Clinical analysis of decitabine combined with ruxolitinib regimen in treatment of newly diagnosed chronic myelomonocytic leukemia

Abstract

Objective To analyze the clinical efficacy of decitabine combined with ruxolitinib regimen in the treatment of patients with newly diagnosed chronic myelomonocytic leukemia (CMML), and explore the effects of gene mutations on the prediction of efficacy and prognosis. Methods From March 2016 to August 2018, five cases of newly diagnosed patients with CMML admitted to the Department of Hematology, Ruijin Hospital North Affiliated to Shanghai JiaoTong University School of Medicine were selected as study subjects. Among them, there were 3 male patients and 2 female patients, with a median age of 60 years. In this study, the treatment regimens were deccitabine combined with rucotinib: deccitabine 20 mg/(m2·d), d1~3; rucotinib 5~10 mg/d, d1~28, 4 weeks as a course of treatment. At the end of each treatment course, the efficacy was evaluated based on the bone marrow cell morphology of the patients. Adverse reactions related to treatment were observed. The variant allele frequency (VAF) of 22 types of acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) related genes was detected before and after treatment. The follow-up period was up to May 1, 2019, with an interval of 1 month. The clinical features and efficacy of 5 patients with CMML were retrospectively analyzed, as well as the changes of related VAF of genes before and after treatment. The procedure of this study is accordance with the requirement of the revised World Medical Association Declaration of Helsinki in 2013. Consent form was obtained from all subjects. Results ① Among the 5 patients received the combination of descitabine and rucotinib regimen, 3 patients obtained overall response, among which patient 2 received complete remission (CR), patient 3 received hematologic improvement (HI), and patient 5 received bone marrow complete remission (mCR). Patient 4 had no effect. Patient 1 had disease progression (PD). All patients′ spleen size decreased (extent of reduction>50%). ② All the 5 patients showed myelosuppression after chemotherapy, among which patient 3 had the most severe myelosuppression and the longest period of myelosuppression, up to 2 months. Chest CT results of patient 1, 3 and 4 showed pulmonary infections, which was improved after active anti-infection treatment. Patient 1 and 4 had diarrhea. Patient 3 presented mild liver function impairment. Patient 5 presented constipation. And all symptoms improved after symptomatic and supportive treatment. ③ The results of VAF of mutations of patients before and 6 months after treatment showed, JAK2 V617F VAF (17% to 0), SRSF2 P95H VAF (44% to 39%) were decreased, and CBL H398P VAF (15% to 60%), TET2 Q273fs VAF (87% to 95%) were increased in the bone marrow specimens of patient 1. In patient 2, SRSF2 P95L VAF (69% to 49%) and CBL R420Q VAF (45% to 1%) were decreased, ASXL1 G710fs VAF (47% to 49%) was almost unchanged, and TET2 L1721W VAF (32% to 50%) was increased. In patient 4, SRSF2 P95L VAF (29% to 7%), TET2 Q705X VAF (95% to 62%) were decreased, and ASXL1 G642fs VAF (18% to 39%) was increased. The results of VAF of mutations of patients before and 2 months after treatment showed, CBL W408S VAF (29% to 31%) in the bone marrow specimens of patient 4 showed almost no change. In patients 5, TET2 R550X VAF (21% to 13%) and CBL C396R VAF (44% to 26%) were decreased, while TET2 C1298Y VAF (22% to 13%) was almost unchanged. Conclusions Decitabine combined with ruxolitinib in the treatment of newly diagnosed CMML can effectively improve the clinical symptoms and the curative effect. There is still a large degree of variability in the evaluation of clinical efficacy based on the VAF of single gene mutations, and this needs to be verified by prospective studies with large samples. Key words: Leukemia, myelomonocytic, chronic; Mutation; Treatment outcome; Decitabine; Ruxolitinib