Predictors of improved progression-free survival after nonmyeloablative allogeneic stem cell transplantation for advanced chronic lymphocytic leukemia.

Abstract

Although chronic lymphocytic leukemia (CLL) remains an incurable disease with standard chemotherapy, the appropriate role and timing of transplantation are unclear. In this analysis, we report the outcomes of 46 patients with advanced CLL who underwent nonmyeloablative stem cell transplantation (NST) from HLA-matched unrelated (67%) or related (33%) donors. Fludarabine (30 mg/m2 x 4) and low-dose intravenous busulfan (0.8 mg/kg/day x 4) were used for conditioning. The 2-year overall survival (OS) and progression-free survival (PFS) rates in this refractory patient population were 54% and 34%, respectively, with a median follow-up of 20 months. The primary cause of treatment failure was relapse, with a 2-year cumulative incidence of 48%. High hematopoietic donor chimerism > or = 75% at day +30 was a significant predictor of 2-year PFS (47% vs 11%; P = .03). In multivariate analysis, chemotherapy-refractory disease at transplantation was associated with a 3.2-fold risk of progression (P = .01) and a 4.6-fold risk of death (P = .02). Increasing number of previous therapies and increasing bone marrow involvement were also associated with decreased PFS and OS. These results suggest that NST using fludarabine and low-dose intravenous busulfan is a reasonable treatment option for patients with advanced CLL, but that NST earlier in the disease course will likely be needed to achieve long-term disease control in a high proportion of patients.

• Authors: Jennifer R Brown, Haesook T Kim, Shuli Li, Katherine Stephans, David C Fisher, Corey Cutler, Vincent Ho, Stephanie J Lee, Edgar L Milford, Jerome Ritz, Joseph H Antin, Robert J Soiffer, John G Gribben, Edwin P Alyea
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 12 Issue 10 Pg. 1056-64 (Oct 2006) ISSN: 1083-8791 [Print] United States
• PMID: 17084369 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Vidarabine
• Busulfan
• fludarabine

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Busulfan (administration & dosage)
• Combined Modality Therapy
• Disease-Free Survival
• Female
• Graft Survival
• Graft vs Host Disease (epidemiology, etiology, prevention & control)
• Graft vs Leukemia Effect
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Kaplan-Meier Estimate
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, mortality, surgery)
• Male
• Middle Aged
• Prognosis
• Retrospective Studies
• Risk
• Risk Factors
• Survival Rate
• Transplantation Conditioning (methods)
• Transplantation, Homologous
• Treatment Outcome
• Vidarabine (administration & dosage, analogs & derivatives)