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Blood, 1 December 2002, Vol. 100, No. 12, pp. 3877-3886
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Graft-versus-host disease and outcome in HLA-identical sibling
transplantations for chronic myeloid leukemia
Alois Gratwohl,
Ronald Brand,
Jane Apperley,
Anja v. Biezen,
Giuseppe Bandini,
Agnes Devergie,
Anton Schattenberg,
Francesco Frassoni,
Cesare Guglielmi,
Simona Iacobelli,
Mauricette Michallet,
Hans-Jochen Kolb,
Tapani Ruutu, and
Dietger Niederwieser for the
Chronic Leukemia Working Party of the European Group for
Blood and Marrow Transplantation (CLWP-EBMT)
From the Division of Hematology, Department of Internal
Medicine, Kantonsspital Basel, Basel, Switzerland; Department of
Medical Statistics, University of Leiden, Leiden, The
Netherlands; Department of Hematology, Royal Postgraduate
Medical School, Hammersmith Hospital, London, United
Kingdom; Institute of Hematology and Medical Oncology Seragnoli,
Hospital San Orsola, Bologna, Italy; Bone Marrow
Transplant Unit, Hôpital St Louis, Paris, France;
Department of Hematology, University Medical Centre, Nijmegen,
The Netherlands; Bone Marrow Transplant Unit, Ospedale San
Martino, Genova, Italy; Allogeneic BMT Unit "Giuseppe
Papa," University La Sapienza, Rome, Italy; Bone Marrow
Transplant Unit, Hôpital E. Herriot, Lyon, France;
Medical Clinic III, Klinikum Grosshadern, Munich, Germany;
Division of Hematology, Department of Internal Medicine, Helsinki
University Central Hospital, Helsinki, Finland; and
Division of Hematology, Department of Internal Medicine, University
Hospital, Leipzig, Germany.
Graft-versus-host disease in its acute (aGvHD) or
chronic form (cGvHD) remains the most important posttransplantation
factor influencing outcome after allogeneic hematopoietic stem cell
transplantation (HSCT). It increases transplantation-related mortality
(TRM) but reduces risk of relapse. The net effect of these 2 discordant effects determines survival. In view of current interests to exploit graft-versus-leukemia (GVL) effects, we analyzed 4174 HLA-identical sibling transplantations for chronic myeloid leukemia in first chronic
phase, depending on the presence or absence and severity of GvHD with a
landmark analysis. During the first 100 days, only aGvHD grades III and
IV had an impact on TRM. During the time period day 100 to 3 years
increasing severity of aGvHD is associated with increased TRM and
decreased relapse incidence (RI) with hazard ratios (HRs) for TRM as
follows: grade 0, HR = 1.0; grade I, HR = 1.52 (1.19-1.96); grade
II, HR = 2.48 (1.95-3.14); grade III, HR = 5.76 (4.44-7.48); grade
IV, HR = 14.7 (10.9-19.9) and likewise for RI: grade I versus
0, HR = 0.94 (0.76-1.16); grade II, HR = 0.60 (0.46-0.77); grade
III, HR = 0.48 (0.29-0.81); grade IV, HR = 0.14 (0.02-0.99). Beyond
3 years, TRM and RI are determined by cGvHD. Limited cGvHD reduces RI
to the same extent as extensive cGvHD but has no impact on TRM and,
hence, results in best survival with an HR = 0.48 (0.32-0.71). aGvHD
grade I has the highest likelihood of subsequent limited cGvHD, which
results in cumulative incidence estimates of survival at 10 years being
best for patients with initial aGvHD grade I: survival at 10 years
grade 0 = 59%, I = 63%, II = 56%, III = 26%,
IV = not applicable. These data clarify the role of GvHD in
posttransplantation outcome. Considerations for long-term outcome are
essential when short-term data of interventions on GvHD are analyzed.
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