title: Possibility of long-term remission in patients with advanced hematologic malignancies after reduced intensity conditioning regimen (RIC) and allogeneic stem cell transplantation.
abstract: High-dose chemotherapy and radiation used as a preparative regimen for allogeneic stem cell transplantation (SCT) produces a considerable morbidity and mortality. An alternative strategy, developed to reduce transplant-related toxicity and to induce graft versus malignancy effect in the presence of full hematopoietic engraftment, includes the application of RIC that provide sufficient immunosuppression. We studied the efficacy and toxicity of RIC followed by allogeneic SCT in elderly patients or with relative contraindications to conventional SCT. In all, 22 patients with hematologic malignancies and HLA-identical sibling donors were included in this study. All patients were either refractory to therapy or beyond first complete remission (CR). The majority of patients received fludarabine 120 mg/m(2)+thiotepa 10 mg/kg as conditioning regimen and cyclosporine as graft versus host disease (GVHD) prophylaxis. Organ toxicity was acceptable and all evaluable patients achieved engraftment. Three patients (15%) showed grade >II aGVHD; extensive chronic GVHD occurred in three out of 15 evaluable patients (20%). With median follow-up of 63.5 months, survival was 31%, disease-free survival (DFS) was 23%. All the durable responses occurred in patients who developed GVHD. Transplant related mortality (TRM) at 100 days was 27.3%, 67% of that caused by infections, while 6-year cumulative incidence of TRM was 38%. Our data show that RIC: (1). allows the engraftment of HLA-matched hematopoietic stem cells (2). provide durable responses in patients not eligible for conventional SCT exploiting the graft-versus-malignancy effect and (3). is loaded by an high rate of fatal infections.
authors.affiliation: Hematology, University Tor Vergata, St Eugenio Hospital, Rome, Italy. picardi.alessandra@aslrmc.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Picardi
authors.forename: Paolo de
authors.initials: Pd
authors.lastname: Fabritiis Pd
authors.forename: Laura
authors.initials: L
authors.lastname: Cudillo
authors.forename: Teresa
authors.initials: T
authors.lastname: Dentamaro
authors.forename: Luca
authors.initials: L
authors.lastname: Cupelli
authors.forename: Giovanna
authors.initials: G
authors.lastname: Ballatore
authors.forename: Adriano
authors.initials: A
authors.lastname: Venditti
authors.forename: Tommaso
authors.initials: T
authors.lastname: Caravita
authors.forename: Maria
authors.initials: M
authors.lastname: Cristina Cox
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Catalano
authors.forename: Sergio
authors.initials: S
authors.lastname: Amadori
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000209:etiology / Q000401:mortality; D012074:Remission Induction; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D016572:Cyclosporine; D014740:Vidarabine; C024352:fludarabine