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

International Journal of Molecular Sciences - Tập 20 Số 9 - Trang 2226
Stefania Stella1,2, Valentina Zammit3, Silvia Rita Vitale1,2, Maria Stella Pennisi1,2, Michele Massimino1,2, Elena Tirrò1,2, Stefano Forte4, Antonio Spitaleri3, Agostino Antolino5, Sergio Siracusa6, Vincenzo Accurso6, Donato Mannina7, Stefana Impera8, Caterina Musolino9, Sabina Russo9, Alessandra Malato10, Giuseppe Mineo11, Maurizio Musso12, Ferdinando Porretto12, Bruno Martino13, Francesco Di Raimondo14,3, Livia Manzella1,2, Paolo Vigneri1,2, Fabio Stagno3
1Center of Experimental Oncology and Hematology, A.O.U. Policlinico Vittorio Emanuele, 95123 Catania, Italy
2Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
3Division of Hematology and Bone Marrow Transplant, AOU Policlinico - V. Emanuele, 95123 Catania, Italy
4Mediterranean Institute of Oncology, 95029 Viagrande, Italy
5Department of Transfusional Medicine, Maria Paternò-Arezzo Hospital, 97100 Ragusa, Italy
6Division of Hematology, A.O.U. Policlinico "P. Giaccone", University of Palermo, 90127 Palermo, Italy
7Division of Hematology, Papardo Hospital, 98158 Messina, Italy
8Division of Oncology and Hematology, ARNAS Garibaldi-Nesima, 95122 Catania, Italy
9Division of Hematology, University of Messina, 98125 Messina, Italy
10Division of Hematology and Bone Marrow Transplant, Villa Sofia-Cervello Hospital, 90146 Palermo, Italy
11Division of Hematology, San Vincenzo Hospital, 98039 Taormina, Italy
12Division of Hematology, La Maddalena Hospital, 90146 Palermo, Italy
13Hematology Department, Grande Ospedale Metropolitano, Reggio Calabria, 89124 Reggio Calabria, Italy
14Department of Surgery, Medical and Surgical Specialities, University of Catania, 95123 Catania, Italy

Tóm tắt

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.

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International Journal of Molecular Sciences

Tập 20 Số 9

2226

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