Case Description
A 3-year-old boy presented with fever for 4 days was admitted to our hospital. The blood count showed elevated white blood cells (WBC, 151G/L), decreased hemoglobin (Hb, 55g/L), neutrophil and lymphocyte percentage was 7.5% and 91.3%, respectively. The peripheral blood and bone marrow smear showed blasts were 79% and 73.5%, respectively. The flow cytometry of bone marrow identified 79.5% abnormal cell population of nuclear cells, which was positive for HLA-DR (91.94%), CD13 (76.22%), CD33 (94.25%), CD34 (30.43%), CD38 (79.99%), CD117 (96.76%), CD123 (98.93%), MPO (47.52%). The boy was diagnosed with AML (M2) and hyperleukemia, tentatively classified as intermediate risk.
Then the boy accepted the routine chemotherapy regimens according to China Childhood Leukemia Collaborative Group (CCLG)-AML 2019 guideline, which included Daunorubicin, Ara-C, Homoharringtonine (HHT) (DAH), followed by the second course of chemotherapy, IAH (Idarubicin, Ara-C, HHT). However, the boy could not achieve CR after two courses of chemotherapies. The results of the deep sequencing and RNA sequencing of hematological malignancies of this boy came out and found GATA2 mutation (NM_032638:exon6:c.1154C>T:p.P385L) and NUP98-NSD1 fusion gene. Consequently, the patient was classified as high-risk AML with NUP98-NSD1 fusion gene. The clinicians thought the routine chemotherapy could not help the patient, and more effective chemotherapy strategies must be employed. Thus, the clinicians collected the primary tumor cells of the patients to carry out a high-throughput drug sensitivity analysis (HDS) as a result of high-risk NUP98-NSD1 fusion.
Subsequently, the eight highly sensitive chemotherapy regimens were screened out according to the high-throughput drug sensitivity analysis of the patient’s primary tumor cells (Table 1 ). However, the first four chemotherapy regimens contain the drugs that have been already employed in the two courses of conventional chemotherapy and have been proved ineffective. Besides, the NUP98-NSD1 fusion gene causes H3K36 methylation, resulting in leukemogenesis. Therefore, the clinicians finally chose the combination chemotherapy regimens of Bcl-2 inhibitor and DCAG, which includes hypomethylation agent decitabine (20mg/m2), aclacinomycin (10mg/m2), Ara-C (10mg/m2), granulocyte-colony stimulating factor (125ug) and venetoclax tablets (DCAG plus venetoclax). Then the MRD gradually decreased to less than 10-4 on days 28 after DCAG plus venetoclax treatment. On the 35th day of this treatment, both of the MRD and bone marrow blasts became negative, and the NUP98-NSD1 fusion ratio decreased to 2.34%. The patient finally achieved CR after DCAG plus venetoclax therapy, then he underwent allo-HSCT with his HLA-haploidentical father as the donor. One month after transplantation, the blood count of the patient returned to normal, both of the peripheral blood and bone marrow blasts were negative, and flow cytometry showed MRD was less than 10-4. Besides, IDH1 mutation, GATA2 mutation and NUP98-NSD1 fusion gene were both negative. The clinical course of this patient can be concluded in Fig. 1 . This patient will have regular bone marrow examinations to be alert for recurrence.