ALLOGENEIC HEMATOPOIETIC STEM-CELL TRANSPLANTATION FOR PATIENTS WITH HIGH-RISK ACUTE LYMPHOBLASTIC-LEUKEMIA - FAVORABLE IMPACT OF CHRONIC GRAFT-VERSUS-HOST DISEASE ON SURVIVAL AND RELAPSE

Background and Objective. The best post-remission therapy for patients with acute lymphoblastic leukemia (ALL) is controversial, and hemopoi etic stem cell transplantation (HSCT) is one therapeutic option. The g oal of this study is to describe long term results of HSCT in high ris k ALL patients. Design and Methods. Between 1978 and 1996, 170 patient with ALL and a median age of 22 years (1-49), underwent an allogeneic HSCT from HLA-identical siblings (n=149), family mismatched donors (n =18) or unrelated HLA matched donors (n=3); 92% of patients had at lea st one adverse prognostic factor for high risk ALL at diagnosis; one t hird (33%) were in first remission (CR1) and the majority (85%) receiv ed an unmanipulated HSCT with cyclosporin-methotrexate prophylaxis of graft-versus-host disease (GVHD). Results. After a median follow-up of over 6 years, 59 patients are alive and 111 patients have died of leu kemia (46%) or transplant related complications (54%). The actuarial 1 0 year survival is 53%, 38% and 20%, for patients in CR1, CR2 or advan ced phase, respectively. The actuarial survival of patients with (n=24 ) or without (n=46) cytogenetic abnormalities, grafted in CR1/CR2 was respectively 45% and 48% (p=0.5). The year of transplant had a signifi cant impact in multivariate analysis on transplant related mortality ( TRM) (p=0.0009) but not on relapse (p=0.3). Chronic GvHD was the most important favorable prognostic factor for survival (p=0.0014) and rela pse (p=0.0019). Interpretation and Conclusions. This study confirms th at long term survival can be achieved with HSCT In ALL patients, even those with cytogenetic abnormalities. Transplant mortality has been si gnificantly reduced in recent years, whereas leukemia rate relapse has remained unchanged: the latter is influenced by the occurrence of chr onic GvHD. Immune intervention post-HSCT may be considered to address this problem. (C) 1998, Ferrata Storti Foundation.