CML-011: Chronic Myeloid Leukemia: Clinico-Laboratory Patterns and Management Options in Relapsed and Refractory Cases

Abstract

Context: The patients with the advanced and relapsed chronic myeloid leukemia (CML) experience marked disease burden in terms of symptoms, and unfavorable impact on their life quality and productivity. Objective: The study purpose was to evaluate the diagnosis and prognosis significance of lactate dehydrogenase (LDH) and T315I mutation, as well as the treatment options in the newly diagnosed and relapsed CML. Design: This cohort study included 27 CML patients, treated at the Institute of Oncology between 1995-2021. The venous blood samples were collected for lactate dehydrogenase (LDH) assay and detection of the ABL gene T315I mutation. Setting: The study was related to the outpatient and hospitalized care. Patients: The patients’ age ranged between 20-68 years (average age – 51.3±2, 14 years). The diagnosis of CML was asserted by the quantitative RT-PCR in chronic phase in 26 (96.3%) cases. Main Outcomes Measures: The survival and relapse rates may suggest the biological significance of LDH and T315I mutation. The ECOG-WHO score, p210 BCR-ABL transcript, and the survival should outline the response to tyrosine kinase inhibitors (TKIs). Interventions: Chemotherapy regimens included antimetabolites, alkylating antineoplastic agents, and TKIs. Results: The ECOG-WHO score was 1-3 at diagnosis. LDH ranged between 169–1107 U/L, and was increased in 14 (63.6%) patients, especially in those with leukocytosis over 100 x 109/l. The complete or major molecular responses followed under the TKIs chemotherapy in 16 (59.3%) cases, including 3 (11.1%) with T315I mutation. The relapses developed in 10 (71.4%) patients with the increased LDH and in 5 of 6 patients with T315I. One (3.7%) patient with T315I mutation evolved into the acute phase. The survival ranged between 23-236.8 months (median survival – 95.87±4.51 months) and was lower in cases with T315I mutation and higher LDH level. The ECOG-WHO score reached 0-1 under the treatment with TKIs. Conclusions: The elevated LDH may assess the activity at diagnosis and relapse of CML. T315I mutation and the increased LDH levels correlated with a higher rate of relapses and resistance to the first generation TKIs. Regardless of the chemotherapy line and in relapses, TKIs significantly improved the complete response rate, survival and ECOG-WHO score.