Autologous Stem Cell Mobilization with Cytokines and in-Vivo Alemtuzumab in Patients with T-Cell Non-Hodgkin's Lymphoma (T-NHL).

The use of anti-CD20 monoclonal antibody during stem cell collection has significantly improved transplant outcomes in b-cell NHL. The CD52 antigen is expressed on T-NHL, making it a suitable target for immunotherapy programs, given the availability of the anti-CD52 alemtuzumab.

In this prospective trial, alemtuzumab was given at 3,10, 30 mg IV (days 1-3) and then 30 mg IV, 7 days later. G-CSF (10mcg/kg) and GM-CSF 250 mcg/m² were provided daily, 5 days after starting alemtuzumab, and until a target of at least 2×10⁶ CD34+ cells/kg was collected. Patients (pts) then underwent conditioning with standard BEAM.

Sixteen pts [Peripheral T-cell (n=6); angioimmunoblatic (n=2); anaplastic large cell (n=4); hepatoslenic (n=2); NK/T (n=2)] were enrolled. Pts were required to have adequate counts (platelets >100K, ANC >1.5). Median age was 44 (range, 22-62) years. Median prior treatments was 1 (range,1-7). At study entry (SE), 8 pts (50%) were in first remission, 7 (44%) had chemosensitive relapse, and one pt had chemorefractory disease. Median IPI at SE, was 0 (range 0-1) and median marrow cellularity was 40% (ranged, 10%-90%). Five of 15 pts tested (33%) had marrow involvement at any time, and 3 of 8 tested (37.5%) had evidence of clonal T-cell by PCR at the time of SE. Eight pts (50%) failed to mobilize an adequate number of stem cells; a rate that is comparable to our historical control with cytokine mobilization alone in b-cell malignancies with rituximab (Am J Hematol 2009;84:335). The median time to start apheresis in the pts who were able to mobilize successfully was 4.5 (range, 2-7) days after initiation of cytokine administration. The median number of CD34×10⁶/Kg collected was 5.9 (range, 4-13.5). The median number of collection days was 4(range, 2-6). Three of the failures underwent successful mobilization with chemotherapy, and 2 underwent marrow harvest. There was a trend for a higher risk of failure in pts who had received more > one chemotherapy regimen, those who had been exposed to Hyper-CVAD (4 of 5 failed), and those with bone marrow cellularity < 30%. Age did not appear to have had an impact. Due to small numbers however, none of these associations reached statistical significance. Only one of the 8 pts who mobilized developed ANC< 1500 and platelets <20K. Seven of the 16 pts experienced CMV reactivation (ELISA test) and responded to foscarnet therapy. Twelve pts (75%) were able to proceed to autologous transplantation. With a median follow-up time of 22 (range 1-47) months, overall survival and progression-free survival rates were 79% and 45%, respectively.

The use alemtuzumab with cytokines is safe and feasible during autologous stem cell collection. In order to decrease the risk of stem cell mobilization failures, futures trials incorporating either chemotherapy or plerixafor with the alemtuzumab are warranted

Khouri:Bayer Pharmaceuticals: Research Funding.