In pediatric and adolescent patients undergoing allogeneic hematopoietic cell transplantation, treatment-related toxicities remain a clinical challenge. A paucity of data investigates the risks for and survival impact of treatment-related toxicities in this population. Here the authors assess the relative toxicity of myeloablative, reduced-toxicity, and reduced-intensity conditioning regimens; identify patient-related predictors of post-transplant toxicities; and investigate the impact of early post-transplant toxicities on transplant-related mortality (TRM). In this retrospective study, 164 patients (aged 1 to 22 years) underwent allogeneic stem cell transplantation after busulfan-based conditioning for malignant and nonmalignant diseases between 2000 and 2014. The number of grades III to IV toxicities between days 0 and +30 was calculated for each patient. TRM was calculated to 2 years. Median patient age was 9 years, and median number of toxicities was 3 (range, 0 to 17). The 100-person day incidence of post-transplant toxicities in myeloablative conditioning was not different from the incidence in reduced-toxicity conditioning (13.88 versus 13.59, P = .812). Reduced intensity was less toxic than both myeloablative and reduced toxicity (13.75 versus 8.41, P <.001). Age ≥ 12 years (.276 with SE = .138, P =.045) and unrelated donor transplant (.318 with SE = 0.113, P = .005) were risk factors for ≥3 toxicities. Having ≥3 toxicities or a performance score < 90 conferred higher risk of TRM (P = .021). In pediatric and adolescent patients undergoing hematopoietic cell transplantation, reduced-toxicity conditioning was not significantly less toxic than myeloablative conditioning. Additionally, the number of post-transplant toxicities correlated with the risk of mortality. Further investigations to confirm our findings are warranted.

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Background: Relapse of leukemia after pediatric hematopoietic cell transplantation (HCT) is a frequent cause of treatment failure. Immune reconstitution (IR) early after HCT is pivotal to generate a potent graft-versus-leukemia effect. We studied the association between IR of various lymphocyte subsets and outcomes in children receiving a cord blood HCT for hematological malignancies. Methods: All consecutive patients with a hematological malignancy receiving a cord blood HCT between 2004-2014 at Great Ormond Street Hospital London and at the UMC Utrecht were included. Patients received a myeloablative regimen AE Thymoglobulin. Primary endpoint was relapse; secondary endpoints were overall survival, non-relapse mortality (NRM), acute GvHD (grade 2-4) and chronic GvHD. Lymphocyte-subsets (CD3+, CD4+, CD8+, NK and B-cells) were monitored every other week after engraftment. Various definitions of IR were analyzed including one in line with a reported association: CD4+ T-cell count >50/mL in 2 consecutive measurements within 100 days post-HCT (Bartelink et al, BBMT 2013). Cox proportional hazard models and logistic regression models were used. Results: 89 patients were included, with a median age of 7.1 years (range 0.7-18): 36 ALL (19 CR1,14 CR2, 3 CR3), 49 AML (14 refractory, 35 CR) and 4 other malignancies. 36 patients received Thymoglobulin (Utrecht only). CD4-IR (count >50, twice <100 days) was the best predictor for endpoints; in multivariate (MV) analyses, CD4-IR was a predictor for lower probability of relapse in AML patients (MV: HR 0.29, 95% CI 0.03-0.98, p¼0.04; figure 1), but not in ALL (p¼0.14). CD4-IR was also a predictor for NRM (MV: HR 0.13, 95% CI 0.03-0.52, p¼0.004; figure 2). CD4-IR predicted OS in AML (MV: HR 0.17, 95% CI 0.06-0.53, p¼0.002), but not in ALL. However, CD4-IR did not have an impact on acute grade 2-4 (p¼0.41) or chronic GvHD (p¼0.12). Successful CD4-IR was less frequent in patients receiving Thymoglobulin (MV: OR 0.04, 95% CI 0.002-0.27, p¼0.005). Associations with the endpoints for the other lymphocyte-subsets were less predictive. Conclusion: Early CD4-IR post cord blood HCT predicts the probability of relapse in AML as well as NRM in all patients. Thymoglobulin negatively impacts CD4-IR post cord blood HCT, hence the use and/or the dosing of Thymoglobulin should be carefully re-considered. Figure 1. Cumulative incidence of relapse according to CD4+ immune reconstitution in myeloid leukemiaFigure 2. Non-relapse mortality according to CD4+ immune reconstitution in all patients Biol Blood Marrow Transplant 21 (2015) S206eS239