Documented Infection Load In Patients with Neutropenia; a Survey From the Italian Registry of Neutropenias

Children with severe congenital (SCN), autoimmune (AN) and idiopathic (IN) neutropenia may have infectious complications with high rate of morbidity/mortality. In spite of this scarce data on the incidence and type of documented infections are available in the literature

To describe incidence and type of documented infections in a large population of patients with different types of neutropenia.

Patients affected with SCN, AN and IN followed from 2000 to 2009 in Centres of the Italian Registry of Neutropenia (IRN) entered the study. Anagraphics and disease–realated data were extracted from the IRN, while details about infections were collected through a dedicated CRF containing uniform criteria to define infection type that was sent to each centre.

The occurrence of infections was calculated during a period “at risk” defined as person-days at risk (pdr). The infection rate (IR) was calculated by dividing the number of events by the pdr and expressed as episodes/1000 pdr (95% CI) and was use to compare infection load of neutropenic patients with that of other haematological diseases.

Seventy three patients (28 females and 45 males) of whom 12 (16%) with SCN, 38 (52%) with AN and 23 (32%) with IN were analyzed. At least one infectious episode was observed in 100% of SCN and in 30% of both AN and IN. Overall 2/73 patients died (2,7%). They were both SCN subjects: one deceased from haplo-identical HSCT related complication that was performed for loss of response to G-CSF and the other from sepsis after the parents decided to stop G-CSF treatment.

In the overall study population from birth to last follow-up, a total of 108 infections occurred in 31/73 subjects (42%). Sixty-nine episodes were observed in 12/12 patients with SCN, 25 infections were concentrated in 12/38 AI patients, and 14 episodes in 7/23 IN subjects. Skin/subcutaneous infections (49%) and pneumonia (18%) were the most frequent localizations. Othomastoiditis, tonsillar phlegmons, osteomyelitis occurred in 10% and deep abdominal infections in 5% of subjects, who were almost exclusively SCN patients. Microbiological characterization was possible in only 25% of the episodes and showed a slight prevalence of Gram-negatives without differences according to the type of neutropenia. Fungal infections were diagnosed only in two different SCN subjects. G-CSF was used in all SCN patients, in 26% of AN and 4% of IN. The IR in SCN was significantly higher than in IN/AN along the entire period of observation (p<0.001). In the whole population and in each subgroup, the IR of the time-span from birth to the diagnosis of neutropenia (coinciding with the start of G-CSF treatment in those patients who received this drug) was significantly higher vs IR calculated from the diagnosis to the last follow up (p<0.01).

Among neutropenic children the highest infectious load was observed in SCN, but was not negligible in AN and IN. Skin was the main involved site whereas deep infections are characteristic of SCN. The incidence of infections in SCN is comparable with that of aplastic anemia and slighty lower than in acute lymphoblastic laeukemia receiving aggressive treatments.

The significant decrease of IR after diagnosis of neutropenia can probably be attributed to the increased awareness of the patients/family, to early antibiotic intervention and to the G-CSF therapy. Overall these data suggest that also non SCN patients may benefit of specific monitoring/follow up programmes.

No relevant conflicts of interest to declare.