Blinatumomab as a bridge to further therapy in cases of overwhelming toxicity in pediatric B-cell precursor acute lymphoblastic leukemia: Report from the Israeli Study Group of Childhood Leukemia.

Tremendous progress in the therapy of pediatric acute lymphoblastic leukemia (ALL) has been achieved through combination cytotoxic chemotherapy, leading to high cure rates, at the cost of significant life-threatening toxicity. The bispecific T-cell engager blinatumomab, recently approved for relapsed/refractory ALL, has a unique nonmyelotoxic toxicity profile. As blinatumomab causes B-cell depletion, the safety of its use during severe chemotherapy-induced toxicity is unclear. We report 11 pediatric patients with ALL, treated with blinatumomab following overwhelming chemotherapy-associated toxicity, with recovery of all patients and successful bridging to further antileukemia therapy. Blinatumomab can be considered for rare patients who cannot tolerate cytotoxic therapy.

Cesarean Delivery and Childhood Malignancies: A Single-Center, Population-Based Cohort Study.

Rising rates of cesarean deliveries worldwide prompt the evaluation of long-term morbidity to the offspring. In this retrospective cohort study, we evaluated whether cesarean delivery influences the development of childhood malignancies. We identified an association of cesarean delivery with acute lymphoblastic leukemia in children, suggesting prudence in the recommendation of cesarean delivery for nonmedically indicated cases.

Skin Necrosis and Purpura Fulminans in Children With and Without Thrombophilia--A Tertiary Center's Experience.

Purpura fulminans (PF) is a very rare clinicopathologic skin disorder comprising dermal microvascular thrombosis associated with perivascular hemorrhage of multiple origins. It may occur as the presenting symptom of severe congenital deficiency of protein C (PC) or protein S (PS) during the newborn period, or later in life following oral anticoagulant therapy with vitamin K antagonists, or of sepsis that may be associated with disseminated intravascular coagulation. Treatment consists of anticoagulants and PC concentrates during acute episodes. We report our experience in the diagnosis and management of pediatric PF. The medical records of the 6 children aged 2-16 years (median: 5 years) who presented with PF to our tertiary care center between 1996 and 2013 were studied. The thrombophilia workup revealed either the presence of congenital homozygous PC deficiency, prothrombotic polymorphisms (factor V Leiden and FIIG20210A heterozygosity), acquired PC/PS deficiency, or no discernible thrombophilia. The skin necrosis resolved following conservative fresh-frozen plasma/anticoagulant therapy in 2 cases, whereas 3 children required interventional plastic surgery. The sixth case, a 10-year-old child with severe PC deficiency, heterozygous factor V Leiden, and FIIG20210A, received recombinant activated PC. PF in childhood is rare and has multiple etiologies. Understanding of the variable pathogenesis and risk factors will facilitate diagnosis and appropriate clinical management.

Rituximab as monotherapy and in addition to reduced CHOP in children with primary immunodeficiency and non-Hodgkin lymphoma.

Children with primary immunodeficiency or chromosomal breakage syndromes are at increased risk of developing non-Hodgkin lymphomas; they cannot tolerate standard chemotherapy regimens. We report two children with diffuse, large, B-cell lymphoma; one had ataxia telangiectasia and one had common variable immunodeficiency. Both were given rituximab, 1 as monotherapy and 1 in combination with a reduced CHOP regimen. Complete remission was obtained in each patient. Use of rituximab as a first-line monotherapy or in conjunction with reduced chemotherapy should be considered to reduce cytotoxic effects.

Treatment of X-linked childhood cerebral adrenoleukodystrophy by the use of an allogeneic stem cell transplantation with reduced intensity conditioning regimen.

Childhood cerebral form of X-linked adrenoleukodystrophy (X-ALD) is a rapidly progressive demyelinating condition affecting the cerebral white matter, which rapidly leads to total disability and death. The only known curative treatment for this condition is allogeneic hematopoietic stem cell transplantation (HSCT). Procedure-related toxicity is assumed to be the cause of death of patients with X-ALD. Three cases of ALD successfully transplanted with the use of non-myeloablative fludarabine based conditioning are described. Patients showed smooth peri-bone marrow transplantation course with fast and stable engraftment. In the 3- to 5 yr follow-up period, patients showed no deterioration in their clinical and neurological condition. Levels of very long chain fatty acids were very variable and had a tendency to decrease in at least one of the three patients. In another patient, an improvement of magnetic resonance imaging changes was found. Non-myeloablative HSCT should be considered as an early treatment for X-ALD.