Cytogenetic and Molecular Remission in Chronic Myeloid Leukemia in Togo

Research Article

Ann Hematol Onco. 2023; 10(6): 1442.

Cytogenetic and Molecular Remission in Chronic Myeloid Leukemia in Togo

Padaro E¹; Womey KMC¹*; Layibo Y²; Kueviakoe MDI²; Magnang H¹; Mawussi K³; Agbetiafa K¹; Agbado KS¹; Vovor A²

¹Department of Hematology, University of Lomé, Togo

²Laboratory of Hematology, University of Lomé, Togo

³Kara Regional Blood Transfusion Center, University of Kara, Togo

*Corresponding author: Womey KMC Department of hematology, University of Lomé, 01BP1515, Togo. Tel: +22892526400 Email: corcellar.womey@gmail.com

Received: October 09, 2023 Accepted: November 13, 2023 Published: November 20, 2023

Abstract

The availability of tyrosine kinase inhibitors (TKIs) in Togo through the GIPAP program has revolutionized the management of chronic myeloid leukemia and increased patient life expectancy. However, diagnosis and molecular monitoring of therapeutic efficacy remain a real challenge due to the inaccessibility of cytogenetic and molecular biology tools. We’ve conducted, a cross-sectional, descriptive study that ran from December 21, 2022, to January 20, 2023, with the aim to evaluate the cytogenetic and molecular remission in CML patients followed at the CHU Campus de Lomé in Togo. Patients diagnosed with chronic-phase CML who had been treated for at least three months with imatinib or dasatinib and had achieved complete hematological remission were included. Dosage of BCR-ABL transcript levels was performed by RQ-PCR in Seattle, USA, using Dried Blood Spot. The transcript detection limit was 0.003% i.e., MR4. A total of 38 patients were included, 68.4% of them were treated with imatinib and 31.6% with dasatinib. In terms of remission, 28.9% had not achieve a partial cytogenetic remission while 15.8% of patients had achieved a MR4 remission and 7.9% a major molecular remission. Major molecular remission was achieved at a mean follow-up time of 95 months for patients taking imatinib and 22 months for those taking dasatinib. Patients in MR4 were on imatinib after a mean of 68 months. All in one, our study showed a high rate of treatment failure. Better access to cytogenetic and molecular biology tools is needed to improve management.

Keywords: CML; TKIs; remission; cytogenetic; molecular biology; Togo

Abbreviations: TKI; GIPAP; CML; RQ-PCR; CHR; MR; MMR; PCyR; CCyR, NR; DBS; ELN; CHR

Introduction

Chronic myeloid leukemia (CML) is a myeloproliferative syndrom resulting from the translocation t(9;22)(q34;q11) which gives rise to the BCR-ABL1 fusion gene encoding a protein with exacerbated tyrosine kinase function [1]. Previously always fatal, CML has become a chronic disease with a life expectancy close to that of the general population, thanks to the discovery of tyrosine kinase inhibitors (TKIs) [2]. International guidelines based on the quantification of BCR-ABL1 mRNA by real-time RT-PCR enable clinicians to regularly assess therapeutic efficacy [3]. In Togo in 2006, according to a study by Kueviakoe et al, CML accounted for 20% of hematological malignancies, with an annual hospital incidence rate of 2.91 cases [4]. This figure is constantly rising. Since the advent of imatinib in 2005, courtesy of The Max Foundation's GIPAP (Glivec International Patient Assistance Program), patient outcomes have improved considerably [5]. The range of TKIs offered by the GIPAP program was subsequently extended with the introduction of dasatinib in 2019 and bosutinib in 2023. However, molecular monitoring of patients is a real challenge because of the difficulty of accessing cytogenetic and molecular tests. The aim of this study, conducted with the support of The Max Foundation, was therefore to investigate the molecular remission to TKIs in patients treated for chronic myeloid leukemia at the CHU Campus in Lomé, Togo.

Materials and Methods

This was a cross-sectional, descriptive study, which took place from 21 December 2022 to 20 January 2023. It concerned patients followed up in the clinical hematology department of the CHU Campus and who were seen in consultation during the study period. Patients diagnosed with chronic-phase CML who had been treated for at least three months with imatinib or dasatinib and had achieved complete hematological remission were included, within the limits of available DBS (Dried Blood Spot) samples. Patients diagnosed during the study period and those with other hematological malignancies were not included. The variables studied were age, sex, length of follow-up, type of TKI received and BCR-ABL molecular transcript level. Cytogenetic and molecular response was assessed according to the International Scale as the ratio of BCR-ABL1 transcripts to ABL1 transcripts and was expressed and reported as BCR-ABL1 % on a log scale. BCR_ABL =10% is equivalent to partial cytogenetic remission (PCyR). BCR-ABL1 transcript level =1% is defined as complete cytogenetic remission (CCyR). BCR-ABL1 transcript level =0.1% is defined as major molecular response (MMR) or MR3. A BCR-ABL1 transcript level =0.01% or undetectable disease in cDNA with >10,000 ABL1 transcripts is defined as MR4 [6]. The BCR-ABL transcript level was measured in Seattle, USA, by RQ-PCR using Dried Blood Spot (DBS). The transcript detection limit was 0.003% i.e MR4.

Results

Thirty-eight patients were included in our study, with a mean age of 42 ± 16 years (8-75) and a sex ratio of 1.4:1. Twenty-six (68.4%) patients were treated with imatinib and 12 (31.6%) with dasatinib. The mean duration of follow-up was 51±55 months (7-211). It was 62 months for patients taking imatinib and 27±15 months for patients taking dasatinib. Overall, 28.9% of patients had no molecular remission, compared with 15.8% who had achieved a MR4 (Figure 1). Depending on the treatment, a MMR was observed in 8.3% of patients taking dasatinib, compared with 7.7% of patients taking imatinib. Table I shows the different types of molecular remission according to TKI. On imatinib, patients on MMR had a mean follow-up of 95 months, compared with 22 months for patients on dasatinib. Tables II and III show the different types of remission obtained according to treatment and duration of follow-up.