High incidence of invasive fungal infection during acute myeloid leukemia treatment in a resource-limited country: clinical risk factors and treatment outcomes.

BACKGROUND: Invasive fungal infection (IFI) causes high morbidity and mortality during acute myeloid leukemia (AML) treatment. Interventions to prevent fungal infection, including air filtration systems and antifungal prophylaxis, may improve outcomes in this group of patients. However, they are expensive and therefore inapplicable in resource-limited countries. The benefit of antifungal therapy is also dependent on the local epidemiology. That led us to conduct the study to evaluate the characteristics and impact of IFI in AML patients without prophylaxis in our setting. METHODS: Clinical data from patients with AML who have been treated with chemotherapy without antifungal prophylaxis were retrieved during a 5-year period at Thailand's hematology referral center. Incidence and risk factors of IFI and outcomes of patients were evaluated. RESULTS: Among 292 chemotherapy courses, there were 65 (22.3%) episodes of IFI. Of those, 10 (15.4%) were proven, 19 (29.2%) were probable, and 36 (55.4%) were categorized as being possible IFI. Molds were the most commonly observed causative pathogens (93.1%). The incidence of probable/proven IFI was highest during first induction (20.5%), followed by second induction (6.1%), and consolidation (2.7%). A long duration of neutropenia, old age, and low serum albumin were the strongest predictors of IFI. Compared with patients who had no IFI, patients with probable/proven IFI had a longer length of hospital stay and higher in-hospital mortality. Patients with proven IFI had a significantly worse outcome at 1 year. CONCLUSIONS: These results suggest the change in health policy to implement IFI preventive measures to improve outcomes of AML treatment.

Correction to: High incidence of invasive fungal infection during acute myeloid leukemia treatment in a resource-limited country: clinical risk factors and treatment outcomes.

Incorrect family name of Warissara Jutidamrongphan.

INVASIVE FUNGAL INFECTION AMONG FEBRILE PATIENTS WITH CHEMOTHERAPY-INDUCED NEUTROPENIA IN THAILAND.

Invasive fungal infections (IFI) can cause serious morbidity and mortality among febrile patients with chemotherapy-induced neutropenia (CIN). In order to evaluate the incidence, treatment outcome and factors associated with IFI in this patient population in Thailand, we retrospectively reviewed the medical record of patients admitted to Siriraj Hospital from January 2008 to June 2010. Criteria used to diagnosed IFI were those of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases/Mycoses Study Group (EORTC/MSG) consensus 2008 criteria. Three hundred ten episodes of chemotherapy-induced neutropenia occurred in 233 patients. IFI were found in 37 episodes (12%) and occurred only in patients who received chemotherapy for hematological malignancies. The incidence of IFI among patients with hematologic malignancies was 14%. Most commonly occurred in AML patients (17%). Patients who received aggressive induction chemotherapy regimens for AML had the highest incidence of IFI (20.5%). Of the 37 episodes, 12 were candidiasis, 5 were aspergillosis, 1 was zygomycosis, 1 was fusariosis, 10 were probable and 9 were possible IFI. The IFI-related mortality was 35%. The clinical factor associated with IFI was a temperature > 39 °C during febrile neutropenia. A higher mortality rate was seen in patients aged > 40 years and those with a serum albumin level < 3 g/dl.

Dihydroartemisinin Induced Apoptosis and Synergized With Chemotherapy in Pleural Effusion Lymphoma Cells.

BACKGROUND/AIM: Primary effusion lymphoma (PEL) is a rare aggressive B-cell lymphoma associated with HHV-8. With a median survival of fewer than six months, the prognosis of the disease with current standard therapies is usually dismal. Dihydroartemisinin (DHA) is a derivative of artemisinin, originally designed as an antimalarial drug. Several studies have shown that this compound also demonstrates anti-cancer activity in various types of cancer, including hematologic malignancies. MATERIALS AND METHODS: Anti-proliferation activity of DHA on 5 PEL cell lines was assessed by MTT assay. Cell cycle arrest was determined by propidium iodide staining and flow cytometry analysis. DHA-induced PEL apoptosis was shown by annexin V/PI staining and western blotting for cleaved caspases 3, 8, and 9. An inhibitory effect on PEL growth was evaluated in a PEL-xenograft mouse model. A synergistic effect of DHA and doxorubicin combination treatment was shown in vitro. RESULTS: DHA showed anti-proliferative activity on PEL and induced caspase-dependent apoptosis in a time- and dose-dependent manner. DHA-induced cell death appeared to be triggered by increased levels of reactive oxygen species (ROS). N-acetylcysteine treatment inhibited DHA-induced ROS elevation and suppressed expression of cleaved caspases leading to significantly reduced PEL apoptosis. DHA treatment also demonstrated an inhibitory effect on PEL cell growth in an in-vivo xenograft model. Moreover, we found that a combination treatment of DHA and doxorubicin, the standard chemotherapy drug for PEL, demonstrated a synergistic effect on PEL cell lines. CONCLUSION: DHA is a potentially effective candidate drug for PEL treatment.

High prevalence of Wilms tumor 1 expression in multiple myeloma and plasmacytoma: A cohort of 142 Asian patients' samples.

Wilms tumor 1 (WT1) is a promising target antigen for cancer immunotherapy. However, WT1 protein expression and its clinical correlation in multiple myeloma (MM) patients are still limited. We, therefore, investigated WT1 expression in 142 bone marrow and plasmacytoma samples of MM patients at different stages of the disease by immunohistochemistry. The correlations between WT1 expression and clinical parameters or treatment outcomes were evaluated. The overall positive rate of WT1 expression was 91.5%; this high prevalence was found in both bone marrow and plasmacytoma samples, regardless of the disease status. Cytoplasmic WT1 expression was correlated with high serum free light chain ratio at presentation. However, no significant association between WT1 expression and treatment outcome was observed. This study confirms the high prevalence of WT1 expression in an Asian cohort of MM, encouraging the development of immunotherapy targeting WT1 in MM patients, particularly in those with extramedullary plasmacytoma or relapsed disease.

Comparative Efficacy and Clinical Outcomes of Haploidentical Stem Cell Transplantation to Other Stem Sources for Treatment in Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients: A Systematic Review and Meta-Analysis.

The use of allogeneic hematopoietic stem cell transplantation (HSCT) is recommended during the first complete remission of acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). However, only 30% of these cases have fully matched sibling donors (MSDs). Alternatively, matched unrelated donors (MUDs) and haploidentical (haplo) donors from first-degree relatives increase the access to transplantation, with some reported differences in outcomes. The current systematic review and meta-analysis was conducted with the aim of summarizing the results of those studies to compare the efficacy and toxicity of MSD-HSCT and MUD-HSCT versus haplo-HSCT for patients with AML or MDS. Articles published before September 15, 2018, were individually searched for in two databases (MEDLINE and EMBASE) by two investigators. The effect estimates and 95% confidence intervals (CIs) from each eligible study were combined using the Mantel-Haenszel method. A total of 14 studies met the eligibility criteria and were included in the meta-analysis. The overall survival rates were not significantly different between the groups, with pooled odds ratios of the chance of surviving at the end of the study when comparing haplo-HSCT to MSD-HSCT and comparing haplo-HSCT to MUD-HSCT of 0.85 (95% CI: 0.70 to 1.04; I2 = 0%) and 1.12 (95% CI: 0.89 to 1.41; I2 = 33%), respectively. The pooled analyses of other outcomes also showed comparable results, except for the higher grade 2 to 4 acute graft-versus-host disease (GvHD) for patients who received haplo-HSCT than those who received MSD-HSCT, and the better GvHD-free, relapse-free survival and the lower chronic GvHD than the patients in the MUD-HSCT group. These observations suggest that haplo-HSCT is a reasonable alternative with comparable efficacy if MSD-HSCT and MUD-HSCT cannot be performed. Nonetheless, the primary studies included in this meta-analysis were observational in nature, and randomized-controlled trials are still needed to confirm the efficacy of haplo-HSCT.