PB1751 HOW WE TREAT PATIENT WITH CHRONIC LYMPHOCYTIC LEUKEMIA AND ACUTE MYELOID LEUKEMIA DEVELOPED FROM MYELODYSPLASTIC SYNDROME
Authors: Mikhaleva M. , Kuvshinov A. , Kuzyaeva A. , Voloshin S. , Martynkevich I. , Kleina E. , Rysev G. 
Published: June 2019

Background:According to various authors, the frequency of concurrent myelodysplastic syndrome (MDS) in patients with chronic lymphocytic leukemia (CLL) is 5%. The observation of patients with combination of lympho‐ and myeloproliferative diseases is clinical interest, due to the rare occurrence, poorer outcomes and absence of optimal treatment strategy for this category of patients.Aims:We present a case of a 71‐year‐old woman with CLL and acute myeloid leukemia (AML) developed from MDS.Methods:The baseline diagnosis CLL III stage (Rai) was established in 2016 at 68 years. FISH: trisomy12 – 9%; del13 – 20.5%; del17p – 17.5%. CT scan demonstrated lymphadenopathy (axillary, epitrochlear, mediastinal, paraaortic). The first line therapy: Ibrutinib 420 mg daily, and Rituximab 375 mg/m2 D1 C1 and 500 mg/m2 D1 C2‐6 of each 28‐day cycle. Despite the treatment, patient still had moderate/severe anemia without reduction of transfusion dependency. The disease evaluation (DE) after cycle 6 of therapy showed the presence of 13.4% blasts and dysplasia in erythroid, granulocyte and megakaryocyte lines (≥10%) in BM. Flow cytometry (FCM) of BM demonstrated the population of myeloid blasts. The BM's biopsy showed combined lesions: MDS with excess of blasts‐2 and CLL (5‐7% of infiltrate). The lymph nodes, spleen and liver were normal sizes by CT scan. The response of CLL was evaluated as partial remission (PR) and the second diagnosis was established: MDS with excess of blasts‐2 (IPSS: high risk, IPSS‐R: very high risk). Azacytidine 75 mg/m2 D1‐7 of each 28‐day cycle, SC was started. Simultaneous, therapy with ibrutinib 420 mg daily was ongoing. After 4 cycles of treatment the patient became transfusion independent; HB level stabilized at 110–115 g/L; BM blasts decreased to 9.8%, and dysplasia changes persisted only in granulocyte line. We observed the decrease of minimal residual disease (MRD) of CLL: 8.6%→5.4%→3.8%. The toxicity grade 3‐4 during therapy was not observed. However, after 8 cycle of therapy the results of laboratory tests showed transformation to AML: HB–73 g/L, WBC–1.6x109/L (NEUT–27%, BANDS–1%, LYM–66%, MON–6%), PLT–44x109/L; BM blasts–24%; FCM of BM ‐ population of myeloid blasts; normal karyotype 46, XX; mutations in genes FLT3, NMP1, BCR/ABL, CBFb/MYH1, RUNX1, TP53, IDH1/2, c‐KIT, ASXL1 were not detected. Treatment with ibrutinib was stopped. Cytozar 38 mg D1‐10 of each 28‐day cycle, SC, and venetoclax 600 mg daily were started.Results:After 1stcycle of therapy: complete remission (CR) with incomplete BM recovery. After 2ndcycle – complete BM recovery. By FCM MRD negative status (MRDneg) AML and MRD positive status (MRDpos) CLL were detected. Patient is ongoing to intake cytozar and venetoclax. Presently, the MRDneg CR of AML and MRDneg PR of CLL are lasting.Summary/Conclusion:Our findings suggest that use of targeted drug in the treatment of patients with AML and CLL is possible and very effective. Also, treatment combination of low dose cytozar with venetoclax is powerful and shows clinical significance. Due to the small number of patients with this combined pathology, further studies are needed to confirm the results obtained.