{"doi":"10.1111/bjh.17517","title":"Immune responses and therapeutic challenges in paediatric patients with new‐onset acute myeloid leukaemia and concomitant COVID‐19","abstract":"Acute myeloid leukaemia (AML) is a medical emergency often presenting with hyperleucocytosis, coagulopathy and pulmonary infiltration necessitating emergent initiation of therapy. AML with concomitant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection presents a unique challenge given the lack of evidence-based guidelines or historical experience. While cohort studies have shown early serological responses to SARS-CoV-2 in healthy adults,1, 2 little is known about the serological responses to infection in patients with AML and the impact of chemotherapy on this response. In the present study, we detail the clinical presentations, treatments, serological and virological responses, and outcomes of two adolescents who presented with AML and concurrent coronavirus disease 2019 (COVID-19). Two adolescents presenting with AML and COVID-19 were enrolled on an Institutional Review Board-approved protocol to collect prospective/residual specimens used for SARS-CoV-2 serological and virological testing. Nasopharyngeal (NP) real-time reverse transcription polymerase chain reaction (RT-PCR), antibody testing by enzyme-linked immunosorbent assay (ELISA), live-virus focus reduction neutralisation assay-mNG, surface plasmon resonance (SPR) assay and viral genetic sequencing were performed (Data S1). Patient details, treatment and outcome data were abstracted from medical records. Patient 1 was a 16-year-old Caucasian male with a history of classical Hodgkin lymphoma who presented with fever, cough and hyperleucocytosis [white blood count (WBC) 176 × 109/l]. His NP SARS-CoV-2 RT-PCR test was positive and peripheral blood flow cytometry (PBFC) confirmed a diagnosis of therapy-related AML. He received hydroxyurea, followed by cytarabine starting on hospital day (HD) 3. Treatment for COVID-19 included hydroxychloroquine, remdesivir and supplemental oxygen (Fig 1). On HD4, the patient had detectable immunoglobulin (Ig)M and IgG antibodies to SARS-CoV-2 (Table I). The patient did not become lymphopenic throughout his COVID-19 course and maintained detectable binding and neutralising antibodies to SARS-CoV-2. SPR demonstrated that binding antibodies to the pre-fusion conformation of S, the receptor-binding domain (RBD) and S2 subunits all peaked by HD26. The patient had detectable IgM, IgA and IgG1 titres in the final sample on HD70 (Figure S1). He cleared the virus on HD16. Bone marrow (BM) on HD20 showed rare blasts on morphology in the setting of pancytopenia, with no disease detected by flow cytometry. He received additional chemotherapy with azacitidine and gemtuzumab starting on HD26. His treatment complications included bacteraemia and perirectal abscess with Pseudomonas aeruginosa and Epstein–Barr virus (EBV) viraemia resulting in multi-organ failure and death on HD74. Patient 2 was a 19-year-old obese (body mass index of 32 kg/m2), Hispanic male who presented with fever, cough, dyspnoea and hyperleucocytosis (WBC count 67 × 109/l). His NP SARS-CoV-2 RT-PCR test upon admission was positive and PBFC confirmed a diagnosis of AML. He began induction chemotherapy with cytarabine, daunorubicin and etoposide (ADE) on HD2 and he clinically deteriorated on HD4 requiring intubation and mechanical ventilation. For treatment of COVID-19, he received convalescent plasma (CP), remdesivir, tocilizumab and therapeutic plasma exchange (Fig 1). The patient was lymphopenic by HD5 and showed no immune response to SARS-CoV-2 with absence of IgM antibodies, waning IgG (post CP) and undetectable neutralisation titres (Table I). Concurrently, the patient’s NP RT-PCR remained positive with low cycle-threshold (Ct) values. Coinciding with haematological recovery on HD25, the patient demonstrated a serological response with rising IgM, IgG, neutralising antibody titres and SARS-CoV-2 RT-PCR Ct values until his first negative NP RT-PCR result on HD48. His SPR antibody profiling demonstrated class switching (Figure S1) and coincided with robust inc","journal":"British Journal of Haematology","year":2021,"id":201294,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9617,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":709070,"name":"Stacey A. Lapp","orcid":"0000-0002-6887-7322","position":1,"is_corresponding":false},{"id":640769,"name":"Gabrielle Grubbs","orcid":"0000-0003-4302-9535","position":2,"is_corresponding":false},{"id":218084,"name":"Venkata Viswanadh Edara","orcid":"0000-0001-9321-7839","position":3,"is_corresponding":false},{"id":94488,"name":"Christina A. Rostad","orcid":"0000-0001-8439-0592","position":4,"is_corresponding":false},{"id":779659,"name":"Claire Stokes","orcid":"0000-0002-1420-5870","position":5,"is_corresponding":false},{"id":779660,"name":"Melinda Pauly","orcid":"0000-0001-8906-5836","position":6,"is_corresponding":false},{"id":94484,"name":"Evan J. Anderson","orcid":"0000-0002-1576-4420","position":7,"is_corresponding":false},{"id":244979,"name":"Anne Piantadosi","orcid":"0000-0002-5942-1534","position":8,"is_corresponding":false},{"id":106937,"name":"Mehul S. Suthar","orcid":"0000-0002-2686-8380","position":9,"is_corresponding":false},{"id":437341,"name":"Surender Khurana","orcid":"0000-0002-0593-7965","position":10,"is_corresponding":false},{"id":779661,"name":"Himalee S. Sabnis","orcid":"0000-0002-3763-3253","position":11,"is_corresponding":false},{"id":779658,"name":"Pratik A. Patel","orcid":"0000-0002-1689-6214","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-18T23:50:52.535403Z","pmid":"34096051","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}