UNEXPECTED SPONTANEOUS REGRESSION IN CLL AFTER LETROZOLE TREATMENT: COINCIDENCE OR CONNECTION?

According to iwCLL guidelines, remissions are divided into two groups: Complete Remission (CR) and Partial Remission (PR). CR in Chronic Lymphocytic Leukemia (CLL) is defined by having peripheral blood lymphocytes less than 4 × 10^9/L, no significant lymphadenopathy (lymph nodes < 1.5 cm), no splenomegaly or hepatomegaly, absence of disease-related constitutional symptoms, and blood counts showing neutrophils ≥ 1.5 × 10^9/L and platelets ≥ 100 × 10^9/L, while PR requires at least two parameters from group A (lymphoid tumor load and constitutional symptoms) and one parameter from group B (hematopoietic system) to improve if previously abnormal. Hence, we present a case with Spontaneous Regression (SR) of CLL right after letrozole treatment. A 74-year-old female was admitted to the hematology clinic in 2018 due to lymphocytosis. The complete blood count of the patient showed a leukocyte count of 9.9 10^9/L with 6 10^9/L lymphocytes, a hemoglobin concentration of 15 g/dL, and 194 10^9/L platelets. The flow cytometry revealed 23% of lymphocytes displayed CD5+, CD20+, CD22+, CD19+, CD23+, Anti-Kappa+, CD38-, HLA DR+ immunophenotypes. In the physical examination, there was no splenomegaly or lymphadenomegaly. The patient was classified as Rai stage 0 CLL and managed with observation. In 2023, the patient had a mass on the left breast. Since they had a family history of breast cancer, the patient was referred to general surgery. The breast biopsy showed invasive lobular carcinoma. The breast cancer profile was T2cN0M0 (IB), estrogen and progesterone receptors were above 95%, cErbB2 (−), and low ki-67 index (13%). The patient was administered to the oncology for treatment. The patient received letrozole 2.5 mg/day and radiotherapy, respectively. One month after letrozole initiation, the peripheral blood lymphocyte count was observed within normal limits (Table 1). Throughout the one-year follow-up period before this case was reported, the levels remained within normal limits. The last flow cytometry still presented CLL, except atypic B-cells’ count decreased to 10%. The patient’s malignancies are considered under remission and the follow-up continues. SR of CLL is rare and not fully understood. Estrogen is known to influence B-cell function and survival, particularly through its interaction with Estrogen Receptors (ER). The study by Ladikou et al.[1] highlights that estrogen receptors are expressed in B-cell malignancies, including CLL, and predominantly involve the ERβ isoform, which has antiproliferative effects when selectively activated. Importantly, the disruption of estrogen-mediated pathways may lead to reduced proliferation and enhanced apoptosis of malignant B-cells. To the best of our knowledge, this is the second case of SR of CLL after letrozole treatment in the literature.[2] Future studies need to focus on the genetic causes of SR of CLL.