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.

Serious graft-versus-host disease after hematopoietic cell transplantation following nonmyeloablative conditioning

“…In this study, we also observed that manifestations typical of acute GVHD began after day 100 in some recipients of nonmyeloablative HCT. 7 Although previous studies have identified risk factors for acute and chronic GVHD after myeloablative HCT, [8][9][10][11][12][13][14][15] analysis of serious consequences of GVHD have not been reported after either myeloablative or nonmyeloablative HCT. The present study focused on serious consequences of either acute or chronic GVHD, using pre-specified criteria to identify fatal or disabling outcomes related to GVHD after nonmyelablative HCT.…”

Risk factors for fatal infectious complications developing late after allogeneic stem cell transplantation

“…Acute GVHD was graded on a scale of 0 (absent) to IV (severe), according to previously published criteria. 12,13 The severity of chronic GVHD was defined as mild, moderate or severe, according to previously published criteria 14 and was classified by the treating physician.…”

Risk-factor analysis for predicting progressive- or quiescent-type chronic graft-versus-host disease in a patient cohort with a history of acute graft-versus-host disease after allogeneic stem cell transplantation

“…16 In addition, the contribution of primary treatment failure to the development of subsequent cGVHD was also found to be substantial, implying that patients with severe aGVHD may benefit from more aggressive treatment without delay.…”