How to differentiate congenital from noncongenital chronic neutropenia at the first medical examination? Proposal of score: A pilot study from the French Severe Chronic Neutropenia registry.

OBJECTIVES: We developed a diagnostic score to differentiate congenital from noncongenital neutropenia at the time of diagnosis using reliable data collected at the first visit of a patients with neutropenia. STUDY DESIGN: In a pilot retrospective study, we included 120 patients diagnosed with chronic neutropenia; 61 had congenital and 59 had noncongenital neutropenia. We reviewed patient medical charts and collected the initial complete blood count (CBC) and other reliable data. We used logistic regression to determine the probability that the neutropenia was congenital. RESULTS: On the initial CBC, the degree of neutropenia had no predictive value; only monocytosis >1.5 × 109 /l, hemoglobin <90 g/l, or mild thrombocytopenia <150 × 109 /l suggested congenital neutropenia. The most predictive factors for congenital neutropenia were a medical history (consanguinity and patient history of neutropenia), severe infections, and oral stomatitis or gingivitis at the time of diagnosis. The age at diagnosis had limited predictive value. CONCLUSION: A diagnosis of congenital neutropenia may be reliably suspected based only on information from the CBC, some basic information from patient and parent interviews, and a clinical examination. A pilot score with six factors that could be readily, reliably collected, should facilitate the diagnosis of congenital neutropenia.

Is pegfilgrastim safe and effective in congenital neutropenia? An analysis of the French Severe Chronic Neutropenia registry.

AIMS: To examine the efficacy and safety of pegfilgrastim in patients with congenital neutropenia (CN). METHODS: Seventeen patients enrolled in the French Severe CN Register received pegfilgrastim. RESULTS: Median age at pegfilgrastim introduction was 19.1 years (range 3.9-52.3 years). In 14 cases pegfilgrastim replaced GCSF (filgrastim or lenograstim), after a median of 6.9 years of GCSF therapy. The dose of pegfilgrastim was usually one full vial per injection (except in five children, who received 1/6 to 1/2 a vial), resulting in a dose of between 50 and 286 microg/kg. The pegfilgrastim schedule ranged from two injections every 7 days to one injection every 30 days, with treatment-free periods. The median interval between the first and last dose of pegfilgrastim was 0.8 years (0.01-4.1 years). The absolute neutrophil count tended to increase more strongly on pegfilgrastim than on GCSF, but the difference was not statistically significant. During pegfilgrastim therapy, a severe infection occurred in two patients and recurrent ENT infections in two other patients. Bone pain was reported by nine patients, anemia and thrombocytopenia occurred in one patient (WHO grade III), chronic urticaria occurred in one patient (WHO grade III), and a single pegfilgrastim injection was followed by respiratory distress and death 15 days later in a patient with GDSIb. At the last update, 10 patients had stopped receiving pegfilgrastim and seven patients were still receiving pegfilgrastim. CONCLUSION: Compared to conventional GCSF, pegfilgrastim is more difficult to use in congenital neutropenia, with more frequent adverse events and sometimes poor efficacy.

Congenital neutropenia: diagnosis, molecular bases and patient management.

The term congenital neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, severe (<0.5 G/l) or mild (between 0.5-1.5 G/l), which may also affect other organ systems such as the pancreas, central nervous system, heart, muscle and skin. Neutropenia can lead to life-threatening pyogenic infections, acute gingivostomatitis and chronic parodontal disease, and each successive infection may leave permanent sequelae. The risk of infection is roughly inversely proportional to the circulating polymorphonuclear neutrophil count and is particularly high at counts below 0.2 G/l.When neutropenia is detected, an attempt should be made to establish the etiology, distinguishing between acquired forms (the most frequent, including post viral neutropenia and auto immune neutropenia) and congenital forms that may either be isolated or part of a complex genetic disease.Except for ethnic neutropenia, which is a frequent but mild congenital form, probably with polygenic inheritance, all other forms of congenital neutropenia are extremely rare and have monogenic inheritance, which may be X-linked or autosomal, recessive or dominant.About half the forms of congenital neutropenia with no extra-hematopoietic manifestations and normal adaptive immunity are due to neutrophil elastase (ELANE) mutations. Some patients have severe permanent neutropenia and frequent infections early in life, while others have mild intermittent neutropenia.Congenital neutropenia may also be associated with a wide range of organ dysfunctions, as for example in Shwachman-Diamond syndrome (associated with pancreatic insufficiency) and glycogen storage disease type Ib (associated with a glycogen storage syndrome). So far, the molecular bases of 12 neutropenic disorders have been identified.Treatment of severe chronic neutropenia should focus on prevention of infections. It includes antimicrobial prophylaxis, generally with trimethoprim-sulfamethoxazole, and also granulocyte-colony-stimulating factor (G-CSF). G-CSF has considerably improved these patients' outlook. It is usually well tolerated, but potential adverse effects include thrombocytopenia, glomerulonephritis, vasculitis and osteoporosis. Long-term treatment with G-CSF, especially at high doses, augments the spontaneous risk of leukemia in patients with congenital neutropenia.