Continuous Complete Remission in Two Patients with Acute Lymphoblastic Leukemia and Severe Fungal Infection Following Short-Term, Dose-Reduced Chemotherapy

Spontaneous remission in acute lymphoblastic leukemia (ALL) is a rare phenomenon, which typically involves a pattern of feverish or septic disease followed by quick but mostly transient remission. We report on two male patients (46-year-old (pt. 1) and 19-year-old (pt. 2)) with CD20 positive, BCR-ABL negative common B-ALL. Patient 1 had received dexamethasone and cyclophosphamide (1.2 g) as a prephase therapy, followed by rituximab and a cumulative dose of 200 mg daunorubicin combined with 2 mg vincristine as an induction therapy. Patient 2 was treated with a reduced therapy regimen (Vincristine 1 mg, dexamethasone and 80 mg daunorubicin, 12-month mercaptopurine maintenance) due to (alcohol-related) toxic liver failure and pontine myelinolysis. Both patients developed severe septic disease just few days into induction treatment. Patient 1 suffered from pulmonary mycosis, which had to be resected eventually. Histological work-up revealed invasive mucor mycosis. Patient 2 presented with elevated serum aspergillus antigen and radiographic pulmonary lesions, indicative of pulmonary mycosis. In both patients, chemotherapy had to be interrupted and could not be resumed. Both patients recovered under broad antimicrobial, antifungal and prophylactic antiviral therapy and achieved molecular complete remission. At data cut-off remissions had been on-going for 34 months (pt. 1) and 8 years (pt. 2). Short-term, reduced intensity induction chemotherapy accompanied by severe fungal infections was followed by long-lasting continuous complete remissions in ALL. Thus, we hypothesize that infection-associated immunogenic responses may not only prevent early relapse of ALL but could also eradicate minimal residual disease. The effects of combined cytotoxic therapy and severe infection may also be mimicked by biomodulatory treatment strategies aiming at reorganizing pathologically altered cellular signaling networks. This could reduce toxicity and comorbidity in adult patients requiring leukemia treatment. Therefore, these two cases should encourage systematic studies on how leukemia stroma interaction can be harnessed to achieve long lasting control of ALL.

Profiling of Pulmonary Fungal Pathogens and the Prevalence of Pulmonary Tuberculosis Fungal Co-Infection in Presumptive Tuberculosis Patients Referred to Saint Peter’s Tuberculosis Referral Hospital, Addis Ababa, Ethiopia

Background: The burden of pulmonary mycosis is increasing and often misdiagnosed as pulmonary tuberculosis in developing countries where the prevalence of pulmonary tuberculosis is high. Objective: To determine the prevalence of pulmonary mycosis and pulmonary tuberculosis fungal co-infections. Methods: A hospital-based, cross-sectional study was conducted between October 2019 and May 2019. Sputum was collected from 636 study subjects. Part of the sputum was inoculated onto Brain Heart Infusion agar and fungi were identified following standard microbiological procedures. The remaining part of the sample was used for the investigation of pulmonary tuberculosis by GeneXpert.Results: Among 636 sputum samples, 75.9% (483), 25.6% (163), and 20% (127) were positive for fungal pathogens, pulmonary tuberculosis, and pulmonary tuberculosis fungal co-infection, respectively. Of 690 fungal isolates, 81.4% were yeasts compromising of 46.3% Candida albicans 52.7% Non-albicans Candida species, and 1.0% Cryptococcus neoformans. The remaining 128 (18.6%) isolates were molds, where Aspergillus species (79; 61.7%), Penicillium species (16; 12.5%), Scedosporium apiospermum (13; 10.2%), and Fusarium species (10;7.8%) being the major isolates. The isolation rate of fungi was higher in males (51.6%) than in females (48.4%). There was no statistically significant association between the prevalence of pulmonary fungal pathogens and sex (P=0.239). Patients in the age group of 35-44 and above were slightly more affected than younger age groups. The association of fungal pathogens and age was not statistically significant (P=0.50). Conclusions: Our study revealed a high prevalence of pulmonary fungal pathogens (75.4%) and pulmonary fungal co-infection (20%). The isolation rate of Non-albicans Candida species out-numbered that of C. albicans. High prevalence of pulmonary fungal pathogens in our study, especially in cases where sputum for pulmonary tuberculosis was negative alerts, the need to employ conventional microbiology tests along with clinical and radiological evidence.