An audit of paroxysmal nocturnal haemoglobinuria (PNH) requesting at University Hospitals of North Midlands

Early identification of PNH, a rare life-threatening disease is essential to ensure appropriate management via the UK PNH service. Since testing for PNH is expensive (75.97 per test), we set out to assess the suitability of PNH requests against guidelines with the aim to feedback to colleagues and reduce unnecessary testing. To determine whether PNH requests at UHNM were in line with criteria in British Society for Haematology (BSH) guidelines. All patients over 18 years of age who had PNH testing for the first time and those who had repeat testing for monitoring between 01/04/2019 and 31/03/2020 were included. Patients were selected from electronic records of PNH sample receipt to laboratories. Hospital records were reviewed for clinical details and investigation Results. 82 requests including 79 individual patients were audited. 57% were male and 43% were female. Median age was 56 years. 97.6% of PNH tests were requested by a haematologist whilst only 2.5% requests were done by non-haematology clinicians. 52.4% requests were in keeping with BSH recommendations, whilst 47.6% tests did not meet criteria for testing. All patients tested outside of guideline recommendations were negative. Of the reasonable requests, only 23.3% (10) were positive. Of the PNH positive patients, 8 patients were known to have a PNH clone with aplastic anaemia;one patient had a hypoplastic bone marrow and a known PNH clone whilst only one patient with cytopenia had a new positivity for PNH. The frequency monitoring for aplastic anaemia and a PNH clone was 100% concordant with BSH recommendations. With appropriate testing, only one new patient was identified. Our audit has limitations. We have not been able to assess whether any patients outside of those monitored for PNH in aplastic anaemia have been overlooked for testing. Also, the time period includes the COVID-19 pandemic so our findings may not reflect usual practice. New BSH guidelines for thrombophilia testing were published in 2022 and recommend testing for PNH in patients with thrombosis at unusual sites and abnormal haematological parameters and for patients with arterial thrombosis and abnormal blood parameters. This will likely limit excess tests although the sensitivity and specificity of such an approach has not been formally evaluated. In a finite health system, it is our responsibility to rationalise investigations. The cost of a year's testing was 6229.54 and that of inappropriate testing was 2962.83. As a department, we could, therefore, save 2962.83.

Clinical profile and outcomes of COVID-19 infection during the first wave in children with hematological illnesses and cancer: An observational study from a tertiary care center in North India

Background: Patients with cancer are at a higher risk of getting infected with the severe acute respiratory syndrome coronavirus 2 owing to their immunocompromised state. Providing care to these patients amidst the first wave of the coronavirus disease-2019 (COVID-19) pandemic was extremely challenging. Objective(s): This study was aimed at evaluating the clinical profile and disease-related outcomes of pediatric patients with hematological illnesses and cancer. Material(s) and Method(s): This retrospective study was conducted at a tertiary care center in North India during the first wave of the pandemic from March 2020 to December 2020. Children aged up to 18 years, who were treated for a hematological illness or malignancy or underwent hematopoietic stem cell transplantation (HSCT) and tested positive for COVID-19 regardless of symptoms were included in the study. Baseline demographic data related to the age, diagnosis, treatment status, and chemotherapy protocol used were collected. Outcomes including the cure rates, comorbidities, and sequelae were recorded. Result(s): A total of 650 tests for COVID-19 were performed for 181 children;22 patients were found to be COVID-19 positive. The most common diagnosis was acute leukemia (63.6%). None of the patients developed COVID-19 pneumonia. The majority of patients had asymptomatic infection and were managed at home. Among those with a symptomatic infection, the most common symptoms were fever and cough. A total of 3 (13.6%) patients needed oxygen therapy, one developed multisystem inflammatory syndrome of children leading to cardiogenic shock. Three patients required intensive care or respiratory support;all the patients had favorable clinical outcomes. The median time from the onset of COVID-19 to a negative result on the reverse transcription-polymerase chain reaction test was 21.3 days. Cancer treatment was modified in 15 patients (68.2%). Conclusion(s): Our results suggest that children with hemato-oncological illnesses rarely experience severe COVID-19 disease. The impact of the first wave of COVID-19 primarily manifested as disruptions in the logistic planning and administration of essential treatment to these children rather than COVID-19 sequelae.Copyright © 2021 Cancer Research, Statistics, and Treatment Published by Wolters Kluwer - Medknow.

New onset of hypomegakaryocytic thrombocytopenia with the potential for progression to aplastic anemia after BNT162b2 mRNA COVID-19 vaccination.

Vaccination with a coronavirus disease-2019 (COVID-19) vaccine is an effective public health measure for reducing the risk of infection and severe complications from COVID-19. However, serious hematological complications after COVID-19 vaccination have been reported. Here, we report a case of new-onset hypomegakaryocytic thrombocytopenia (HMT) with the potential for progression to aplastic anemia (AA) that developed in a 46-year-old man 4 days after the fourth mRNA COVID-19 vaccination. Platelet count rapidly decreased after vaccination and white blood cell count declined subsequently. Bone marrow examination immediately after disease onset showed severely hypocellular marrow (cellularity of almost 0%) in the absence of fibrosis, findings that were consistent with AA. Since the severity of pancytopenia did not meet the diagnostic criteria for AA, the patient was diagnosed with HMT that could progress to AA. Treatment with eltrombopag and cyclosporine was started immediately after diagnosis and cytopenia improved. Although it is difficult to determine whether the post-vaccination cytopenia was vaccine induced or accidental because the association was chronological, vaccination with an mRNA-based COVID-19 vaccine may be associated with development of HMT/AA. Therefore, physicians should be aware of this rare, but serious adverse event and promptly provide appropriate treatment.

COVID-19 in children with severe aplastic anemia

Introduction: Coronavirus disease 2019 (COVID-19) affects children but mostly has mild course. There is meagre published data on the impact of COVID-19 illness in children with Severe Aplastic anemia (SAA). We describe our experience of managing COVID-19 in children with SAA. Method: Three children of SAA who developed SARS-CoV-2 infection are included in this study. Results: Patient 1 was post Immunosuppressive therapy (IST) for SAA and had an asymptomatic course and uneventful recovery. Patient 2 was several months post IST with no response and had an asymptomatic COVID-19 illness but had delayed viral clearance, however he succumbed to bacterial sepsis soon after. Patient 3 was awaiting IST and while he contracted severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) infection, he had symptomatic COVID-19 illness followed by bacterial and fungal sepsis to which he succumbed. Conclusion: COVID-19 in children with SAA can be mild to fatal course and virus may have delayed clearance. It can lead to delay in therapy of SAA. © 2022 Pediatric Hematology Oncology Chapter of Indian Academy of Pediatrics

Remdesivir Reduces Mortality in Immunocompromised Patients Hospitalized for Covid-19

Background: There is limited information on effectiveness of COVID-19 therapies in immunocompromised patients, who are at higher risk of hospitalizations, complications, and mortality due to COVID-19. We examined hospital all-cause mortality for early RDV use vs. no RDV use among immunocompromised COVID-19 patients across several distinct dominant variants of concern (VOC) periods: pre-Delta (Dec'20-Apr'21), Delta (May-Nov'21) and Omicron (Dec'21-Apr'22). Method(s): Using the Premier Healthcare Database, we identified adults with an immunocompromised condition (cancer, solid organ and hematopoietic stem cell transplant, hematologic malignancies, primary immunodeficiencies, asplenia, bone marrow failure/aplastic anemia, severe combined immunodeficiencies or HIV), hospitalized with a primary diagnosis of COVID-19. Patients treated with RDV in first 2 days of admission vs. those not treated with RDV during the hospitalization were matched using 1:1 preferential withinhospital propensity matching with replacement. Patients were excluded if discharged within 3 days of RDV initiation. Cox Proportional Hazards Model was used to examine time to 14-and 28-day mortality. Result(s): Overall (Dec'20-Apr'22), 14,169 RDV-treated patients were matched to 5,341 unique non-RDV patients. Post-matching balance was achieved with 59% being 65+ years, 40.5% with no supplementary oxygen charges, 39% received low-flow oxygen, 19% on high-flow oxygen/non-invasive ventilation and 1.5% on invasive mechanical ventilation/ECMO at baseline. During the study period, unadjusted mortality rate was significantly lower for RDV patients at 14 days (11% [95% CI: 11%-12%] vs 15% [15%-16%];p< .0001) and 28 days (18% [17%-18%];p< .0001 vs 22% [22%-23%];p< .0001) as compared to patients that did not receive RDV. After adjusting for baseline and clinical covariates, 14-day results showed that RDV had significantly lower mortality risk compared to non-RDV across all VOC periods [overall (30% lower risk), pre-delta (41%), Delta (23%), Omicron (25%)]. Similarly, 28-day results showed that RDV had significantly lower mortality risk compared to non-RDV across all VOC periods [overall (25%), pre-delta (35%), Delta (21%), Omicron (16%)] (Fig). Conclusion(s): Timely initiation of RDV in first two days of hospital admission demonstrated significant mortality reduction in immunocompromised patients hospitalized with primary diagnosis of COVID-19. RDV demonstrated consistent benefit in an immunocompromised cohort across all variant periods of the pandemic.

Challenges and Results of Haploidentical Stem Cell Transplantation for Adult Patients in Cuba

The Hermanos Ameijeiras Hospital (HAH) in Havana is the only center performing allogeneic hematopoietic stem cell transplantation (HSCT) in adult patients in Cuba. Because transplants from unrelated donors are not possible due to political restrictions and economic embargo, in 2016 HAH and University of Illinois at Chicago (UIC) started a collaboration to support the training of a physician, annual educational programs and exchange of guidelines and protocols to perform haploidentical transplants. The first haploidentical transplant was performed at HAH in 2016. Because of limited resources, disease risk stratification is based on morphologic assessment, as cytogenetic is tested on an irregular basis. Peripheral blood stem cells (PBSC) were infused based on total nucleated cell count (TNC) due to lack of reagents for flow cytometry. Posttransplant chimerism and CMV monitoring cannot be performed. Transplant activity was stopped in 2020 due to high expenses allocated for COVID19 pandemic in Cuba. From 2016 to 2020, 16 haploidentical HSCT in 15 patients (9 males/ 6 females) were completed at HAH. The median age of patients was 34 years (range:21-54). Diagnoses included: acute leukemia, n=12, myelodysplastic syndrome, n=1, Hodgkin disease, n=1, and severe aplastic anemia, n=1. At the time of transplant, 11 patients were in morphologic remission and 5 had active disease. Conditioning regimens utilized were myeloablative (Flu/Bu) in 10 cases and at reduced intensity (Flu/Cy/ TBI200 +/- ATG) in 6 cases, and GVHD prophylaxis was standard PTCy on D3 and 4, CsA and mycophenolate. The donors were mother (n=10), father (n=1), child (1), or sibling (n=3) and the median age was 48 years (range: 26-68). All patients received fresh stem cells from PBSC(n=13) or bone marrow (n=3). Median cell dose infused was 5.5x108 TNC/kg (range: 2.2-8). All patients but 1 engrafted and median time to neutrophil and platelet engraftment was 17 days (range:12-28) and 16 days (range:11-30), respectively. Acute graft-versus-host disease (GVHD) grade 2-3 occurred in 50% of patients and chronic GVHD in 2 out of 8 that were evaluable. Day 100 and 2-year overall survival rates were 73% and 40%, respectively. With a medium follow-up of 18.8 months (range: 0.3-64), 5 of 15 patients (30%) are alive and complete remission. Causes of death in the remaining 10 patients included relapse of original disease, n= 4;bacterial infection, n=2;brain hemorrhage, n=1;VOD, n=1;graft failure, n=1;and multi-organ failure, n=1. Despite significant difficulties, HAH implemented a haploidentical transplant program for adult patients in Cuba. Among future steps, improving access to molecular testing and using younger donors will be pursued to improve on the results. The partnership between HAH and UIC has been instrumental in building clinical and research capacity and continues to support HAH in its mission to provide care to patients in Cuba.(Figure Presented)Copyright © 2023 American Society for Transplantation and Cellular Therapy

Eosinophilic fasciitis triggered by intensive exercise

A 59-year-old white female who was previously fit and well, developed gradual tightening and thickening of the skin on her forearms progressing to the abdomen, chest and lower legs associated with restricted movement. She also noticed bruise-like patches on her trunk. There were no systemic symptoms and no history of Raynaud syndrome. Since the beginning of the COVID-19 lockdown, the patient had engaged in increasing amounts of exercise compared with normal;this included yoga once weekly for 75 min, high-intensity interval training for 20 min on alternate days, running three times weekly for 45 min, lifting 2.5 kg weights for the arms every day and regular long walks. Examination showed a 'groove' sign on her forearms and a peau d'orange appearance of the skin with a woody induration and hardness on palpation. Symmetrical and circumferential involvement on the forearms and lower legs and bruise-like indurated patches on the abdomen were noted. Differential diagnoses included eosinophilic fasciitis (EF), morphoea, EF/morphoea overlap, scleroderma, scleromyxoedema and nephrogenic systemic fibrosis. Blood investigations showed an eosinophilia of 1.2 x 109 cells L-1, erythrocyte sedimentation rate of 31 mm h-1, a C-reactive protein of 20 mg L-1 and negative autoimmune and viral serology. She underwent two incisional biopsies down to fascia. The first was taken from the back, which showed an interstitial inflammatory cell infiltrate composed of lymphocytes, plasma cells and very occasional eosinophils. The subcutaneous septa were minimally thickened. The second biopsy taken from the left forearm showed striking thickening of the subcutaneous septa, with an associated inflammatory cell infiltrate, composed predominantly of lymphocytes and plasma cells. This process was deeper and more established than that seen in the biopsy from the trunk. The appearances were clearly those of a sclerosing process of the dermis and subcutis and consistent with eosinophilic fasciitis. Our diagnosis was EF with morphoea overlap and she was treated with oral methotrexate 15 mg weekly and oral prednisolone 50 mg once daily (weight 60 kg), reducing the dose by 5 mg every 2 weeks. An 80% improvement was seen in functionality within 3 months, but the skin remained tight and thickened and therefore the patient was referred for phototherapy [ultraviolet A 1 (UVA1)] as combination therapy. We present a rare case of EF, which appears to have been triggered by intensive exercise. Other causes include insect bites, radiation, infections (Mycoplasma and Borrelia) and paraneoplastic. Haematological associations have been seen, including aplastic anaemia and lymphoma. Treatment options for EF include prednisolone, UVA1/psoralen + UVA, immunosuppressive systemic agents (including ciclosporin and methotrexate), biological agents (including infliximab and rituximab) and physiotherapy.

Renaissance of Equine Antithymocyte Globulin in Renal Transplantation

Introduction: Anti Thymocyte Globulin(ATG) is very effective as an Induction and antirejection therapy (ART) agent in renal Transplantation. Equine ATG (eATG) has been used less compared to rabbit ATG(rATG) in tranplantation. Cost of eATG as induction agent is 200 USD, in comparison to rATG, which costs minimum 700 USD per dose (approximately four times more than eATG). Experience with eATG initially was not good because of drug reactions but over the years the molecule has evolved into a better drug and is the preferred drug over rATG in severe Aplastic Anemia without any reactions. Covid pandemic has affected the supply chain of rATG because of vaccine production leading to shortage of rATG. Hence eATG is the only available ATG. Method(s): We present our experience with eATG in a tertiary care nephrology centre for the last 95 renal transplants. Patients have been divided into two groups. Group A- contained HLA matched first degree relatives as renal donors and induction agent was injection Methylprednisolone (MP). Group B- Had Recipients of Deceased or Spousal donors and received eATG 10mg/kg as induction agent single dose. Monitoring of renal function and observation for complications including, infections was done. Blood lymphocyte count was monitored for intial 2 weeks to look for lymphocyte depletion as an indicator of eATG efficacy. Patients were followed upto 5 years post transplant (PTX) and assessment was done at 1,3 and 5 years for graft and patient survival. eATG usage as anti rejection therapy (ART) agent in acute T- cell-mediated rejection(TCMR) : All acute TCMRs (biopsy proved) were treated with eATG 10mg/kg body for 5 consecutive days followed by repeat biopsy and additional eATG therapy depending on patient response. Result(s): Induction Therapy: Table 1,2,3 Number of recipients in GrA were 41 and GrB were 54. Marked decrease in Lymphocyte count in Gr B indicated efficacy of eATG (p<0.05). In the first 90 days post transplant, Acute TCMR ( biopsy proved) was seen in 5(9.7 %) of GrA and 7(12.9 %) of GrB (p>0.05). In GrA 1(2.4%) patient had acute antibody mediated rejection (ABMR) but could not be treated with ART because of presence of active infection. In Gr B 1(1.8%) patient had histopathological features suggestive of ABMR but was C4D negative and patient responded to eATG alone. Infections were noticed in 9.7% (5/41) of GrA patients and 11.1% (6/54) of GrB patients in the first 180 days PTX (p>0.05). Urinary tract infections, respiratory tract infections and soft tissue infections were commonly seen. Post ART oppurtunistic infections were not seen. Comparison of incidence of Acute rejection rates, graft survival, complications rate and patient survival rate show similar results in both the groups. We achieved good efficacy with eATG as induction and ART agent in biopsy proved acute TCMR. No adverse events and no malignancies were observed after eATG therapy. Conclusion(s): eATG can be used as induction and antirejecton therapy agent in TCMR in renal transplantation. eATG is economical compared to rATG. No conflict of interestCopyright © 2023

Clinical case of COVID-19 course in a child with aplastic anemia.

The problem of the non-smooth course of COVID-19 and deaths in children with severe comorbid pathology is urgent. Among all registered cases of a new coronavirus infection in the Russian Federation, children account for up to 8,6%, of which severe forms are noted, as a rule, in patients with concomitant diseases. A clinical observation of the course of a new coronavirus infection in a child with a severe form of idiopathic aplastic anemia complicated by pancytopenia is presented. COVID-19 infection caused a sharp deterioration in the child's condition. Despite the use of modern methods of therapy, there was a rapid deterioration of clinical and laboratory parameters: an increase in febrility, respiratory failure, interstitial changes in the lungs, a decrease in oxygen saturation to 70%, hemorrhagic, anemic syndromes and multiple organ failure with the development of a fatal outcome. Aplastic anemia is a factor predisposing to the severe course of COVID-19 and contributing to an unfavorable outcome.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.

Clinical case of COVID-19 course in a child with aplastic anemia.

The problem of the non-smooth course of COVID-19 and deaths in children with severe comorbid pathology is urgent. Among all registered cases of a new coronavirus infection in the Russian Federation, children account for up to 8,6%, of which severe forms are noted, as a rule, in patients with concomitant diseases. A clinical observation of the course of a new coronavirus infection in a child with a severe form of idiopathic aplastic anemia complicated by pancytopenia is presented. COVID-19 infection caused a sharp deterioration in the child's condition. Despite the use of modern methods of therapy, there was a rapid deterioration of clinical and laboratory parameters: an increase in febrility, respiratory failure, interstitial changes in the lungs, a decrease in oxygen saturation to 70%, hemorrhagic, anemic syndromes and multiple organ failure with the development of a fatal outcome. Aplastic anemia is a factor predisposing to the severe course of COVID-19 and contributing to an unfavorable outcome.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.

Perniosis: a rare cutaneous manifestation of paroxysmal nocturnal haemoglobinuria

Perniosis is a vaso-occlusive phenomenon that features the formation of discrete erythematous papules, macules, nodules or patches. Perniotic lesions are induced by the cold and are symptomatic in terms of burning, pain or itching. Secondary complications such as overlying infections and ulceration may occur (Takci Z, Vahaboglu G, Eksioglu H. Epidemiological patterns of perniosis, and its association with systemic disorder. Clin Exp Dermatol 2012;37: 844-9). While most cases of perniosis are idiopathic, studies have shown a link between secondary perniosis, connective tissue diseases and haematological disorders. Paroxysmal nocturnal haemoglobinuria (PNH) is a haematological aberrant stem cell disorder. It is a very rare condition (1-1 5 cases per million population) and results in the death of approximately 50% of affected individuals as a result of thrombotic complications. Cutaneous sequelae are uncommon and may present as purpura due to dermal vein thrombosis (Zhao H, Shattil S. Cutaneous thrombosis in PNH. Blood 2013;122: 3249). To date, there have been no previously reported cases of perniosis as a cutaneous manifestation of PNH. A 42-year-old man, with a background of PNH and aplastic anaemia, presented with recurrent painful, erythematous macules and blisters along the palmar and plantar aspects of his fingers and toes. These lesions occurred over 4 years previously, coinciding with the diagnosis of PNH and aplastic anaemia. Physical examination revealed a solitary blistering lesion on the palmar aspect of his third right finger. In addition, there were multiple erythematous macules on the plantar aspect of the first and second toe of his left foot. A biopsy was performed. An autoimmune screen and antibodies for COVID-19 were all negative. Histopathological findings showed epidermal blister formation with the presence of some apoptotic keratinocytes admixed with superficial chronic perivascular inflammatory infiltrate. The inflammatory infiltrate was predominantly chronic lymphocytic and locally involved perieccrine glands noted to be underlying the blister formation, consistent with perniosis. The patient is currently awaiting treatment with eculizumab. This is a case of perniosis occurring as a cutaneous manifestation of PNH. Perniosis typically requires investigation for connective tissue diseases;however, we also warn dermatologists that perniosis could be a presenting feature of underlying paroxysmal nocturnal haemoglobinuria, a rare, life-threatening condition with a high mortality rate related to thromboembolism. This case highlights an interesting and previously unreported cutaneous manifestation of PNH.

Severe Hepatitis-associated Aplastic Anemia Following COVID-19 mRNA Vaccination.

We herein report a case of hepatitis-associated aplastic anemia (HAAA) that occurred after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. In this patient, progressive pancytopenia observed two months after acute hepatitis following the second dose of the SARS-CoV-2 vaccine indicated the development of HAAA. Although some reports have suggested that SARS-CoV-2 vaccination may be involved in the development of autoimmune diseases, no cases of HAAA developing after SARS-CoV-2 vaccination have been reported. SARS-CoV-2 vaccination in children has only started relatively recently, so the range of side effects in children has not yet been thoroughly described. Therefore, we need to strengthen surveillance for symptoms of children who are vaccinated.

[Analysis of anti-SARS-CoV-2 IgG antibody titers after mRNA booster vaccination in patients with nonmalignant hematological disorders].

In our facility, anti-SARS-CoV-2 mRNA vaccines were given to 21 patients, including 8 with aplastic anemia (AA), 3 with pure red cell aplasia (PRCA), and 10 with immune thrombocytopenic purpura (ITP), and IgG antibody titers were assessed one month after vaccinations. After receiving both a second vaccine and a booster shot, all patients with AA/PRCA treated with cyclosporine A aside from one, had IgG titers that were lower than the median levels of healthy controls. Even if prednisolone (PSL) doses did not go over 10 mg/day, ITP patients receiving PSL therapy were unable to achieve adequate levels of IgG after booster immunizations.

A Novel Case Report of Severe Aplastic Anemia with COVID Infection.

Aplastic anemia is a rare disease of the hematopoietic system. Although some viral agents have been implicated, the association between COVID-19 and aplastic anemia is unclear. In this way, several cases of aplastic anemia have been reported following infection with COVID-19. Importantly, we reported a 16-year-old girl with severe aplastic anemia with no history of disease following an Omicron infection who did not respond well to treatment despite supportive treatment and immunosuppression.

Case reports of management of aplastic anemia after COVID-19 vaccination: a single institute experience in Taiwan.

Global vaccination against the coronavirus disease 2019 (COVID-19) is thought to be the most effective way to end or at least contain the COVID-19 pandemic. However, despite the good safety profiles and effectiveness of the available COVID-19 vaccines, rare but serious hematological complications have emerged, including thromboembolic outcomes with thrombocytopenia following the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and Ad26.COV.2.S (Johnson & Johnson/Janssen) vaccines. Moreover, COVID-19 vaccination may be linked to the development of aplastic anemia (AA). We discuss four cases of AA that arose after COVID-19 vaccination in our hospital and two other such cases identified in our literature review.

Aplastic Anemia with Epstein-Barr Virus Reactivation after Anti-thymocyte Globulin Therapy.

Lymphoproliferative disorders and Epstein-Barr virus reactivation (EBV-LPDs) have various forms of onset, ranging from infectious mononucleosis-like syndrome (IM-like) to lymphoma, although whether or not IM-like progresses to lymphoma remains unclear. A 61-year-old man was diagnosed with aplastic anemia (AA). Polyclonal atypical B-lymphocytes were observed in the peripheral blood, and IM-like was diagnosed. Atypical lymphocytes disappeared, but a gastrointestinal examination revealed diffuse large B-cell lymphoma (DLBCL). Rituximab was initiated but later discontinued because of severe acute respiratory syndrome coronavirus 2 infection. Pancytopenia due to AA exacerbation recurred. The patient ultimately died of multiple organ failure due to bacterial infection.

A fatal SARS-coronavirus-2 induced bone marrow aplasia complicated with invasive fungal infection and severe neutropenic enterocolitis.

BACKGROUND: Immunization against the coronavirus disease 2019 (COVID-19) began in January 2021 in Iran; nonetheless, due to a lack of vaccination among children under 12, this age group is still at risk of SARS-CoV-2 infection and its complications. CASE PRESENTATION: SARS-CoV-2 infection was diagnosed in a 6-year-old girl who had previously been healthy but had developed a fever and pancytopenia. The bone marrow aspiration/biopsy demonstrated just hypocellular marrow without signs of leukemia. She was worked up for primary and secondary causes of pancytopenia. Except for a repeated reactive HIV antibody/Ag P24 assay, all test results were inconclusive. After a thorough diagnostic investigation, the cross-reactivity of the HIV antibody/Ag P24 test with SARS-CoV-2 antibodies was confirmed. The patient did not develop any COVID-19-related signs and symptoms, but she did get a severe invasive fungal infection and neutropenic enterocolitis. She died as a result of disseminated intravascular coagulopathy. CONCLUSION: It is critical to recognize children infected with SARS-CoV-2 who exhibit atypical clinical manifestations of COVID-19, such as persistent pancytopenia. SARS-CoV-2 infection can cause severe and deadly consequences in children; thus, pediatricians should be aware of COVID-19's unusual signs and symptoms mimicking other conditions such as aplastic anemia.

Aplastic Anemia Following SARS-COV-2 Infection

Introduction: COVID 19 is caused by a novel virus SARS-CoV-2.It has become a pandemic as declared by WHO with its first case being reported in China. Among children the intensity is usually mild and without any further impact. Aims & Objectives: Unusual presentation of aplastic anemia following SARS-CoV-2 infection: A rare case report. Material(s) and Method(s): A 6 year old male child presented with complaints of rashes and epistaxis for 2 weeks and also one episode of blood in stools.Two weeks prior to the onset of above complaints, the patient had a history of recovery from COVID -19.Blood investigations revealed pancytopenia with hemoglobin of 5.6 gm/dl,total leukocyte count of 2000/cumm and platelets were 43,000/cumm.The corrected reticulocyte count was 0.3%.Bone marrow examination done showed completely hemodilutedsmears.Bone marrow biopsy revealed a markedly hypocellular marrow with cellularity of 10% and the cellular components being replaced by fat spaces. Result(s): Based on the above findings, and other viral markers being negative a diagnosis of aplastic anaemia following SARS CoV-2 was made. Conclusion(s): COVID-19 being a relatively new disease,it's sequelae in children is not much studied.Aplasticanemia following an infection of SARS-CoV-2 is extremely rare with only two cases reported in literature till date.Hence this entity should be kept in mind by the treating physician encountering a case of pancytopenia following COVID-19.

Clinical Profile and Treatment Outcome of Severe Aplastic Anemia in Adults: An Experience from Tertiary Care Centre in North India

Introduction: Untreated/refractory severe aplastic anemia (SAA) is associated with very high mortality. Allogenic bone marrow transplantation or immunosuppressive therapy remains mainstay of treatment but these treatments are timely available to only a select subset of patients. Recently eltrombopag has been approved for treatment of SAA. Aims & Objectives: We aimed to describe clinical profile and treatment response in patients with SAA from a tertiary care centre. Material(s) and Method(s): A retrospective analysis of patients diagnosed with SAA over a period of 7 years from January 2015-December 2021 was performed. The details of demographic profile, laboratory features, treatment given and response were analyzed. Result(s): Ninety patients were diagnosed with SAA during this period out of which 18 patients went elsewhere for treatment. Seventy-two patients who received treatment in our hospital were included in the analysis. Sixty-two patients were SAA while 10 VSAA. PNH screening was done in 24 patients, out of which 17 (70%) had small clone. The details of treatment and response achieved is shown in Table 1. Eight patients (11.1%) received matched related donor allogenic hemopoietic cell transplant, out of which one had rejection followed by auto recovery while one died 6 months later due to covid 19 disease. Sixty-four patients received immunosuppressive therapy, forty-nine (76%) responded. Recurrence of SAA occurred in two patients who has achieved complete response to ATG therapy;one received second course of horse ATG + CSA + ETP and responded again. Conclusion(s): Timely diagnosis and appropriate treatment selection is of utmost importance to achieve optimal outcome in severe aplastic anemia. Eltrombopag has become an important addition not only in front line but also in relapsed refractory aplastic anemia. Patients lacking donor, or resources for ATG should be treated with cyclosporine and eltrombopag as early as possible. (Table Presented).