Busulfan (BU) has a narrow therapeutic window and the average concentration of BU at steady state (Css) is critical for successful engraftment in children receiving BU as part of the preparative regimen for allogeneic transplants. Sixteen patients with sickle cell disease (SCD) underwent allogeneic bone marrow transplant (BMT) from HLA-identical siblings. The preparative regimen consisted of intravenous BU 0.8-1 mg/kg/dose for 16 doses, cytoxan (CY) of 50 mg/kg daily for four doses and equine anti-thymocyte globulin (ATG) 30 mg/kg daily for three doses. BU levels were adjusted to provide a total exposure Css of 600-700 ng/mL. The median age at the time of transplant was 6.2 years (range 1.2-19.3). Fourteen (87%) patients required adjustment of the BU dose to achieve a median Css of 652 ng/mL (range 607-700). All patients achieved neutrophil and platelet engraftment without significant toxicity. Median donor engraftment at the last follow-up was 100% (range 80-100). None of the patients experienced sickle cell-related complications post transplant. With a median follow-up of 3 years (range 1.3-9), the event-free survival (EFS) and overall survival (OS) are both 100%. We conclude that targeting of BU Css between 600 and 700 ng/mL in this regimen can result in excellent and sustained engraftment in young patients with SCD.

We evaluated the incidence and risk factors for hypogammaglobulinemia after allogeneic hematopoietic SCT (HSCT) in pediatric patients. Ig levels were measured pre-transplant, every 2 weeks until day 100 and then monthly post SCT in 185 patients undergoing myeloablative HSCT. Median age was 9 years; 142 (77%) had malignant disease and 114 (62%) received stem cells from an unrelated source. Hypogammaglobulinemia (IgG o500 mg/dL) developed in 143 (77%) of the patients at a median of 56 days (range 15-339) post SCT. The cumulative incidence of hypogammaglobulinemia at 1 year was higher among patients who developed acute GVHD (97% vs 54%, Po0.001), and for those receiving stem cells from an unrelated source (94% vs 51%, Po0.001). The cumulative incidence of TRM was significantly higher for patients with hypogammaglobulinemia (P ¼ 0.026). In multivariable analysis, lower pre-transplant IgG level (Po0.001), younger age (P ¼ 0.012), diagnosis of malignant disease (Po0.001), receiving unrelated SCT (Po0.001) and development of acute GVHD (Po0.001) were all significantly associated with higher risk of hypogammaglobulinemia post HSCT. We conclude that hypogammaglobulinemia is common, following allogeneic HSCT in pediatric patients, especially in those with malignant diseases, those who receive an unrelated transplant or patients who develop GVHD. Keywords: hypogammaglobulinemia; allo-SCT; children; IVIG; IgG; GVHD INTRODUCTION Hematopoietic SCT (HSCT) is an established therapy for various malignant and non-malignant disorders in children. The recovery of the immune system after allogeneic HSCT depends on multiple variables including preparative regimen, age and the presence of GVHD. 1 In a study of 93 adult patients, the number of B cell precursors in the BM 1-year post transplant was significantly lower in patients with chronic GVHD. Neither the CD34 þ cell dose, stem cell source (BM vs peripheral blood), donor or patient age were associated with B cell recovery. 2 In another study, low immunoglobulin levels have been associated with decreased survival and increased TRM in adult patients post allogeneic HSCT. In this study, factors associated with low IgG level were age o30 years, female donor to male recipient, not receiving antithymocyte globulin in the preparative regimen and the GVHD prophylaxis regimen. 3 The authors reported a decreased survival and increased TRM in these patients. The slow recovery of immune function post SCT has been linked to poor thymic function. 4 Pediatric patients have more intact thymic function compared with adult patients, which may influence the recovery of B cell function following HSCT. Unlike adult patients, one-third of the pediatric patients undergo an allogeneic HSCT for diseases other than malignancy. Except for patients with primary immune deficiency, those patients have generally an intact immune system prior to transplant. There are no published studies examining the incidence and risk factors for hypogammaglobulinemia post myeloablative allogeneic HSCT in pediatric patients.

Obesity has become a pandemic, affecting both children and adults. We sought to determine the effect of obesity among 200 children who were prospectively enrolled on a multicenter cord blood transplant (CBT) trial. All patients received myeloablative preparative regimens. Children were classified into groups according to body mass index percentile. Normal weight was defined as body mass index between the 5th and 85th percentile (n=117), overweight between the 85th and 95th percentile (n=35) and obesity above 95th percentile (n=39) for age and gender. A total of 55 patients (27%) had AML, 113 patients (57%) had ALL and 32 patients (16%) had other malignant diseases. There was no evidence for a difference in all major characteristics among the groups. Time to neutrophil and platelet engraftment, TRM, risk of acute GVHD, disease-free survival and OS were not significantly different in overweight or obese patients compared with normal weight patients. There was a trend towards increased risk of chronic GVHD in obese patients (P=0.05) compared with normal weight patients. In conclusion, there is insufficient evidence from this sample that obesity has an effect on multiple outcomes after unrelated CBT in children with malignant diseases.