title: Impact of lymphocyte and monocyte recovery on the outcomes of allogeneic hematopoietic SCT with fludarabine and melphalan conditioning.
abstract: We have recently shown that lymphocyte and monocyte recovery by day +100 are associated with survival post myeloablative allogeneic hematopoietic transplant for acute leukemia. We hypothesized that lymphocyte and monocyte recovery would have a similar impact on survival in the reduced intensity setting. To test this hypothesis, we analyzed clinical data from 118 consecutive fludarabine/melphalan-conditioned patients by correlating peripheral blood absolute lymphocyte counts and monocyte counts (ALC and AMC, respectively) at days +15, +30, +60 and +100 with the outcomes. Multivariate analysis revealed that day +100 AMC (risk ratio (RR) 0.22, 95% confidence interval (CI) 0.07-0.73, P=0.01) and mild chronic GVHD (RR 0.09, 95% CI 0.005-0.43, P=0.008) were independently associated with survival. To explore whether the patterns of lymphocyte and monocyte recovery had a prognostic value, we performed unsupervised hierarchical clustering on the studied hematopoietic parameters and identified three patient clusters, A-C. Patient clusters A and B both had improved OS compared with cluster C (77.8 months vs not reached vs 22.3 months, respectively, P<0.001). No patient in cluster C had a day +100 AMC >300. Both severe acute GVHD and relapse occurred more frequently in cluster C. Our data suggest that patients with low AMC by day +100 post fludarabine/melphalan-conditioned allogeneic hematopoietic SCT may be at risk for poor outcomes.
authors.affiliation: Department of Medicine, Division of Hematology, Mayo Clinic Graduate School of Medicine, Rochester, MN, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: DeCook
authors.forename: M
authors.initials: M
authors.lastname: Thoma
authors.forename: T
authors.initials: T
authors.lastname: Huneke
authors.forename: N D
authors.initials: ND
authors.lastname: Johnson
authors.forename: R A
authors.initials: RA
authors.lastname: Wiegand
authors.forename: M M
authors.initials: MM
authors.lastname: Patnaik
authors.forename: M R
authors.initials: MR
authors.lastname: Litzow
authors.forename: W J
authors.initials: WJ
authors.lastname: Hogan
authors.forename: L F
authors.initials: LF
authors.lastname: Porrata
authors.forename: S G
authors.initials: SG
authors.lastname: Holtan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology; D019337:Hematologic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000276:immunology / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan