A 17-year-old young woman was admitted to our hospital in December 2019 because of increased urine foam and fatigue for 3 weeks.
Laboratory examinations showed protein(3+) and occult blood(2+) in urine. The blood urea nitrogen was 5.39mmol/L, the serum creatinine was 69µmol/L, and the lymphocyte ratio was 62.01%. Kidney color Doppler ultrasound showed increased volume in both kidneys as well as enhanced parenchymal echo. Then kidney biopsy was performed, indicating lymphoblastic lymphoma or leukemia with kidney involvement(Fig. 1A and 1B)and immunohistochemistry showed TdT(+), CD99(+), CD3(-), CD20(part +),CD73(-), PAX5(+), and LCA(part +). Fluorescence in situ hybridization (FISH) result of the kidney biopsy sample showed ZNF384 rearrangement (Fig. 1E). Then bone marrow aspiration and biopsy was performed, revealing disappearance of fat vacuoles and appearance of immature lymphoid cells. A suspected diagnosis of ALL was made, with extreme lymphocyte proliferation and the proportion of lymphoblasts was 50.8% (Fig. 1C and 1D). Flow cytometry(FCM) of bone marrow revealed CD34(+),CD117(-),CD33(+),CD64(-),CD13(+),CD14(-),CD274(-),TSLPR(-),CD11b(-),IgM(+),CD71(-),CD56(+),CD2(-),CD7(-),CD5(-),CD10(+),CD3(-),CD4(-),CD8(-),CD38(+),CD81(+),HLA-DR(+),CD19(+),CD22(+),CD20(+),cMPO(-),cCD3(-), cCD79a(+),TDT(+),CD58(+),CD61(-),CD235a(-),CD11c(-), which was compatible with BCP-ALL(Fig. 2). Next generation sequencing (NGS) showed STAG2 gene mutation in bone marrow and reverse transcription-polymerase chain reaction (RT-PCR) showed negative for leukemia fusion gene.
Her medical history was unremarkable. On physical examination, the patient had an anemic appearance without ecchymosis. The initial laboratory evaluation revealed lymphocytosis (2.37×10 9/L) and moderate anemia (Hb78 g/L, Vitamin B12 164pg/mL, folic acid3.00ng/mL and serum ferritin426.7ug/L). She was diagnosed with BCP-ALL with both kidneys involvement.
After a cycle of VCDLP regimen, the bone marrow was obviously hyperplastic and active, and immature lymphocytes were occasionally observed. FCM showed the ratio of lymphoblasts was 42% with CD34(+),CD10(-),CD19(+),CD38(+),HLA-DR(+),CD64(-),CD13(+),CD20(-),and CD33(+). Since the patient did not achieve remission, a cycle of FLAG salvage treatment was administrated, then the patient was assessed as complete remission(CR). No lymphoblasts were seen in the bone marrow. FCM showed the ratio of lymphoblasts was 0.8% with CD34(+),CD10(-),CD19(+),CD38(+),HLA-DR(+),CD13(+) and STAG2 gene mutation. The volume of both kidneys returned to normal according to color Doppler ultrasound. After the patient achieved CR, an intrathecal drug injection was performed for consolidation therapy. Eight months after the continued complete remission(CCR), the disease relapsed according to bone marrow smear revealing 55.2% of lymphoblasts and FCM showing ALL with the partial expression of CD33. FISH showed ZNF384 rearrangement (39%) according to its probe (Fig. 1F) and positive for IgH rearrangement (37%). The leukemia fusion gene and mutation panel were both negative. But there was no remission in the bone marrow after she was treated with chidamide and a dose-adjusted FLAG plus VP chemotherapeutic regimen, as well as highly sensitive treatment, HAD. The percentage of lymphoblasts was 14.4% and ZNF384 was positive (17.6%) according to FISH. Now the patient has been admitted to the hospital and is receiving chemotherapy regularly. The details of the treatment process were summarized in Supplement Table 1.