title: Allogeneic hemopoietic stem cell transplantation for patients with high risk acute lymphoblastic leukemia: favorable impact of chronic graft-versus-host disease on survival and relapse.
abstract: OBJECTIVE
  The best post-remission therapy for patients with acute lymphoblastic leukemia (ALL) is controversial, and hemopoietic stem cell transplantation (HSCT) is one therapeutic option. The goal of this study is to describe long term results of HSCT in high risk ALL patients.
  
  
  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 least one adverse prognostic factor for high risk ALL at diagnosis; one third (33%) were in first remission (CR1) and the majority (85%) received 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 leukemia (46%) or transplant related complications (54%). The actuarial 10 year survival is 53%, 38% and 20%, for patients in CR1, CR2 or advanced phase, respectively. The actuarial survival of patients with (n = 24) of without (n = 46) cytogenetic abnormalities, grafted in CR1/CR2 was respectively 45% and 48% (p = 0.5). The year of transplant had a significant 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 relapse (p = 0.0019).
  
  
  CONCLUSIONS
  This study confirms that long term survival can be achieved with HSCT in ALL patients, even those with cytogenetic abnormalities. Transplant mortality has been significantly reduced in recent years, whereas leukemia rate relapse has remained unchanged: the latter is influenced by the occurrence of chronic GvHD. Immune intervention post-HSCT may be considered to address this problem.
authors.affiliation: Divisione Ematologia Il, Ospedale San Martino, Genoa, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Zikos
authors.forename: M T
authors.initials: MT
authors.lastname: Van Lint
authors.forename: T
authors.initials: T
authors.lastname: Lamparelli
authors.forename: F
authors.initials: F
authors.lastname: Gualandi
authors.forename: D
authors.initials: D
authors.lastname: Occhini
authors.forename: S
authors.initials: S
authors.lastname: Bregante
authors.forename: G
authors.initials: G
authors.lastname: Berisso
authors.forename: N
authors.initials: N
authors.lastname: Mordini
authors.forename: M
authors.initials: M
authors.lastname: Incagliato
authors.forename: G
authors.initials: G
authors.lastname: Fugazza
authors.forename: M
authors.initials: M
authors.lastname: Sessarego
authors.forename: A
authors.initials: A
authors.lastname: Bacigalupo
mesh_terms: D000328:Adult; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D012008:Recurrence; D016019:Survival Analysis; D014184:Transplantation, Homologous