Implication of Faster Neutrophil and Lymphocyte Recovery after Allogeneic Stem Cell Transplantation (SCT) in Children with Leukemia

The repopulating neutrophils and lymphocytes after allogeneic SCT have an important role, not only on the prevention of serious infections in the early transplantation period, but on killing the residual leukemic cells by graft versus leukemia (GVL) effect. Previous studies have suggested that earlier neutrophil recovery was associated with less infections and better survival, while earlier lymphocyte recovery was associated with a lower relapse and a better survival in adult patients. The aim of this study was to compare the impact of neutrophil and lymphocyte recovery after SCT on predicting the survival, relapse, and GvHD in children with hematologic malignancies. We retrospectively evaluated 69 children transplanted for ALL (n=34: CR1, 22; CR2, 10; > CR2, 2), AML (n=26: CR1, 19; secondary AML, 4; > CR1, 3), chronic leukemia (n=7: CML, 6; CEL, 1) and JMML (n=2) at the Chonnam National University Hospital between Jan. 1996 and Mar. 2008. Conditioning regimes were TBI-based (n=41), and non-TBI based (n=28). Stem cell sources were: BM (n=46), PBSCs (n=10), UCB (n = 12), and BM + PB (n=1). Matched sibling donor was used in 26, while unrelated donors in 43. Three AML patients who received the 2nd allogeneic SCTs following autotransplants were included. The patients were grouped according to the absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) at D+21 and D+30. The best discriminating cutoff values for ANC and ALC were 1,000/μL and 500/μL, respectively. The groups were: Low ANC at D+21 (LNC21, n=25) vs. High ANC at D+21 (HNC21, n=44); Low ANC at D+30 (LNC30, n=15) vs. High ANC at D+30 (HNC30, n=54); Low ALC at D+21 (LLC21, n=28) vs. High ALC at D+21 (HLC21, n=41); Low ALC at D+30 (LLC30, n=19) vs. High ALC at D+30 (HLC30, n=50). The patients were 41 males and 28 females. The median age at transplant was 7.1 years (range, 0.4–18). The median day of neutrophil engraftment (≥ 1,000/μL) was D+21 for LLC21 vs. D+16 for HLC21 (P =.001); and D+20 for LLC30 vs. D+17 for HLC30 (P =.02), respectively. The median day of platelet engraftment (≥ 20,000/μL) was D+38 for LLC21 vs. D+19 for HLC21 (P =.04); and D+40 for LLC30 vs. D+22 for HLC30 (P =.07), respectively. The HNC21 and HNC30 group showed a better survival than LNC 21 and LNC30 group, but statistically not significant (69% vs. 58%; 67% vs. 59%, respectively). The HLC30 group exhibited a better 5 year overall survival (71% vs. 53%, P =. 04) and event free survival (72% vs 53%, P =. 06) than LLC30 group. The LNC21 group was associated with a high incidence of aGvHD (36% vs. 14%, P =. 03), but the incidence of Gr II-IV aGvHD and cGvHD was not different by the ALC counts. Relapse rate was not different between ANC and ALC groups. Six of 15 (40%) in LNC30 and 15 of 54 (28%) in HNC30 died, while 9 of 19 (47.4%) in LLC30 and 12 of 50 (24%) in HLC30 died (P = NS). In this study, we found that lymphocyte recovery ≥ 500/μL on D+30 was associated with better survival, faster myeloid and platelet engraftment without increasing the incidence of GvHD or mortality. Also faster neutrophil recovery ≥ 1,000/μL on D+21 was associated with a lower incidence of aGvHD. However, faster lymphocyte recovery was not translated into decreased relapse rate. Further studies incorporating larger number of cases and longer follow-up are warranted in children with leukemias.