Case Presentation: We describe a case of a pediatric patient with a heterozygous pathogenic germline CHEK2 mutation (c.1100delC; p.Thr367Metfs*15) successfully treated with
tisagenlecleucel for relapsed B-ALL to avoid hematopoietic cell transplant (HCT). The twelve-year-old boy was diagnosed with National Cancer Institute (NCI) high-risk B-ALL (white blood cell count >50,000/mcL), with no extramedullary disease. Cytogenetic analysis revealed normal karyotype but fluorescent in situ hybridization (FISH) showed 93% positivity for CRLF2::P2RY8 rearrangement. He was treated as per Children's Oncology Group (COG) AALL1131
therapy and achieved a complete remission. Seven months after diagnosis, he was found to have
papillary thyroid carcinoma with no evidence of metastatic disease. The patient underwent a total
thyroidectomy with central lymph node biopsy and radioactive
iodine therapy. The patient's
biological mother and fraternal twin brother carry the same germline CHEK2 mutation with no history of
malignancy. The
biological father tested negative for the familial mutation. The patient's genetic panel also identified three variants of unclear significance: CDKN2A (c.37 °C > T; p.Arg124Cys), FLCN (c.62G > A; p.Cys21Tyr) and SDHAF2 (c.139A > G; p.Met47Val). Extended family history also revealed a diagnosis of
anaplastic thyroid cancer in maternal uncle at the age of 44 years. Fifteen months after diagnosis the patient had a relapse of B-ALL (both medullary and extramedullary with blasts in CSF), which was successfully treated with
tisagenlecleucel. The patient remains in remission 3 years after receiving
tisagenlecleucel.
Conclusion: