General AML

Long-Lasting Protective Effect of Posaconazole Prophylaxis in Patients with AML Receiving Allo-HSCT

Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) is considered to be curative treatment in Acute Myeloid Leukemia (AML) patients with high risk of relapse or whom have already relapsed after treatment. However, Invasive Fungal Infections (IFIs) are a major cause of concern for recipients of allo-HSCT. Patients are often treated with immunosuppressant therapy in order to prevent graft rejection and to alleviate graft versus host reactions. Unfortunately, this can result in the patients becoming immunocompromised and vulnerable to systemic infections.

These type of infections are problematic and often lead to increased morbidity and mortality in patients. Since allo-HSCT procedures are frequently used to treat AML, IFIs need to be managed in order to improve the unfavorable outcomes. According to Busca et al., there have been four main approaches to managing fungal infections in immunocompromised patients. These include the following1:

  1. Prophylaxis with an antifungal during the period the patient is at high risk of infection
  2. Initiation of an antifungal treatment as soon as the patient displays symptoms of an infection
  3. The employment of a diagnostic driven approach using laboratory markers to correctly identify the type of fungal infection, then treating the infection during the early phase
  4. The treatment of an already established infection where the diagnosis was based on the EORTC/MSG criteria

Azoles tend to be the mainstay of IFI therapy in immunocompromised patients. In another recent study, Busca et al. investigated whether the risk of IFI in AML patients receiving allo-HSCT could be reduced through antifungal prophylaxis with posaconazole administered during induction/salvage chemotherapy treatment.

The potential antifungal prophylactic effects of posaconazole was compared to conventional azole therapy in 229 patients.

The authors reported that the 1-year cumulative incidence of proven/probable IFI after allo-HSCT for patients treated with the conventional azole therapy versus posaconazole was 14% and 4%, respectively (P = .012). They concluded that the prophylactic use of posaconazole during induction/salvage chemotherapy may help to reduce the risk of fungal infection post–HSCT, thus potentially improving patient outcomes.

The study was published in Biology of Blood and Marrow Transplant in September 2016.

Please find the published abstract below:

Long-Lasting Protective Effect of Posaconazole Prophylaxis in Patients with Acute Myeloid Leukemia Receiving Allogeneic Hematopoietic Stem Cell Transplantation
Highlights
  • We analyzed invasive fungal infections after hematopoietic stem cell transplantation in 229 patients with acute myeloid leukemia who received antifungal prophylaxis with posaconazole or conventional azoles, during induction/salvage chemotherapy
  • The 1-year cumulative incidence of invasive fungal infections after hematopoietic stem cell transplantation was 14% and 4% in patients who received conventional azoles (group A) or (group B), respectively (P = .012)
  • Multivariate analysis identified the use of alternative donors, prophylaxis with conventional azoles, and reduced-intensity conditionings as independent risk factors for the development of invasive fungal infections after hematopoietic stem cell transplantation
  • Posaconazole prophylaxis during induction/salvage chemotherapy may significantly reduce the fungal burden, thereby limiting the development of overt infection in later phases of the disease including the post–hematopoietic stem cell transplantation period
Abstract

Patients with acute myeloid leukemia (AML) during induction chemotherapy and those who receive allogeneic hematopoietic stem cell transplantation (HSCT) are at higher risk of invasive fungal infections (IFI). In the present study, we investigated whether the risk of IFI in AML patients receiving HSCT might be affected by the antifungal prophylaxis with posaconazole administered during the induction/salvage chemotherapy treatment. Between August 2001 and April 2015, 130 patients with AML received itraconazole/fluconazole (group A) and 99 received posaconazole (group B) as antifungal prophylaxis after induction/salvage chemotherapy at 7 Italian centers and all patients received fluconazole as antifungal prophylaxis after HSCT. The median duration of antifungal prophylaxis after induction/salvage chemotherapy was significantly longer for patients in group A than for those in group B (24 days versus 20 days, P = .019). The 1-year cumulative incidence of proven/probable IFI after HSCT was 14% and 4% in group A and group B, respectively (P = .012). Fungal-free survival and overall survival at 1 year after HSCT were 66% and 70% in group A, and 75% and 77% in group B (P = .139 and P = .302), respectively. Multivariate logistic analysis identified the use of alternative donors (matched unrelated donor: odds ratio [OR], 3.25; haploidentical/partially matched related donor: OR, 3.19), antifungal prophylaxis with itraconazole/fluconazole (OR, 3.82), and reduced-intensity conditioning (OR, 4.92) as independent risk factors for the development of IFI after HSCT. In summary, the present study suggests that the protective effects of posaconazole during induction/salvage chemotherapy for AML patients may have long-lasting benefits and eventually contribute to reduce the risk of IFI when patients undergo allogeneic HSCT.

References
  1. Busca A. & Pagano L. Antifungal therapy in Hematopoietic Stem Cell Transplant Recipients. Mediterr J Hematol Infect Dis. 2016 Sep 1; 8(1):e2016039. doi: 10.4084/MJHID.2016.039. eCollection 2016.
  2. Busca A. et al. Long-Lasting Protective Effect of Posaconazole Prophylaxis in Patients with Acute Myeloid Leukemia Receiving Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2016 Sep 22. pii: S1083-8791(16)30359-7. doi: 10.1016/j.bbmt.2016.09.019. [Epub ahead of print].