title: CD34+ cell dose and establishment of full donor chimerism at day +100 are important factors for survival with reduced-intensity conditioning with fludarabine and melphalan before allogeneic hematopoietic SCT for hematologic malignancies.
abstract: The combination of fludarabine and melphalan as a reduced-intensity conditioning (RIC) regimen extends allogeneic hematopoietic SCT (HSCT) as a therapeutic option for elderly or frail patients with relapsed, refractory or other high-risk hematologic malignancies. Whether any modifiable factors exist that could improve survival before or immediately after HSCT is unknown. We reviewed the medical records of the first 50 patients at our institution to undergo fludarabine/melphalan RIC from September 2000 to September 2007 to determine factors associated with survival. A total of 25 (50%) patients had undergone prior HSCT and as such was a high-risk group of patients. On multivariate analysis, CD34(+) cell dose greater than 5.5 × 10(6) per kg (risk ratio (RR) 0.44, 95% CI 0.19-0.98, P=0.02) and full donor chimerism at day +100 (RR 0.17, 95% CI 0.06-0.64, P=0.002) remained independent prognostic factors. In our series, achievement of full donor chimerism at day +100 was associated with an approximately 70% 2-year survival, a favorable outcome in this high-risk group of patients. Although the infused CD34(+) cell dose is a modifiable variable, whether donor lymphocyte infusions or other immunologic interventions should be performed to promote the establishment of full chimerism early post transplant remains unknown.
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic Graduate School of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Holtan
authors.forename: W J
authors.initials: WJ
authors.lastname: Hogan
authors.forename: M A
authors.initials: MA
authors.lastname: Elliott
authors.forename: S M
authors.initials: SM
authors.lastname: Ansell
authors.forename: D J
authors.initials: DJ
authors.lastname: Inwards
authors.forename: L F
authors.initials: LF
authors.lastname: Porrata
authors.forename: P B
authors.initials: PB
authors.lastname: Johnston
authors.forename: I N
authors.initials: IN
authors.lastname: Micallef
authors.forename: M Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: D A
authors.initials: DA
authors.lastname: Gastineau
authors.forename: M R
authors.initials: MR
authors.lastname: Litzow
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D012189:Retrospective Studies; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan