The diversity of mutations and clinical outcomes for ELANE-associated neutropenia.

Purpose Of Review: Mutations in the gene for neutrophil elastase, ELANE, cause cyclic neutropenia (CyN) and severe congenital neutropenia (SCN). This study summarized data from the Severe Chronic Neutropenia International Registry (SCNIR) on genotype-phenotype relationships of ELANE mutations to important clinical outcomes. We also summarize findings for ELANE mutations not observed in SCNIR patients.

Stable long-term risk of leukaemia in patients with severe congenital neutropenia maintained on G-CSF therapy.

In severe congenital neutropenia (SCN), long-term therapy with granulocyte colony-stimulating factor (G-CSF) has reduced mortality from sepsis, revealing an underlying predisposition to myelodysplastic syndrome and acute myeloid leukaemia (MDS/AML). We have reported the early pattern of evolution to MDS/AML, but the long-term risk remains uncertain. We updated a prospective study of 374 SCN patients on long-term G-CSF enrolled in the Severe Chronic Neutropenia International Registry.

The Severe Chronic Neutropenia International Registry: 10-Year Follow-up Report.

Background: The Severe Chronic Neutropenia International Registry (SCNIR) was organized 10 years ago to improve understanding and treatment of the group of rare hematologic disorders causing blood neutrophil counts to be < 500/muL for months or years.

Patients And Methods: Patients now enrolled include those with severe congenital neutropenia (n = 526), cyclic neutropenia (n = 205), idiopathic neutropenia (n = 349), autoimmune neutropenia (n = 68), and other (n = 15). More than 90% (1053 of 1163) of patients in the SCNIR have been treated with granulocyte colony-stimulating factor (G-CSF), median dose 3.

Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia.

Severe congenital neutropenia (SCN) is a heterogeneous bone marrow failure syndrome predisposing to myelodysplastic syndrome and acute myeloid leukaemia (MDS/AML). We studied 82 North American and Australian SCN patients enrolled in the Severe Chronic Neutropenia International Registry who were on long-term treatment with granulocyte colony-stimulating factor and for whom the neutrophil elastase (ELA2) gene was sequenced. There was no significant difference in the risk of MDS/AML in patients with mutant versus wild-type ELA2: the respective cumulative incidences at 15 years were 36% and 25% (P = 0.

The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy.

In patients with severe congenital neutropenia (SCN), sepsis mortality is reduced by treatment with granulocyte colony-stimulating factor (G-CSF), but myelodsyplastic syndrome and acute myeloid leukemia (MDS/AML) have been reported. We studied 374 patients with SCN and 29 patients with Shwachman-Diamond syndrome (SDS) on long-term G-CSF enrolled in the Severe Chronic Neutropenia International Registry. In SCN, sepsis mortality was stable at 0.

A phase I clinical, pharmacologic, and biologic study of thrombopoietin and granulocyte colony-stimulating factor in children receiving ifosfamide, carboplatin, and etoposide chemotherapy for recurrent or refractory solid tumors: a Children's Oncology Group experience.

Purpose: Ifosfamide, carboplatin, and etoposide (ICE) are associated with grade III/IV dose-limiting thrombocytopenia. The Children's Oncology Group conducted a phase I dose escalation, pharmacokinetic, and biological study of recombinant human thrombopoietin (rhTPO) after ICE in children with recurrent/refractory solid tumors (CCG-09717) to assess the toxicity and maximum tolerated dose of rhTPO administered at 1.2, 2.

Severe chronic neutropenia: treatment and follow-up of patients in the Severe Chronic Neutropenia International Registry.

Severe chronic neutropenia (SCN) is defined as an absolute neutrophil (ANC) of less than 0.5 x 10(9)/L, lasting for months or years. Congenital, cyclic, and idiopathic neutropenia are principal categories of SCN.

Neutropenia associated with primary immunodeficiency syndromes.

The primary immunodeficiency diseases are a heterogeneous group of more than 75 disorders characterized by intrinsic defects in the functions of the immune system. Many are associated with abnormalities of hematopoiesis as well. This article will review those primary immunodeficiency syndromes in which neutropenia is a prominent finding, including X-linked agammaglobulinemia (XLA), hyper IgM syndrome, common variable immunodeficiency (CVID), IgA deficiency, cartilage-hair hypoplasia (CHH), and reticular dysgenesis, with regards to pathophysiologic findings and treatment.