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Article

Clinical Implications of Discordant Early Molecular Responses in CML Patients Treated with Imatinib

1
Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
2
Center of Experimental Oncology and Hematology, A.O.U. Policlinico Vittorio Emanuele, 95123 Catania, Italy
3
Division of Hematology and Bone Marrow Transplant, AOU Policlinico - V. Emanuele, 95123 Catania, Italy
4
Mediterranean Institute of Oncology, 95029 Viagrande, Italy
5
Department of Transfusional Medicine, Maria Paternò-Arezzo Hospital, 97100 Ragusa, Italy
6
Division of Hematology, A.O.U. Policlinico “P. Giaccone”, University of Palermo, 90127 Palermo, Italy
7
Division of Hematology, Papardo Hospital, 98158 Messina, Italy
8
Division of Oncology and Hematology, ARNAS Garibaldi-Nesima, 95122 Catania, Italy
9
Division of Hematology, University of Messina, 98125 Messina, Italy
10
Division of Hematology and Bone Marrow Transplant, Villa Sofia-Cervello Hospital, 90146 Palermo, Italy
11
Division of Hematology, San Vincenzo Hospital, 98039 Taormina, Italy
12
Division of Hematology, La Maddalena Hospital, 90146 Palermo, Italy
13
Hematology Department, Grande Ospedale Metropolitano, Reggio Calabria, 89124 Reggio Calabria, Italy
14
Department of Surgery, Medical and Surgical Specialities, University of Catania, 95123 Catania, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(9), 2226; https://doi.org/10.3390/ijms20092226
Received: 23 March 2019 / Revised: 1 May 2019 / Accepted: 2 May 2019 / Published: 6 May 2019
(This article belongs to the Special Issue Advances in Molecular Biology and Targeted Therapy of Leukemias)
A reduction in BCR-ABL1/ABL1IS transcript levels to <10% after 3 months or <1% after 6 months of tyrosine kinase inhibitor therapy are associated with superior clinical outcomes in chronic myeloid leukemia (CML) patients. In this study, we investigated the reliability of multiple BCR-ABL1 thresholds in predicting treatment outcomes for 184 subjects diagnosed with CML and treated with standard-dose imatinib mesylate (IM). With a median follow-up of 61 months, patients with concordant BCR-ABL1/ABL1IS transcripts below the defined thresholds (10% at 3 months and 1% at 6 months) displayed significantly superior rates of event-free survival (86.1% vs. 26.6%) and deep molecular response (≥ MR4; 71.5% vs. 16.1%) compared to individuals with BCR-ABL1/ABL1IS levels above these defined thresholds. We then analyzed the outcomes of subjects displaying discordant molecular transcripts at 3- and 6-month time points. Among these patients, those with BCR-ABL1/ABL1IS values >10% at 3 months but <1% at 6 months fared significantly better than individuals with BCR-ABL1/ABL1IS <10% at 3 months but >1% at 6 months (event-free survival 68.2% vs. 32.7%; p < 0.001). Likewise, subjects with BCR-ABL1/ABL1IS at 3 months >10% but <1% at 6 months showed a higher cumulative incidence of MR4 compared to patients with BCR-ABL1/ABL1IS <10% at 3 months but >1% at 6 months (75% vs. 18.2%; p < 0.001). Finally, lower BCR-ABL1/GUSIS transcripts at diagnosis were associated with BCR-ABL1/ABL1IS values <1% at 6 months (p < 0.001). Our data suggest that when assessing early molecular responses to therapy, the 6-month BCR-ABL1/ABL1IS level displays a superior prognostic value compared to the 3-month measurement in patients with discordant oncogenic transcripts at these two pivotal time points. View Full-Text
Keywords: chronic myeloid leukemia; BCR-ABL1; imatinib mesylate; European Leukemia Net; early molecular response chronic myeloid leukemia; BCR-ABL1; imatinib mesylate; European Leukemia Net; early molecular response
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Figure 1

MDPI and ACS Style

Stella, S.; Zammit, V.; Vitale, S.R.; Pennisi, M.S.; Massimino, M.; Tirrò, E.; Forte, S.; Spitaleri, A.; Antolino, A.; Siracusa, S.; Accurso, V.; Mannina, D.; Impera, S.; Musolino, C.; Russo, S.; Malato, A.; Mineo, G.; Musso, M.; Porretto, F.; Martino, B.; Di Raimondo, F.; Manzella, L.; Vigneri, P.; Stagno, F. Clinical Implications of Discordant Early Molecular Responses in CML Patients Treated with Imatinib. Int. J. Mol. Sci. 2019, 20, 2226. https://doi.org/10.3390/ijms20092226

AMA Style

Stella S, Zammit V, Vitale SR, Pennisi MS, Massimino M, Tirrò E, Forte S, Spitaleri A, Antolino A, Siracusa S, Accurso V, Mannina D, Impera S, Musolino C, Russo S, Malato A, Mineo G, Musso M, Porretto F, Martino B, Di Raimondo F, Manzella L, Vigneri P, Stagno F. Clinical Implications of Discordant Early Molecular Responses in CML Patients Treated with Imatinib. International Journal of Molecular Sciences. 2019; 20(9):2226. https://doi.org/10.3390/ijms20092226

Chicago/Turabian Style

Stella, Stefania, Valentina Zammit, Silvia R. Vitale, Maria S. Pennisi, Michele Massimino, Elena Tirrò, Stefano Forte, Antonio Spitaleri, Agostino Antolino, Sergio Siracusa, Vincenzo Accurso, Donato Mannina, Stefana Impera, Caterina Musolino, Sabina Russo, Alessandra Malato, Giuseppe Mineo, Maurizio Musso, Ferdinando Porretto, Bruno Martino, Francesco Di Raimondo, Livia Manzella, Paolo Vigneri, and Fabio Stagno. 2019. "Clinical Implications of Discordant Early Molecular Responses in CML Patients Treated with Imatinib" International Journal of Molecular Sciences 20, no. 9: 2226. https://doi.org/10.3390/ijms20092226

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