**10. General management**

**9. Prognosis and mortality rate**

194 Hematology - Latest Research and Clinical Advances

reported to range from 4 to 24 days.

(neutrophil count ≥1.5 × 10<sup>9</sup>

phil count ≥0.5 × 10<sup>9</sup>

of <0.1 × 109

Age > 65 years

Idiosyncratic drug-induced severe neutropenia usually resolves over time, with supportive care and management of infection [2, 3]. The time to neutrophil recovery has typically been

In our aforementioned cohort study (n = 203), the mean duration of hematological recovery

In this context, the mortality rate for idiosyncratic agranulocytosis has recently fallen from 10 to 16 to 5% (range 2.5–10%) [2, 3]. This is likely due to improved recognition, management, and treatment of the condition. The highest mortality rate is observed in "frailty" patients: older patients (>65 years), with poor performance status, as well as those with several comorbidities as renal failure (defined as serum creatinine level > 120 μmol/L), chronic heart failure; bacteremia septicemia at diagnosis; or shock at diagnosis (**Table 3**); or low neutrophil count levels [2, 6]. Previously, we have found demonstrated that several variables were significantly associated

significantly associated with a longer neutrophil recovery time. In our cohort, bone marrow showing a lack of myeloid cells was not found to be associated with a delayed recovery (using

It is worth noting, that in elderly patients, clinical manifestations were generally more severe, with septicemia or septic shock in at least two-thirds of patients, as we have previously published [8]. It is also the case in patients with associated morbidities as chronic cardiac failure, chronic obstructive pulmonary disease, renal failure and immune disorders. In our experience, the depth of the neutropenia impacts the severity of the clinical, manifestations [7].

/L at diagnosis, as well as septicemia and/or shock [7], were variables that were

antibiotherapy

antibiotherapy

/L.

antibiotherapy and of mortality

recovery and hospitalization

/L is 6.8 days (range: 1–24).

with a longer neutrophil recovery time (>1.5 × 109

/L

\*Prognosis: hematological recovery, duration of hospitalization and antibiotherapy, mortality).

**Table 3.** Impact factors for the prognosis\* of idiosyncratic drug-induced agranulocytosis.

Clinical status: Deep severe infections or bacteremia or septic

\*\*Hematological recovery: absolute neutrophil count >1.5 × 109

Severe underlying disease or severe co-morbidity: Renal failure, cardiac or respiratory failure, systemic auto-

Management with pre-established procedures and hematopoietic growth factor for use in severe conditions

uni- and multivariate analysis) [5].

Neutrophil count at diagnosis: ≤0.1 × 10<sup>9</sup>

shock (versus isolated fever)

inflammatory diseases

/L) is 7.8 days (range: 2–20) [5]. The median duration for neutro-

/L), as: that an absolute neutrophil count

Negative impact on duration of hematological recovery\*\*, duration of hospitalization and

Negative impact on duration of hematological recovery, duration of hospitalization and

Negative impact on duration of hematological

duration of hospitalization and of mortality

Negative impact on duration of hospitalization and

Positive impact on duration of hematological recovery,

The management of idiosyncratic drug-induced severe neutropenia and agranulocytosis begins with the immediate withdrawal of any medications, which may potentially be responsible [2, 3]. Thus, the patient's medication history must be carefully obtained in chronological order so that the suspected agent(s) may be identified.

For experts, routine monitoring for agranulocytosis is required in some high-risk drugs, such as clozapine, ticlopidine, and antithyroid drugs [2, 3]. All cases of drug-induced neutropenia must be notified to the pharmacovigilance center. All febrile patients should be admitted to hospital, without any delay [2, 3].

Concomitant measures include realization of multiple microbial samples (blood, urine, stool, and sputum cultures) and aggressive treatment of confirmed or potential sepsis, as well as the prevention of secondary infections. It should be noted that as a result of neutrophil deficiency, both the patient's symptoms and the physical findings may be altered, and fever may be the only clinical sign [3]. Preventive measures include good hygiene and infection control, paying particular attention to high-risk areas such as the mouth, skin, and perineum [2, 3].

Patients with a low-risk of infection, and good performance status may be managed in home with intensive supervision and monitoring! The occurrence of sepsis requires prompt management, without any delay, including the administration of broad-spectrum intravenous antibiotic therapy [2, 3].

In case of fever or for "frailty" patients, prompt hospitalization without delay may be required [2, 3]. In this setting, patient isolation and the use of prophylactic antibiotics (e.g., for the gastrointestinal tract) have been proposed, but their usefulness in limiting the risk of infection has not been documented or at least, has not been clinically proven [3].
