Mitra Anupam, Ladenheim Alexander, Datta-Mitra Ananya, Honeychurch Kaitlyn Lauren, Dwyre Denis M, Graff John Paul
Department of Pathology and Laboratory Medicine, University of California Davis Medical Center, Sacramento, CA, USA.
Department of Pediatrics, University of California Davis Medical Center, Sacramento, CA, USA.
Clin Pathol. 2024 Sep 6;17:2632010X241278180. doi: 10.1177/2632010X241278180. eCollection 2024 Jan-Dec.
COVID-19 infection is still a mystery in terms of its long-term effect on health and its consequences on hematological disorders. Prior studies including ours have shown the abnormal changes in hematopoietic cells in COVID-19 patients. In this article, we are presenting 2 cases of pediatric B-lymphoblastic leukemia (B-ALL) with a previous history of COVID-19 infection. The first case describes a 22-month-old boy presenting with lymphadenopathy, neutropenia, and anemia with concurrent COVID-19 infection without any evidence of a hematolymphoid neoplasm as per bone marrow and lymph node biopsy. However, he presented after 2 months with bone marrow biopsy confirming B-ALL. The second case is that of a 4-year-old girl presenting with B-ALL who has had asymptomatic COVID-19 infection 5 months before this current presentation. Both the cases had complete resolution of COVID-19 infection during the time of presentation with acute leukemia. There were notably 2 rare findings along the course of the patients' illnesses. First, the unusual plasmacytosis in the marrow during active COVID-19 infection in the first patient and the second, is predilection of development of B-ALL following COVID-19. In both the cases the fluorescence in situ hybridization (FISH) studies showed pathologic alteration of the gene. Overall, there are no literature to support a causal association between acute B-ALL and COVID-19. The diagnosis of B-ALL in these patients after COVID-19 infection may be totally unrelated. However, if we consider Greaves proposed 2-hit model for childhood acute leukemia, that an infectious agent can precipitate development of B-ALL in a genetically susceptible individual. Alteration of the RUNX1 gene in both the patients, opens a door for further exploration of the "second-hit" hypothesis regarding an infectious agent precipitating development of B-ALL in a genetically susceptible individual.
就新冠病毒感染对健康的长期影响及其对血液系统疾病的后果而言，它仍是一个谜。包括我们的研究在内，先前的研究已表明新冠病毒感染患者造血细胞存在异常变化。在本文中，我们报告了2例曾有新冠病毒感染史的儿童B淋巴细胞白血病（B-ALL）病例。首例病例为一名22个月大的男孩，出现淋巴结病、中性粒细胞减少和贫血，同时感染新冠病毒，根据骨髓和淋巴结活检，当时无血液淋巴系统肿瘤的任何证据。然而，2个月后他经骨髓活检确诊为B-ALL。第二例是一名4岁女孩，患有B-ALL，在此次就诊前5个月曾有无症状新冠病毒感染。这两例患者在急性白血病就诊时新冠病毒感染均已完全缓解。在患者病程中尤其有2个罕见发现。其一，首例患者在新冠病毒感染活跃期骨髓中出现异常浆细胞增多；其二，是新冠病毒感染后B-ALL的易发性。在这两例病例中，荧光原位杂交（FISH）研究均显示该基因的病理改变。总体而言，尚无文献支持急性B-ALL与新冠病毒之间存在因果关联。这些患者在新冠病毒感染后诊断为B-ALL可能完全无关。然而，如果我们考虑格里夫斯提出的儿童急性白血病双打击模型，即感染因子可促使基因易感个体发生B-ALL。这两例患者中RUNX1基因的改变，为进一步探索关于感染因子促使基因易感个体发生B-ALL的“二次打击”假说打开了一扇门。
