Chronic graft-versus-host-disease (cGVHD) is a major cause of late morbidity and mortality after allogeneic hematopoietic cell transplantation (alloHCT). However, it may be accompanied by graft-versus-leukemia (GVL) reaction contributing to decreased risk of relapse. The aim of this study was to evaluate the influence of cGVHD on outcome of adult acute lymphoblastic leukemia (ALL) patients treated with alloHCT. Fifty-five ALL patients, aged 24 (18-54) years, who survived without progression at least 100 days after alloHCT from HLA-identical sibling (n = 40, 73%) or an unrelated volunteer (n = 15, 27%) were included in the analysis. 24 patients 44% were given alloHCT in first complete remission, whereas the remaining 31 patients (44%) were in more advanced disease. The probability of overall survival (OS) and disease-free survival (DFS) equaled 57% and 48% at 8 years, respectively. Cumulative incidence of relapse and non-relapse mortality (NRM) was 39% and 13%, respectively. OS rate equaled 51% for patients without cGVHD, 94% for patients with limited cGVHD, and 38% for those with extensive cGVHD. In the respective subgroups relapse incidence was 60%, 9% and 0%, whereas the incidence of NRM equaled 3%, 6% and 62%. In multivariate analysis the lack of cGVHD was the most important factor associated with increased risk of relapse and deteriorated DFS. Extensive, but not limited cGVHD was associated with increased risk of NMR. Our findings confirm that in adults with ALL, cGVHD is accompanied by a strong GVL reaction. Induction of limited cGVHD may constitute the most effective prophylaxis of relapse in this group of patients.