Therapy-Related Myelodysplasia and Secondary Acute Myelogenous Leukemia After High-Dose Therapy With Autologous Hematopoietic Progenitor-Cell Support for Lymphoid Malignancies

• Published in: Journal of clinical oncology Vol. 18; no. 5; pp. 947 - 955
• Main Authors: MICALLEF, I. N. M, LILLINGTON, D. M, ROHATINER, A. Z. S, APOSTOLIDIS, J, AMESS, J. A. L, NEAT, M, MATTHEWS, J, CLARK, T, FORAN, J. M, SALAM, A, LISTER, T. A
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01.03.2000; Lippincott Williams & Wilkins
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Drug toxicity and drugs side effects treatment; Female; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Leukemia, Myeloid, Acute - epidemiology; Leukemia, Myeloid, Acute - etiology; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - mortality; Lymphoma, Non-Hodgkin - complications; Lymphoma, Non-Hodgkin - therapy; Male; Medical sciences; Middle Aged; Miscellaneous (drug allergy, mutagens, teratogens...); Myelodysplastic Syndromes - epidemiology; Myelodysplastic Syndromes - etiology; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - mortality; Neoplasms, Second Primary - etiology; Neoplasms, Second Primary - genetics; Outcome Assessment (Health Care); Pharmacology. Drug treatments; Risk Factors; Survival Rate; Transplantation, Autologous - adverse effects; Antineoplastic agent; Human; Toxicity; Acute; Malignant hemopathy; Non Hodgkin lymphoma; Myelodysplastic syndrome; Blood; Incidence; Myeloproliferative syndrome; Autograft; Chemotherapy; Second cancer; Lymphoproliferative syndrome; Risk factor; High dose; Progenitor cell; Acute myelocytic leukemia
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2000.18.5.947

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). 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. 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). 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.