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Blood, 15 July 2008, Vol. 112, No. 2, pp. 426-434.
Prepublished online as a Blood First Edition Paper on April 8, 2008; DOI 10.1182/blood-2007-12-128918.
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TRANSPLANTATION
Unrelated donor transplants in adults with Philadelphia-negative acute lymphoblastic leukemia in first complete remission
David I. Marks1,
Waleska S. Pérez2,
Wensheng He2,
Mei-Jie Zhang2,
Michael R. Bishop3,
Brian J. Bolwell4,
Christopher N. Bredeson5,
Edward A. Copelan4,
Robert Peter Gale6,
Vikas Gupta7,
Gregory A. Hale8,
Luis M. Isola9,
Ann A. Jakubowski10,
Armand Keating7,
Thomas R. Klumpp11,
Hillard M. Lazarus12,
Jane L. Liesveld13,
Richard T. Maziarz14,
Philip L. McCarthy15,
Mitchell Sabloff16,
Gary Schiller17,
Jorge Sierra18,
Martin S. Tallman19,
Edmund K. Waller20,
Peter H. Wiernik21, and
Daniel J. Weisdorf22
1 Adult Blood and Marrow Transplantation (BMT) Unit, United Bristol Healthcare Trust, Bristol, United Kingdom;
2 Center for International BMT Research, Medical College of Wisconsin, Milwaukee;
3 National Cancer Institute, Bethesda, MD;
4 Cleveland Clinic Foundation, OH;
5 Medical College of Wisconsin, Milwaukee;
6 Center for Advanced Studies in Leukemia, Los Angeles, CA;
7 Princess Margaret Hospital, Toronto, ON;
8 St Jude Children's Research Hospital, Memphis, TN;
9 Mount Sinai Hospital, New York, NY;
10 Memorial Sloan-Kettering Cancer Center, New York, NY;
11 Fox Chase-Temple BMT Program, Philadelphia, PA;
12 University Hospitals of Cleveland, OH;
13 University of Rochester Medical Center, NY;
14 Oregon Health and Science University, Portland;
15 Roswell Park Cancer Institute, Buffalo, NY;
16 Ottawa Hospital, Ottawa, ON;
17 University of California, Los Angeles;
18 Hospital Santa Creu Sant Pau, Barcelona, Spain;
19 Northwestern Memorial Hospital, Chicago, IL;
20 Emory University Hospital, Atlanta, GA;
21 Our Lady of Mercy Medical Center, Bronx, NY; and
22 University of Minnesota, Minneapolis
We report the retrospective outcomes of unrelated donor (URD) transplants in 169 patients with acute lymphoblastic leukemia (ALL) in first complete remission (CR1) who received transplants between 1995 and 2004. Median age was 33 years (range, 16-59 years). A total of 50% had a white blood cell count (WBC) more than 30 x 109/L, 18% extramedullary disease, 42% achieved CR more than 8 weeks from diagnosis, 25% had adverse cytogenetics, and 19% had T-cell leukemia. A total of 41% were HLA well-matched, 41% partially matched with their donors, and 18% were HLA-mismatched. At 54-month median follow-up, incidences of acute grade 2-IV, III to IV, and chronic graft-versus-host disease were 50%, 25%, and 43%, respectively. Five-year treatment-related mortality (TRM), relapse, and overall survival were 42%, 20%, and 39%, respectively. In multivariate analyses, TRM was significantly higher with HLA-mismatched donors and T-cell depletion. Relapse risk was higher if the diagnostic WBC was more than 100 x 109/L. Factors associated with poorer survival included WBC more than 100 x 109/L, more than 8 weeks to CR1, cytomegalovirus seropositivity, HLA mismatching, and T-cell depletion. Nearly 40% of adults with ALL in CR1 survive 5 years after URD transplantation. Relapse risks were modest; TRM is the major cause of treatment failure. Selecting closely HLA-matched URD and reducing TRM should improve results.
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