title: Nonmyeloablative allogeneic stem cell transplantation in relapsed/refractory chronic lymphocytic leukemia: long-term follow-up, prognostic factors, and effect of human leukocyte histocompatibility antigen subtype on outcome.
abstract: BACKGROUND
  The role of nonmyeloablative allogeneic stem cell transplantation (NST) in the treatment of chronic lymphocytic leukemia (CLL) is not well established. The authors report on long-term experience with NST in relapsed/refractory CLL and define prognostic factors associated with outcome.
  
  
  METHODS
  The authors reviewed the outcome of 86 patients with relapsed/relapsed CLL enrolled in sequential NST protocols.
  
  
  RESULTS
  The median patient age was 58 years. Patients were heavily pretreated before transplantation, and 43 required immunomanipulation after NST for persistent or recurrent disease. Immunomanipulation included withdrawal of immunosuppression, rituximab, and step-wise donor lymphocyte infusions. Of 43 patients receiving immunomanipulation, 20 (47%) experienced a complete remission. Patients with human leukocyte antigen (HLA) genotype A1(+) /A2(-) /B44(-) were more likely to experience a complete remission (P = .0009), with rates of 9%, 36%, 50%, and 91%, respectively, for 0, 1, 2, and 3 of these HLA factors. This resulted in significant improvement in progression-free-survival rates of 68.2% at 5 years for patients with all 3 HLA factors. Overall, the estimated 5-year survival rate was 51%. In a multivariate model, a CD4 count of <100/mm(3) and a below normal serum immunoglobulin G level at study entry were associated with a short survival duration (P < .0001).
  
  
  CONCLUSIONS
  These results confirm the potential cure of relapsed/refractory CLL with NST and provide the first evidence that immunoglobulin G and CD4 levels are predictive of overall survival after NST in CLL and that human leukocyte antigen alleles predict response to immunomanipulation.
authors: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, USA. ikhouri@mdanderson.org
authors: Issa F
authors: IF
authors: Khouri
authors: Roland
authors: R
authors: Bassett
authors: Nancy
authors: N
authors: Poindexter
authors: Susan
authors: S
authors: O'Brien
authors: Carlos E
authors: CE
authors: Bueso-Ramos
authors: Yvonne
authors: Y
authors: Hsu
authors: Alessandra
authors: A
authors: Ferrajoli
authors: Michael J
authors: MJ
authors: Keating
authors: Richard
authors: R
authors: Champlin
authors: Marcelo
authors: M
authors: Fernandez-Vina
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D015395:Histocompatibility Antigens Class I / Q000097:blood / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007155:Immunologic Factors / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000401:mortality / Q000601:surgery* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D012307:Risk Factors; D000069283:Rituximab; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069283:Rituximab