Important Role for Absolute Lymphocyte Count in Predicting Risk of Relapse in Pediatric Acute Lymphoblastic Leukemia Post Allogeneic Hematopoietic Stem Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is currently an established treatment for children with relapsed or high risk acute lymphoblastic leukemia (ALL). Relapse is a major risk post HSCT and an important cause of treatment failure with abysmal outcome. An important therapeutic mechanism of allogeneic HSCT is the immune-mediated destruction of recipient leukemic cells by donor lymphocytes, the graft-versus-leukemia-effect (GVL). Our hypothesis was to determine if delayed lymphocyte recovery measured by the absolute lymphocyte count (ALC) at two time points post HSCT at day 21 and day 30 correlates with leukemia relapse. We reviewed 136 consecutive paediatric patients with ALL who received allogeneic HSCT between 1994 and 2005 in the Hospital for Sick Children, Toronto, Canada. All patients were in complete morphological remission prior to HSCT and remission status at time of HSCT were as follows; Complete remission 1 (CR1, n=36); Complete remission 2 (CR2, n=79); Complete remission 3 (CR3, n=21). Conditioning regimens included single dose of VP16 (60mg/kg infused over 4 hours) and fractionated total body irradiation (TBI; 1200cGy) in six fractions over 3 days (VP16/TBI) in 49 patients (1994–1998) and cyclophosphamide 50mg/kg infused over 1 hour daily for 4 days followed by the same dose of fractionated TBI (CY/TBI) in 83 patients (1999–2005) and 4 patients received other conditioning regimens. Fifty-six patients received matched sibling donor (MSD), 12 patients received one antigen mismatched related donor (MMRD), 64 received unrelated donors and 4 patients received cord progenitor stem cells. Two groups were identified based on absolute lymphocyte count at day 21 and day 30 post HSCT. Patients with absolute lymphocyte count <0.3×10⁹/L at day 21 (n=104) had more than 5 times risk of relapse compared to those with ALC count >0.3 × 10⁹/L (n=32) (Hazard ratio 0.19; P=0.0004). Patients with ALC <0.3×10⁹/L (n=48) at day 30 were more than twice likely to relapse compared to those with ALC >0.3×10⁹/L (n=88) (Hazard ratio 0.46; P=0.01).

Conclusion: ALC, at day 21 and day 30 post HSCT identifies a patient population of pediatric ALL with delayed lymphocyte recovery and a significant risk of relapse post HSCT. Such patients could be considered for early intervention targeted to prevent relapse such as reduction of immunosuppressive therapy or other means of immunotherapy to enhance the graft versus leukemia effect.