title: Low tumor burden is associated with early B-cell reconstitution and is a predictor of favorable outcome after non-myeloablative stem cell transplant for chronic lymphocytic leukemia.
abstract: Abstract Reconstitution, engraftment kinetics and tumor cell clearance were analyzed after reduced intensity conditioning hematopoietic cell transplant (RIC-HCT) in patients with chronic lymphocytic leukemia (CLL). Patients were transplanted from unrelated (n = 40) or related (n = 10) donors after fludarabine and 2 Gy total body irradiation followed by cyclosporine and mycophenolate mofetil. The vast majority of patients (96%) engrafted with absolute neutrophil count (ANC) > 0.5 × 10(9)/L at day + 22. CLL cells decreased (median 2%, range 0-69%) within 28 days, but disappeared by day + 180 after HCT. Donor T-cell chimerism increased to > 95% at day 56 and donor B-cell chimerism to 94% at day + 360. Overall survival was 51 ± 8%, incidence of progression 37 ± 7% and non-relapse related mortality (NRM) 30 ± 7% at 4 years. The most common causes of NRM were graft-versus-host disease (GvHD) (14%) and sepsis (6%). Disease status at HCT was significantly associated with early B-cell reconstitution (p = 0.04) and with increased risk of relapse/progression in univariate and multivariate analysis (p = 0.022). Tumor cells were undetectable by day + 180, although B-cell reconstitution did not occur until 1.5 years after RIC-HCT. The best predictors for progression-free survival (PFS) and overall survival (OS) were complete response (CR) or first partial response (PR1) and the absence of bulky disease at transplant, respectively.
authors: Department of Hematology/Oncology, University of Leipzig , Leipzig , Germany.
authors: Karin
authors: K
authors: Hebenstreit
authors: Simona
authors: S
authors: Iacobelli
authors: Sabine
authors: S
authors: Leiblein
authors: Ann-Kathrin
authors: AK
authors: Eisfeld
authors: Christian
authors: C
authors: Pfrepper
authors: Simone
authors: S
authors: Heyn
authors: Vladan
authors: V
authors: Vucinic
authors: Georg-Nikolaus
authors: GN
authors: Franke
authors: Rainer
authors: R
authors: Krahl
authors: Stephan
authors: S
authors: Fricke
authors: Cornelia
authors: C
authors: Becker
authors: Wolfram
authors: W
authors: Pönisch
authors: Gerhard
authors: G
authors: Behre
authors: Dietger
authors: D
authors: Niederwieser
authors: Thoralf
authors: T
authors: Lange
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes; D002423:Cause of Death; D018450:Disease Progression; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D007958:Leukocyte Count; D038041:Lymphopoiesis; D008297:Male; D008875:Middle Aged; D009026:Mortality; D011379:Prognosis; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D047368:Tumor Burden
keywords: Hematopoietic cell transplant; allogeneic HCT; chronic lymphocytic leukemia; related donors; unrelated donors