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Blood, 15 July 2002, Vol. 100, No. 2, pp. 406-414
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Severity of chronic graft-versus-host disease: association with
treatment-related mortality and relapse
Stephanie J. Lee,
John P. Klein,
A. John Barrett,
Olle Ringden,
Joseph H. Antin,
Jean-Yves Cahn,
Matthew H. Carabasi,
Robert
Peter Gale,
Sergio Giralt,
Gregory A. Hale,
Osman Ilhan,
Philip L. McCarthy,
Gerard Socie,
Leo F. Verdonck,
Daniel J. Weisdorf, and
Mary M. Horowitz
From the Graft vs Host Disease Working Committee of the
International Bone Marrow Transplant Registry, Health Policy Institute,
Medical College of Wisconsin, Milwaukee; the Coordinating Center of the
National Marrow Donor Program, Minneapolis, MN; Dana-Farber Cancer
Center, Boston, MA; National Heart, Lung, and Blood Institute,
Bethesda, MD; Huddinge Hospital, Huddinge, Sweden; Hopital Jean Minjoz,
Besancon, France; University of Southern California/Norris Cancer
Center, Los Angeles; Center for Advanced Studies in Leukemia, Los
Angeles, CA; MD Anderson Cancer Center, Houston, TX; St Jude
Children's Research Hospital, Memphis, TN; Ibni Sina Hospital, Ankara,
Turkey; Roswell Park Cancer Institute, Buffalo, NY; Hôpital Saint
Louis, Paris, France; University Hospital Utrecht, The Netherlands; and
Fairview University Medical Center, Minneapolis, MN.
Chronic graft-versus-host disease (cGVHD) is the
leading cause of late treatment-related deaths among recipients of
allogeneic bone marrow and blood transplants. However, cGVHD is also
associated with fewer relapses. We sought to determine whether severity
of cGVHD predicts the magnitude of these effects. One impediment to
such an analysis is the current limited/extensive grading system for
cGVHD because this classification was designed to identify patients
likely to benefit from systemic immune suppression and does not capture
the severity of multiorgan involvement. We, therefore, first developed
a grading system predictive for survival by using data from 1827 HLA-matched sibling allotransplant recipients reported to the
International Bone Marrow Transplant Registry (IBMTR). We found
Karnofsky performance score, diarrhea, weight loss, and cutaneous and
oral involvement to be independent prognostic variables, from which we
generated a grading scheme. We tested this scheme, the
limited/extensive classification system, and a classification based on
clinical impression of overall cGVHD severity (mild/moderate/severe) in
parallel analyses of 1092 HLA-matched sibling transplant recipients from the IBMTR and 553 recipients of unrelated donor marrow from the
National Marrow Donor Program. Presence of cGVHD was associated with
fewer relapses (relative risk [RR], 0.5-0.6) but more
treatment-related mortality (RR, 1.8-2.8) in the 3 analyses. No grading
scheme correlated cGVHD severity with relapse rates, but all schemes
predicted treatment-related mortality. Survival and disease-free
survival of the most favorable cGVHD group in each scheme were similar,
or better, than those of patients without cGVHD; these patients may not
need aggressive or extended immune suppression.
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