Correction: Expert Opinions on the Management of Hemophilia A in India: The Role of Emicizumab.

[This corrects the article DOI: 10.7759/cureus.58941.].

Expert Opinions on the Management of Hemophilia A in India: The Role of Emicizumab.

Hemophilia A (HA) is a genetic disorder of hemostasis associated with a deficiency or reduced activity of clotting factor VIII (FVIII). This disorder remains unacceptably underdiagnosed in India. Early diagnosis and appropriate management of HA can substantially prevent morbidity and mortality. Currently, HA is managed with regular replacement therapy using standard or extended half-life FVIII concentrates or non-factor drug products. The challenges associated with FVIII concentrates include plateauing of drug effect, issues with its administration and adherence to treatment, breakthrough bleeds, and the development of inhibiting antibodies against administered clotting factors. Emicizumab is a bispecific antibody, launched in India in April 2019, for managing patients with HA. To investigate the role of emicizumab in Indian patients with HA, opinions were sought from 13 eminent hematologists and experts from India on the effectiveness of emicizumab in preventing all bleeds, spontaneous bleeds, perioperative bleeds, and intracranial hemorrhage; resolving target joints; and reducing the rate of hospitalizations and fatality associated with HA in children and adults, with or without inhibitors. The benefits of emicizumab over traditional FVIII concentrates include the subcutaneous route of delivery, less frequent dosing, and a lack of inhibitor development, in addition to providing sustained hemostasis without in-depth monitoring. It is a safe and effective management option for all HA patients, especially for patients with certain archetypes, such as those with inhibitors, those with high annualized bleed rates, those living far away from hemophilia care centers, pediatric patients and infants with intravenous access challenges, and those with a history of life-threatening bleeding events.

Survey-based assessment of hematopoietic stem cell graft manipulation (minimal) by cell therapy labs supporting hematopoietic stem cell transplants in India.

BACKGROUND AIMS: Hematopoietic stem cell transplants (HSCTs) are increasingly being offered to patients in India for various conditions. The Indian Stem Cell Transplant Registry shows that a total of 2533 transplants were done in India in 2019. METHODS: An epidemiological descriptive cross-sectional survey (55 questions) of centers providing HSCT in India was planned to analyze variations in policies and practices regarding HSCT graft manipulation (i.e., plasma reduction, red blood cell [RBC] depletion and cryopreservation). A total of 63 of 102 centers responded to the survey (response rate, 61.7%), mostly from the northern part of India (27 of 63 [42.8%]). RESULTS: The majority of responding centers reported performing >50 HSCTs annually (n = 24 [38%]), and 92% (58 of 63) performed stem cell collections from a pediatric donor/patient (age <18 years). A total of 56 of 63 responding centers indicated that they did product manipulations involving cryopreservation (n = 45), plasma reduction (n = 42) and RBC depletion (n = 28). Cryopreservation was primarily done by blood centers (27 of 45 [60%]), with dimethyl sulfoxide (DMSO) being the primary constituent, used most commonly at a concentration of 5-10% (28 of 45 centers). Dump freezing was most commonly used (27 of 45) with a -80°C deep freezer. A 7-aminoactinomycin D based viability assessment was also most commonly used (30 of 45). Thawing of the product was done mainly at the bedside (30 of 45) using a wet-type thawer (36 of 45), and washing of DMSO was done by a few centers (seven of 45). Plasma reduction and RBC depletion were primarily done for ABO incompatibility at blood centers. CONCLUSIONS: This survey demonstrates the lack of standardization and uniformity in the minimal manipulation of hematopoietic stem cell grafts in centers supporting HSCT in India. This work also highlights the need for more studies and country-specific recommendations to establish best practices.

Cost-effectiveness analysis of emicizumab prophylaxis in patients with haemophilia A in India.

INTRODUCTION: Emicizumab is the initial subcutaneously administered bispecific antibody approved as a prophylactic treatment for patients with haemophilia A (PwHA). AIM: This study assessed the economic evaluation of emicizumab treatment for non-inhibitor severe haemophilia A (HA) patients in India. METHODS: A Markov model evaluated the cost-effectiveness of emicizumab prophylaxis compared to on-demand therapy (ODT), low-dose prophylaxis (LDP; 1565 IU/kg/year), intermediate-dose prophylaxis (IDP; 3915 IU/kg/year) and high-dose prophylaxis (HDP; 7125 IU/kg/year) for HA patients without factor VIII inhibitors. Inputs from HAVEN-1 and HAVEN-3 trials included transition probabilities of different bleeding types. Costs and benefits were discounted at a 3.5% annual rate. RESULTS: In the base-case analysis, emicizumab was cost-effective compared to HDP, with an incremental cost-effectiveness ratio (ICER) per quality-adjusted life-years (QALY) of Indian rupees (INR) 27,869. Compared to IDP, ODT and LDP, emicizumab prophylaxis could be considered a cost-effective option if the paying threshold is >1 per capita gross domestic product (GDP) with ICER/QALY values of INR 264,592, INR 255,876 and INR 305,398, respectively. One-way sensitivity analysis (OWSA) highlighted emicizumab cost as the parameter with the greatest impact on ICERs. Probabilistic sensitivity analysis (PSA) indicated that emicizumab had a 94.7% and 49.4% probability of being cost-effective at willingness-to-pay (WTP) thresholds of three and two-times per capita GDP. CONCLUSION: Emicizumab prophylaxis is cost-effective compared to HDP and provides value for money compared to ODT, IDP, and LDP for severe non-inhibitor PwHA in India. Its long-term humanistic, clinical and economic benefits outweigh alternative options, making it a valuable choice in resource-constrained settings.

An assessment of childhood cancer care services in India - gaps, challenges and the way forward.

Background: Childhood cancers are emerging as an essential concern in India where there is lack of a specific programme component or policy to address childhood cancer control. There is limited information on the status and quality of childhood cancer care services in India. This paper describes the childhood cancer care services available at secondary and tertiary-level hospitals in India through a cross sectional study design. Methods: The survey was conducted in 137 tertiary-level and 92 secondary-level hospitals in 26 states and 4 Union Territories (UTs), ensuring a uniform representation of public and private care hospitals. The study tool collected data on the organisational infrastructure, type of oncology services, health workforce, equipment, treatment and referral protocols, and treatment guidelines. Descriptive statistics was used to primarily present the health service status and data on childhood cancer care services in proportions and mean. Findings: A dedicated pediatric oncology department was available in 41.6% of the public, 48.6% of private, and 64% Non Government Organization (NGO) managed tertiary-level hospitals. In 36 (39%) of the 92 hospitals providing secondary care, childhood cancer care was provided. The availability of bone (41.5%) and positron emission tomography (PET) scans (25.9%) was lower in public tertiary hospitals, whereas histopathology, computerised tomography (CT scan), and magnetic resonance imaging (MRI) were lower in public secondary hospitals than private and NGO managed hospitals for the corresponding level of care. Most tertiary hospitals had the required supportive care facilities except for play therapy and hospice care. Less than 50% of the public tertiary hospitals had stocks of the four categories of cancer-treating drugs and essential infrastructure for radiotherapy and chemotherapy. Most secondary-level hospitals not treating childhood cancer had referral linkages with tertiary hospitals. Interpretation: The situational analysis of childhood cancer care services in India showed the concentration of availability of childhood cancer care services at the tertiary level of health care. There were gaps in the availability of specialised pediatric oncology care in all the tertiary hospitals. The availability of childhood cancer care services was higher in private and NGO-managed hospitals than in public hospitals. Integration of childhood cancer as a part of the national cancer control response should be taken up as a matter of priority. The need of the hour is to formulate a childhood cancer policy that will enable timely access to care universally. Funding: World Health Organization, India provided funding and technical support.

Therapeutic Response to Sublingual Methylcobalamin in Children With Vitamin B12 Deficiency Anemia.

OBJECTIVE: To evaluate the efficacy and safety of sublingual methylcobalamin for the treatment of vitamin B12 deficiency anemia in children. METHODS: A single arm intervention study was conducted between November, 2020 and April, 2022 in children aged 1-12 years with vitamin B12 deficiency anemia. Children aged 1-6 years received a tablet of methylcobalamin (1500 mcg) by sublingual route every alternate day (three doses) while those aged 7-12 years received five such doses. Thereafter, one such sublingual tablet was given weekly and all participants were followed-up for 6 weeks. RESULTS: 37 children with a mean (SD) age of 8.2 (4.1) years were treated and followed up prospectively. On day 10, no child needed rescue therapy with parenteral methylcobalamin. After 6 weeks, the mean (SD) serum cobalamin (mL) increased from 123.3 (35.5) pg/mL to 507.3 (274.2) pg/mL (P<0.001), plasma homocysteine (L) decreased from 48.9 (17.8) pg/mL to 16.3 (8.5) µmol/L (P<0.001), the mean (SD) hemoglobin increased by 2.3 (1.1) g/dL (P<0.001), and MCV decreased by 12.9 (6.8) fL (P<0.001). 67.6% children persisted to have anemia, albeit majority of them had mild or moderate anemia. There were no unsolicited side-effect reported. CONCLUSION: Sublingual methylcobalamin is effective for the treatment of vitamin B12 deficiency anemia in children; although, the duration of treatment needs to be longer than six weeks.

Concomitant Langerhans and Interdigitating Reticulum Cell Hyperplasia in a Reactive Lymph Node of an Infant with Omenn Syndrome: A Diagnostic Pitfall for Langerhans Cell Histiocytosis.

Omenn syndrome, a rare form of combined immunodeficiency in infants, presenting with recurrent infections, erythroderma, lymphadenopathy, hepatosplenomegaly, eosinophilia, and increased serum IgE levels. It is a fatal condition unless treated by hematopoietic stem cell transplant. Hence, an early diagnosis and a prompt treatment can lead to better outcome in these unfortunate babies afflicted with Omenn syndrome. Here, we present an 8-week-old infant with typical features of Omenn syndrome, both clinically as well as on laboratory analysis, but surprising immunohistochemical findings on lymph node biopsy.

Diagnosis, Treatment and Prevention of Nutritional Anemia in Children: Recommendations of the Joint Committee of Pediatric Hematology-Oncology Chapter and Pediatric and Adolescent Nutrition Society of the Indian Academy of Pediatrics.

JUSTIFICATION: Anemia in children is a significant public health problem in our country. Comprehensive National Nutrition Survey 2016-18 provides evidence that more than 50% of childhood anemia is due to an underlying nutritional deficiency. The National Family Health Survey-5 has reported an increase in the prevalence of anemia in the under-five age group from 59% to 67.1% over the last 5 years. Clearly, the existing public health programs to decrease the prevalence of anemia have not shown the desired results. Hence, there is a need to develop nationally acceptable guidelines for the diagnosis, treatment and prevention of nutritional anemia. OBJECTIVE: To review the available literature and collate evidence-based observations to formulate guidelines for diagnosis, treatment and prevention of nutritional anemia in children. PROCESS: These guidelines have been developed by the experts from the Pediatric Hematology-Oncology Chapter and the Pediatric and Adolescent Nutrition (PAN) Society of the Indian Academy of Pediatrics (IAP). Key areas were identified as: epidemiology, nomenclature and definitions, etiology and diagnosis of iron deficiency anemia (IDA), treatment of IDA, etiology and diagnosis of vitamin B12 and/or folic acid deficiency, treatment of vitamin B12 and/or folic acid deficiency anemia and prevention of nutritional anemia. Each of these key areas were reviewed by at least 2 to 3 experts. Four virtual meetings were held in November, 2021 and all the key issues were deliberated upon. Based on review and inputs received during meetings, draft recommendations were prepared. After this, a writing group was constituted which prepared the draft guidelines. The draft was circulated and approved by all the expert group members. RECOMMENDATIONS: We recommend use of World Health Organization (WHO) cut-off hemoglobin levels to define anemia in children and adolescents. Most cases suspected to have IDA can be started on treatment based on a compatible history, physical examination and hemogram report. Serum ferritin assay is recommended for the confirmation of the diagnosis of IDA. Most cases of IDA can be managed with oral iron therapy using 2-3 mg/kg elemental iron daily. The presence of macro-ovalocytes and hypersegmented neutrophils, along with an elevated mean corpuscular volume (MCV), should raise the suspicion of underlying vitamin B12 (cobalamin) or folic acid deficiency. Estimation of serum vitamin B12 and folate level are advisable in children with macrocytic anemia prior to starting treatment. When serum vitamin B12 and folate levels are unavailable, patients should be treated using both drugs. Vitamin B12 should preferably be started 10-14 days ahead of oral folic acid to avoid precipitating neurological symptoms. Children with macrocytic anemia in whom a quick response to treatment is required, such as those with pancytopenia, severe anemia, developmental delay and infantile tremor syndrome, should be managed using parenteral vitamin B12. Children with vitamin B12 deficiency having mild or moderate anemia may be managed using oral vitamin B12 preparations. After completing therapy for nutritional anemia, all infants and children should be advised to continue prophylactic iron-folic acid (IFA) supplementation as prescribed under Anemia Mukt Bharat guidelines. For prevention of anemia, in addition to age-appropriate IFA prophylaxis, routine screening of infants for anemia at 9 months during immunization visit is recommended.

Answers to common questions about COVID-19 vaccines in children with cancer.

BACKGROUND: The SARS-CoV-2 outbreak in 2020 evolved into a global pandemic, and COVID-19 vaccines became rapidly available, including for pediatric patients. However, questions emerged that challenged vaccine acceptance and use. We aimed to answer these questions and give recommendations applicable for use in pediatric patients with cancer by healthcare professionals and the public. METHODS: A 12-member global COVID-19 Vaccine in Pediatric Oncology Working Group made up of physicians and nurses from all world regions met weekly from March to July 2021. We used a modified Delphi method to select the top questions. The Working Group, in four-member subgroups, answered assigned questions by providing brief recommendations, followed by a discussion of the rationale for each answer. All Working Group members voted on each recommendation using a scale of 1 to 10, 10 being complete agreement. A "pass" recommendation corresponded to an agreement ≥7.5. RESULTS: We selected 15 questions from 173 suggested questions. Based on existing published information, we generated answers for each question as recommendations. The overall average agreement for the 24 recommendations was 9.5 (95% CI 9.4-9.6). CONCLUSION: Top COVID-19 vaccine-related questions could be answered using available information. Reports on COVID-19 vaccination and related topics have been published at record speed, aided by available technology and the priority imposed by the pandemic; however, all efforts were made to incorporate emerging information throughout our project. Recommendations will be periodically updated on a dedicated website.

Allergic manifestations of inborn errors of immunity and their impact on the diagnosis: A worldwide study.

Background: Allergies have long been observed in Inborn Errors of Immunity (IEI) and might even be the first presentation resulting in delayed diagnosis or misdiagnosis in some cases. However, data on the prevalence of allergic diseases among IEI patients are limited and contradictory. Objective: To provide a worldwide view of allergic diseases, across a broad spectrum of IEI, and their impact on the timely diagnosis of IEI. Methods: This is a worldwide study, conceived by the World Allergy Organization (WAO) Inborn Errors of Immunity Committee. A questionnaire was developed and pilot-tested and was sent via email to collect data from 61 immunology centers known to treat pediatric and/or adult IEI patients in 41 countries. In addition, a query was submitted to The United States Immunodeficiency Network (USIDNET) at its website. Results: Thirty centers in 23 countries caring for a total 8450 IEI patients responded. The USIDNET dataset included 2332 patients. Data from responders showed that a median (IQR) of 16.3% (10-28.8%) of patients experienced allergic diseases during the course of their IEI as follows: 3.6% (1.3-11.3%) had bronchial asthma, 3.6% (1.9-9.1%) atopic dermatitis, 3.0% (1.0-7.8%) allergic rhinitis, and 1.3% (0.5-3.3%) food allergy. As per the USIDNET data, the frequency of allergy among IEI patients was 68.8% (bronchial asthma in 46.9%). The percentage of IEI patients who presented initially with allergic disorders was 8% (5-25%) and diagnosis delay was reported in 7.5% (0.9-20.6%). Predominantly antibody deficiencies had the highest frequency of allergic disease followed by combined immunodeficiency with a frequency of 40.3% (19.2-62.5%) and 20.0% (10-32%) respectively. As per the data of centers, anaphylaxis occurred in 25/8450 patients (0.3%) whereas per USIDNET dataset, it occurred in 249/2332 (10.6%); drugs and food allergy were the main causes in both datasets. Conclusions: This multinational study brings to focus the relation between allergic diseases and IEI. Major allergies do occur in IEI patients but were less frequent than the general population. Initial presentation with allergy could adversely affect the timely diagnosis of IEI. There is a need for policies to raise awareness and educate primary care and other referring specialties on the association of allergic diseases with IEI. This study provides a network among centers for future prospective studies in the field.

Shared care for children with cancer in India through social and healthcare partnerships during the COVID-19 pandemic.

BACKGROUND: The COVID pandemic posed a challenge for the tertiary centers to continue treatment. Some tertiary centers were designated as COVID-only hospitals, making it difficult for existing childhood cancer patients to continue their treatment at those centres. The need for shared care in childhood cancer was perceived by Cankids and its partnering childhood cancer-treating centers in North and East India. AIM: We aim to show how Cankids upscaled its shared care model to ensure that COVID designated hospitals connected with other hospitals who have to continue to provide care to childhood cancer patients in the pandemic and thus ensured the continuation of treatment for these patients. METHODS AND RESULT: The need assessment of the beneficiaries was done in discussion with the hospital of origin and destination hospital. The need for shared care was also discussed with the families and consent was taken before shifting their children. Cankids with the help of advisors identified cases of high risk that need immediate attention, proactive regular monitoring, and help in care planning with the perspective and recommendation of the multiple providers. The shared care unit came forward with reasonable and discounted packages for treatment. There was a total of five hospitals requiring shared care, and 55 children were supported from April to November 2020. The median age was 8 years and their hospital of origin are in Bihar, Uttar Pradesh, West Bengal, and Delhi. The expenditure on the treatment of the 55 patients was INR 61 61 636 ($ 84 843), with a median of INR 41765 (IQR 19491-174 129) on each patient. Total 291 trips for the transport were arranged and all the patients combined stayed 174 days at Cankids accommodation facility. CONCLUSION: The shared care helped the patients access standard treatment and reduce the financial burden.

Autoimmune hemolytic anemia in children: Clinical presentation and treatment outcome.

BACKGROUND: Autoimmune hemolytic anemias (AIHA) are characterized by the destruction of red cells following the production of autoantibodies directed against them. Although AIHA in children is usually self-limiting, many still succumb to the illness due to delay in the diagnosis and treatment. AIHA in children may be secondary to autoimmune diseases, drugs, or immune deficiencies. Early diagnosis and appropriate immunohematological evaluation can aid in the diagnosis and treatment. OBJECTIVE: To analyze the evaluation, treatment, and outcome of AIHA in children. METHODS: Prospective data of patients aged 0-18 years diagnosed with AIHA between June 2017 and May 2019 were collected. INTERVENTION: Prednisolone was the first-line agent in all; second-line agents included cyclosporine and rituximab. Red cell transfusion was given in those with severe anemia with cardiac decompensation. RESULTS: Eleven patients were diagnosed during the study period. Hemoglobin ranged from 1.2 to 9 g/dl. The initial presentation was severe anemia in 8 children and moderate anemia with thrombocytopenia in 3. The trigger was infection in 5. Polyspecific direct coomb's test (DCT) was positive in 10 patients. 2/10 polyspecific DCT-positive cases on further evaluation had immunoglobulin G (IgG) and C3d positivity, whereas rest 8 had only IgG. One infant was diagnosed with DCT-negative immunoglobulin A-mediated AIHA. 4/11 attained remission following the short course of prednisolone. Cyclosporine was used as the second-line agent in 2 and rituximab was used in 3. Seven children are in sustained remission and off medication. One died within 12 h of diagnosis. CONCLUSION: AIHA is not an uncommon problem in children and can vary in its clinical severity. Early and correct diagnosis helps in deciding appropriate treatment.

A comprehensive molecular study identified 12 complementation groups with 56 novel FANC gene variants in Indian Fanconi anemia subjects.

Fanconi anemia (FA) is a rare autosomal or X-linked genetic disorder characterized by chromosomal breakages, congenital abnormalities, bone marrow failure (BMF), and cancer. There has been a discovery of 22 FANC genes known to be involved in the FA pathway. This wide number of pathway components makes molecular diagnosis challenging for FA. We present here the most comprehensive molecular diagnosis of FA subjects from India. We observed a high frequency (4.42 ± 1.5 breaks/metaphase) of chromosomal breakages in 181 FA subjects. The major clinical abnormalities observed were skin pigmentation (70.2%), short stature (46.4%), and skeletal abnormalities (43.1%), along with a few minor clinical abnormalities. The combination of Sanger sequencing and Next Generation Sequencing could molecularly characterize 164 (90.6%) FA patients and identified 12 different complementation groups [FANCA (56.10%), FANCG (16.46%), FANCL (12.80%), FANCD2 (4.88%), FANCJ (2.44%), FANCE (1.22%), FANCF (1.22%), FANCI (1.22%), FANCN (1.22%), FANCC (1.22%), FANCD1 (0.61%) and FANCB (0.61%)]. A total of 56 novel variants were identified in our cohort, including a hotspot variant: a deletion of exon 27 in the FANCA gene and a nonsense variant at c.787 C>T in the FANCG gene. Our comprehensive molecular findings can aid in the stratification of molecular investigation in the diagnosis and management of FA patients.

Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India.

Mendelian Susceptibility to Mycobacterial diseases (MSMD) are a group of innate immune defects with more than 17 genes and 32 clinical phenotypes identified. Defects in the IFN-γ mediated immunity lead to an increased susceptibility to intracellular pathogens like mycobacteria including attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains and non-tuberculous environmental mycobacteria (NTM), Salmonella, fungi, parasites like Leishmania and some viruses, in otherwise healthy individuals. Mutations in the IL12RB1 gene are the commonest genetic defects identified. This retrospective study reports the clinical, immunological, and molecular characteristics of a cohort of 55 MSMD patients from 10 centers across India. Mycobacterial infection was confirmed by GeneXpert, Histopathology, and acid fast bacilli staining. Immunological workup included lymphocyte subset analysis, Nitro blue tetrazolium (NBT) test, immunoglobulin levels, and flow-cytometric evaluation of the IFN-γ mediated immunity. Genetic analysis was done by next generation sequencing (NGS). Disseminated BCG-osis was the commonest presenting manifestation (82%) with a median age of presentation of 6 months due to the practice of BCG vaccination at birth. This was followed by infection with Salmonella and non-typhi Salmonella (13%), Cytomegalovirus (CMV) (11%), Candida (7%), NTM (4%), and Histoplasma (2%). Thirty-six percent of patients in cohort were infected by more than one organism. This study is the largest cohort of MSMD patients reported from India to the best of our knowledge and we highlight the importance of work up for IL-12/IL-23/ISG15/IFN-γ circuit in all patients with BCG-osis and suspected MSMD irrespective of age.

Clinical and Laboratory Profiles of 17 Cases of Chronic Granulomatous Disease in North India.

A primary immune deficiency disorder is often suspected in children with recurrent deep seated and fungal infections and those admitted to pediatric intensive care units. Chronic granulomatous disease (CGD) is inherited disorder leading to infections caused due to defective superoxide production. Cases referred for testing for a primary immunodeficiency disorder were tested for Dihydrorhodamine 123 (DHR) assay by flow cytometry and nitroblue tetrazolium dye (NBT) slide test. The unstimulated and stimulated samples were tested for oxidative burst activity which gives bright fluorescence due to formation of Rhodamine 123 on flow cytometry and blue formazan pigment in NBT slide test. The test results were reported in real time. From a total of 330 patients screened for chronic granulomatous disease using DHR and NBT slide test, 17 patients (5.1%) were found to have CGD. These included 12 boys and 5 girls. They presented with deep seated infections, recurrent and multiple abscess, recurrent pneumonia and granulomatous lymphadenitis. The causative organisms were Mycobacteriae, Staphylococcus, Burkholderia cepacia, Pseudomonas, Aspergillus and Cytomegalovirus. In 6 out of 17 positive cases family studies were carried out. On follow up five children succumbed to disease, two patients underwent allogeneic bone marrow transplant, the chimerism status was demonstrated by repeat DHR assay at day 50 post-transplant. Rest are in follow up under prophylactic antibiotics and supportive care. As facilities for molecular testing are not easily available for primary immuno deficiency disorders, flow cytometry based clinical laboratories can help to screen for some of the frequently suspected disorders like chronic granulomatous disease. This has aided in paediatric care in our centre.

Convalescent plasma to aid in recovery of COVID-19 pneumonia in a child with acute lymphoblastic leukemia.

The natural history of COVID-19 infection in children is still evolving as the pandemic unfolds. Few cases of severe and often fatal COVID-19 have been reported although the infection is mild in the large majority. Children with cancers are recognised as a high risk group for all infections. Since there aren't any definite treatment guidelines established in children with severe COVID, treatment is guided by adult recommendations which too are often not evidence based. We report the case of a 4-year-old girl with severe COVID-19 associated pneumonia who presented to us as febrile neutropenia. The use of convalescent plasma along with steroids and IVIG showed dramatic results in this child and she recovered without the need for any specific treatment. This is highlighted as one of the earliest cases that is reporting the use of convalescent plasma in a child; the first ever in a child with underlying malignancy.