To differentiate the leprosy agents Mycobacterium leprae and Mycobacterium lepromatosis and correlate them with geographic distribution and clinicopathologic features.
Species-specific polymerase ...chain reactions were used to detect each bacillus in archived skin biopsy specimens from patients with leprosy from Brazil (n = 52), Malaysia (n = 31), Myanmar (n = 9), and Uganda (n = 4). Findings were correlated with clinical and pathologic data.
Etiologic species was detected in 46 of the 52 Brazilian patients, including 36 patients with M leprae, seven with M lepromatosis, and three with both bacilli. The seven patients with sole M lepromatosis all had tuberculoid leprosy, whereas only nine of the 36 patients infected with M leprae exhibited this type, and the rest were lepromatous (P < .001). All patients with dual infections had lepromatous leprosy. Of the nine patients from Myanmar, six were test positive: four with M leprae and two with M lepromatosis. Of the Malaysian and Ugandan patients, only M leprae was detected in 27 of the 31 Malaysians and two of the four Ugandans.
The leprosy agents vary in geographic distribution. Finding M lepromatosis in Brazil and Myanmar suggests wide existence of this newly discovered species. The leprosy manifestations likely vary with the etiologic agents.
The use of centrifugation-based approaches for processing donated blood into components is routine in the industrialized world, as disparate storage conditions require the rapid separation of 'whole ...blood' into distinct red blood cell (RBC), platelet, and plasma products. However, the logistical complications and potential cellular damage associated with centrifugation/apheresis manufacturing of blood products are well documented. The objective of this study was to evaluate a proof-of-concept system for whole blood processing, which does not employ electromechanical parts, is easily portable, and can be operated immediately after donation with minimal human labor.
In a split-unit study (n = 6), full (~500mL) units of freshly-donated whole blood were divided, with one half processed by conventional centrifugation techniques and the other with the new blood separation system. Each of these processes took 2-3 hours to complete and were performed in parallel. Blood products generated by the two approaches were compared using an extensive panel of cellular and plasma quality metrics. Comparison of nearly all RBC parameters showed no significant differences between the two approaches, although the portable system generated RBC units with a slight but statistically significant improvement in 2,3-diphosphoglyceric acid concentration (p < 0.05). More notably, several markers of platelet damage were significantly and meaningfully higher in products generated with conventional centrifugation: the increase in platelet activation (assessed via P-selectin expression in platelets before and after blood processing) was nearly 4-fold higher for platelet units produced via centrifugation, and the release of pro-inflammatory mediators (soluble CD40-ligand, thromboxane B2) was significantly higher for centrifuged platelets as well (p < 0.01).
This study demonstrated that a simple, passive system for separating donated blood into components may be a viable alternative to centrifugation-particularly for applications in remote or resource-limited settings, or for patients requiring highly functional platelet product.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Donor-specific anti-HLA antibodies (DSAs) are a major cause of engraftment failure in patients receiving haploidentical stem cell transplantation (HaploSCT). Effective treatments are needed for these ...patients, who often have no other donor options and/or are in need to proceed urgently to transplantation. We studied a multimodality treatment with alternate-day plasma exchange (PE), rituximab, intravenous γ globulin (IVIg) and an irradiated donor buffy coat for patients with DSAs at 2 institutions. Thirty-seven patients with a median age of 51 years were treated with this desensitization protocol. Treatment outcomes were compared with a control group of HaploSCT patients without DSAs (n = 345). The majority of patients in the DSA group were female (83.8% vs 37.1% in controls, P < .001) and received stem cells from a child as the donor (67.6% vs 44.1%, P = .002). Mean DSA level before and after desensitization was 10 198 and 5937 mean fluorescence intensity (MFI), respectively, with mean differences of 4030 MFI. Fourteen of 30 tested patients (46.7%) had C1q positivity, while 8 of 29 tested patients (27.6%) remained positive after desensitization. In multivariable analysis, patients with initial DSA > 20 000 MFI and persistent positive C1q after desensitization had a significantly lower engraftment rate, which resulted in significantly higher non-relapse mortality and worse overall survival (OS) than controls, whereas graft outcome and survival of patients with initial DSA < 20 000 MFI and those with negative C1q after treatment were comparable with controls. In conclusion, treatment with PE, rituximab, IVIg, and donor buffy coat is effective in promoting engraftment in patients with DSAs ≤20 000 MFI.
•Treatment with PE, rituximab, IVIg, and donor buffy coat is effective in promoting engraftment in patients with DSA <20 000 MFI.•Patients with persistent positive C1q at transplant have a higher risk of engraftment failure and poor survival.
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BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of alternative donor transplants, ...which are being performed in increasing numbers. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option.
We performed a clinical trial (ClinicalTrials.gov identifier: NCT02479698) to assess the feasibility, safety, and efficacy of administering most closely HLA-matched third-party BKV-specific cytotoxic T lymphocytes (CTLs), generated from 26 healthy donors and banked for off-the-shelf use. The cells were infused into 59 patients who developed BKV-HC following AHSCT. Comprehensive clinical assessments and correlative studies were performed.
Response to BKV-CTL infusion was rapid; the day 14 overall response rate was 67.7% (40 of 59 evaluable patients), which increased to 81.6% among evaluable patients at day 45 (40 of 49 evaluable patients). No patient lost a previously achieved response. There were no cases of de novo grade 3 or 4 graft-versus-host disease, graft failure, or infusion-related toxicities. BKV-CTLs were identified in patient blood samples up to 3 months postinfusion and their in vivo expansion predicted for clinical response. A matched-pair analysis revealed that, compared with standard of care, after accounting for prognostic covariate effects, treatment with BKV-CTLs resulted in higher probabilities of response at all follow-up timepoints as well as significantly lower transfusion requirement.
Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BKV-HC after AHSCT.
While advancements in cellular therapy have improved outcomes for patients with refractory leukemia, severe infections may hinder access. Granulocyte transfusions, in combination with anti-microbial ...therapy, may be a safe option to facilitate candidacy for chimeric antigen receptor T-cell therapy in patients with leukemia and prolonged immune-compromised status.
Cyclooxygenase (COX) is the rate-limiting enzyme in conversion of arachidonic acid to prostanoids, and has two isoforms, COX1 and COX2, which share ~65% amino acid homology. COX1 is universally ...expressed in many cell types including platelets; however, expression of COX2 is known to be more limited. We examined expression of COX2 mRNA and protein in platelets and platelet-derived microparticles (MPs); using quantitative RT-PCR, immunostaining, and Western blotting. We have detected a significant amount of COX2 in platelets, both at mRNA and protein levels. We found that COX1/COX2 mRNA and protein ratios in platelets were 370:1 and 17:1, respectively. Expression level of COX2 in platelets was less than COX1, but comparable to the expression of COX2 in malignant epithelial cells. Considering the important role of COX2 in tumorigenesis and thrombosis, and the large number of circulating platelets, we propose that platelet COX2 may play an important role in physiologic and pathologic conditions.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
COVID-19 Convalescent plasma (CCP) is safe and effective, particularly if given at an early stage of the disease. Our study aimed to identify an association between survival and specific antibodies ...found in CCP.
Patients ≥18 years of age who were hospitalized with moderate to severe COVID-19 infection and received CCP at the MD Anderson Cancer Center between 4/30/2020 and 8/20/2020 were included in the study. We quantified the levels of anti-SARS-CoV-2 antibodies, as well as antibodies against antigens of other coronavirus strains, in the CCP units and compared antibody levels with patient outcomes. For each antibody, a Bayesian exponential survival time regression model including prognostic variables was fit, and the posterior probability of a beneficial effect (PBE) of higher antibody level on survival time was computed.
CCP was administered to 44 cancer patients. The median age was 60 years (range 37-84) and 19 (43%) were female. Twelve patients (27%) died of COVID-19-related complications. Higher levels of two non-SARS-CoV-2-specific antibodies, anti-HCoV-OC43 spike IgG and anti-HCoV-HKU1 spike IgG, had PBE = 1.00, and 4 SARS-CoV-2-specific antibodies had PBEs between 0.90 and 0.95. Other factors associated with better survival were shorter time to CCP administration, younger age, and female sex.
Common cold coronavirus spike IgG antibodies anti-HCoV-OC43 and anti-HCoV-HKU1 may target a common domain for SARS-CoV-2 and other coronaviruses. They provide a promising therapeutic target for monoclonal antibody production.
P132 Aung, Fleur M
Human immunology,
10/2014, Letnik:
75
Journal Article
Recenzirano
Amyloidosis is a rare disorder that results in tissue deposition of insoluble fibrils. Systemic amyloid deposits are formed by immunoglobulin light chains or mutant protein, may involve various ...organs and cause organ damage. Heart involvement is observed in 50% of patients with light-chain amyloidosis and is a relevant factor for poor prognosis. A 68 year old white male with a significant past medical history received a 1/6 HLA matched orthotropic heart transplant for restrictive cardiomyopathy and diastolic congestive heart failure New York Heart Association class III. The native heart was found to be positive for amyloidosis (lambda light chain restricted). He had a prolonged and complicated post-transplant course during which he developed right ventricle failure, recurrent pleural effusions, adrenal insufficiency and end stage renal disease requiring hemodialysis. Multiple endomyocardial biopsies post-transplant were negative for rejection and amyloidosis. A bone marrow biopsy 2 months post-transplant was consistent with myeloma with no evidence of amyloidosis. He was treated with Cytoxan/ Bortezomib/ Dexamethasone x2 for 8 weeks with complete remission but continued to require hemodialysis 3 x weekly. Eight months later he received an autologous stem cell transplant with standard of care Melphalan 140 mg/mm2. His counts recovered on post-transplant day 12. He was discharged on post-transplant day 15 with a serum creatinine of 2.43 mg/dl which had decreased from a baseline of 2.97 mg/dl. His renal dialysis was discontinued, to be done on as needed basis and his urine output was 1700 cc on post-transplant day 21. He continues to be on prednisone and tacrolimus for his heart transplant. The case is interesting as the workup for amyloidosis pre-heart transplant was negative despite bone marrow, endomyocardial and abdominal fat pad biopsies. The diagnosis of multiple myeloma was made after his explanted heart showed amyloidosis. The generally accepted therapeutic approach to improve survival and quality of life is chemotherapy and autologous stem cell transplant. Bortezomib benefits elderly patients with newly diagnosed multiple myeloma. Identification of high risk patients with cardiac amyloidosis is a goal to implement individualized treatment strategies to enable curative therapy.
Summary
Major ABO mismatching is not considered a contraindication to allogeneic haematopoietic stem cell transplantation (HSCT). Modern reduced‐intensity conditioning and reduced‐toxicity regimens ...cause much less myeloablation than conventional myeloablative regimens, such as cyclophosphamide with busulfan or total body irradiation, which may affect the incidence of pure red cell aplasia (PRCA). We estimated the incidence and described the natural history of PRCA in patients with major ABO‐mismatched donor stem cells. Between 2007 and 2008, 161 (27% of all patients undergoing HSCT) underwent allogeneic HSCT with major ABO‐mismatched stem cells and 12 (7·5%) of these patients developed PRCA. Thirty and ninety day T‐cell and myeloid cell chimerism and neutrophil and platelet engraftment did not differ between patients who developed PRCA and those who did not. The only risk factor associated with PRCA was the use of a fludarabine/busulfan conditioning regimen. All patients with PRCA needed red cell transfusion for several months after HSCT resulting in significant iron overload. Pure red cell aplasia resolved spontaneously in the majority (seven patients) but only resolved after stopping tacrolimus in three patients. Hence, after major ABO‐mismatched HSCT, the incidence of PRCA was 7·5% and it resolved spontaneously or after withdrawal of immunosuppression in the majority of patients.
•There is heterogeneity in the management of bleeding during platelet transfusion refractoriness (PTR).•Antifibrinolytics are more commonly used in patients who suffered severe bleeding.•Grade A and ...B1U HLA-matched platelets are not always readily available.•The HLA typing and HLA antibody screen/identification testing are not always performed prior to PTR.•There is a significant morbidity impact on clinical outcomes due to PTR and its bleeding related complications.
Platelet transfusion refractoriness (PTR) secondary to human leukocyte antigen (HLA) alloimmunization is a challenge in the treatment of hematology-oncologypatients and increases the risk of morbidity and mortality from bleeding events. Guidelines for treating PTR have not been clearly described in literature. We aim to describe the practice patterns for the management of PTR secondary to HLA alloimmunization, and to assess the mortality, thrombosis and bleeding-related clinical outcomes at 30 days from diagnosis.
A retrospective review of 51 cases of PTR secondary to HLA alloimmunization were analyzed.
The majority of patients (98 %) had a diagnosis of hematological malignancy of which 88.2 % were undergoing active chemotherapy. Clinically relevant bleeding, by ISTH criteria, was observed in 33.3 %; hemorrhagic shock was diagnosed in 7%. The rate of bleeding-related mortality was estimated at 7.8 %. The use of antifibrinolytics and plasma products (including intravenous immunoglobulin) was more common in cases with major versus non-major bleeding. Grade A or B1U HLA matched products were available in less than half of cases.
There is heterogeneity in the management of the bleeding risk and bleeding events during PTR, with antifibrinolytics more commonly used in patients who suffered severe bleeding. Grade A and B1U HLA-matched platelets are not always readily available, and HLA-typing and HLA-antibody testing are not always performed prior to PTR. Prospective randomized control trials may help to determine the safety and efficacy of antifibrinolytics and other supportive measures in the management of PTR.
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