title: Risk factors for moderate-to-severe chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
abstract: Among 810 consecutive hematopoietic stem cell transplantation (HSCT) patients, 679 survived more than 3 months and were evaluated for chronic GVHD. The aim of this study was to find predisposing factors increasing the risk of development of moderate-to-severe chronic GVHD. Many of the donors were HLA-identical siblings or related (n = 435), 185 were HLA-matched unrelated, and 59 were mismatched related or unrelated donors. Most of the patients had a hematological malignancy (n = 568), but 111 patients with a nonmalignant disease were included. Two hundred twenty-three patients (33%) developed mild, 41 (6%) moderate, and 15 (2.2%) severe chronic GVHD. The 5-year probability of development of moderate-to-severe chronic GVHD was 10%. We analyzed 30 potential risk factors for chronic GVHD. In the multivariate analysis, acute GVHD) grades II to IV (relative hazard [RH], 2.30; 95% CI, 1.29-4.10; P = .005), CML diagnosis (RH, 2.37; CI, 1.38-4.08; P = .002) and transplantation from an immunized female donor to a male recipient (RH, 2.16; CI, 1.14-4.11; P = .02) were independent risk factors for moderate-to-severe chronic GVHD. Recipient age also was significant (RH, 2.42; CI, 1.23-4.77; P = .01) if CML was not included in the analysis. In patients with no risk factors, the 5-year probability of development of moderate-to-severe chronic GVHD was 5%. In patients with 1 risk factor, the probability was 13%; 2 risk factors, 23%; and 3 risk factors, 45%. Among patients who developed chronic GVHD (n = 279), acute GVHD grades II to IV (RH, 2.18; CI, 1.23-3.86; P < .01) was the only predictive factor for moderate-to-severe chronic GVHD versus mild disease. Patients with previous acute GVHD grades II to IV may benefit from more aggressive initial treatment. This possibility would have to be examined in clinical trials.
authors.affiliation: Centre for Allogeneic Stem Cell Transplantation, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden. Mats.Remberger@impi.ki.se
authors.forename: Mats
authors.initials: M
authors.lastname: Remberger
authors.forename: Gunilla
authors.initials: G
authors.lastname: Kumlien
authors.forename: Johan
authors.initials: J
authors.lastname: Aschan
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Barkholt
authors.forename: Patrik
authors.initials: P
authors.lastname: Hentschke
authors.forename: Per
authors.initials: P
authors.lastname: Ljungman
authors.forename: Jonas
authors.initials: J
authors.lastname: Mattsson
authors.forename: Johan
authors.initials: J
authors.lastname: Svennilson
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003586:Cytomegalovirus Infections / Q000453:epidemiology; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000401:mortality / Q000628:therapy; D011336:Probability; D012189:Retrospective Studies; D012307:Risk Factors; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D016019:Survival Analysis; D014184:Transplantation, Homologous / Q000009:adverse effects