Abstract
Between 12/1993 and 5/2004, 80 patients with chronic myeloid leukemia (CML) received a T cell depleted stem cell transplant from an HLA identical sibling, with delayed add-back of donor T cells on days 30–45 and again on day 60–100 for patients not developing ≥ grade II acute GVHD. Four transplant regimens were evaluated (1) total body irradiation (TBI) + cyclophosphamide (Cy) and standard dose (SD) cyclosporine (CSA) + bone marrow transplantation (BMT) (N=25); (2) TBI + Cy + SD-CSA + peripheral blood stem cell transplantation (PBSCT) (N=16); (3) TBI + Cy + PBSCT and low dose or no (LD/N) CSA (N=22); (4) TBI + fludarabine (Flu) + Cy and LD/N CSA (N=17). Median CD34 and CD3 doses were 4.5 x 106/kg and 0.75 x 105/kg respectively Prior to transplantation 54 patients had chronic phase (CP) and 26 had more advanced CML. Kaplan-Meier survival plots were created for overall survival, current disease free survival (DFS); and transplant-related mortality (TRM). Outcomes were analyzed using log rank tests. The outcomes for chronic versus more advanced CML were respectively 85±5% vs 36±10%, p=<0.0001 for overall survival; 13±5% vs 42±11%, p<0.01 for TRM; 76±6% vs 33.5±9% p=<0.0001 for current DFS (figure). Of patients in CP, 22/48 were negative for BCR/ABL at 3 months post transplant, increasing to 35/46 at 12 months, and 42/46 are currently disease free. Factors affecting outcome in 54 CP patients were (1) source of transplant: there was a survival benefit for the PBSCT group compared to BMT recipients (p=0.03). and (2) Day 30 lymphocyte count (LC30): there was a higher survival and lower TRM for patients with a count above the median of 300/μl: 100 vs 70±9%; p=0.003; 0 vs 26±8%, p=0.006 respectively. Similar differences were observed in the PBSCT. Molecular response (PCR for BCR/ABL negative at 3, 6, 12 and months) was also highly correlated with higher LC30 at all time points (p=<0.0001; <0.0001; 0.0004 respectively). (3) CD34 dose above the median dose of 4.5 x 106/kg in 28 CP patients was associated with 100% survival and zero TRM vs 69±9% and 27±9% for 26 patients below the median; p=0.002 and 0.003 respectively). Higher than median CD34 doses significantly correlated with molecular response at 3, 6 months. (p=<0.0001; <0.0001 respectively). Higher CD34 dose also correlated significantly with higher LC30 (p= 0.03) (figure). These results show that T cell depleted SCT for CML CP results in favorable long-term survival with low TRM. Results for more advanced disease were complicated by high relapse and TRM but showed the same improved outcome with higher CD34 doses. The results highlight a predictive importance for LC30, not only for TRM, but also for a graft versus leukemia effect. Since LC30 was highly correlated with CD34 dose, our results suggest that transplant outcome in T depleted CML allografts can be improved by transplanting more than 4.5 x 106 CD34 cells/kg.
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