Estimating prognostic relevant cutoff values for a multiplex PCR detecting BCR::ABL1 in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy in resource-limited settings.
BCR::ABL1 fusion gene
Chronic myeloid leukemia (CML)
Clinical lab performance
Low- and middle-income countries (LMICs)
Multiplex PCR
Prognostic relevant cutoff values
Journal
Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
received:
29
12
2022
accepted:
23
04
2023
medline:
14
6
2023
pubmed:
22
5
2023
entrez:
22
5
2023
Statut:
ppublish
Résumé
The prognosis of chronic myeloid leukemia (CML) on tyrosine kinase inhibitor (TKI) treatment is based on the quantification of BCR::ABL1 fusion gene transcript copy number, harmonized by an international scale (IS) based on TaqMan-based real-time quantitative PCR (qRT-PCR). In Ethiopia, as in most low- and middle-income countries (LMICs), access to standard diagnostic, follow-up, and prognostic tools is very limited, and it has been challenging to strictly follow international guidelines. This seriously compromises clinical outcome, despite the availability of TKIs through the Glivec International Patient Assistance Program (GIPAP). Multiplex PCR (mpx-PCR), conventionally regarded as a "screening tool," offers a potential solution to this problem. A total of 219 samples from confirmed CML patients were assayed. In reference to qRT-PCR, the AUC of ROC curve for mpx-PCR was 0.983 (95% CI: 0.957 to 0.997). At the optimum cut-off value, equivalent to BCR::ABL1 (IS) transcript copy number of 0.6%, the specificity and sensitivity were 93% and 95%, respectively, with 94% accuracy. Albeit the sensitivity and accuracy of mpx-PCR decrease below the optimum cutoff of 0.6% (IS), the specificity at 0.1% (IS) was 100%, making it an attractive means to rule-out relapse and drug non-adherence at later stages of treatment, which is particularly an issue in a low income setting. We conclude that the relative simplicity and low cost of mpx-PCR and prognostic relevant cutoff values (0.1-0.6% IS) should allow its use in peripheral clinics and thus maximize the positive impact of TKIs made available through GIPAP in most LMICs.
Identifiants
pubmed: 37212909
doi: 10.1007/s00277-023-05254-x
pii: 10.1007/s00277-023-05254-x
pmc: PMC10261237
doi:
Substances chimiques
Tyrosine Kinase Inhibitors
0
Fusion Proteins, bcr-abl
EC 2.7.10.2
Imatinib Mesylate
8A1O1M485B
Protein Kinase Inhibitors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1723-1729Informations de copyright
© 2023. The Author(s).
Références
Léglise MC, Pluchon-Rivière E, Le Calvez G et al (1996) Molecular diagnosis and follow up in myeloproliferative syndromes and acute leukemias: correlation between expression of fusion transcripts and disease progression in chronic myeloid leukemia. Leuk Lymphoma 21(3-4):187–199. https://doi.org/10.3109/10428199209067600
doi: 10.3109/10428199209067600
pubmed: 8726399
Deininger MW, Goldman JM, Melo JV (2000) The molecular biology of chronic myeloid leukemia. Blood 96(10):3343–3356
doi: 10.1182/blood.V96.10.3343
pubmed: 11071626
Faderl S, Talpaz M, Estrov Z et al (1999) The biology of chronic myeloid leukemia. N Engl J Med 341(3):164–172. https://doi.org/10.1056/NEJM199907153410306
doi: 10.1056/NEJM199907153410306
pubmed: 10403855
Bower H, Björkholm M, Dickman PW et al (2016) Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J Clin Oncol 34(24):2851–2857. https://doi.org/10.1200/JCO.2015.66.2866
doi: 10.1200/JCO.2015.66.2866
pubmed: 27325849
Mahon F-X, Réa D, Guilhot J et al (2010) Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 11(11):1029–1035. https://doi.org/10.1016/S1470-2045(10)70233-3
doi: 10.1016/S1470-2045(10)70233-3
pubmed: 20965785
Radich JP, Briercheck E, Chiu DT et al (2022) Precision medicine in low- and middle-income countries. Annu Rev Pathol 17:387–402. https://doi.org/10.1146/annurev-pathol-042320-034052
doi: 10.1146/annurev-pathol-042320-034052
pubmed: 35073168
pmcid: 9275191
Tadesse F, Asres G, Abubeker A et al (2021) Spectrum of BCR-ABL mutations and treatment outcomes in ethiopian imatinib-resistant patients with chronic myeloid leukemia. JCO global oncology 7:1187–1193. https://doi.org/10.1200/GO.21.00058
doi: 10.1200/GO.21.00058
pubmed: 34292760
Hochhaus A, Baccarani M, Silver RT et al (2020) European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia 34(4):966–984. https://doi.org/10.1038/s41375-020-0776-2
doi: 10.1038/s41375-020-0776-2
pubmed: 32127639
pmcid: 7214240
Deininger MW, Shah NP, Altman JK et al (2020) Chronic myeloid leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Nat Compr Cancer Netw 18(10):1385–1415. https://doi.org/10.6004/jnccn.2020.0047
doi: 10.6004/jnccn.2020.0047
Maheshwari VK, Slader C, Dani N et al (2021) Enabling access to molecular monitoring for chronic myeloid leukemia patients is cost effective in China. PLoS One 16(10):e0259076. https://doi.org/10.1371/journal.pone.0259076
doi: 10.1371/journal.pone.0259076
pubmed: 34695169
pmcid: 8544861
Pramesh CS, Badwe RA, Bhoo-Pathy N et al (2022) Priorities for cancer research in low- and middle-income countries: a global perspective. Nat Med 28(4):649–657. https://doi.org/10.1038/s41591-022-01738-x
doi: 10.1038/s41591-022-01738-x
pubmed: 35440716
pmcid: 9108683
Garcia-Gonzalez P, Boultbee P, Epstein D (2015) Novel humanitarian aid program: the Glivec International Patient Assistance Program-lessons learned from providing access to breakthrough targeted oncology treatment in low- and middle-income countries. J Glob Oncol 1(1):37–45. https://doi.org/10.1200/JGO.2015.000570
doi: 10.1200/JGO.2015.000570
pubmed: 28804770
pmcid: 5551649
Jobbagy Z, van Atta R, Murphy KM et al (2007) Evaluation of the Cepheid GeneXpert BCR-ABL assay. J Mol Diagnos 9(2):220–227. https://doi.org/10.2353/jmoldx.2007.060112
doi: 10.2353/jmoldx.2007.060112
Rowley S, Garcia-Gonzalez P, Radich JP et al (2021) Analysis of the gap in PCR monitoring availability for patients with chronic myeloid leukemia in 60 low- and middle-income countries. Cost Effect Resour Alloc 19(1):18. https://doi.org/10.1186/s12962-021-00271-x
doi: 10.1186/s12962-021-00271-x
Sastre D, Argaraña CE, Heller V et al (2007) An analysis of multiplex-PCR in the detection of BCR-ABL transcripts in hematological disorders. Gen Mol Biol 30:520–523. https://doi.org/10.1590/S1415-47572007000400003
doi: 10.1590/S1415-47572007000400003
Burmeister T, Reinhardt R (2008) A multiplex PCR for improved detection of typical and atypical BCR-ABL fusion transcripts. Leuk Res 32(4):579–585. https://doi.org/10.1016/j.leukres.2007.08.017
doi: 10.1016/j.leukres.2007.08.017
pubmed: 17928051
Cross NC, Melo JV, Feng L et al (1994) An optimized multiplex polymerase chain reaction (PCR) for detection of BCR-ABL fusion mRNAs in haematological disorders. Leukemia 8(1):186–189
pubmed: 8289486
Gabert J, Beillard E, van der Velden VHJ et al (2003) Standardization and quality control studies of 'real-time' quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia - a Europe Against Cancer program. Leukemia 17(12):2318–2357. https://doi.org/10.1038/sj.leu.2403135
doi: 10.1038/sj.leu.2403135
pubmed: 14562125
Franke G-N, Maier J, Wildenberger K et al (2020) Comparison of real-time quantitative PCR and digital droplet PCR for BCR-ABL1 monitoring in patients with chronic myeloid leukemia. J Mol Diagn 22(1):81–89. https://doi.org/10.1016/j.jmoldx.2019.08.007
doi: 10.1016/j.jmoldx.2019.08.007
pubmed: 31669230
White H, Deprez L, Corbisier P et al (2015) A certified plasmid reference material for the standardisation of BCR-ABL1 mRNA quantification by real-time quantitative PCR. Leukemia 29(2):369–376. https://doi.org/10.1038/leu.2014.217
doi: 10.1038/leu.2014.217
pubmed: 25036192
Müller MC, Munjal U, Erben P et al (2010) Stability of conversion factors for BCR-ABL monitoring -– implications for the frequency of validation rounds. Blood 116(21):893. https://doi.org/10.1182/blood.V116.21.893.893
doi: 10.1182/blood.V116.21.893.893
Biswas B (2016) Clinical performance evaluation of molecular diagnostic tests. J Mol Diagn 18(6):803–812. https://doi.org/10.1016/j.jmoldx.2016.06.008
doi: 10.1016/j.jmoldx.2016.06.008
pubmed: 27639547
Hochhaus A, Larson RA, Guilhot F et al (2017) Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med 376(10):917–927. https://doi.org/10.1056/NEJMoa1609324
doi: 10.1056/NEJMoa1609324
pubmed: 28273028
pmcid: 5901965
Umeh CA, Garcia-Gonzalez P, Tremblay D et al (2020) The survival of patients enrolled in a global direct-to-patient cancer medicine donation program: the Glivec International Patient Assistance Program (GIPAP). EClinicalMedicine 19:100257. https://doi.org/10.1016/j.eclinm.2020.100257
doi: 10.1016/j.eclinm.2020.100257
pmcid: 7046500
Ning L, Hu C, Lu P et al (2020) Trends in disease burden of chronic myeloid leukemia at the global, regional, and national levels: a population-based epidemiologic study. Exp Hematol Oncol 9(1):29. https://doi.org/10.1186/s40164-020-00185-z
doi: 10.1186/s40164-020-00185-z
pmcid: 7607878
Hu Y, Li Q, Hou M et al (2021) Magnitude and temporal trend of the chronic myeloid leukemia: on the basis of the Global Burden of Disease Study 2019. JCO global oncology 7:1429–1441. https://doi.org/10.1200/GO.21.00194
doi: 10.1200/GO.21.00194
pubmed: 34591599
Neelakantan P, Gerrard G, Lucas C et al (2013) Combining BCR-ABL1 transcript levels at 3 and 6 months in chronic myeloid leukemia: implications for early intervention strategies. Blood 121(14):2739–2742. https://doi.org/10.1182/blood-2012-11-466037
doi: 10.1182/blood-2012-11-466037
pubmed: 23380743
pmcid: 6143156
Stella S, Zammit V, Vitale SR et al (2019) Clinical implications of discordant early molecular responses in CML patients treated with imatinib. Int J Mol Sci 20(9). https://doi.org/10.3390/ijms20092226
Mulu Fentie A, Tadesse F, Engidawork E et al (2019) Prevalence and determinants of non-adherence to Imatinib in the first 3-months treatment among newly diagnosed Ethiopian's with chronic myeloid leukemia. PLoS One 14(3):e0213557. https://doi.org/10.1371/journal.pone.0213557
doi: 10.1371/journal.pone.0213557
pubmed: 30845227
pmcid: 6405163