SUMMARYThe rising success rate of solid organ (SOT) and haematopoietic stem cell transplantation (HSCT) and modern immunosuppression make transplants the first therapeutic option for many diseases affecting a considerable number of people worldwide. Consequently, developing countries have also grown their transplant programs and have started to face the impact of neglected tropical diseases (NTDs) in transplant recipients. We reviewed the literature data on the epidemiology of NTDs with greatest disease burden, which have affected transplant recipients in developing countries or may represent a threat to transplant recipients living in other regions. Tuberculosis, Leprosy, Chagas disease, Malaria, Leishmaniasis, Dengue, Yellow fever and Measles are the topics included in this review. In addition, we retrospectively revised the experience concerning the management of NTDs at the HSCT program of Amaral Carvalho Foundation, a public transplant program of the state of São Paulo, Brazil.
To address the prognostic value of minimal residual disease (MRD) before unrelated cord blood transplantation (UCBT) in children with acute lymphoblastic leukemia (ALL), we analyzed 170 ALL children transplanted in complete remission (CR) after myeloablative conditioning regimen. In all, 72 (43%) were in first CR (CR1), 77 (45%) in second CR (CR2) and 21 (12%) in third CR (CR3). The median interval from MRD quantification to UCBT was 18 days. All patients received single-unit UCBT. Median follow-up was 4 years. Cumulative incidence (CI) of day-60 neutrophil engraftment was 85%. CI of 4 years relapse was 30%, incidence being lower in patients with negative MRD before UCBT (hazard ratio (HR) ¼ 0.4, P ¼ 0.01) and for those transplanted in CR1 and CR2 (HR ¼ 0.3, P ¼ 0.002). Probability of 4 years leukemia-free survival (LFS) was 44%, (56, 44 and 14% for patients transplanted in CR1, CR2 and CR3, respectively (P ¼ 0.0001)). Patients with negative MRD before UCBT had better LFS after UCBT compared with those with positive MRD (54% vs 29%; HR ¼ 2, P ¼ 0.003). MRD assessment before UCBT for children with ALL in remission allows identifying patients at higher risk of relapse after transplantation. Approaches that may decrease relapse incidence in children given UCBT with positive MRD should be investigated to improve final outcomes.
Wilms' tumor is one of the most common abdominal childhood malignancies. Wilms' tumor rates in Brazil are among the highest in the world. This prompted the Brazilian Wilms' Tumor Study Group to conduct a hospital-based, multicenter, case-control investigation of environmental risk factors for the disease. Between April 1987 and January 1989, the authors collected information on relevant occupational exposures by interviewing the parents of 109 Wilms' tumor cases admitted to hospitals in Sao Paulo, Salvador, Belo Horizonte, and Jau. Also interviewed were the parents of 218 age- and sex-matched control children who had been admitted for treatment of nonneoplastic diseases to the same or nearby hospitals. Odds ratios (ORs) adjusted for income and education were calculated by conditional logistic regression. Consistently elevated risks were seen for farm work involving frequent use of pesticides by both the father (OR = 3.24, 95% confidence interval (CI) 1.2-9.0) and the mother (OR = 128.6, 95% CI 6.4-2,569). These risk elevations were restricted to cases diagnosed after 2 years of age (ORs > 4), for paternal exposure, and after 4 years of age (OR = 14.8, 95% CI 2.2-98.8), for maternal exposure. Risk elevations were also more pronounced among boys (paternal exposure OR = 8.56, 95% CI 2.1-35.1; maternal exposure OR = 4.60, 95% CI 0.8-26.4) than among girls (paternal exposure OR = 1.31, 95% CI 0.4-4.1; maternal exposure OR = 2.03, 95% CI 0.5-8.9).
Fever, skin rash, headache, and thrombocytopenia are considered hallmarks of dengue infection. However, these symptoms are frequently observed in infectious and non-infectious complications of hematopoietic stem cell transplant recipients and oncohematological patients. Thus, laboratory confirmation of dengue is relevant for prompt intervention and proper management of dengue in endemic and non-endemic regions. Because no prospective study of dengue has been conducted in these populations, the actual morbidity and mortality of dengue is unknown. In the present series, we describe five cases of dengue in patients living in endemic areas, emphasizing the prolonged course of the disease and the occurrence of prolonged viremia.
Dendritic cells (DCs) are antigen-presenting cells that drive immune responses and tolerance and are divided in different subsets: myeloid DCs (mDCs: lineage-; HLA-DR+, 11c+), plasmacytoid dendritic cells (pDCs: HLA-DR+, CD123+), and monocyte-derived DCs (moDC: lineage-, 11c+, 16+). After hematopoietic stem cell transplantation (HSCT), low DC counts in the recipients' peripheral blood (PB) have been associated with worse outcomes, but the relevance of DC graft content remains unclear, and there are few data in the setting of unrelated donor HSCT. We evaluated the DC graft content and monitored DC recovery in PB from 111 HSCT recipients (median age, 17 years; range 1 to 74), who received bone marrow (46%), umbilical cord blood (32%), or PB (22%) from unrelated (81%) or related donors (19%). In 86 patients with sustained allogeneic recovery, patients with higher counts of all DC subsets (pDC, mDC, and moDC) 3 weeks after engraftment had lower incidence of nonrelapse mortality (NMR) and acute graft-versus-host disease (aGVHD) and better survival. pDC counts were associated with more striking results: patients with higher pDC counts had much lower incidences of NRM (3% versus 47%, P < .0001), lower incidence of aGVHD (24% versus 67%, P < .0001), and better overall survival (92% versus 45%, P < .0001). In contrast, higher pDC counts in the graft was associated with an increased risk of aGVHD (55% versus 26%, P = .02). Our results indicate that DC counts are closely correlated with HSCT outcomes and warrant further prospective evaluation and possible early therapeutic interventions to ameliorate severe aGVHD and decrease mortality.
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