A Story about a Mother with Chronic Lymphocytic Leukemia after Chronic Phase of Chronic Myeloid Leukemia and Her Daughter with Chronic Myeloid Leukemia: Case Report and Literature Review

The occurrence of chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) in the same patient is a rare event. And the event that both mother and daughter are diagnosed with CML is also rare. We report the case of a 53 years old female was diagnosed with CLL 25 months after CML diagnosis. At that time, the patient has got complete cytogenetic response (CCyR) and major molecular response (MMR) of CML clone for 16 months. The patient presented signs of CLL clone expansion. The fluorescence in situ hybridization (FISH) analysis of CLL prognostic factors showed positive for tumor protein p53 (TP53). Imatinib was continued and patient received chemotherapy until obtained partial response. And then Ibrutinib was used for maintemance. After 4 cycles of chemotherapy, The FISH analysis was negative and flowcytometry (FCM) did not detect any CLL clone. But 39 months after CML diagnosis of the patient, her 30 years old daughter found her white blood cells (WBC) increased very high occasionally, and then bone marrow examination was performed and CML was diagnosed. We did not find any CLL clone or TP53 mutation in daughter's peripheral blood and bone marrow. We alse performed the next generation sequencing (NGS) for both the two patients. But we did not find any mutation both existed in the two patients. The daughter was received Imatinib for treatment.

In published literature, patients had concomitant CML and CLL or CML developed several years after treatment for CLL in most cases. There are only four case reports in which CLL diagnosis after the diagnosis of chronic phase of CML. The times of that CLL clone was detected after the diagnosis of CML were respectively 20, 36, 60 and 74 months. Our report is the first report of CLL occurrence after CML diagnosis combined with her daughter of CML.

There are several hypotheses to be considered according to two hematological malignances occurring in the same patient: the same clone origin, Li-Fraumeni syndrome (LFS), leukemogenesis triggered by failure of bone marrow microenvironment of long-term exposure to TKIs. LFS is a hereditary cancer predisposition syndrome. LFS is most commonly caused by a mutation of TP53. About 70% of LFS patients had a mutation in the TP53 gene. In a study reported by MD Anderson Cancer Centre, of 1445 patients with CML or other hematological malignancies treated with TKIs, 66 patients developed 80 second cancers, including skin, prostate, melanoma, digestive system, kidney, thyroid, breast, CLL (3%), hepatobiliary and other cancers. and the risk of second cancer was lower than expected. In our case, the mother developed CLL when she has got CCyR and MMR of CML clone for 16 months. TP53 was positive in the CLL clone. But her daughter developed CML without TP53 and any other mutation. And no evidence suggests that CML is a hereditary cancer at this moment. The occurrence of CLL and CML in the mother and CML in the daughter is a rare event and there seems no significance relationship between the two cancers and the two patients.