Clinical Lymphoma, Myeloma & Leukemia, Vol.22, Suppl.2 - October 2022

Abstracts Clinical Lymphoma, Myeloma & Leukemia October 2022 S292 CML-313 Kinetics of CITED2 Gene Expression in Chronic Myeloid Leukemia Patients Basma Atef MD 1 , Shaimaa El-Ashwah MD 1 , Layla M. Saleh MD 2 , Hanan Gawish MD 3 , Mohamed Mabed MD 1 1 Hematology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 2 Clinical Pathology Department, Hematology Section, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 3 Diabetes & Endocrinology Unit, Internal Medicine Department, Faculty of Medicine Mansoura University, Mansoura, Egypt Co n text: In CML, BCR-ABL1 oncoprotein induces overexpression of STAT5 and its target genes for example CITED2 gene. This gene is involved in regulating the proliferation and quiescence states of leukemic stem cells (LSCs). Recently, studies reported that adding pioglitazone (PPAR  agonist approved for T2DM treatment) to imatinib may decrease the transcription of both STAT5 and CITED2 gene, eliminate the quiescent LSCs (resist TKIs), and ameliorate the patients’ response. Objecti v es: The primary objective is to clarify the value of combining pioglitazone with imatinib to downregulate the CITED2 gene aiming to eradicate the LSCs in CML treatment. D esig n : In the context of a clinical trial (approved by the Ethical Committee of the Faculty of Medicine Mansoura University), the study group patients (N=26) were treated with combination therapy after having their consent. The planned follow-up time is 2 years. Setti n g: Hematology unit, Oncology Center, Mansoura University. Patie n ts or Other Participa n ts: The eligibility criteria for study group patients were de novo, Philadelphia+ve CML (chronic phase) aged 18-60 years old. I n ter v e n tio n s: Those patients were treated with imatinib 400 mg and pioglitazone 15 mg once daily for 6 months. Pre- and post-treatment samples (after 6 months) were collected to assess the expression levels of the CITED2 gene. Responders continued on the same TKI and their sequential BCR/ABL Q-PCR was monitored. Mai n Outco m e Measures: The study proposed that this combination therapy can put more patients into deeper and faster molecular response via eliminating the LSCs. Results: The study group included 15 males (5 7 . 7 %) and 11 females (42.3%) with a mean age of 43.2 years. The BCR-ABL and CITED2 genes’ pre- treatment expression levels decreased significantly after 6 months of combined treatment (p<0.001 and p=0.005, respectively). Moreover, at 6 months 65.4% and 23% of the patients had response  CCyR and  MMR respectively. The most frequent complaints among patients were increased body weight and edema (p<0.001). Co n clusio n s: Adding pioglitazone to imatinib improved the patients’ response and downregulate the overexpressed CITED2 gene. A longer follow-up is planned and needed to confirm the safety and efficacy of the combination. Keywords: CML, STAT5, CITED2 gene, pioglitazone, molecular response CML-337 Therapeutic Results of Second- Generation TKIs in a CML Multicentric Study in the West Region of Algeria Siali Nadjat MD, Benlazar Mohamed MD CHU Sidibelabbes, Sidibelabbes, Algeria I n troductio n : Historically, treatments for chronic myeloid leukemia (CML) are palliative, except for bone marrow allograft. Despite the results obtained using imatinib, a first-generation tyrosine kinase inhibitor (TKI), some patients (pts) have weak responses. The second-generation TKIs dasatinib and nilotinib are therapeutic alternatives in pts resistant to imatinib. Material a n d Methods: This retrospective, multicenter study included 7 hematology centers in western Algeria. Pts older than 15 years treated with dasatinib or nilotinib as second-line therapy were included. The analysis of prognostic factors and the study of therapeutic responses were conducted according to ELN 2013. Event-free survival, progression- free survival, and overall survival (OS) were calculated according to the Kaplan–Meier method. Results: Between January 200 7 and December 2018, we collected 494 pts with CML, 154 of whom were treated with second-generation TKIs at a median age of 45 years (16, 83). The sex ratio was 0.8 7 . The average splenic overflow was 8 cm. The average leukocytosis was 100 Giga/L. The average hemoglobin level was 10 g/dl (5.5–15). The average platelet rate was 35.5 Giga/L (2 7 –1120). The majority of pts (120, 80%) had intermediate or high Sokal scores. The myelocytic phase was detected in 132 pts (86%), accelerated phase in 19 pts (13%), and acute transformation phase in 1 pt (1%). The indication for second-generation TKI was pts in accelerated phase in 7 0% of cases, failure to respond to first- generation TKI in 25% of cases, and intolerance in 5% of cases. Dasatinib was used in 7 5 pts (50%), nilotinib in 44 pts (30%), and dasatinib then nilotinib in 33 pts (20%). Evaluable pts (154) included 61% in MMR and 39% in failure, 25 pts died, and 25 pts were lost to follow-up. Toxicity was primarily hematological and digestive. OS was 80% at 5 years. Co n clusio n s: The results obtained in our series are encouraging because second-generation TKIs as second-line therapy allowed treatment of 62% of pts who were intolerant or failing to respond to imatinib with acceptable digestive and hematological toxicity. Keywords: CML, chronic myeloid leukemia, second-generation TKI, nilotinib, dasatinib CML-344 Adherence to Imatinib Mesylate in Patients Newly Diagnosed With Chronic Myeloid Leukemia in India Over the First Year of Treatment and How to Improve Compliance Sasmith Menakuru MD 1 , Amir Beirat MD 1 , Ibrahim Khan MD 1 , Sruti Kalla MBBS 2 1 Indiana University Health Ball Memorial Hospital, Muncie, USA. 2 Maharaja Institute of Medical Sciences, Vizianagaram, India