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Philippe Armand,
Haesook T Kim,
Mei-Jie Zhang,
Waleska S Perez,
Paola S Dal Cin,
Thomas R Klumpp,
Edmund K Waller,
Mark R Litzow,
Jane L Liesveld,
Hillard M Lazarus, [......],
Donald W Bunjes,
Effie W Petersdorf,
Steven M Devine,
Richard T Maziarz,
Martin Bornhauser, Victor A Lewis,
David I Marks,
Christopher N Bredeson,
Robert J Soiffer,
Daniel J Weisdorf
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ABSTRACT: Cytogenetics play a major role in determining the prognosis of patients with acute myelogenous leukemia (AML). However, existing cytogenetics classifications were developed in chemotherapy-treated patients and might not be optimal for patients undergoing allogeneic hematopoietic cell transplantation (HCT). We studied 821 adult patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) who underwent HCT for AML in first or second complete remission between 1999 and 2004. We compared the ability of the 6 existing classifications to stratify patients by overall survival. We then defined a new scheme specifically applicable to patients undergoing HCT using this patient cohort. Under this scheme, inv(16) is favorable, a complex karyotype (4 or more abnormalities) is adverse, and all other classified abnormalities are intermediate in predicting survival after HCT (5-year overall survival, 64%, 18%, and 50%, respectively; P = .0001). This scheme stratifies patients into 3 groups with similar nonrelapse mortality, but significantly different incidences of relapse, overall and leukemia-free survival. It applies to patients regardless of disease status (first or second complete remission), donor type (matched related or unrelated), or conditioning intensity (myeloablative or reduced intensity). This transplantation-specific classification could be adopted for prognostication purposes and to stratify patients with AML and karyotypic abnormalities entering HCT clinical trials.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2011; 18(2):280-8. · 3.15 Impact Factor
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Peter J Shaw,
Fangyu Kan,
Kwang Woo Ahn,
Stephen R Spellman,
Mahmoud Aljurf,
Mouhab Ayas,
Michael Burke,
Mitchell S Cairo,
Allen R Chen,
Stella M Davies, [......],
Machteld Oudshoorn,
Effie W Petersdorf,
Olle Ringdén,
Jean Sanders,
Kirk R Schultz,
Adriana Seber,
Michelle Setterholm,
Donna A Wall,
Lolie Yu,
Michael A Pulsipher
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ABSTRACT: Although some trials have allowed matched or single human leukocyte antigen (HLA)-mismatched related donors (mmRDs) along with HLA-matched sibling donors (MSDs) for pediatric bone marrow transplantation in early-stage hematologic malignancies, whether mmRD grafts lead to similar outcomes is not known. We compared patients < 18 years old reported to the Center for International Blood and Marrow Transplant Research with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and myelodysplastic syndrome undergoing allogeneic T-replete, myeloablative bone marrow transplantation between 1993 and 2006. In total, patients receiving bone marrow from 1208 MSDs, 266 8/8 allelic-matched unrelated donors (URDs), and 151 0-1 HLA-antigen mmRDs were studied. Multivariate analysis showed that recipients of MSD transplants had less transplantation-related mortality, acute graft-versus-host disease (GVHD), and chronic GVHD, along with better disease-free and overall survival than the URD and mmRD groups. No differences were observed in transplant-related mortality, acute and chronic GVHD, relapse, disease-free survival, or overall survival between the mmRD and URD groups. These data show that mmRD and 8/8 URD outcomes are similar, whereas MSD outcomes are superior to the other 2 sources. Whether allele level typing could identify mmRD recipients with better outcomes will not be known unless centers alter practice and type mmRD at the allele level.
Blood 11/2010; 116(19):4007-15. · 9.90 Impact Factor
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David I Marks, Tao Wang,
Waleska S Pérez,
Joseph H Antin,
Edward Copelan,
Robert Peter Gale,
Biju George,
Vikas Gupta,
Joerg Halter,
H Jean Khoury,
Thomas R Klumpp,
Hillard M Lazarus, Victor A Lewis,
Philip McCarthy,
David A Rizzieri,
Mitchell Sabloff,
Jeff Szer,
Martin S Tallman,
Daniel J Weisdorf
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ABSTRACT: We examined the efficacy of reduced-intensity conditioning (RIC) and compared outcomes of 93 patients older than 16 years after RIC with 1428 patients receiving full-intensity conditioning for allografts using sibling and unrelated donors for Philadelphia-negative acute lymphoblastic leukemia (ALL) in first or second complete remission. RIC conditioning included busulfan 9 mg/kg or less (27), melphalan 150 mg/m(2) or less (23), low-dose total body irradiation (TBI; 36), and others (7). The RIC group was older (median 45 vs 28 years, P < .001) and more received peripheral blood grafts (73% vs 43%, P < .001) but had similar other prognostic factors. The RIC versus full-intensity conditioning groups had slightly, but not significantly, less acute grade II-IV graft-versus-host disease (39% vs 46%) and chronic graft-versus-host disease (34% vs 42%), yet similar transplantation-related mortality. RIC led to slightly more relapse (35% vs 26%, P = .08) yet similar age-adjusted survival (38% vs 43%, P = .39). Multivariate analysis showed that conditioning intensity did not affect transplantation-related mortality (P = .92) or relapse risk (P = .14). Multivariate analysis demonstrated significantly improved overall survival with: Karnofsky performance status more than 80, first complete remission, lower white blood count, well-matched unrelated or sibling donors, transplantation since 2001, age younger than 30 years, and conditioning with TBI, but no independent impact of conditioning intensity. RIC merits further investigation in prospective trials of adult ALL.
Blood 07/2010; 116(3):366-74. · 9.90 Impact Factor
