Conditioning with Fludarabine, Busulfan, and ATG Prior to Reduced-Intensity Allogeneic Stem Cell Transplant for CLL Is Associated with a Low Incidence of Acute Graft-Versus-Host Disease.

Allogeneic stem cell transplant (SCT) is the only potentially curative treatment available for CLL. While transplant-related mortality has decreased with use of reduced-intensity conditioning (RIC) regimens, acute and chronic graft-versus-host-disease (GVHD) remain important causes of morbidity and mortality, with up to 50% of patients developing chronic GVHD (cGVHD). While the optimal way to combat this has not been established, in vitro T cell depletion with ATG or alemtuzumab has been employed to attempt to lessen its incidence. Herein, we report our institutional experience with each of these agents.

Information on all patients who underwent RIC allogeneic SCT at Ohio State from January 1, 2002 to June 29, 2010 was obtained following approval from the ORRP. Data collected by the transplant coordinators was correlated with data in our electronic databases. Comparative statistics were performed using the Fisher exact test and all p-values are two-sided.

Between January 1, 2002 and June 29, 2010, 50 patients with CLL/SLL underwent RIC allogeneic SCT at Ohio State. Pretransplant characteristics are listed in Table 1. Thirty patients received fludarabine, busulfan, and ATG (FBA) as a preparative regimen, and 8 patients received alemtuzumab, fludarabine, and TBI (Cam/Flu/TBI). Another 6 patients received fludarabine and busulfan, 4 received fludarabine and cyclophosphamide, one received pentostatin, fludarabine, and ATG, and the patient who had a cord blood transplant received fludarabine, cyclophosphamide, TBI, and ATG. The breakdown of characteristics between patients who received FBA and Cam/Flu/TBI is also provided in Table 1. None of the characteristics were statistically different. Time to count recovery is provided in Table 2. There was not a statistically significant difference in the time to count recovery between FBA and Cam/Flu/TBI. Patients who received Cam/Flu/TBI received significantly more DLIs; patients who received FBA have not required any DLIs. Incidence of acute and chronic GVHD is provided in Table 3. There was not a statistically significant difference in rates or grades of aGVHD, but patients who received Cam/Flu/TBI were more likely to develop extensive cGVHD.

While patients who received Cam/Flu/TBI were more likely to receive DLI, these were all done to treat disease recurrence, reflecting changes in group practice over time. There were no failures to engraft with FBA, and while not statistically significant in comparison to Cam/Flu/TBI, only 10% of patients developed grade 3 or 4 aGVHD. All of the patients who received Cam/Flu/TBI and developed cGVHD developed extensive disease. While the Cam/Flu/TBI sample is small, the FBA patients appear to fare no worse in terms of count recovery and development of GVHD without exposure to TBI, and this has become our institutional practice for patients with CLL.

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