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ORIGINAL ARTICLE
Year : 2020  |  Volume : 11  |  Issue : 3  |  Page : 108-111

Eradication of prior-to-treatment compound BCR-ABL mutations by interferon-alpha in chronic myeloid leukemia: Long-term follow-up studies and review of literature


1 Department of Zoology, Hematology, Oncology and Pharmaco-Genetic Engineering Sciences Group, Health Sciences Research Laboratories, Lahore, Pakistan; Molecular Genetics/Hematology & Oncology Section, Clinical Laboratory Sciences Program/Department, CoAMS-A, King Saud Bin Abdulaziz University for Health Sciences/KAIMRC, King Abdulaziz Medical City, National Guard Health Affairs, Al-Ahsa, Saudi Arabia; Department aNext-Generation Medical Biotechnology Division, Universaity of Sialkot, Sialkot, Pakistan
2 Department of Zoology, Hematology, Oncology and Pharmaco-Genetic Engineering Sciences Group, Health Sciences Research Laboratories, Lahore, Pakistan
3 Department aNext-Generation Medical Biotechnology Division, Universaity of Sialkot, Sialkot, Pakistan
4 Hematology/Oncology Division, Department of Medicine, KKUH and College of Medicine, King Saud University, Riyadh, Saudi Arabia
5 Department of Zoology, University of the Punjab, Lahore, Pakistan
6 Faculty of Applied Medical, Saudi Arabia
7 Allied Hospital, Faisalabad, Pakistan
8 Department of Zoology, Hematology, Oncology and Pharmaco-Genetic Engineering Sciences Group, Health Sciences Research Laboratories, Lahore; Department aNext-Generation Medical Biotechnology Division, Universaity of Sialkot, Sialkot, Pakistan
9 Department of Medicine, Asian Medical Institute, Kartik, Kyrgyzstan
10 Khyber Teaching Hospital and Hayatabad Medical Complex, Peshawar, Pakistan
11 Molecular Genetics/Hematology & Oncology Section, Clinical Laboratory Sciences Program/Department, CoAMS-A, King Saud Bin Abdulaziz University for Health Sciences/KAIMRC, King Abdulaziz Medical City, National Guard Health Affairs, Al-Ahsa, Saudi Arabia

Correspondence Address:
Dr. Zafar Iqbal
CoAMS-A, King Saud Bin Abdulaziz University for Health Sciences/KAIMRC, King Abdulaziz Medical City, National Guard Health Affairs, Al-Ahsa

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/joah.joah_13_20

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BACKGROUND: Although tyrosine kinase inhibitors (TKIs) are the gold standard in clinical management of chronic myeloid leukemia, it is not feasible to use these drugs in at least some cases when patients are resistance to all available TKIs due to compound BCR-ABL mutations, due to patient safety profile or due to the nonavailability of drugs in developing countries on account of cost or logistic issues. We reported earlier that interferon alpha can eradicate compound BCR-ABL mutations and induce stable responses. Here, we report a follow-up of this study. PATIENTS AND METHODS: Some chronic myeloid leukemia (CML) patients did not get TKIs directly because of very high cost of imatinib and were given interferon alpha (experimental group) until the provision of imatinib free of cost through GLIVEC® International Patient Assistance Program while the other groups of patients (control group) were directly given imatinib. A very sensitive allele-specific polymerase chain reaction was employed to detect BCR-ABL compound mutations before treatment and confirmation of mutations was carried out using reliable molecular assays. Mutations were reinvestigated at all important time points during the long-term follow-up studies. RESULTS: The use of interferon-alpha for 6 months prior to TKIs eradicated compound BCR-ABL mutations (Phe311Val/Met351Thr and Thr315Ile/Phe311Val/Met351Thr) and provided deep molecular responses without any progression or mortality in CML patients (experimental group) as compared with patients who did not use interferon and was directly given TKIs (control group). CONCLUSIONS: Interferon alpha can eradicate highly resistant BCR-ABL mutations and lead to durable deep molecular responses to TKIs in CML. Therefore, interferon-alpha is recommended for CML patients with compound mutations resistant to TKIs, specifically in those scenarios where some TKIs are not available or not safe to use for CML patients. Our long-term follow-up study is well supported by recently published literature.


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