CRISPR-based gene therapy for the induction of fetal hemoglobin in sickle cell disease.

Introduction: Sickle cell disease is ameliorated and perhaps can be 'cured' if enough fetal hemoglobin is present in most erythrocytes. Hydroxyurea, which increases fetal hemoglobin levels, is widely available and effective, especially in children. Nevertheless, only cell-based gene therapy can achieve a 'curative' fetal hemoglobin threshold.

Phase I Study of Clofarabine and 2-Gy Total Body Irradiation as a Nonmyeloablative Preparative Regimen for Hematopoietic Stem Cell Transplantation in Pediatric Patients with Hematologic Malignancies: A Therapeutic Advances in Childhood Leukemia Consortium Study.

Clofarabine is a purine nucleoside analog with immunosuppressive and antileukemic activity and its inclusion in reduced-intensity regimens could potentially improve outcomes. We performed a prospective phase I study of clofarabine combined with 2 Gy total body irradiation (TBI) as a nonmyeloablative preparative regimen for allogeneic stem cell transplantation in pediatric patients who were considered at high risk of mortality from standard myeloablative regimens. The main goal of the study was to delineate the maximum feasible dose (MFD) of clofarabine in combination with 2 Gy TBI.

Deficient Neutrophil Extracellular Trap Formation in Patients Undergoing Bone Marrow Transplantation.

Overwhelming infection causes significant morbidity and mortality among patients treated with bone marrow transplantation (BMT) for primary immune deficiencies, syndromes of bone marrow failure, or cancer. The polymorphonuclear leukocyte (PMN; neutrophil) is the first responder to microbial invasion and acts within the innate immune system to contain and clear infections. PMNs contain, and possibly clear, infections in part by forming neutrophil extracellular traps (NETs).

Safety of high dose trivalent inactivated influenza vaccine in pediatric patients with acute lymphoblastic leukemia.

Background: Although children with acute lymphoblastic leukemia (ALL) mount immune responses after vaccination with the trivalent influenza vaccine (TIV), these responses are lower compared to controls. Recently, a high dose (HD) TIV was found to increase the level of antibody response in elderly patients compared to the standard dose (SD) TIV. We hypothesized that the HD TIV would be well-tolerated and more immunogenic compared to the SD TIV in pediatric subjects with ALL.

Comparison of pre-cryopreserved and post-thaw-and-wash-nucleated cell count on major outcomes following unrelated cord blood transplant in children.

Engraftment and OS after umbilical CBT is highly dependent on the TNC. The contribution of the wash step to cell loss and ultimately the dose of cells available for transplant is not well described. To investigate the amount of cell loss after washing and its impact on major outcomes compared to pre-cryopreserved TNC, we analyzed data from patients prospectively enrolled on a National Heart, Lung and Blood Institute sponsored cord blood transplant study between 1999 and 2003.

Acquired factor XI deficiency in a child with membranoproliferative glomerulonephritis.

We describe a 7-year-old male with membranoproliferative glomerulonephritis who presented with nephrotic syndrome and subsequently developed factor XI (fXI) deficiency. An association between these conditions has not been described previously. In this case, fXI deficiency was caused by an antibody to fXI that enhanced clearance of the protein from plasma.