Early lymphocyte recovery post-allogeneic hematopoietic stem cell transplantation is associated with significant graft-versus-leukemia effect without increase in graft-versus-host disease in pediatric acute lymphoblastic leukemia

Abstract

To study the effect of early lymphocyte recovery post-allogeneic hematopoietic stem cell transplantation (HSCT) on outcome in pediatric ALL, we reviewed 136 consecutive pediatric patients with ALL who received allogeneic HSCT between 1994 and 2005 at the Hospital for Sick Children, Toronto, Canada. Patients with an absolute lymphocyte count (ALC) o0.3 Â 10 9 per liter at day 21 (n ¼ 104) had more than five times risk of relapse compared to those with ALC 40.3 Â 10 9 per liter (n ¼ 32) (hazard ratio (HR) 5.3; P ¼ 0.002) and had inferior 3-year event-free survival, (EFS), 0.42 (95% confidence interval (CI) 0.32, 0.51) compared to 0.66 (95% CI 0.48, 0.82; P ¼ 0.02). Similarly, patients with an ALC o0.3 Â 10 9 per liter (n ¼ 48) at day 30 were more than twice as likely to relapse compared to those with an ALC 40.3 Â 10 9 per liter (n ¼ 88) (HR 2.2; P ¼ 0.01) and had an inferior 3-year EFS, 0.30 (95% CI 0.18, 0.45) compared to 0.57 (95% CI 0.46, 0.68; P ¼ 0.0001). Interestingly, increasing ALC at days 21 and 30 was not associated with increased incidence of acute or chronic GVHD or transplant-related mortality (TRM). Early lymphocyte recovery post-HSCT is associated with a significant GVL without increase in GVHD.

Early immune reconstitution and efficient graft vs tumor effect after unrelated partially matched double cord blood transplantation in refractory 8p11 syndrome

“…6 Early lymphocyte recovery after allogeneic hematopoietic SCT is associated with a marked GVL effect with no concomitant increase in GVHD. 7 This is supported by data indicating that early lymphocyte recovery decreases leukemic relapse and improves survival in recipients of unrelated CB transplantation. 8 We observed an accelerated recovery of CD4 þ T cells with a central output of naive thymic emigrants (CD4 þ CR45RA þ CD31 þ cells), 9 which is known to decrease infection mortality rate and to be critical for a long-term beneficial outcome in adults receiving CB transplantation.…”

Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo costimulatory blockade: results of 2 phase 1 studies

“…In contrast naive CD4 ϩ T cells were not detectable in the periphery until 6 months post-BMT. Although the favorable prognostic value of early ALC recovery reported after adult and pediatric matched sibling HSCT 25,26 has not been established after haploidentical BMT, and cannot be inferred from our limited data, the observed recovery of ALC suggests donor lymphocytes maintained their capacity to expand in vivo after alloanergization. Indeed, rapid reconstitution of T-cell subsets occurred in patients evaluable for immune reconstitution (all of whom were less than 18 years of age).…”

Early lymphocyte recovery after allogeneic hematopoietic SCT is associated with significant GVL effect in pediatric ALL but not acute myelogenous leukemia—Update study

“…ALL data were published earlier. 9 Only AML data are presented in this report. A total of 75 transplantations were carried out for 71 children with AML.…”

“…7,8 In our earlier study of 136 children with ALL and HSCT, we proved that early lymphocyte recovery is associated with significant GVL effect without increase in GVHD. 9 Nonetheless, historically AML is regarded to be more responsive to GVL effect compared with ALL and this, in part, may be explained by the better response to donor leucocyte infusion (DLI) in AML compared with ALL. 10,11 Hence, our objective herein was to extend our patient cohort to include all consecutive AML children who received HSCT in our institution and asking the same question, is early lymphocyte recovery post HSCT predictive of survival?…”