T-Cell Replete Peripheral Blood Stem Cell Transplantation after Non-Myeloablative Conditioning with Post-Transplant High Dose Cyclophosphamide Is Safe and Is Associated with Acceptable Outcomes

Introduction:  Multiple approaches have been made to minimize graft versus host disease (GvHD) after allogeneic hematopoietic cell transplantation (allo-HCT) without compromising graft versus leukemia (GvL) effect. Use of high dose cyclophosphamide in the early post-transplant period (PT-Cy) has significantly improved the outcomes of allo-HCT and encouraging results using this regimen have been recently reported in both haploidentical and non-haploidentical transplant setting (Bashey et al JCO, 2013, Fuchs et al, Blood, 2010). However, so far the use of peripheral blood stem cells (PBSC) with non-myeloablative (NMA) conditioning PT-Cy has not been reported in literature.

Patients and methods:  A total of 21 patients (median age 45 (22-74) years, 12 males and 9 females) between July 2009 and June 2013 underwent allo-HCT on this regimen. The NMA conditioning consisted of Fludarabine (30mg/m²/day on days -6 to -2), Cyclophosphamide (14.5 mg/kg/day on D -6 and -5) and TBI (200cGy on D -1) and Cyclophosphamide (50mg/kg-bw on D +3 and D +4). PBSC was used a graft source with a median CD34+ count of 5 x 10⁶/kg-bw and CD3+ T cell dose of 19.7 x 10⁷/kg-bw. GvHD prophylaxis included MMF plus Tacrolimus. Median follow-up for the patients was 235 (17-1174) days. Diagnosis of the patients included AML (n=14), ALL (n=2), CML (n=1), NHL (n=2), CLL (n=1) and Aplastic anemia (n=1). 10 out of 21 patients underwent transplant in active disease and 4 of these patients had prior history of allo-HCT.

Results:  19 patients (95%) engrafted with median neutrophil engraftment on day 15 (12-28) days and median platelet engraftment on day 16 (11-40) days. None of these patients had secondary graft failure. 1 year over all survival rates (OS) of 57% were encouraging. The 1-year OS for those underwent transplant with active disease and in remission were 63% and 56% respectively (Figure 1a). 1-year relapse free survival (RFS) was 56% for those who underwent transplant in remission and 41% in those who underwent transplant in active disease (Figure 1b). 100 day and 1-year NRM rates were 9.5% and 14% respectively. Cumulative incidence of aGvHD at 2 months and 90 days was 38% and 47% respectively (grade III-IV in 4 patients). Cumulative incidence of cGvHD at 1 and 2 years were both at 12% (extensive in 1 patient). CMV reactivation occurred in 14 patients (66%) without the development of CMV disease. 

Conclusions: Here we report for the first time the results of a novel regimen combining NMA conditioning with T-cell replete G-CSF mobilized PBSC for allo-HCT with high dose PT-Cy. We show it is a safe regimen, with high engraftment rates, encouraging survival rates and very low grade III-IV aGvHD and extensive cGVHD rates despite relatively high T cells doses. The results from this relatively small number of mostly high-risk patients are encouraging and form basis for testing it in a larger cohort of patients.