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Case report We present the case of a 63-year- old man with two consecutive admissions, due to COVID19 infection and subsequent bacterial superinfection. Three days after the second admission (04/28), and 43 days from the beginning of the infection an assessment by dermatology and allergology is then requested. The patient had generalized erythematous maculopapular rash in the trunk, back, groin and limbs. On the left side and back, pustular lesions not focused on follicles were also added, with a fever of 37.7degreeC. There were no oral and genital lesions. No psoriasis. The drugs used during the present and previous admissions were reviewed. Previous admission (04/04-22/ 20): Linezolid, ciprofloxacin, meropenem 04/13-22, piperacillin/tazobactam, hydroxychloroquine, azithromycin, ceftriaxone. Upon discharge amoxicillin/acid clavulanic. Present admission (04/25) Cutaneous reaction 04/28. 04/25: meropenem, paracetamol, enoxaparin, insulin, omeprazole, venlafaxine. 04/26: Darbepoetin, furosemide, mycophenolate in single dose. 04/27: Linezolid, macrogol, Clopidogrel, Magnesium, Calcitriol. Medical records: DM type 2, liver transplantation due to HCV cirrhosis, HCV recurrence, uninodular hepatocarcinoma, advanced CKD, secondary hyperparathyroidism, multiple neurological antecedents. We performed a detailed study. We hypothesized with a pharmagological/ drug reaction with several drugs possibly involved and our main suspicion was an allergic reaction to beta-lactams. Biopsy: Subcorneal pustules, basal spongiosis and presence in the superficial dermis of edema and an inflammatory infiltrate with abundant neutrophils. No fungi. Findings compatible with clinical diagnosis of generalized acute exanthematic pustulosis (PEGA). Immunohistochemical study Covid19. (Jimenez Diaz Foundation) Finely granular positivity in endothelium and more coarse in sweaty epithelium. Neutrophilic superficial inflammatory component with presumably spure staining. ACe-2 (positive external control) is not detected. The patient presents a EuroSCAR score of 9, sum of the clinic and the pathological anatomy, and therefore defined diagnosis. Clinical diagnosis: PEGA secondary to meropenem. Conclusion(s): We present the case of a PEGA by meropenem, not very often described in the literature. We highlight the importance of differential diagnosis with viral infections. Skin tests, especially epicutaneous tests, are key to the diagnosis. (Figure Presented).
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Background: Erythropoietin plays a significant role in the growth of red blood cells, hemoglobin levels, and tissue oxygenation in critically ill patients, as well as anti-inflammatory and neuroprotective effects. Objectives: This study aimed to evaluate the effect of recombinant erythropoietin on improving COVID-19 patients. Methods: This study was conducted on 20 COVID-19 participants with hemoglobin of ≥ 9. The inclusion criteria was at least one severe COVID-19 symptom/sign in this interventional study. The primary outcome was a combination of hospital stay length and paraclinical evaluation (LDH and hemoglobin level). The outcomes and side effects were evaluated on day 0 (before the intervention) and five (post-intervention). Results: The mean hemoglobin level was 10 ± 1.1 gr/dL in the intervention group and 8 ± 0.7 gr/dL in the control group post-treatment, indicating a significant difference between the groups (P = 0.04). The mean hospital stay length (6 ± 2 days) in the intervention group was significantly less than the control group (9 ± 4 days) (P = 0.001). At the end of the treatment, the mean LDH was significantly lower in the intervention group (503 ± 264 µ/L) than in the control group (725 ± 320 µ/L;P = 0.017). Conclusions: According to the results, this study provides the first solid evidence for the positive effects of recombinant erythropoietin on COVID-19.
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The proceedings contain 357 papers. The topics discussed include: evaluation of the nurse staffing level in the IRCCS Rizzoli through the use of ICA method;gender differences in patients hospitalized for COVID-19 disease;clinical study on the efficacy and safety of arginine administered orally in association with other active ingredients for the prevention and treatment of sarcopenia in patients with COVID-19-related pneumonia;regional efficacy and safety results of roxadustat compared with placebo or darbepoetin alfa in non-dialysis-dependent chronic kidney disease patients with anemia;C1s-targeted inhibition of classical complement pathway by sutimlimab in cold agglutinin disease: efficacy and safety results from the 26-week, randomized, placebo-controlled phase 3 CADENZA study (NCT03347422);octreotide LAR in patients with intestinal angiectasies and anticoagulation treatment;and implementation of 'Bedside modified-ISBAR' in nursing handover of COVID-patients in urgent-care medicine of Azienda Sanitaria Locale Biella (ASL BI): a phenomenological qualitative study.
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Goals: ESA are recombinant human erythropoietin preparations which stimulate bone marrow to produce RBC. Apart from relieving anaemia symptoms, the application of ESA can prevent the necessity of the red blood cells transfusion in patients with CIA and thus avoid transfusion-related complications. During the Covid-19 pandemic, the absence of the necessity of hospitalization to transfuse blood products presents an additional value. The aim of the study is to assess the results of the application of darbepoetin alfa in the treatment of anaemia in pts undergoing neoadjuvant chemotherapy for EBC. Methods: A retrospective assessmentwas carried out of the results of darbepoetin alfa (Aranesp®) treatment of 98 pts receiving neoadjuvant chemotherapy for EBC in the National Institute of Oncology in Poland in whom therapy was initiated in the period from 02 January 2019 to 16 February 2020. The drug was given to symptomatic anaemia patients, with a haemoglobin (Hb) level of 8–11 g/dL. In addition, it was also applied in chemotherapy-undergoing patients, with asymptomatic anaemia, with a haemoglobin concentration of <8 g/dL. The treatment was continued until a stable Hb level was reached ensuring the security of further oncological treatment without the necessity of RBC transfusion or termination of chemotherapy. Results: The results of darbepoetin alfa treatment were assessed in a group of 98 subsequent pts, in the course of neadjuvant chemotherapy for EBC. The pts received the following chemotherapy regimens: AC/PCL (35%), AC/PCL + carboplatin (9%), TCH (33%), TCH-P (8%), other (15%). At the moment of the initiation of ESA administration, 18% pts were aged 65 or more (max 76) while 82% below 65 yrs. of age (min 28). In the majority (90) of pts the number of Aranesp® doses administered did not exceed 3, only 8 received 4 doses. The estimated effectiveness in the <65 vs ≥65 years of age groups was 84.8% vs 79.8%, respectively. The estimated effectiveness values in the following BMI-dependent groups, namely: underweight + normal weight (BMI: 16–24.99), overweight (BMI 25–29.99) and obesity (BMI 30–43.1), were 86.3%, 76.6% and 72.0%, respectively. Conclusion(s): Darbepoetin alfa proved effective in the treatment of anaemia in chemotherapy-treated pts for EBC. The response to the treatment in the assessed group of pts was 85.7% There were no statistically significant age and BMI-related differences in ESA effectiveness. No significant side effects of darbepoetin alfa therapy were observed. Conflict of Interest: No significant relationships.
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Introduction: Aplastic anemia (AA) is a life-threatening disorder characterized by pancytopenia and a hypocellular bone marrow. Pure red cell aplasia (PRCA) is a similar disorder with primary reduction in the red blood cell population and virtual absence of erythroid precursors in the bone marrow. While the etiology of immune mediated marrow failure is multifactorial, preceding viral infections have been associated with the disease;these include parvovirus B19, cytomegalovirus, and Epstein-Barr virus. We present four cases of immune mediated marrow failure with either preceding or simultaneous SARS-CoV-2 infection. Methods: The medical records of patients treated for AA or PRCA at the University of Texas Southwestern Medical Center, Parkland Hospital, and the National Institutes of Health (NIH) were reviewed for SARS-CoV-2 infection. Four patients without prior hematological diseases were identified who had SARS-CoV-2 infection prior to or with simultaneous the diagnosis of AA or PRCA. Results: Patient #1 was a 22-year-old white female who was diagnosed with asymptomatic COVID-19 10 days prior to her pancytopenia and AA diagnosis was confirmed by bone marrow biopsy (5% cellularity;Table 1). Her extensive work-up including HIV, hepatitis panel, immunoglobulins, B12 and folate was negative, and she underwent HLA-matched family donor hematopoietic stem cell transplant. Patient #2 was a 69-year-old Asian female who presented to her primary care physician with symptoms of fatigue and was found to be pancytopenic. CBC from a few months prior was completely normal. Further work-up was positive for COVID-19 and negative for HIV, nutritional deficiency, or hemolysis. She did not have respiratory symptoms, was eventually diagnosed with pRBC and platelet transfusion-dependent severe AA (5-10% cellularity on bone marrow), and underwent treatment with cyclosporine, equine antithymocyte globulin, and eltrombopag. She has had a partial response to this therapy. Both patients had bone marrow specimens stained for SARS-CoV-2 by immunohistochemistry that were negative. Patient #3 was a 76-year-old white male who was diagnosed with COVID-19 4 months prior to presenting with a non-ST segment myocardial infarction and found to be profoundly anemic, requiring pRBC transfusion. He re-presented with chest pain one week later and was found to be anemic again, and required transfusion. A trial of darbepoetin alfa was unsuccessful. Extensive work-up for malignancy, infection, and autoimmune etiologies were negative. He was diagnosed with PRCA based on the bone marrow biopsy and initiated treatment with cyclosporine. Patient # 4 was diagnosed with severe AA (presenting as pancytopenia) and COVID-19 infection. He had fatigue for one month and fever, chills and sore throat one-week prior seeking medical care. Testing for hepatitis, HIV, EBV, and CMV was negative. He was treated on a clinical trial (NCT04304820) at NIH with cyclosporine and eltrombopag until SARS-CoV-2 PCR was negative then received equine anti-thymocyte globulin. He has achieved a complete hematologic response at 6 months and remains well at last follow-up. Conclusion: The four patients described had minimal respiratory COVID-19 symptoms, but they presented with cytopenia and were eventually diagnosed with bone marrow failure. It is possible that this is co-incidental due to the high prevalence of SARS-CoV-2. However, there is emerging evidence that COVID-19 pneumonia is a hyperinflammatory and immune dysregulated state improved by dexamethasone therapy. Other immune mediated hematologic conditions, such as autoimmune hemolytic anemia and immune thrombocytopenia, have been reported. The onset from infection to cytopenia appears rapid, although patients often presented with symptoms for many days prior to diagnosis and thus testing may have been delayed from the onset of infection. This case series does not provide a mechanistic link between SARS-CoV-2 infection and bone marrow failure, but it raises the possibility that SARS-CoV-2 may mediate an immunologic response that cont ibutes to marrow failure. Patients appear to respond well to standard immunosuppressive treatment. Further cases and studies are needed to determine if this is directly linked to SARS-CoV-2 and whether the natural history and response to standard therapy is different than idiopathic cases. [Formula presented] Disclosures: Young: Novartis: Research Funding.
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SARS-CoV-2 infection and vaccination have raised concerns in paroxysmal nocturnal hemoglobinuria (PNH). In fact, PNH patients carry an increased infectious risk secondary to complement inhibition treatment or associated bone marrow failure (BMF), and may therefore benefit from preventive strategies such as vaccinations. On the contrary, vaccines can be numbered among inflammatory complement amplifiers (e.g., infections, traumas, surgery), potentially triggering a disease exacerbation. In PNH patients on complement inhibitors, this phenomenon has been defined pharmacodynamic breakthrough hemolysis (BTH). Based on isolated reports of BTH following SARS-CoV-2 vaccines, we conducted a survey among 5 Italian reference centers to evaluate complications and BTH occurrence in PNH patients who completed the SARS-CoV-2 vaccination schedule from January, 2 2021 until the time of writing. Adverse events, hematologic and hemolytic parameters were recorded within 7-10 days before and after each dose of vaccine. A total of 67 patients (females/males 43/24, median age 47.6 years, range 21-90.5) were eligible for the analysis. According to the International PNH Interest Group classification, 45 patients suffered from hemolytic PNH, 20 from PNH in the context of BMF syndromes (aplastic anemia or myelodysplastic syndrome), and 2 from subclinical PNH. Fifty-five subjects (82%) were on regular complement inhibition therapy, i.e., eculizumab (N=35), ravulizumab (N=13), subcutaneous anti-C5 (N=3), anti-factor B (N=2) and ravulizumab + anti-factor D combination (N=2). Vaccines (Comirnaty/Pfizer-BioNTech N=53, mRNA-1273/Moderna N=12, and ChAdOx1 nCov-19/AstraZeneca N=2) were complessively well-tolerated, with 3 non-hematologic adverse events after the first dose (2 fever and 1 exercise-induced tachycardia, grade 1 according to CTCAE v5.0) and 2 after the second one (fever, accompanied by vomit in one patient, grade 1). During the observation period, 3 BTH and 1 hemolytic exacerbation were recorded (5.9% of patients), as detailed in Table 1. The most severe episode occurred in a young woman (Patient 3) on subcutaneous ravulizumab who experienced a hemoglobin (Hb) drop >2 g/dL, marked clinical signs of intravascular hemolysis and lactate dehydrogenase (LDH) increase >1.5 x upper limit of normal (ULN) from baseline, which is considered a clinical BTH according to the criteria proposed by the Severe Aplastic Anemia Working Party of the European group for Bone Marrow Transplantation. The patient required hospitalization for additional treatment with recombinant erythropoietin and anti-thombotic/bacterial prophylaxis. The second more severe BTH was registered in a male patient (Patient 1) on oral anti-factor B who experienced a Hb drop >2 g/dL without an overt hemolytic flare, and required hospitalization for intravenous antibiotic therapy (concomitant urinary tract infection). The remaining two patients experienced a subclinical BTH (Patient 2) and a hemolytic flare (Patient 4, not on complement inhibition). On the whole, a median delta variation from usual values of Hb and LDH of -25% (range -26+3%) and +80% (+18+105%) were observed, respectively. Of note, 3 episodes occurred after the second dose of vaccine, generally within 24-48 hours. Anti-complement drugs were not modified/discontinued in any of the 3 patients on regular treatment. Patients not experiencing BTH (94.1%) showed stable hematologic parameters after the first dose (Hb/LDH median delta variations from baseline -1%/+1%, range -14+12%/-32+40%) and the second dose of vaccine (Hb/LDH median delta variations from baseline +1%/0%, range -18+47%/-76+41%). Of note, 4 patients with a previous SARS-CoV-2 infection completed the vaccination without any complication/PNH exacerbation. In conclusion, this survey shows that BTH/hemolytic flares following SARS-CoV-2 vaccines are observed in about 6% of PNH patients, may be clinically relevant but manageable, and should not discourage vaccination. BTH has been registered mostly few days after the second dose of vaccine, suggesting a “boosterâ effect favoring a higher inflammatory response. Watchful clinical and laboratory monitoring is advised, in order to promptly recognize severe hemolytic flares in both treated and naïve patients. [Formula presented] Disclosures: Fattizzo: Novartis: Speakers Bureau;Kira: Speakers Bureau;Alexion: Speakers Bureau;Annexon: Consultancy;Momenta: Honoraria, Speakers Bureau;Apellis: Speakers Bureau;Amgen: Honoraria, Speakers Bureau. Bianchi: Agios pharmaceutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sica: Jazz Pharma: Consultancy;Alexion: Consultancy. Barcellini: Novartis: Other: Invited speaker, Research Funding;Agios: Membership on an entity's Board of Directors or advisory committees;Alexion Pharmaceuticals, Inc: Membership on an entity's Board of Directors or advisory committees, Other: Invited speaker, Research Funding;Bioverativ: Membership on an entity's Board of Directors or advisory committees;Incyte: Membership on an entity's Board of Directors or advisory committees.
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Introduction:Plasmablastic lymphoma (PBL) is a rare and aggressive lymphoma most commonly seen in the setting of chronic immunosuppression, such as HIV infection and organ transplantation, or in patients with pre-existing lymphoproliferative or autoimmune disorders. PBL commonly presents at extranodal sites and carries a poor prognosis with a global overall survival of 9-15 months after initial diagnosis. Despite poor prognosis for patients with PBL, therapeutic strategies to target this disease are limited, as CHOP-like regimens have failed to produce durable remission, and no standard of care has been established. The cell of origin for PBL is believed to be the plasmablast, as PBL cells possess immunoblastic morphology and contain an immunohistochemical profile positive for plasmablast markers, such as CD38, CD138, and MUM1/IRF4, and negative for B cell markers, such as CD20, CD19, and PAX5. The similarities between PBL cells and multiple myeloma (MM) cells, a plasma cell neoplasm, have led to investigations of the efficacy of MM therapeutics for the treatment of PBL. Daratumumab is a first-in-class monoclonal antibody directed against CD38 that has shown efficacy in treating relapsed/refractory and newly diagnosed MM. Here, we describe the treatment of four patients with advanced-stage PBL in the context of varying degrees of immunosuppression using combination treatment with daratumumab and EPOCH. Methods:Four consecutive patients were treated with daratumumab plus chemotherapy. Three of the four patients were treated in the frontline setting and received low-dose EPOCH (vincristine, doxorubicin, etoposide daily for 4 days;cyclophosphamide day 5) with 16mg/kg daratumumab dosed on days 1 and 8 for 6 cycles. Patient #4 showed partial CD20 positivity, prompting Rituximab co-administration (R-EPOCH). Patient #3 was treated in the relapsed setting with 16mg/kg daratumumab in combination with lenalidomide, dexamethasone, and doxorubicin. She was treated for 12 months. Responses were followed by PET/CT imaging. Results:The four consecutive patients (2 female, 2 male) ranged in age from 26-88 and all had advanced-stage PBL (Table 1). Three of the four patients had some degree of immunosuppression (Patient #1- post-transplantation lymphoproliferative disorder (PTLD), Patient #2- HIV/AIDS, Patient #3- Chron's disease, Patient #4- no history of immunosuppression). All patients had a Ki67 proliferation index over 70% and demonstrated extranodal involvement of disease (bone n=3, intestine n=2, liver n=2;kidney n=1;adrenal n=1). The three patients that received daratumumab in combination with EPOCH demonstrated a complete response at their first disease assessment by PET/CT scan after cycle 2 (Patient #1) or cycle 4 (Patients #2,4) (Fig1). Patient #3, who demonstrated a mixed response to previous therapy, achieved a complete response 5 months after starting treatment with daratumumab in combination with chemotherapy. As of July 2021, three of the four patients continued to have no evidence of disease for a median of 17 months (range 15-19 months). Patient #4 relapsed in July 2021, 3 months after demonstrating a complete response. Adverse events that required hospitalization were rarely noted following daratumumab treatment but included neutropenic fever (n=2, one event following treatment cycle 4 and the other event 2 months after completion of daratumumab administration), COVID-19 infection (n=1), and a PICC line-associated thrombus (n=1). Minor events were also noted and included self-limiting bradycardia (n=1), neuropathy (n=1), and rigor (n=1). Conclusions:We describe four patients with varying degrees of immunosuppression and HIV-status with aggressive-stage PBL that achieved complete response following treatment with daratumumab in combination with low-dose EPOCH or other chemotherapy. Three of four patients obtained durable responses. At the time of this writing, three additional HIV +patients have initiated treatment with daratumumab but have not yet reached their first disease assessment. Disease progression for these patients will be monitored and presented as part of this study. Our findings suggest a potential efficacy and warrant further investigation of using daratumumab for the treatment of HIV +and HIV - PBLs. [Formula presented] Disclosures: Amengual: Epizyme, Inc.: Speakers Bureau;Appia Pharmaceuticals: Research Funding;Daiichi Sankyo, Inc: Consultancy;Seagen: Consultancy. OffLabel Disclosure: our work uses daratumumab, a first-in-class monoclonal antibody against CD38 for the treatment of plasmablastic lymphoma
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OBJECTIVES: To evaluate the effect of recombinant erythropoietin on hospitalised COVID-19 patients. TRIAL DESIGN: Concealed, randomized, single-blinded, phase 2 controlled clinical trial with two arm parallel-group design of 20 patients allocated with 1:1 ratio and using the placebo in the control group. PARTICIPANTS: This study will be performed at Shahid Mohammadi Hospital in Bandar Abbas, Hormozgan in Iran. All positive (PCR confirmed) COVID-19 patients ≤65 years old who have Hb≤9 and at least one of the severe COVID-19 symptoms (tachypnea (breathing rate> 30 beats per minute), hypoxemia (O2 ≤93 saturation, the partial pressure ratio of arterial oxygen <300), Lung infiltration (> 50% of lung field within 24 to 48 hours), progressive lymphopenia, LDH>245 U/I, CRP>100) and are willing to cooperate in this project will be included in the study. Patients with a history of coronary heart disease, thrombosis, deep vein thrombosis, chronic lung disease, diabetes mellitus, weakened immune system, end-stage renal disease, liver disease, and patients with a history of taking oral contraceptive pills, systolic blood pressure more than 160 mm Hg, diastolic blood pressure more than 90 mm Hg and age over 65 and erythropoietin above 500 are excluded. INTERVENTION AND COMPARATOR: Patients will receive the standard of care (SOC) based on the treatment protocols of the Iranian National Committee of COVID-19 and recombinant erythropoietin (EPREX Manufactured by Johnson and Johnson Pharmaceutical Company) 300 units / Kg or 4000IU as subcutaneous (SQ) injection three times a day for 5 days and simultaneously Enoxaparin 1 mg/kg SQ daily is also taken to prevent thrombosis in the intervention group. Patients' blood pressure, along with other vital signs, are checked regularly and at regular intervals. In the control group, patients received SOC and the placebo (distilled water) is given as a subcutaneous injection three times a day for 5 days. We use sterile water for injection (EXIRpharmaceutical company) as the placebo. To the same appearance of the placebo and the recombinant erythropoietin, they are taken in a separate room in the same size syringes and cover with labels before injection. MAIN OUTCOMES: The main outcome for this study is a composite endpoint for Patient clinical symptoms (Respiratory rate, Oxygen saturation state and arterial oxygen partial pressure ratio, Lung infiltration status, blood pressure), Laboratory tests (LDH, CRP, Lymphocyte count, Endogenous erythropoietin, and Haemoglobin level). All of these will be assessed at the beginning of the study (before the intervention) and day 5 after the intervention. The study will also evaluate side effects and how to manage them. RANDOMISATION: Eligible participants (20) will be randomized in two arms in the ratio of 1: 1 (10 per arm) by permuted block randomization method using online web-based tools. BLINDING (MASKING): Patients participating in the study will not be aware of the assignment to the intervention or control group. The principal investigator, health care personnel, data collectors, and those evaluating the outcome are aware of patient grouping. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 20 patients will participate in this study, who are randomly allocated to the 2 arms with a 1:1 ratio; 10 patients in the intervention group will receive SOC and recombinant erythropoietin, and 10 patients in the control group will receive SOC and placebo. TRIAL STATUS: The protocol version is 3.0, approved by the Deputy of Research and Technology and the ethics committee of Hormozgan University of Medical Sciences on 6th June 2020, with the local grant number of 990108. The expected recruitment end date was on 21th December 2020 but since we had a wide and careful exclusion criteria because of the adverse reactions of the medication, the recruitment (for both cases and controls) was not so easy and did not finish on the expected date and we are still recruiting now. Recruitment began on 17th August 2020 and the updated expected recruitment end date is 1st August 2021. TRIAL REGISTRATION: The protocol was registered before starting subject recruitment under the title: Evaluation of the effect of recombinant erythropoietin on the improvement of COVID-19 patients, IRCT20200509047364N1, at Iranian Registry of clinical trials ( https://en.irct.ir/trial/49282 ) on 2020/08/09. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).