2. Case summary
In March 2016, a 63-year-old female patient was admitted to The Affiliated Hospital of Qingdao University due to the enlargement of the bilateral cervical lymph nodes. The patient had no obvious medical history. Upon systemic examination, several enlarged lymph nodes were detected in both the cervical and inguinal locations. The volume of the largest cervical lymph node was approximately 3 x 2 cm; however, no tenderness or adhesion was detected. Further, the spleen was enlarged with Line I, Line II, and Line III measuring 6 cm, 7 cm, and 2 cm, respectively. No tenderness was noted. Hematological examination revealed the following results: WBC 87.40 × 109/L, NEU 4.95 × 109/L, RBC 3.43 × 1012/L, HGB 94 g/L, PLT 86 × 109/L, LYM 81.03 × 109/L;
An examination of the bone marrow revealed that the proliferation of granulocytes was inhibited. The proliferation of erythrocytes was normal. Further, erythroblasts of slightly different sizes were noted. Lymphatic hyperplasia was significant (88.5%) with most cells being abnormal, small lymphocytes. Morphologically, the lymphocytes were small, round, possessed large round nuclei, dense chromatin, and little sky-blue cytoplasm. Together, these observations are indicative of lymphoproliferative disease (LDP). Mature lymphocytes and abnormal cell populations expressing CD19, CD5, CD43, CD23, CD200, and weakly expressing of CD20, CD79b, CD38, CD81, CD22, Kappa, and SIgD accounted for 93.2% and 91.78% of the nuclear cells, respectively. Together, these lines of evidence are indicative of a CLL/SLL phenotype. Fluorescence in situ hybridization (FISH) analysis highlighted that the patients’ samples was positive for the rearrangement of IGH and IGK. Further, the patient was negative for the ATM, CCND1/IGH, CEP12, P53, and RB-1 genes. Based on these data, the patient was diagnosed with CLL (Rai Stage Ⅳ; Binet Stage C; High-risk group).
From the 28th of March 2016, a 5-course FC chemotherapy regimen (on days 1-3, fludarabine 50 mg and cyclophosphamide 0.4 g) was initiated following symptomatic supportive treatment. Bone marrow suppression was observed after each course of chemotherapy, hematopoiesis returned to normal after symptomatic supportive treatment, e.g., stimulating the hematopoiesis. From the examination of the bone marrow, the patient was determined to be in complete remission (CR). On the 22nd of September 2016, the sixth course of FC chemotherapy was started, and the patient was discharged after the bone marrow hematopoiesis was recovered. No additional chemotherapy was carried out.
The patient was admitted to the hospital again on the 3rd of November 2016. Hematological examination revealed: WBC (2.18 × 109/L), NEU (1.41 × 109/L), RBC (2.33 × 1012/L), HGB (64 g/L), PLT (15 × 109/L), and LYM (1.29 × 109/L). Further, the absolute number of the reticulocytes was decreased. Additionally, there was no evidence of viral infection or hemolysis. Symptomatic supportive treatment to stimulate hematopoiesis was given; however, these treatments were not effective and additional blood transfusions were necessary. On the 15th of November 2016, the re-examination of bone marrow morphology found that the proliferation of bone marrow cells was less active. Cells at each stage were rare and the size and morphology of the erythroblasts were good. Furthermore, 18% were lymphocytes and an occasional 1% were prolymphocytes. On the whole film, no megakaryocytes were observed and platelets were rare which is indicative of a poor proliferation of bone marrow cells. No clonal abnormality on the chromosome was observed. The patient refused a multi-site bone marrow biopsy for personal reasons. On the 24th of November 2016, after relevant disease progression was excluded, additional CsA (100 mg) was supplemented empirically, twice a day. At the same time, hematopoiesis stimulation and intermittent transfusion of blood components were given. The patient’s platelet level gradually increased, and the hemoglobin count also increased to 70 g/L where it stabilized. The patient was successfully weaned off the blood transfusions. The patient did not receive FC chemotherapy, however, oral CsA treatment was continued at home. On the 12th of January 2018, a follow-up bone marrow biopsy revealed that no clonal abnormalities were observed in the B-lymphocytes and that there was a low proliferation of bone marrow cells (~30%). FISH analysis was negative. To date, the patient has remained in remission of CLL 5 years and 3 months as confirmed by routine assessments.