ALBERT

Description: Shwachman-Diamond Syndrome (SDS) is an autosomal recessive disorder characterized by pancreatic insufficiency and variable degrees of neutropenia. Additional clinical features include short stature, skeletal abnormalities and bone marrow dysfunction. SDS patients are at increased risk of developing myelodysplasia, aplastic anemia and leukemic transformation. The role and timing of allogeneic hematopoietic stem cell transplantation (HSCT) in SDS remains controversial due to a poorly defined predisposition toward peri-transplant complications and overall poor survival. Here we report three SDS patients (age 13 mo, 16 mo and 8 yr) with severe aplasia successfully transplanted using 5/6 HLA matched unrelated umbilical cord blood. All patients received a previously described “cardiac sparing” conditioning regimen consisting of Melphalan (180 mg/m2), Etoposide (1200 mg/m2), anti-thymocyte globulin (90 mg/kg), and low dose total lymphoid irradiation (500 cGy) with graft versus host disease (GVHD) prophylaxis consisting of cyclosporine and prednisone. Patients received grafts containing 6.7 – 9.1 x 105 CD34+ cells/kg. Myeloid engraftment occurred promptly with the ANC 〉 500 cells/mm3 on day 15 ± 5. Platelet recovery (〉20k without transfusion) occurred on day 20, 30 and 140 days post transplant. All patients displayed 100% donor chimerism by 2 months post transplant. Patients were discharged between 25 – 60 days post transplant without severe complications, though all patients displayed grade II or III acute GVHD, and one developed chronic GVHD. The patients are alive 85, 390 and 850 days post transplant. Factors that may be important in HSCT outcome for SDS include transplantation at a relatively young age prior to malignant transformation, avoidance of cyclophosphamide in the preparative regimen, and adequate GVHD prophylaxis. Importantly, these cases also suggest that unrelated umbilical cord blood, in the absence of a matched family member, should be considered as the preferred source of donor stem cells in SDS patients undergoing HSCT.

Description: Background: Pneumocystis jirovecii pneumonia (PCP) is an opportunistic fungal infection that can develop in the setting of deficient cell-mediated immunity. Children with hematologic malignancies and children undergoing immunosuppressive treatment for other types of cancer are at risk of developing PCP. However, the epidemiology of PCP in children with cancer is not well described. We sought to determine the prevalence of PCP in hospitalized children with cancer in the U.S. and to identify risk factors for PCP in this population. Methods: This retrospective cohort study included pediatric patients with newly diagnosed cancer at 45 children's hospitals in the U.S. between January 1, 2004, and December 31, 2009. Data was obtained from the Pediatric Health Information System (PHIS). Patients were included if they were 0 to 20 years of age and had an index hospitalization with an ICD-9 diagnosis code for a malignant condition (140 to 239.39). Patients who had a benign tumor, 〉1 cancer type, or non-specific cancer codes, and those who received a hematopoietic stem cell transplant were excluded. Groups were defined for cancer types by ICD-9 codes: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Non-Hodgkin lymphoma (NHL), Hodgkin disease (HD), central nervous system (CNS), and solid non-CNS tumors. Patients within the cohort who had a diagnosis of PCP (ICD-9 code 136.3) within 3 years of their cancer diagnosis were considered PCP cases. The relative risk for PCP was calculated according to demographics and cancer types. The data were analyzed for trends in the incidence of PCP cases by year, the time to PCP diagnosis following cancer diagnosis, and the regional distribution of PCP in the U.S. Results: A total of 33,067 pediatric cancer patients met the criteria for inclusion in the study. Of these patients, 169 (0.5%) were classified as PCP cases (Table 1). Patients with ALL and AML had the highest relative risks of PCP, when compared with other cancer types. Patients of Asian race had the highest relative risk of PCP, when compared with patients of other races. Table 1: Relative Risk of PCP Diagnosis by Demographics and Cancer Types Table 1:. Relative Risk of PCP Diagnosis by Demographics and Cancer Types Figure 1 depicts that the time to the development of PCP was relatively short in patients with NHL (median 33 days, IQR: 0-253 days) and AML (median 70 days, IQR: 0-149 days). In contrast, PCP was diagnosed later in patients with ALL, (median 347 days, IQR; 168-675 days). The number of new PCP cases did not significantly vary by year of diagnosis. Regional differences in the diagnosis of PCP by the locations of PHIS institutions were not identified. Figure 1: Number of days from cancer diagnosis to PCP diagnosis (Kaplan-Meier survival curves) Figure 1:. Number of days from cancer diagnosis to PCP diagnosis (Kaplan-Meier survival curves) Conclusions: This study represents the largest cohort analysis of PCP in children with cancer. Among children with cancer who were hospitalized at major U.S. children's hospitals during the study period, the prevalence of PCP was 0.5%. The relative risk of PCP was increased in patients with leukemia when compared with other cancer types. However, PCP was identified in all cancer types. The variation in time to diagnosis of PCP is hypothesized to be due to differences in the intensity and duration of immunosuppressive therapy by cancer type. Disclosures No relevant conflicts of interest to declare.