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.