A previously healthy 38-year-old woman was diagnosed with precursor B-lymphoblastic leukemia/lymphoma weeks after her second mRNA COVID-19 vaccine dose, prompting researchers to examine similar reported cases, according to a recent study.
The report details the patient’s diagnostic timeline and treatment course and identifies 30 published studies describing confirmed malignancies reported after vaccination, the majority involving lymphoid neoplasms.
The patient received her second dose in July 2021 and developed fever, neck and jaw rigidity, diffuse pain, and systemic symptoms within 24 hours. Serial laboratory testing from August through October 2021 showed neutropenia, lymphocytosis, progressive anemia, and a rising erythrocyte sedimentation rate from 59 to 118 mm/hour. Positron emission tomography in November 2021 revealed diffuse hypermetabolic uptake throughout the axial and appendicular bone marrow and spleen. Bone marrow biopsy in December 2021 showed approximately 95% blast infiltration with expression of terminal deoxynucleotidyl transferase, cluster of differentiation 34, cluster of differentiation 79a, paired box 5, and cluster of differentiation 10, consistent with precursor B-lymphoblastic leukemia/lymphoma.
The patient achieved remission following chemotherapy but experienced central nervous system relapse in January 2025 and subsequently underwent high-dose cytarabine, methotrexate, and allogeneic stem cell transplantation.
The researchers noted that mild leukopenia documented months before vaccination could not exclude a preexisting evolving hematologic process. However, they also wrote that the isolated abnormality was more consistent with benign transient neutropenia than an already established leukemia.
To contextualize the case, the investigators conducted a systematic search of PubMed, Scopus, and Google Scholar from December 2020 through October 2025 using predefined oncology- and vaccine-related search terms. Eligible publications included case reports, case series, observational studies, letters, regulatory documents, systematic reviews, and meta-analyses describing confirmed malignancies reported after vaccination. Thirty publications met inclusion criteria, 28 involving hemato-lymphoproliferative disorders — including 9 B-cell, 13 T-cell, and 6 myeloid malignancies — as well as 2 solid tumors. In many reports, symptom onset was described within days to weeks of vaccination.
The review also discussed a population-based cohort study from Pescara province in Italy that reported an association between vaccination and increased cancer-related hospitalizations, as well as a large retrospective analysis from South Korea that found a higher overall risk of cancer diagnoses among vaccinated individuals compared with unvaccinated populations. The authors noted that potential sources of bias, including the “healthy vaccinee effect” and case-counting window bias, should be considered when interpreting these findings.
The investigators summarized biologic mechanisms proposed in prior literature to explain a possible link between immune stimulation and oncogenesis, including altered programmed cell death protein 1/programmed death-ligand 1 signaling, impaired type I interferon responses, immunoglobulin G4 class switching after repeated antigen exposure, transforming growth factor beta–mediated epithelial-mesenchymal transition, and concerns raised in the literature about residual plasmid deoxyribonucleic acid fragments in vaccine manufacturing. The authors stressed that these mechanisms remain theoretical.
Lead author Patrizia Gentilini, of the “Allineare Sanità e Salute” Foundation and the Independent Medical Scientific Commission in Milano, Italy, and colleagues wrote that the findings “should be interpreted with caution” and acknowledged that available studies limit “their ability to provide definitive evidence for interpreting a potential causal link.” They also noted that meta-analyses and systematic reviews predominantly indicate that COVID-19 modified mRNA vaccines are safe and provide clinical benefit to patients with cancer.
The authors reported no conflicts of interest.
Source: Oncotarget
