**13. Conclusions**

**Type of study and target population Main results**

significantly recovery (neutrophil count >1.5 × 10<sup>9</sup>

**12. Hematopoietic growth factors (HGF)**

196 Hematology - Latest Research and Clinical Advances

Treatment with hematopoietic growth factors was associated with a statistically significantly lower rate of infectious and fatal complications, in cases with a neutrophil count <0.1 × 109

/L) was observed in the HGF group: 2.1 days

*G-CSF* or *GM-CSF* (100 to 600 μg/day) reduced the mean time

*G-CSF* and *GM-CSF* (100 to 600 μg/day) reduced the recovery of neutrophil count from 7 to 4 days, particularly in patients with a

*G-CSF* (300 μg/day) significantly reduced the mean duration for hematological recovery from 8.8 to 6.6 days (p < 0.04). *G-CSF*

*G-CSF* (300 μg/day) significantly reduced the mean durations of hematological recovery, antibiotic therapy and hospitalization from: 11.6 to 6.8 days, 12 to 7.5 days and 13 to 7.3 days, respectively

*G-CSF* shortens time to recovery in patients with agranulocytosis

*G-CSF* (300 μg/day) reduced the mean durations of hematological

*G-CSF* (100 to 200 μg/day) did not significantly reduce the mean

to neutrophil recovery (neutrophil count >0.5 × 109

7.7 days, in cases with a neutrophil count <0.1 × 109

/L

(p < 0.05 in all cases). *G-CSF* reduced the global cost

the mortality rate from 16 to 4.2%

neutrophil count <0.1 × 109

is considered in patients at high-risk of serious Gram-positive infections or after 48 hours of

In patients with persistent fever despite broad-spectrum antibiotics against Gram-negative bacilli or Gram-positive cocci or systematically after 1 week of persistent fever, the addition of empirical antifungal agents should be considered, as amphotericin B or related derivates (e.g.,

Since 1985, two-thirds of reported cases of idiosyncratic agranulocytosis have been treated with HGF, especially *granulocyte-colony stimulating factor* (G-CSF) [9]. The most recent, major studies on hematopoietic growth factors (HGF) use in drug-induced agranulocytosis are described in **Table 4** [2, 5, 10–15]. In our aforementioned cohort, a faster hematological non-

continued fever despite first-line of antibiotics with at least cephalosporins [2, 3].

liposomal preparation of amphotericin), and voriconazol or caspofungin [2, 3].

reduced the global cost

recovery for 2.1 days (p = 0.057).

duration for hematological recovery

G-CSF: Granulocyte-Colony Stimulating factor; GM-CSF: Granulocyte-Macrophage-Colony Stimulating factor

**Table 4.** Recent studies on the use of hematopoietic growth factors in idiosyncratic drug-induced agranulocytosis.

/L

/L) from 10 to

/L, and reduced

Systematic review of all published cases (n = 492); all patients with idiosyncratic drug-

Meta-analysis (n = 118); all patients with idiosyncratic drug-induced agranulocytosis [10]

Case control study, retrospective analysis (n = 70); all patients with idiosyncratic drug-

Cohort study, retrospective analysis (n = 54); patients with idiosyncratic drug-induced agranulocytosis >65 years of age, with poor

Cohort study, retrospective analysis (n = 20); patients with antithyroid drug-induced agranulocytosis and poor prognostic factors

Cohort study, retrospective analysis (n = 145); all patients with idiosyncratic drug-induced

Cohort study, retrospective analysis (n = 201); all patients with idiosyncratic drug-induced

Prospective randomized study (n = 24); all patients with antithyroid drug-induced

induced agranulocytosis [2]

induced agranulocytosis [11]

prognostic factors [12]

agranulocytosis [14]

agranulocytosis [5]

agranulocytosis [15]

[13]

In conclusion, it is important to keep in mind that idiosyncratic drug-induced or drug-associated, severe neutropenia and agranulocytosis remains a potentially serious adverse event due to the frequency of severe sepsis, with severe deep tissue infections (e.g., pneumonia), life-threatening infections, septicemia, and septic shock in two-thirds of all hospitalized patients. In this setting, several poor prognostic factors, impacting the hematological recovery, the duration of hospitalization, and the outcome have been documented: old age, poor performance status, septicemia or shock, comorbidities such as renal failure, and a neutrophil count below 0.1 × 109 /L. In this situation, modern management, with broad-spectrum antibiotics in case of any sepsis sign and HGF is likely to improve the prognosis, with a currently mortality rate around 5%.
