Evelio Perez-Albuerne

OUTCOME OF UNRELATED DONOR STEM CELL TRANSPLANTATION FOR CHILDREN WITH SEVERE APLASTIC ANEMIA

For children with severe aplastic anemia (SAA) who fail immunosuppressive therapy and lack a human leucocyte antigen (HLA)‐matched sibling donor, unrelated donors provide a source of hematopoietic stem cells. Data from 195 children with acquired SAA who underwent unrelated donor transplantation between 1989 and 2003 were analyzed. Neutrophil recovery (86% at day‐28) was higher with total body irradiation‐containing conditioning regimen and in younger recipients (aged ≤16 years) receiving grafts from older donors (aged >40 years). Recovery was lower after mismatched transplants and transplantations prior to 1997. Mortality rates were higher after mismatched transplants, in recipients with a poor performance score, and when the interval between diagnosis and transplantation was longer than 4 years. When restricted to donor‐recipient pairs with allele‐level HLA typing (8‐loci; n = 118), mortality rates were also higher after mismatched transplants and older recipients receiving grafts from older donors; 5‐year probabilities of overall survival after HLA‐A, ‐B, ‐C, ‐DRB1 matched and mismatched transplants adjusted for donor and recipient age were 57% and 39%, respectively (P = 0·008). The data suggest that unrelated donor transplantation is an acceptable alternative for children; early referral for transplantation and identification of an HLA‐matched (allele‐level) donor offers the best outcome.

Outcome for children <4 years of age with malignant central nervous system tumors treated with high‐dose chemotherapy and autologous stem cell rescue

Children <4 years of age (yo) with malignant central nervous system (CNS) tumors have a dismal prognosis. In an attempt to delay or obviate radiation therapy (XRT) and improve outcome, our institution has treated children <4 yo with newly diagnosed malignant CNS tumors with high‐dose chemotherapy (HDC) and autologous stem cell rescue (ASCR) followed by selective XRT.

Allogeneic donor availability for hematopoietic stem cell transplantation in children with sickle cell disease

Hematopoietic stem cell transplant is curative of sickle cell disease (SCD) but limited by donor availability. Searches for 85 patients with SCD without matched sibling donors from 2009–2013 using modern techniques (allele‐level HLA matching for unrelated donors and higher total nucleated cell doses for umbilical cord blood (UCB)) showed potential match probabilities of 20% for 8/8 HLA‐matched unrelated donors, 84% for 7/8 donors, and 97% for two 4‐6/6 UCBs suitable for ex‐vivo expanded/double cord transplant. Searches performed by age 43 months would have a 90% chance of finding a suitable 5‐6/6 UCB. Pediatr Blood Cancer 2015;62:1285–1287.

CD34+ collection efficiency as a function of blood volumes processed in pediatric autologous peripheral blood stem cell collection

To characterize the relationship between CD34+ collection efficiency and blood volumes processed in pediatric patients undergoing autologous peripheral blood stem cell (PBSC) collection.

Extracorporeal photopheresis performed on the CELLEX® compared with the UVAR-XTS® instrument is more efficient and better tolerated in children with steroid-refractory graft-versus-host disease

Extracorporeal photopheresis (ECP) is an effective therapy in children with refractory graft‐versus‐host disease (GVHD). The two most frequently used instruments are UVAR‐XTS® and CELLEX®. We performed a retrospective chart review of ten patients who underwent ECP with both UVAR‐XTS® and CELLEX® instruments for steroid‐refractory acute or chronic GVHD to compare instrument run times, percentages of cells treated, and complication rates. We found that compared to the UVAR‐XTS® instrument, use of the CELLEX® instrument resulted in shorter run times, increased percentage of mononuclear cells treated, reduced incidence of line occlusions requiring TPA treatment, and decreased incidence of patient‐related complications. Pediatr Blood Cancer 2015;62:1485–1488.

Analysis of pediatric autologous PBSC apheresis and transplant: Age is a major factor affecting post-transplant toxicity†

High‐dose chemotherapy followed by autologous hematopoietic cell transplantation (HCT) is used in many therapeutic protocols for pediatric intra‐ and extra‐cranial solid tumors. HCT can be curative, but is associated with significant toxicity.

RNA-Dependent Protein Kinases

RNA molecules conduct various functions in living organisms by interacting with other biological molecules. The recognition of RNA molecules, usually by proteins, is often dependent on the shape into which the RNA folds, rather than on any specific nucleotide sequence (1). This review focuses on double-stranded RNA (dsRNA) dependent protein kinase (PKR), which phosphorylates the a subunit of eukaryotic initiation factor-2 (eIF-2α) (2). PKR contains two amino acid sequence motifs called dsRNA-binding motifs (DRBM that allow binding to dsRNA and subsequently convert the protein from a latent to an active serine/threonine protein kinase (3). PKR is the only known kinase that depends on dsRNA for activation, although two closely related eIF-2a kinases, pancreatic eIF-2α kinase (PEK) (4) and PKR-like endoplasmic reticulum kinase (PERK) (5), have been described. PKR presents a unique paradigm for studying RNA: protein interaction because its activity depends on binding to dsRNA but not DNA, single-stranded RNA, or RIVA:DNA hybrids. Well-known for mediating the antiviral effects of interferons (IFNs), PKR is also implicated in regulating cell differentiation, signal transduction, and in eliciting apoptosis in response to various stress induction agents (3, 6). Although the protein is ubiquitous in cells, PKR activity is suppressed during cell proliferation and in tumor cells, suggesting a role for the kinase in the regulation of cell proliferation. This review summarizes the viral and cellular proteins and dsRNAs that activate and inhibit PKR, and the most recent findings in PKR knockout mice.

Growth Arrest and Selective Reduction in Cyclin D1/D2 Protein Expression By the Double-Stranded RNA-Dependent Protein Kinase

Growth Arrest and Selective Reduction in Cyclin D1/D2 Protein Expression By the Double-Stranded RNA-Dependent Protein Kinase