Despite the 2000 CDC guidelines, wide variation in post-HSCT immunization practices still exists. Updated guidelines have been needed, particularly to address the use of the pneumococcal conjugate vaccine. In conjunction with multiple other groups, the CDC recently released new immunization guidelines in October 2009. Additional data are still needed to adequately address the utility of incorporating immunologic parameters with the timing of vaccination after HSCT.

Sonic hedgehog (SHh) signaling is important in the pathogenesis of various human cancers, such as medulloblastomas, and it has been identified as a valid target for anti-cancer therapeutics. The SHh inhibitor cyclopamine induces apoptosis. The bioactive sphingolipid ceramide mediates cell death in response to various chemotherapeutic agents; however, ceramide’s roles/mechanisms in cyclopamine-induced apoptosis are unknown. Here, we report that cyclopamine mediates ceramide generation selectively via induction of N-SMase2 expression in Daoy human medulloblastoma cells. Importantly, siRNA-mediated knockdown of N-SMase2 prevented cyclopamine-induced ceramide generation, and protected Daoy cells from drug-induced apoptosis. Accordingly, ectopic expression of wild type N-SMase2 caused cell death, compared to controls, expressing the catalytically inactive N-SMase2 mutant. Interestingly, knockdown of smoothened (Smo), a target protein for cyclopamine, or Gli1, a down-stream signaling transcription factor of Smo, did not affect N-SMase2 expression, or apoptosis. Mechanistically, our data showed cyclopamine induced N-SMase2 mRNA and cell death selectively via increased nitric oxide (NO) generation by neuronal-nitric oxide synthase (n-NOS) induction, in Daoy medulloblastoma, and multiple other human cancer cell lines. Accordingly, N-SMase2 activity-deficient skin fibroblasts isolated from homozygous fro/fro (fragilitas ossium) mice exhibited resistance to NO-induced cell death. Thus, our data suggest a novel off-target function of cyclopamine in inducing apoptosis, at least in part, by Nnos/NO-dependent induction of N-SMase2 expression/ceramide axis, independent of Smo/Gli inhibition.

We present a case of pancytopenia in a 9-month-old infant with total parenteral nutrition (TPN) dependence due to short bowel syndrome. Bone marrow examination revealed left-shifted myeloid maturation, erythroid and myeloid dysplasia with normal iron stores. Serum copper level was 2 microm/dl (normal range 90-190 mcg/dl). After supplementation, copper levels normalized at 143 mcg/dl, and the macrocytic anemia, neutropenia, and thrombocytopenia resolved. Copper deficiency should be considered in the differential diagnosis of cytopenias and myelodsyplasia, particularly in the growing number of pediatric patients with TPN dependency or malabsorption.