Five-year follow-up of patients with advanced chronic lymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning

Abstract

Purpose: We reported encouraging early results of allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning in 64 patients who had advanced chronic lymphocytic leukemia (CLL). Here, we have extended the follow-up to a median of 5 years and have included data on an additional 18 patients.

Patients and methods: Eighty-two patients, age 42 to 72 years, who had fludarabine-refractory CLL were conditioned with 2 Gy total-body irradiation alone or combined with fludarabine followed by HCT from related (n = 52) or unrelated (n = 30) donors.

Results: Complete remission (CR) and partial remission were achieved in 55% and 15% of patients, respectively. Higher CR rates were noted after unrelated HCT (67% v 48%). The 5-year incidences of nonrelapse mortality (NRM), progression/relapse, overall survival, and progression-free survival were 23%, 38%, 50%, and 39%, respectively. Among 25 patients initially reported in CR, 8% relapsed and 8% died as a result of NRM, whereas 84% have remained alive and in CR. Among 14 responding patients who were tested and who had molecular eradication of their disease, two died as a result of NRM, two relapsed, and 10 have remained negative. At 5 years, 76% of living patients were entirely well, whereas 24% continued to receive immunosuppression for chronic graft-versus-host disease; the median performance status in each group was 100% and 90%, respectively. Lymphadenopathy > or = 5 cm, but not cytogenetic abnormalities at HCT, predicted relapse. In a risk-stratification model, patients who had lymphadenopathy less than 5 cm and no comorbidities had a 5-year OS of 71%.

Conclusion: Nonmyeloablative HCT resulted in a median survival of 5 years for patients who had fludarabine-refractory CLL with sustained remissions and in the continued resolution of chronic graft-versus-host disease in surviving patients.

Fig A1.

Kaplan-Meier probabilities of (A) overall and (B) progression-free survival among the initially reported 64 patients compared with the 18 patients who recently underwent transplantation; both groups were diagnosed with advanced chronic lymphocytic leukemia and were treated with allogeneic nonmyeloablative hematopoietic cell transplantation.

Fig A2.

Kaplan-Meier probabilities of (A) overall and (B) progression-free survival among patients who underwent transplantation at Seattle, WA (n = 48), compared with patients who underwent transplantation at other collaborating institutions (n = 34).

Fig 1.

Cumulative incidences and rates of (A) achieving complete remission, (B) disease progression or relapse, (C) nonrelapse mortality, (D) Kaplan-Meier estimates of overall survival and prevalence of chronic graft-versus-host disease, and (E) progression-free survival among recipients of related and unrelated grafts. MRD, matched related donor; URD, unrelated donor.

Fig 2.

Cumulative incidences of relapse and Kaplan-Meier estimates of progression-free survival among patients diagnosed with advanced chronic lymphocytic leukemia and treated with nonmyeloablative conditioning followed by related or unrelated allogeneic hematopoietic cell transplantation as stratified by lymph node (LN) diameter.

Fig 3.

Kaplan-Meier probabilities of survival among patients with advanced chronic lymphocytic leukemia who were treated with allogeneic nonmyeloablative hematopoietic cell transplantation (HCT) as stratified into four risk groups on the basis of consolidated HCT-specific comorbidity index sores and lymph node diameter. Group I included patients who had no comorbidities and who had lymphadenopathy of less than 5 cm (n = 28); group II, patients with comorbidities only (n = 34); group III, patients with lymphadenopathy of ≥ 5 cm only (n = 7); and group IV, patients with both comorbidities and lymphadenopathy of ≥ 5 cm (n = 13).