The Post-Transplant Day 30 Lymphocyte Count Strongly Correlates with Transplanted Cd34 Dose and Is Predictive for Minimal Residual Disease and Mortality in Patients with Cml Undergoing Allogeneic Stem Cell Transplants from Matched Siblings.

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. [Display omitted]