TY - JOUR
T1 - Nonmyeloablative allogeneic stem cell transplantation in relapsed/refractory chronic lymphocytic leukemia
T2 - Long-term follow-up, prognostic factors, and effect of human leukocyte histocompatibility antigen subtype on outcome
AU - Khouri, Issa F.
AU - Bassett, Roland
AU - Poindexter, Nancy
AU - O'Brien, Susan
AU - Bueso-Ramos, Carlos E.
AU - Hsu, Yvonne
AU - Ferrajoli, Alessandra
AU - Keating, Michael J.
AU - Champlin, Richard
AU - Fernandez-Vina, Marcelo
PY - 2011/10/15
Y1 - 2011/10/15
N2 - 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/mm3 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. Cancer 2011;. © 2011 American Cancer Society. The authors found that immunoglobulin G and CD4 levels are predictive of survival after nonmyeloablative allogeneic transplantation for chronic lymphocytic leukemia and that human leukocyte antigen alleles predict response to immunomanipulation.
AB - 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/mm3 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. Cancer 2011;. © 2011 American Cancer Society. The authors found that immunoglobulin G and CD4 levels are predictive of survival after nonmyeloablative allogeneic transplantation for chronic lymphocytic leukemia and that human leukocyte antigen alleles predict response to immunomanipulation.
KW - chronic lymphocytic leukemia
KW - human leukocyte histocompatibility antigen
KW - nonmyeloablative allogeneic transplantation
KW - stem cell transplantation
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U2 - 10.1002/cncr.26091
DO - 10.1002/cncr.26091
M3 - Article
C2 - 21455998
AN - SCOPUS:80053901737
SN - 0008-543X
VL - 117
SP - 4679
EP - 4688
JO - Cancer
JF - Cancer
IS - 20
ER -