Allogeneic Hematopoietic Cell Transplantation for Chronic Lymphocytic Leukemia (CLL) with 17p Deletion: A Retrospective EBMT Analysis.

Purpose: Patients with advanced CLL and 17p deletion have a very poor prognosis even after intensive chemotherapy. While allogeneic hematopoietic cell transplantation (HCT) has the potential to cure patients with advanced CLL it is not known whether this holds true for patients with 17p deletion.

Patients and Methods: Patients with 17p- CLL who had received HCT were identified by an EBMT-based survey. Baseline data were downloaded from the EBMT database. Additional information on the course of the disease, the cytogenetic diagnosis and last follow up was collected by a questionnaire. Data were analysed as of February 2007.

Results: 56 patients were identified. Twelve patients with autologous HCT, haplo-identical donors or the detection of 17p- after HCT were excluded from further analysis. 44 patients had received an allogeneic HCT between March 1995 and July 2006 from a matched related donor (n=27) or unrelated volunteer donor (n=17). The median age at HCT was 54 years (range, 35 to 64 years). Until HCT the maximum stage had been Binet A or B in 37% of patients and Binet C in 61% of patients. The diagnosis of deletion 17p- was made by FISH in 82% and by conventional banding in 18% of patients. The median interval between first diagnosis and detection of 17p- was 2.3 years (range, 1 to 11 years) and the median interval between detection of 17p- and HCT was 0.5 years (range, 0 to 3 years). Patients had received a median of 3 chemotherapy regimens (range, 2 to 7 lines), including fludarabine in 93% of patients and alemtuzumab in 41% of patients. At HCT, 53% of patients were in remission while 47% of patients were in stable or progressive disease. Reduced intensity conditioning was applied in 89% of patients. Peripheral blood stem cells were transplanted in 93% of the patients. GVHD prophylaxis was performed heterogeneously. One patient experienced primary graft failure. Acute GVHD grades II to IV occurred in 44% of patients and extensive chronic GVHD in 46% of patients. After a median follow-up of 23 months (range, 2 to 90 months) of 26 patients who are alive, 18 were in complete remission, 4 in partial remission and 4 patients had progressive disease at last follow up. 4-year overall survival and progression-free survival was 48% (95% CI, 28% to 68%) and 37% (95% CI, 18% to 56%). The cumulative incidences of relapse and non-relapse mortality at 4 years were 36% and 27%. No late-relapse occurred in five patients with a follow-up of more than 4 years.

Conclusion: Allogeneic HCT has the potential to induce long-term disease-free survival in selected patients with advanced 17p- CLL. Given the otherwise very dismal outcome of this disease, prospective studies on allogeneic HCT earlier in the course of 17p- CLL seem warranted.