title: Outcome of Second Allogeneic Hematopoietic Cell Transplantation after Relapse of Myeloid Malignancies following Allogeneic Hematopoietic Cell Transplantation: A Retrospective Cohort on Behalf of the Grupo Español de Trasplante Hematopoyetico.
abstract: Allogeneic stem cell transplantation (allo-HCT) represents the most effective immunotherapy for acute myeloid leukemia (AML) and myeloid malignancies. However, disease relapse remains the most common cause of treatment failure. By performing a second allo-HCT, durable remission can be achieved in some patients. However, a second allo-HCT is of no benefit for the majority of patients, so this approach requires further understanding. We present a retrospective cohort of 116 patients diagnosed with AML, myelodysplastic syndromes, and myeloproliferative disorders who consecutively underwent a second allo-HCT for disease relapse. The median age was 38 years (range, 4 to 69 years). Sixty-three patients were alive at last follow-up. The median follow-up of the whole cohort was 193 days (range, 2 to 6724 days) and the median follow-up of survivors was 1628 days (range, 52 to 5518 days). Overall survival (OS) at 5 years was 32% (SE ± 4.7%). Multivariate analysis identified active disease status (P < .001) and second allo-HCT < 430 days (the median of the time to second transplantation) after the first transplantation (P < .001) as factors for poor prognosis, whereas the use of an HLA-identical sibling donor for the second allo-HCT was identified as a good prognostic factor (P < .05) for OS. The use of myeloablative conditioning (P = .01), active disease (P = .02), and a donor other than an HLA-identical sibling (others versus HLA-identical siblings) (P = .009) were factors statistically significant for nonrelapse mortality in multivariate analysis. Time to second transplantation was statistically significant (P = .001) in the relapse multivariate analysis, whereas multivariate analysis identified active disease status (P < .001) and time to second transplantation (P < .001) as poor prognosis factors for disease-free survival. This study confirms active disease and early relapse as dismal prognostic factors for a second allo-HCT. Using a different donor at second allo-HCT did not appear to change outcome, but using an HLA-identical sibling donor for a second transplantation appears to be associated with better survival. Further studies are warranted.
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain. Electronic address: g.ortivh@gmail.com.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Orti
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Sanz
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: Arancha
authors.initials: A
authors.lastname: Bermudez
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Caballero
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Martinez
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sierra
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: José R
authors.initials: JR
authors.lastname: Cabrera Marin
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: Ildefonso
authors.initials: I
authors.lastname: Espigado
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Solano
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: Christelle
authors.initials: C
authors.lastname: Ferrà
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: García-Noblejas
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Jimenez
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Sampol
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: Lucrecia
authors.initials: L
authors.lastname: Yañez
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: Valentin
authors.initials: V
authors.lastname: García-Gutiérrez
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: Maria Jesus
authors.initials: MJ
authors.lastname: Pascual
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Jurado
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Moraleda
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Valcarcel
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain; REDMO, Josep Carreras Foundation and Leukaemia Research Institute, Barcelona, Spain.
authors.forename: Enric
authors.initials: E
authors.lastname: Carreras
authors.affiliation: Grupo Español de Trasplante Hematopoyetico, GETH, Spain.
authors.forename: Rafael F
authors.initials: RF
authors.lastname: Duarte
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000401:mortality* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012189:Retrospective Studies; D035781:Siblings; D015996:Survival Rate; D014019:Tissue Donors
keywords: Acute myeloid leukemia; Myeloid malignancies; Relapse; Second allogeneic stem cell transplantation