C Calder

Incidence and outcome of idiopathic pneumonia syndrome in pediatric stem cell transplant recipients.

Idiopathic pneumonia syndrome (IPS) is a rare complication following stem cell transplant (SCT) and its incidence among pediatric SCT recipients is not known. To assess the incidence of IPS, we retrospectively reviewed the incidence of IPS at our center. IPS is defined as the presence of multilobar infiltrates by chest radiograph or computed tomography scan, need for supplemental oxygenation with declining pulse oximetry and no identifiable pulmonary infection. Between July 1999 and August 2005, 11 of 93 children who received a fully ablative allogeneic SCT (11.8%) developed IPS. All 11 patients had normal pulmonary evaluation before transplant. IPS developed at a median of 17 days (range 8–42 days) after transplant. Recipients of unrelated donor transplant had increased risk of developing IPS. There was a significant association between acute or hyperacute graft-versus-host disease (GVHD) and IPS (P=0.035). All patients had significant hypoxia and five patients required assisted ventilation. IPS was the cause of death in two patients. Although there was complete resolution of respiratory symptoms in the other nine patients, overall transplant-related mortality was significantly higher among patients with IPS (64 vs 17%, P=0.002). IPS is a relatively common complication in pediatric SCT recipients and acute GVHD is an important associated factor.

Pericardial effusion and cardiac tamponade in pediatric stem cell transplant recipients.

Summary:Pericardial effusion and cardiac tamponade is a rarely reported complication following stem cell transplant (SCT). The incidence among pediatric SCT recipients is not well defined. To assess the frequency of clinically significant pericardial effusions, we retrospectively examined clinically significant cardiac effusions at our center. Between January of 1993 and August 2004, clinically significant pericardial effusions were identified in nine of 205 patients (4.4%). The median age at the time of transplant was 9 years (range 0.6–18 years) and seven received an allogeneic transplant. All nine had normal cardiac function prior to transplant. The effusion developed at a median of 30 days (range 18–210 days). All allogeneic recipients had acute or clinically extensive graft-versus-host disease (GVHD) at the time the effusion was diagnosed. Seven patients (78%) required pericardiocentesis or surgical creation of a pericardial window. No patient died as a complication of the effusion or the therapeutic procedures. Clinically significant pericardial effusions are more common than previously reported in pediatric SCT recipients. Acute and chronic GVHD is an associated factor.

Unrelated umbilical cord blood transplantation in children with immune deficiency: results of a multicenter study

In the absence of a related donor, unrelated cord blood transplant (CBT) may be a potential option for patients with a primary immune deficiency (PID). Most published experience consists of single-center data using multiple preparative regimens and GVHD prophylaxis. We report the results of a multicenter prospective trial of unrelated CBT for PID. A total of 24 children with PID, with a median age of 1 year (range: 0.23–7.81 years) and a median weight of 10.5 kg (range: 4–24.4 kg) received unrelated CBT between 1999 and 2003. All patients received a fully ablative conditioning regimen with identical GVHD prophylaxis and supportive care. Most patients (79%) received a 1 or 2 HLA Ag-mismatched cord unit with a median nucleated cell infused of 9.3 × 107/kg (range: 1.0–31.2) and a median CD34 of 2.7 × 105/kg 2.9 (range: 0.6–84.5). The cumulative incidence of neutrophil engraftment by day 42 was 58% (95% CI: 38–79%) at a median of 19 days. Cumulative incidence estimates of grade III–IV acute GVHD at day 100 and chronic GVHD at 1 year were 29% (95% CI: 10–48%) and 24% (95% CI: 3–44%), respectively. The probability of survival at 180 days and 1 year was 66.7% (95% CI: 44.3–81.7%) and 62.5% (95% CI: 40.3–78.4%), respectively. Unrelated CBT should be considered in children with PID.

Incidence and clinical complications of vancomycin-resistant enterococcus in pediatric stem cell transplant patients

Summary:Vancomycin-resistant enterococcus (VRE) are increasingly important pathogens in stem cell transplant (SCT). In all, 61 pediatric SCT patients had surveillance stool cultures for VRE between July 1999 and November 2002. When VRE was identified, the patients were placed on strict contact isolation. VRE was detected in 15 patients (24.6%). The median age was 3.6 years (range 0.6–18.5 years). Of the 15, 13 (87%) received an allogeneic transplant (six unrelated and seven related). Five of the 15 (33%) colonized patients developed VRE bacteremia. The bacteremia resolved in all five patients after therapy with quinupristin/dalfopristin; three patients required central line removal. Four patients died (38–153 days) post-SCT due to relapse or transplant complication not related to VRE. Of the 11 surviving patients, seven cleared the colonization at a median of 144 days (range 61–198 days) postcolonization. Four patients remain colonized at 68–702 days after the first positive culture. Intestinal colonization with VRE occurred commonly in pediatric SCT patients. Although the morbidity from VRE was not substantial, transplant patients were colonized for prolonged periods. Our results indicate that surveillance for VRE is an effective way to identify colonized patients and may lead to a decrease in transmission to other patients.

Targeted Busulfan therapy with a steady-state concentration of 600-700 ng/mL in patients with sickle cell disease receiving HLA-identical sibling bone marrow transplant

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.

Unrelated stem cell transplant for infantile idiopathic myelofibrosis

Idiopathic myelofibrosis (IMF) is a rare disease in children that can present during infancy and have a protracted course. The only known curative approach for this disease in adult patients is allogeneic stem cell transplant. We present two cases of IMF during infancy that did not resolve with supportive care measures. Both patients underwent unrelated stem cell transplant with complete resolution of their hematologic manifestations and resolution of the bone marrow fibrosis. Pediatr Blood Cancer 2009;52:893–895.

Matched unrelated bone marrow transplantation with reduced-intensity conditioning for leukocyte adhesion deficiency.

Matched unrelated bone marrow transplantation with reduced-intensity conditioning for leukocyte adhesion deficiency

The effect of obesity on outcome of unrelated cord blood transplant in children with malignant diseases.

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.

Unrelated bone marrow transplant for congenital amegakaryocytic thrombocytopenia: Report of two cases and review of the literature

Frangoul H, Keates‐Baleeiro J, Calder C, Manes B, Crossno C, Castaneda VL, Domm J. Unrelated bone marrow transplant for congenital amegakaryocytic thrombocytopenia: Report of two cases and review of the literature.
Pediatr Transplantation 2010: 14:E42–E45.

Incidence and risk factors for hypogammaglobulinemia in pediatric patients following allo-SCT.

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 <500 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%, P<0.001), and for those receiving stem cells from an unrelated source (94% vs 51%, P<0.001). The cumulative incidence of TRM was significantly higher for patients with hypogammaglobulinemia (P=0.026). In multivariable analysis, lower pre-transplant IgG level (P<0.001), younger age (P=0.012), diagnosis of malignant disease (P<0.001), receiving unrelated SCT (P<0.001) and development of acute GVHD (P<0.001) 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.