Infection risk in AML- ASH 2020 education program

Leukemia- infectious prophylaxis

AML and infections

 1. FN occurs in >80% of patients undergoing chemotherapy for acute leukemia. Infection is identified in < 50%.

2. A number of small studies indicate that de-escalation after 72 hours is safe in clinically stable patients with no infection identified, regardless of ongoing neutropenia and in some cases ongoing fever.

3. National Comprehensive Cancer Network (NCCN) guidelines now also suggest that clinically stable patients with persistent neutropenia without fever can be evaluated for discontinuation or de-escalation of BSAs to prophylaxis in some settings.

4. de-escalation to prophylaxis in patients with resolution of fever and no documented infection after 48 to 72 hours does not lead to a significant increase in subsequent bacterial infections, clinical decompensation, or in-hospital mortality.

5. voriconazole has not been approved for use as primary prophylaxis. It has activity against some opportunistic molds and is a first-line agent for the treatment of invasive aspergillosis.

6. Posaconazole is now recommended for primary fungal prophylaxis in patients with AML undergoing induction chemotherapy. A trough level after 5 to 7 days of therapy with a goal concentration of >0.7 μg/mL is recommended. 

7. Isavuconazole is a newer second-generation azole approved for the treatment of both invasive aspergillosis and invasive mucormycosis. It is available in oral and IV formulations, has a broad spectrum of activity, and has a more favorable adverse effect profile and less significant drug-drug interactions compared with other triazoles. It is not routinely used for prophylaxis, although 1 study demonstrated safety and tolerability for use in high-risk patients. Unlike other triazoles, isavuconazole does not induce prolongation of the QTc interval,

8. IDH1 ( ivosidenib) and IDH2( enasidenib) inhibitors are used in the appropriate patients in the relapsed or refractory setting. Typically no increased risk of infections, but avoid azoles. If the two ie azole and IDH inhibitor need to be used together esp reduce the ivosidenib dose.

9. Glasdegib is a selective inhibitor of the Hedgehog signaling pathway with primary use in patients who are not candidates for intensive chemotherapy. There has been no additional infection risk associated with the use.

10.  Mylotarg (gemtuzumab ozogamicin) therapy is associated with hepatic veno-occlusive disease in patients who have not received stem cell transplantation. demonstrated rates of infection are comparable to other regimens causing neutropenia. Standard prophylactic strategies for patients with AML.

Therapeutics for ALL

1. TKI such as imatinib etc: TK inhibitors significantly impair B-cell responses leading to less robust response to vaccinations. modest increase in the risk of infection, more so with dasatinib, notably CMV and hepatitis B virus (HBV) reactivation. Screening for chronic HBV infection is recommended prior to therapy. No routine antiinfective prophy required.

2. Blinatumomab- anti CD 19 BiTE Ab. Risk of herpes reactivation, acyclovir recommended. Risk of PJP, so prophy. Screen for Hep B. consider antifungal.