National Institutes of Health Chronic Graft-versus-Host
Disease Staging in Severely Affected Patients: Organ
and Global Scoring Correlate with Established Indicators
of Disease Severity and Prognosis
Kristin Baird1,*, Seth M. Steinberg2, Lana Grkovic3,4, Drazen Pulanic3,4,14,
Edward W. Cowen5, Sandra A. Mitchell6, Kirsten M. Williams3,7,
Manuel B. Datiles8, Rachel Bishop8, Carol W. Bassim9, Jacqueline W. Mays9,
Dean Edwards9, Kristen Cole3, Daniele N. Avila3, Tiffany Taylor3,
Amanda Urban3, Galen O. Joe10, Leora E. Comis10, Ann Berger11,
Pamela Stratton12, Dan Zhang3, James H. Shelhamer13,
Juan C. Gea-Banacloche3, Claude Sportes3, Daniel H. Fowler3,
Ronald E. Gress3, Steven Z. Pavletic3
1Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland
2Biostatistics and Data Management Section, National Cancer Institute, Center for Cancer Research, National Institutes of Health,
3Experimental Immunology and Transplantation Branch, National Cancer Institute, Center for Cancer Research, National Institutes
of Health, Bethesda, Maryland
4Division of Hematology, Department of Internal Medicine, Clinical Hospital Center Zagreb, Zagreb, Croatia
5Dermatology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland
6Division of Cancer Control and Population Sciences, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland
7The Center for Cancer and Blood Disorders, Blood and Marrow Transplantation, Children’s National Medical Center, Washington, DC
8National Eye Institute, National Institutes of Health, Bethesda, Maryland
9National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland
10Rehabilitation Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland
11Department of Pain and Palliative Care, Clinical Center, National Institutes of Health, Bethesda, Maryland
12Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Bethesda, Maryland
13Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland
14Faculty of Medicine Osijek, J.J. Strossmayer University of Osijek, Osijek, Croatia
Received 31 October 2012
Accepted 16 January 2013
National Institutes of Health
Stem cell transplant
a b s t r a c t
Between 2004 and 2010, 189 adult patients were enrolled on the National Cancer Institute’s cross-sectional
chronic graft-versus-host disease (cGVHD) natural history study. Patients were evaluated by multiple disease
scales and outcome measures, including the 2005 National Institutes of Health (NIH) Consensus Project
cGVHD severity scores. The purpose of this study was to assess the validity of the NIH scoring variables as
determinants of disease severity in severely affected patients in efforts to standardize clinician evaluation and
staging of cGVHD. Out of 189 patients enrolled,125 met the criteria for severe cGVHD on the NIH global score,
62 of whom had moderate disease, with a median of 4 (range, 1-8) involved organs. Clinician-assigned
average NIH organ score and the corresponding organ scores assigned by subspecialists were highly corre-
lated (r ¼ 0.64). NIH global severity scores showed significant associations with nearly all functional and
quality of life outcome measures, including the Lee Symptom Scale, Short Form-36 Physical Component Scale,
2-minute walk, grip strength, range of motion, and Human Activity Profile. Joint/fascia, skin, and lung
involvement affected function and quality of life most significantly and showed the greatest correlation with
outcome measures. The final Cox model with factors jointly predictive for survival included the time from
cGVHD diagnosis (>49 versus ?49 months, hazard ratio [HR] ¼ 0.23; P ¼.0011), absolute eosinophil count at
the time of NIH evaluation (0-0.5 versus >0.5 cells/mL, HR ¼ 3.95; P ¼ .0006), and NIH lung score (3 versus
0-2, HR ¼ 11.02; P <.0001). These results demonstrate that NIH organs and global severity scores are reliable
measures of cGVHD disease burden. The strong association with subspecialist evaluation suggests that NIH
organ and global severity scores are appropriate for clinical and research assessments, and may serve as
a surrogate for more complex subspecialist examinations. In this population of severely affected patients, NIH
lung score is the strongest predictor of poor overall survival, both alone and after adjustment for other
Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation.
Allogeneic hematopoietic stem cell transplantation (allo-
HSCT) is curative for many diseases. However, roughly 50% of
allo-HSCT recipients develop chronic graft-versus-host-
disease (cGVHD), a serious and potentially life-threatening
Financial disclosure: See Acknowledgments on page 638.
* Correspondence and reprint requests: Kristin Baird, M.D., Pediatric
Oncology Branch, National Cancer Institute, National Institutes of Health,
Building 10, Room 1W-3940, Bethesda, Maryland 20892.
E-mail address: firstname.lastname@example.org (K. Baird).
1083-8791/$ e see front matter Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation.
Biol Blood Marrow Transplant 19 (2013) 632e639
American Society for Blood
and Marrow Transplantation
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