Thyroid carcinoma at King Edward VIII Hospital, Durban, South Africa

(East African Medical Journal: 2001 78(5): 242-245

Alternative Versus Matched Donor Allogeneic Hematopoietic Transplantation for Afro-Caribbean and Latin American HTLV1-Associated Adult T Cell Leukemia/Lymphoma

Adult T-cell Leukemia/Lymphoma (ATLL) is a rare and aggressive malignancy caused by the human T-cell leukemia virus type 1 (HTLV-1). ATLL carries a dismal prognosis given early relapses and a low durable remission rate. When feasible, hematopoietic stem cell transplantation (HSCT) is pursued to maximize chances for cure and long-term survival. A recent meta-analysis affirmed the utility of allo-HSCT, reporting complete remission (CR) rates of 70%, overall survival (OS) rates of 40%, and progression-free survival (PFS) rates of 37% at 3 years (Iqbal, 2019). However, most data in ATLL consists of Japanese populations. There is limited data on the Afro-Caribbean and Latin American population which is more commonly encountered in the USA and Europe. This study aims to evaluate the outcomes of HSCT in patients of Afro-Caribbean and Latin American descent, comparing them to HSCT recipients who received grafts from matched donors at the Sylvester Comprehensive Cancer Center, the University of Pennsylvania, and M.D. Anderson Cancer Center. We compiled the databases of three cancer centers to study the demographic characteristics and immunohistochemical signatures, therapeutic interventions, and survival outcomes. Kaplan-Meier survival curves were constructed. Nineteen Afro-Caribbean ATLL patients who underwent HSCT were included in the analysis. The median age at the time of transplant was 54 years, 58% were female, and the most common subtype of ATLL was lymphomatous (70%). Median number of lines of therapy before HSCT was 2. Sixteen (84.2%) patients were in CR prior to transplant. Alternative donors were used in 63.2% of patients (12), and reduced intensity conditioning was used in 79% (15 patients). Peripheral blood stem cell source was used in 15 patients (79%). After HSCT, at a median follow-up of 11.7 months, the median OS was 44.4 months and PFS was 31 months. 6/19 patients (32%) remain alive and in remission. Non-relapse mortality was noted in 21% (4) patients. Post-HSCT relapse was seen in 47.4% (9 patients). In this group, 36.8 % (7) of patients developed acute GVHD and 16% (3) developed chronic GVHD. In this small cohort, there was no difference in the median OS between matched versus alternative donor HSCT (36.8 months versus 27.6 months, p=0.72). Our multicenter study demonstrates that while HSCT can lead to durable PFS and OS in a subset of patients, outcomes still leave room for improvement and new treatment advances. We demonstrate the high frequency of alternative donor transplantation, as well as a high rate of post-HSCT relapse and toxicity. Our next step is to expand this database nationwide to identify modifiable transplant risk factors to optimize survival

Microanatomic Distribution of Myeloid Heme Oxygenase-1 Protects against Free Radical-Mediated Immunopathology in Human Tuberculosis

Summary: Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that controls inflammatory responses and redox homeostasis; however, its role during pulmonary tuberculosis (TB) remains unclear. Using freshly resected human TB lung tissue, we examined the role of HO-1 within the cellular and pathological spectrum of TB. Flow cytometry and histopathological analysis of human TB lung tissues showed that HO-1 is expressed primarily in myeloid cells and that HO-1 levels in these cells were directly proportional to cytoprotection. HO-1 mitigates TB pathophysiology by diminishing myeloid cell-mediated oxidative damage caused by reactive oxygen and/or nitrogen intermediates, which control granulocytic karyorrhexis to generate a zonal HO-1 response. Using whole-body or myeloid-specific HO-1-deficient mice, we demonstrate that HO-1 is required to control myeloid cell infiltration and inflammation to protect against TB progression. Overall, this study reveals that zonation of HO-1 in myeloid cells modulates free-radical-mediated stress, which regulates human TB immunopathology. : Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that controls inflammation and redox homeostasis; however, its role in tuberculosis (TB) is unclear. Using freshly resected human lung tissue and HO-1-deficient mice, Chinta et al. demonstrate that HO-1 in myeloid cells is important for controlling inflammatory and free-radical-mediated tissue damage in TB. Keywords: mycobacterium tuberculosis, heme oxygenase-1, human pulmonary tuberculosis, histopathological spectrum, human TB pathology, myeloid cell inflammation, macrophage, neutrophil, karyorrhexis, free radica