Prognostic Role of Human Leukocyte Antigen Alleles and Cytokine Single-Nucleotide Polymorphisms in Patients with Chronic Myeloid Leukemia Treated with Tyrosine Kinase Inhibitor Drugs.

Tyrosine kinase inhibitor (TKI) drugs have significantly improved chronic myeloid leukemia (CML) outcomes. Neopeptides from CML cells may induce specific immune responses, which are crucial for deep molecular (DMR) and treatment-free remission (TFR). In this study of Ethiopian patients with CML (n = 162), the HLA alleles and single-nucleotide polymorphisms of five cytokines revealed significant associations with clinical outcomes. Clinically unfavorable outcomes correlated with HLA alleles A*03:01/02, A*23:17:01, B*57:01/02/03, and HLA-DRB4*01:01 (p-value = 0.0347, p-value = 0.0285, p-value = 0.037, and p-value = 0.0127, respectively), while HLA-DRB4*01:03:01 was associated with favorable outcomes (p-value = 0.0058). After assigning values for the 'low', 'intermediate', and 'high' gene expression of the SNPs' respective cytokine genes, Kaplan-Meier estimates for relapse-free survival, adjusted for age, treatment duration, and relapse risk among patients after the administration of TKIs, indicated that a gene expression ratio above the overall median of TNF-α, IL-6, and the combination of TGF-ß1/IL-10, IFNγ, and IL-6/IL-10 TGF-ß1 was correlated with a higher likelihood of treatment failure ((RR: 3.01; 95% CI: 1.1-8.3; p-value = 0.0261) and (RR: 2.4; 95% CI: 1.1-5.2; p-value = 0.022), respectively). Multi-SNPs, surpassing single-SNPs, and HLA allele polymorphisms showed promise in predicting outcomes of patients with CML during TKI treatment, prompting further exploration into their potential utility.

Estimating prognostic relevant cutoff values for a multiplex PCR detecting BCR::ABL1 in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy in resource-limited settings.

The prognosis of chronic myeloid leukemia (CML) on tyrosine kinase inhibitor (TKI) treatment is based on the quantification of BCR::ABL1 fusion gene transcript copy number, harmonized by an international scale (IS) based on TaqMan-based real-time quantitative PCR (qRT-PCR). In Ethiopia, as in most low- and middle-income countries (LMICs), access to standard diagnostic, follow-up, and prognostic tools is very limited, and it has been challenging to strictly follow international guidelines. This seriously compromises clinical outcome, despite the availability of TKIs through the Glivec International Patient Assistance Program (GIPAP). Multiplex PCR (mpx-PCR), conventionally regarded as a "screening tool," offers a potential solution to this problem. A total of 219 samples from confirmed CML patients were assayed. In reference to qRT-PCR, the AUC of ROC curve for mpx-PCR was 0.983 (95% CI: 0.957 to 0.997). At the optimum cut-off value, equivalent to BCR::ABL1 (IS) transcript copy number of 0.6%, the specificity and sensitivity were 93% and 95%, respectively, with 94% accuracy. Albeit the sensitivity and accuracy of mpx-PCR decrease below the optimum cutoff of 0.6% (IS), the specificity at 0.1% (IS) was 100%, making it an attractive means to rule-out relapse and drug non-adherence at later stages of treatment, which is particularly an issue in a low income setting. We conclude that the relative simplicity and low cost of mpx-PCR and prognostic relevant cutoff values (0.1-0.6% IS) should allow its use in peripheral clinics and thus maximize the positive impact of TKIs made available through GIPAP in most LMICs.

Microbial spectrum and drug-resistance profile of isolates causing bloodstream infections in febrile cancer patients at a referral hospital in Addis Ababa, Ethiopia.

BACKGROUND: The spectrum of pathogens causing bloodstream infections (BSIs) in cancer patients has shown significant fluctuations in different geographical areas and time. We studied the microbial spectrum and drug-resistance profile of pathogens causing BSIs in febrile cancer patients at a referral hospital in Ethiopia. METHODS: This cross-sectional study was conducted between December 2011 and June 2012 at Tikur Anbessa Hospital in Addis Ababa. Blood cultures from febrile cancer patients (n=107) were performed. Bacterial and fungal pathogens were identified and antimicrobial susceptibility testing done for the bacterial isolates using the Kirby-Bauer disk diffusion method. RESULTS: A total of 82 pathogens were isolated from 112 blood culture tests of the 76 patients: 71 (86.6%) of the isolates were bacteria and 11 (13.4%) were fungi. The majority (60.5% [43 of 71]) of the isolates were Gram-positive bacteria, where Staphylococcus aureus was predominant (72% [31 of 43]), and 68% of S. aureus isolates were resistant to ceftriaxone and oxacillin. Gram-negative bacteria accounted for 39.5% (28 of 71) of the isolates. Stenotrophomonas maltophilia (17.9% [five of 28]) was the most frequent Gram-negative isolate. In Gram-negative bacteria, the highest rates of resistance were observed in amoxicillin-clavulanic acid (80% [12 of 15]), followed by ceftriaxone (73.3%) and trimethoprim-sulfamethoxazole (73.3%). Multidrug resistance (resistance to three or more types of antibiotics, in this case to ceftriaxone, tetracycline, and trimethoprim-sulfamethoxazole) was observed in 26.3% (13 of 43) of Gram-positive and 40% (six of 16) of Gram-negative bacteria. Neutropenia was an independent risk factor for BSIs (P=0.02). CONCLUSION: Gram-positive bacteria were the predominant etiologic agents of BSIs in Ethiopian patients with cancer. Both Gram-positive and Gram-negative bacteria showed an increasing level of resistance for most of the antibiotics used for empiric therapy. Routine bacterial surveillance and study of their resistance patterns must be an essential component of cancer-related infection control and care in our setting.

Toronto Addis Ababa Academic Collaboration: A Relational, Partnership Model for Building Educational Capacity Between a High- and Low-Income University.

Educational partnerships between academic health sciences centers in high- and low-resource settings are often formed as attempts to address health care disparities. In this Perspective, the authors describe the Toronto Addis Ababa Academic Collaboration (TAAAC), an educational partnership between the University of Toronto and Addis Ababa University. The TAAAC model was designed to help address an urgent need for increased university faculty to teach in the massive expansion of universities in Ethiopia. As TAAAC has developed and expanded, faculty at both institutions have recognized that the need to understand contextual factors and to have clarity about funding, ownership, expertise, and control are essential elements of these types of collaborative initiatives. In describing the TAAAC model, the authors aim to contribute to wider conversations and deeper theoretical understandings about these issues.

Thalassemia syndrome.

A 16 years old female patient diagnosed to have thalassemia syndrome in Black lion Hospital based on clinical presentation, complete blood count, peripheral morphology and bone marrow findings.

Non-secretary multiple myeloma in a young Ethiopian: case report.

Non secretary multiple myeloma (NSMM) is a rare variant of multiple myeloma (MM) with similar clinical and radiologic picture but without monoclonal gammopathy in the serum or urine. A non-secretary type multiple myeloma was diagnosed clinically and radiologically in a young Ethiopian presenting with low back pain. He had a diffuse osteopenia of the iliac bone, punched out lytic skull lesions and plasmacytosis on the bone marrow aspiration. But the serum electrophoresis of the patient did not show M component. Both the variant and the age of the patient are unique features observed in this case report.