Abstract
Alemtuzumab is an effective agent in the treatment of various B- and T-cell malignancies that express CD52. Patients with advanced or refractory ALL have poor outcome after allogeneic stem cell transplantation (SCT). We investigated whether the addition of alemtuzumab to a standard myeloablative conditioning regimen would have any additional therapeutic effect and improve outcome after SCT in CD52+ ALL.
Patients and Methods: Patients were eligible if their disease expressed CD52 in >20% blasts by flow cytometry. The conditioning regimen consisted of cyclophosphamide (Cy, 60 mg/kg daily x 2 doses) and total body irradiation (TBI, 12 Gy in four daily fractions). Alemtuzumab at 10 mg was intravenously administered daily on days -6 to -2 prior to day of stem cell infusion. Patients received additional graft versus host disease (GVHD) prophylaxis with tacrolimus and methotrexate.
Results: Fifteen patients (9 M/6 F) with median age 33 years (range 22–57) were studied. Twelve patients had B-lineage and 3 had T-lineage disease. Cytogenetic data were available for 12 patients; all had high-risk cytogenetics, including 5 with Ph+ disease. The median number of prior chemotherapy regimens was 3 (range 1–6). At time of study entry, 3 patients were in CR1, 3 were in ≥ CR1, and 9 were in primary or refractory relapse. Five patients received a matched related donor transplant and 10 received an unrelated donor graft. The source of stem cells was bone marrow (n=7) or peripheral blood (n=8). The median CD34+ cell dose infused was 4.67 x 106/kg (range 1.85–6.43). Median time to ANC ≥ 0.5 x 109/L was 15 days (range 11–20). Median time to platelet count ≥ 20 x 109/L was 19 days (range 13–34). The cumulative incidence of non-relapse mortality at 2 years was 13% (95% CI, 4%–43%). The incidence of grade II-IV acute GVHD was 7% (95% CI, 1%–38%); no grade III/IV acute GVHD was observed. The incidence of chronic extensive GVHD was 20%. Overall survival at 2 years was 16% (95% CI, 3%–40%). Failure was related mainly to progression; thirteen of 15 patients had disease progression at a median time of 4 months (range 1–22).
Conclusion: These data suggest that alemtuzumab can be safely added to the standard transplant conditioning regimen for ALL without delayed engraftment or increased regimen-related toxicity. However, any potential direct antileukemia effect in CD52+ ALL patients with advanced disease appears to be negated by in-vivo T-cell depletion of the donor graft. Strategies to restore the graft-versus-leukemia effect in this setting are needed.
Author notes
Corresponding author
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal