Lymphocyte Count on Day 56 Predicts for Reduced Risk of Infection Related Mortality Following Non-Myeloablative Allogeneic Haematopoietic Stem Cell Transplantation.
Authors: Alvares Caroline , Kulkarni Samar , Kaczmarek Pawel , Saso Radovan , Woods Helena , Brennan Joy , Horton Clive , Treleaven Jennifer , Ethell Mark , Dearden Claire , Morgan Gareth , Potter Michael 
Published: October 2019

Abstract
In vivo T-cell depletion using Alemtuzumab containing conditioning regimens are commonly employed in high risk patients undergoing non-myeloablative allogeneic transplants (NMT). The effect of lymphocyte count on mortality due to infection following NMT has not been previously reported. We examined lymphocyte counts as a surrogate marker of immune reconstitution following NMT. Between August 2000 and August 2006, 70 patients (M:48, F: 22, median age:49, range: 17–63) underwent NMTs for haematological malignancies [ALL, n=6; AML, n=24; CML, n=2; HD, n=5; NHL, n=16 and MM, n=17]. Donors were matched siblings in 25 patients and 45 received matched unrelated transplants. All patients received standard induction and consolidation therapy and 39 patients had previously received autologous transplant (31 had 1 procedure and 8 had 2 procedures). Three patients received NMT as a part of tandem transplantation. Fifty two transplants were from HLA identical donors, 16 received single antigen class I mismatched grafts and 2 patients received single antigen class II mismatched transplants. Thirty two patients (32/70, 46%) and 51 donors (51/70, 73%) were CMV sero-negative. Conditioning therapy was Alemtuzumab based in 48 patients (69%), low dose TBI in 14 cases (20%) and 8 patients (11%) received other combinations. All patients received cyclosporine with or without mycophenolate as GVHD prophylaxis. At the time of transplantation 19 patients were in CR1 (27%), 26 were in subsequent CR (37%), 14 had partial remission (20%) and 11 had active disease (16%). Overall 73% patients had high risk disease. With a median follow-up of 10 months (range: 0–46), the probability of overall survival (OS) at 2 yr. was 24% (95% CI: 10.8–36.8, median OS: 10 months). Forty-three patients died and death was attributed to infection in 23/43 (54%), progressive disease in 14/43 (32%), GVHD in 5/43(12%) and secondary cancer in 1/43 (2%). Twenty-seven patients relapsed (38.6%) and the probability of relapse at 2yr. was (37%, 95% CI: 18–56). The median lymphocyte count on day 28 (L28) post transplant was significantly lower with use of Alemtuzumab (0.1 vs. 0.6, p<0.001) but this effect was not seen on the day 56 lymphocyte count (0.2 vs. 0.5, p=0.8). Recursive partitioning of L28 and L56 identified L56 count of 0.4×109/L to have a significant impact on OS. Patients with L56 >0.4 (n=26) had a significantly better survival (median OS: 15 vs. 8 months, p=0.033). This survival advantage was related to reduction in infectious deaths. There was no effect on mortality due to relapse or GVHD. The incidence of CMV reactivation within the first 100 days was independent of L56 (39% vs. 36%, p=0.7). In conclusion, this study shows that lymphocyte count >0.4 on day 56 post-NMT is associated with better overall survival due to reduction in infection related deaths. This finding warrants further investigation in a larger cohort of patients.