Little Britain, West Smithfield, London EC1A 7BE, United Kingdom; email a.rohatiner@ icrf.icnet.uk.
PURPOSE: To evaluate the incidence of and risk factors for therapy-related myelodysplasia (tMDS) and secondary acute myelogenous leukemia (sAML), after high-dose therapy (HDT) with autologous bone marrow or peripheral-blood progenitor-cell support, in patients with non-Hodgkin’s lymphoma (NHL).
PATIENTS AND METHODS: Between January 1985 and November 1996, 230 patients underwent HDT comprising cyclophosphamide therapy and total-body irradiation, with autologous hematopoietic progenitor-cell support, as consolidation of remission. With a median follow-up of 6 years, 27 (12%) developed tMDS or sAML.
RESULTS: Median time to development of tMDS or sAML was 4.4 years (range, 11 months to 8.8 years) after HDT. Karyotyping (performed in 24 cases) at diagnosis of tMDS or sAML revealed complex karyotypes in 18 patients. Seventeen patients had monosomy 5/5q-, 15 had -7/7q-, seven had -18/18q-, seven had -13/13q-, and four had -20/20q-. Twenty-one patients died from complications of tMDS or sAML or treatment for tMDS or sAML, at a median of 10 months (range, 0 to 26 months). Sixteen died without evidence of recurrent lymphoma. Six patients were alive at a median follow-up of 6 months (range, 2 to 22 months) after diagnosis of tMDS or sAML. On multivariate analysis, prior fludarabine therapy (P = .009) and older age (P = .02) were associated with the development of tMDS or sAML. Increased interval from diagnosis to HDT and bone marrow involvement at diagnosis were of borderline significance (P = .05 and .07, respectively).
CONCLUSION: tMDS and sAML are serious complications of HDT for NHL and are associated with very poor prognosis. Alternative strategies for reducing their incidence and for treatment are needed.
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