title: GVHD prophylaxis with sirolimus-tacrolimus may overcome the deleterious effect on survival of HLA mismatch after reduced-intensity conditioning allo-SCT.
abstract: Large studies, mostly based on series of patients receiving CSA/tacrolimus (TKR) plus MTX as immunoprophylaxis, have demonstrated a deleterious effect on survival of the presence of a single mismatch out of eight loci after allogeneic hematopoietic SCT (alloHSCT). We retrospectively analyzed a series of 159 adult patients who received sirolimus(SRL)/TKR prophylaxis after alloHSCT. We compared overall outcomes according to HLA compatibility in A, B, C and DRB1 loci at the allele level: 7/8 (n=20) vs 8/8 (n=139). Donor type was unrelated in 95% vs 70% among 7/8 vs 8/8 pairs, respectively (P=0.01). No significant differences were observed in 3-year OS (68 vs 62%), 3-year EFS (53 vs 49%) and 1-year non-relapse mortality (9 vs 13%). Cumulative incidence of grades II-IV acute GVHD (aGVHD) was significantly higher in 7/8 alloHSCT (68% vs 42%, P<0.001) but no significant differences were found for III-IV aGVHD (4.5% vs 11%), overall (35% vs 53%) and extensive (20% vs 35%) chronic GHVD in 7/8 vs 8/8 subgroups, respectively. In summary, the present study indicates favorable outcomes after alloHSCT using the combination of SRL/TKR combination as GVHD prophylaxis with OS in the range of 55-70%, and non-significant differences in overall outcomes, irrespective of the presence of any mismatches at obligatory loci.
authors.affiliation: Servicio de Hematología, Hospital Universitario / Instituto de Biomedicina (IBIS)/CSIC, Seville, Spain.
authors.forename: R
authors.identifier: 0000000303757570
authors.initials: R
authors.lastname: Parody
authors.affiliation: Hospital Clínico de Salamanca, Salamanca, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Lopez-Corral
authors.affiliation: Hospital Clínico de Salamanca, Salamanca, Spain.
authors.forename: O L
authors.initials: OL
authors.lastname: Godino
authors.affiliation: Hospital Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: I G
authors.initials: IG
authors.lastname: Cadenas
authors.affiliation: Hospital Clínico de Valencia, Valencia, Spain.
authors.forename: A P
authors.initials: AP
authors.lastname: Martinez
authors.affiliation: Hospital Clínico de Salamanca, Salamanca, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Vazquez
authors.affiliation: Hospital Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Martino
authors.affiliation: Hospital Clinic de Barcelona, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Martinez
authors.affiliation: Hospital Clínico de Valencia, Valencia, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Solano
authors.affiliation: Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Barba
authors.affiliation: Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Valcarcel
authors.affiliation: Servicio de Hematología, Hospital Universitario / Instituto de Biomedicina (IBIS)/CSIC, Seville, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Caballero-Velazquez
authors.affiliation: Servicio de Hematología, Hospital Universitario / Instituto de Biomedicina (IBIS)/CSIC, Seville, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Marquez-Malaver
authors.affiliation: Hospital Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Sierra
authors.affiliation: Hospital Clínico de Salamanca, Salamanca, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Caballero
authors.affiliation: Servicio de Hematología, Hospital Universitario / Instituto de Biomedicina (IBIS)/CSIC, Seville, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Perez-Simón
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D006680:HLA Antigens; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage*; D033581:Stem Cell Transplantation; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage*; D019172:Transplantation Conditioning
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus