Decreasing blood donor exposure in the neonates by using dedicated donor transfusions

Critically ill infants receive frequent red cell transfusions for replacement of blood drawn for laboratory analysis and in treatment of symptomatic anemia. Since blood for multiple transfusions on a given day is typically obtained from one fresh RBC unit, each multiply transfused neonate is exposed to many donors increasing the risk of transfusion transmitted disease. We hypothesized that the number of donor exposures per infant would decrease by instituting DDTP and that more infants will be exposed to only a single donor. We started a Dedicated Donor Transfusion Program (DDTP) in our NICU. One unit of red cells is dedicated to each baby for the life of the unit (35 days). We compared the donor exposure in infants for one year, before and after DDTP. The infants were divided into three birth weight groups. Group I were infants < 1000 g; Group II infants were 1000-1500 g; Group III infants were > 1500g. The average number of transfusions per patient decreased significantly from 7.5 +/- 6.0 to 4.7 +/- 4.2 (P < 0.001) in Group I while it remained unchanged in Groups II and III. The Dedicated Donor Transfusion Program significantly reduced the donor exposure in NICU infants. The program also facilitated the reduction of the number of transfusions in the infants under 1000 g.     

Distinct Biomarker Profiles in Ex Vivo T Cell Depletion Graft Manipulation Strategies: CD34+ Selection versus CD3+/19+ Depletion in Matched Sibling Allogeneic Peripheral Blood Stem Cell Transplantation

Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft-versus-host disease (GVHD). Direct comparisons of T cell depletion strategies have not been well studied, however. We evaluated cellular and plasma biomarkers in 2 different graft manipulation strategies, CD3⁺CD19⁺ cell depletion (CD3/19D) versus CD34⁺ selection (CD34S), and their associations with clinical outcomes. Identical conditions, including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source, were used in the 2 cohorts. Major clinical outcomes were similar in the 2 groups in terms of overall survival, nonrelapse mortality, and cumulative incidence of relapse; however, the cumulative incidence of acute GVHD trended to be higher in the CD3/19D cohort compared with the CD34S cohort. A distinct biomarker profile was noted in the CD3/19D cohort: higher levels of ST2, impaired Helios^? FoxP3⁺Treg reconstitution, and rapid reconstitution of naïve, Th2, and Th17 CD4 cells in the early post-transplantation period. In vitro graft replication studies confirmed that CD3/19D disproportionately depleted Tregs and other CD4 subset repertoires in the graft. This study confirms the utility of biomarker monitoring, which can be directly correlated with biological consequences and possible future therapeutic indications.     

Haploidentical Peripheral Blood Stem Cell Transplantation Demonstrates Stable Engraftment in Adults with Sickle Cell Disease

We report on the screening and development of haploidentical hematopoietic stem cell transplantation (HSCT) for adult patients with clinically aggressive sickle cell disease (SCD) at our institution. Of 50 adult SCD patients referred for HSCT between January 2014 and March 2017, 20% were denied by insurance. Of 41 patients initially screened, 10% lacked an available haploidentical donor, 29% had elevated donor-specific antibodies (DSAs), and 34% declined to proceed to HSCT. All 10 patients who were transplanted received peripheral blood stem cells. The initial 2 were conditioned with alemtuzumab/total body irradiation (TBI) 3?Gy followed by post-transplant cyclophosphamide and failed to engraft. The next 8 patients received the regimen developed at Johns Hopkins University with TBI 3?Gy. Granulocyte colony-stimulating factor was administered from day +12 in those with HbS < 30%. All 8 patients engrafted with a median time to neutrophil >.5 × 10⁹/L of 22 days (range, 18 to 23). One patient subsequently lost the graft, and 7 (87.5%) maintained >95% donor cell chimerism at 1-year post-HSCT. Two patients developed acute graft-versus-host disease (GVHD) of at least grade II. One had chronic GVHD and died >1 year after HSCT of unknown causes. With a median follow-up of 16 months (range, 11 to 29), 7 patients (87.5%) are alive. Our findings suggest that limited insurance coverage, high rate of DSAs, and patient declining HSCT may limit the availability of haploidentical HSCT in adult SCD patients. The modified Hopkins regimen used here demonstrates high engraftment and low morbidity rates and should be tested in larger, multicenter, prospective clinical trials.     

Cardiotoxicity of cancer chemotherapy in clinical practice

Several anticancer agents are associated with significant cardiotoxicity. The list of cardiotoxic cancer therapeutic agents includes anthracyclines, trastuzumab, alkylating agents, antimetabolites, which have been in use for decades; and recently introduced anticancer therapies such as tyrosine kinase inhibitors, angiogenesis inhibitors, checkpoint inhibitors and proteasome inhibitors. Cardiac imaging using echocardiography, nuclear imaging techniques, and magnetic resonance (MR) imaging can help in the early detection of chemotherapy-related cardiotoxicity. This can prevent the morbidity and mortality resulting from the cardiotoxicity of these agents. Further research is needed to improve our understanding of the underlying mechanism of their cardiotoxicity and to develop newer preventive and therapeutic strategies for chemotherapy related cardiotoxicity.     

A Comparison of the Antemortem Clinical Diagnosis and Autopsy Findings for Patients Who Die in the Emergency Department

OBJECTIVES: In spite of advances in medical technology, there remains a high discrepancy rate between the antemortem clinical diagnosis and postmortem examination diagnosis for patients who die in hospitals. The aim of this study was to compare the clinical and postmortem examination diagnoses of patients who died in the emergency department (ED) of a tertiary hospital, and to analyze any discrepancy between them. METHODS: The study was a retrospective chart review of patients who died in the ED of a tertiary referral teaching hospital and a comparison of the antemortem diagnosis with the autopsy diagnosis. Any missed diagnosis was classified, according to the Goldman criteria, into major and minor missed diagnoses. RESULTS: A total of 59 patients were eligible for inclusion in the study. There was complete agreement between the antemortem diagnosis and the autopsy result in 51% of cases. The incidence of major missed diagnoses-where if the diagnosis had been known before the patient died, treatment may have been altered or survival may have been prolonged-was 7%. CONCLUSIONS: There is a significant discrepancy rate between the antemortem diagnosis and the autopsy diagnosis. However, in this study, serious missed diagnoses in which outcome may have been significantly altered are unusual among those who die in the ED of a tertiary referral hospital.     

Molecular characterisation of a case of dicentric Y presented as nonobstructive azoospermia with testicular early maturation arrest

The dicentric Y chromosome is the most common cytogenetically visible structural abnormality of Y chromosome. The sites of break and fusion of dicentric Y are variable, but break and fusion at Yq12 (proximal to the pseudoautosomal region 2/PAR 2) is very rare. Dicentric Y chromosome is unstable during cell division and likely to generate chromosomal mosaicism. Here, we report a case of infertile male with nonmosaic 46,XY where chromosome Y was dicentric with break and fusion at Yq12 (proximal to PAR 2). Clinical presentation of the case was nonobstructive azoospermia due to early maturation arrest at the primary spermatocyte stage. Various molecular techniques such as FISH, STS‐PCR and DNA microarray were carried out to characterise genetic defect leading to testicular maturation arrest in the patient. The break and fusion was found at Yq12 (proximal to PAR 2) and resulted in near total duplication of Y chromosome (excluding PAR 2). The reason for maturation arrest seems due to CNVs of PARs (gain in PAR 1 and loss of PAR 2) and azoospermia factors (gain).