{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:13:03Z","timestamp":1790176383185,"version":"4.1.0"},"reference-count":45,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"18","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2002,9,15]]},"abstract":"<jats:p> PURPOSE: Patients with chronic lymphocytic leukemia (CLL) may have disease transformation to non-Hodgkin\u2019s lymphoma or prolymphocytic leukemia; however, development of therapy-related acute myeloid leukemia (t-AML) is unusual. A series of patients enrolled onto an intergroup CLL trial were examined for this complication. <\/jats:p><jats:p> PATIENTS AND METHODS: A total of 544 previously untreated B-cell CLL patients were enrolled onto a randomized intergroup study comparing treatment with chlorambucil, fludarabine, or fludarabine plus chlorambucil. Case report forms from 521 patients were reviewed for t-AML. <\/jats:p><jats:p> RESULTS: With a median follow-up of 4.2 years, six patients (1.2%) to date have developed therapy-related myelodysplastic syndrome (t-MDS; n = 3), t-AML (n = 2), or t-MDS evolving to t-AML (n = 1), from 27 to 53 months (median, 34 months) after study entry. This included five (3.5%) of 142 patients treated with fludarabine plus chlorambucil and one (0.5%) of 188 receiving fludarabine; no chlorambucil-treated patients developed t-MDS or t-AML (P = .007). At study entry, the median age among these six patients was 56 years (range, 44 to 72 years); three were male; the CLL Rai stage was I\/II (n = 4) or III\/IV (n = 2). Response to CLL therapy was complete (n = 4) or partial remission (n = 1) and stable disease (n = 1). Marrow cytogenetics, obtained in three of six cases at diagnosis of t-MDS or t-AML, were complex, with abnormalities in either or both chromosomes 5 and 7. Other abnormalities involved chromosomes X, 1, 8, 12, 17, and 19. Median survival after diagnosis of t-MDS\/AML was 3.5 months (range, 0.5 to 10.1 months). <\/jats:p><jats:p> CONCLUSION: Our findings raise the possibility that alkylator-purine analog combination therapy may increase the risk of therapy-related myeloid malignancies, which is of particular relevance with regard to ongoing trials using these combination therapies. <\/jats:p>","DOI":"10.1200\/jco.2002.08.128","type":"journal-article","created":{"date-parts":[[2002,9,12]],"date-time":"2002-09-12T17:42:13Z","timestamp":1031852533000},"page":"3878-3884","source":"Crossref","is-referenced-by-count":147,"title":["Therapy-Related Myeloid Leukemias Are Observed in Patients With Chronic Lymphocytic Leukemia After Treatment With Fludarabine and Chlorambucil: Results of an Intergroup Study, Cancer and Leukemia Group B 9011"],"prefix":"10.1200","volume":"20","author":[{"given":"Vicki A.","family":"Morrison","sequence":"first","affiliation":[{"name":"From the Veterans Affairs Medical Center, Minneapolis, MN; Long Island Jewish Medical Center, New Hyde Park, and North Shore University Hospital, Manhasset, NY; Cancer and Leukemia Group B Statistical Center, Durham, NC; University of New Mexico Health Sciences Center, Albuquerque, NM; Fred Hutchinson Cancer Research Center, Seattle, WA; The Case Western Reserve University School of Medicine, Cleveland, OH; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanti R.","family":"Rai","sequence":"additional","affiliation":[{"name":"From the Veterans Affairs Medical Center, Minneapolis, MN; Long Island Jewish Medical Center, New Hyde Park, and North Shore University Hospital, Manhasset, NY; Cancer and Leukemia Group B Statistical Center, Durham, NC; University of New Mexico Health Sciences Center, Albuquerque, NM; Fred Hutchinson Cancer Research Center, Seattle, WA; The Case Western Reserve University School of Medicine, Cleveland, OH; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bercedis L.","family":"Peterson","sequence":"additional","affiliation":[{"name":"From the Veterans Affairs Medical Center, Minneapolis, MN; Long Island Jewish Medical Center, New Hyde Park, and North Shore University Hospital, Manhasset, NY; Cancer and Leukemia Group B Statistical Center, Durham, NC; University of New Mexico Health Sciences Center, Albuquerque, NM; Fred Hutchinson Cancer Research Center, Seattle, WA; The Case Western Reserve University School of Medicine, Cleveland, OH; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan E.","family":"Kolitz","sequence":"additional","affiliation":[{"name":"From the Veterans Affairs Medical Center, Minneapolis, MN; Long Island Jewish Medical Center, New Hyde Park, and North Shore University Hospital, Manhasset, NY; Cancer and Leukemia Group B Statistical Center, Durham, NC; University of New Mexico Health Sciences Center, Albuquerque, NM; Fred Hutchinson Cancer Research Center, Seattle, WA; The Case Western Reserve University School of Medicine, Cleveland, OH; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Elias","sequence":"additional","affiliation":[{"name":"From the Veterans Affairs Medical Center, Minneapolis, MN; Long Island Jewish Medical Center, New Hyde Park, and North Shore University Hospital, Manhasset, NY; Cancer and Leukemia Group B Statistical Center, Durham, NC; University of New Mexico Health Sciences Center, Albuquerque, NM; Fred Hutchinson Cancer Research Center, Seattle, WA; The Case Western Reserve University School of Medicine, Cleveland, OH; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick R.","family":"Appelbaum","sequence":"additional","affiliation":[{"name":"From the Veterans Affairs Medical Center, Minneapolis, MN; Long Island Jewish Medical Center, New Hyde Park, and North Shore University Hospital, Manhasset, NY; Cancer and Leukemia Group B Statistical Center, Durham, NC; University of New Mexico Health Sciences Center, Albuquerque, NM; Fred Hutchinson Cancer Research Center, Seattle, WA; The Case Western Reserve University School of Medicine, Cleveland, OH; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Hines","sequence":"additional","affiliation":[{"name":"From the Veterans Affairs Medical Center, Minneapolis, MN; Long Island Jewish Medical Center, New Hyde Park, and North Shore University Hospital, Manhasset, NY; Cancer and Leukemia Group B Statistical Center, Durham, NC; University of New Mexico Health Sciences Center, Albuquerque, NM; Fred Hutchinson Cancer Research Center, Seattle, WA; The Case Western Reserve University School of Medicine, Cleveland, OH; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lois","family":"Shepherd","sequence":"additional","affiliation":[{"name":"From the Veterans Affairs Medical Center, Minneapolis, MN; Long Island Jewish Medical Center, New Hyde Park, and North Shore University Hospital, Manhasset, NY; Cancer and Leukemia Group B Statistical Center, Durham, NC; University of New Mexico Health Sciences Center, Albuquerque, NM; Fred Hutchinson Cancer Research Center, Seattle, WA; The Case Western Reserve University School of Medicine, Cleveland, OH; National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada; University..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Larson","sequence":"additional","affiliation":[{"name":"From the Veterans Affairs Medical Center, Minneapolis, MN; Long Island Jewish Medical Center, New Hyde Park, and North Shore University Hospital, Manhasset, NY; 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