Treatment of Chronic Phase Chronic Myeloid Leukemia with Imatinib

Ganesan, Prasanth; Rajendranath, Rejiv; Kandakumar, Vignesh; Sagar, Tenali Gnana

doi:10.1007/s12098-014-1492-6

Cited by 6 publications

(6 citation statements)

References 17 publications

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“…Certain unique adverse events have been described in the Indian population, such as extensive hypopigmentation of the skin. 19,35,52 …”

Section: Methodsmentioning

confidence: 99%

“…62 The majority of childhood CML in India occurs in patients older than 12 years of age. 35,38 In the pre-imatinib era, a dismal median survival of approximately 13 months was noted. 38 Currently, survival outcomes are similar to those reported in the West.…”

Section: Methodsmentioning

confidence: 99%

“…38 Currently, survival outcomes are similar to those reported in the West. 35 Most of the reports of pediatric CML in India pertain to patients with no access to second-line TKIs or allogeneic transplants and, as such, reflect the natural history of pediatric CML treated with imatinib alone. 35,37 Children can have growth retardation due to long-term imatinib therapy, which has also been reported in Indian studies.…”

Section: Methodsmentioning

confidence: 99%

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Chronic Myeloid Leukemia in India

Ganesan

Kumar

2017

JGO

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BackgroundIn the last decade, the use of imatinib has brought a paradigm shift in the management of chronic myeloid leukemia (CML). In India, imatinib has been available for more than a decade and has been made accessible to all segments of the population because of patient assistance programs and cheaper generic versions. Despite improvements in survival, there are unique challenges in the Indian context.MethodsWe reviewed published data pertaining to CML in India for the period of 1990 to 2016, using PubMed advanced search with the terms chronic myeloid leukemia and India, and included studies that reported on epidemiology, monitoring for therapy, treatment outcomes, and resistance. Additionally, the references in retrieved articles were also reviewed.ResultsThirty-seven studies were identified. The incidence of CML may be slightly lower in India than in the West, but there was only a single article reporting population-based data. Indian patients presented with more advanced disease. Most centers have access to imatinib as first-line therapy, but there is limited availability of molecular monitoring and second-line therapy. Most of the outcome data were retrospective but seemed comparable with that reported in Western centers. Drug adherence was impaired in at least one third of patients and contributed to poor survival.ConclusionFocused prospective studies and cooperative studies might improve the quality of data available. Future studies should focus on adherence, its effects on outcomes, and methods to address this problem.

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“…Certain unique adverse events have been described in the Indian population, such as extensive hypopigmentation of the skin. 19,35,52 …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Chronic Myeloid Leukemia in India

Ganesan

Kumar

2017

JGO

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“…2 It has been developed as the rst-line antineoplastic agent for both chronic myeloid leukemia and acute lymphoblastic leukemia. 3 By selectively blocking the autophosphorylation and substrate phosphorylation of tyrosine kinase, imatinib has achieved excellent curative effects in clinical practice and has saved the lives of many patients who were suffering from the hematological malignancy. 4,5 Unfortunately, with the increasing application of imatinib in clinics, the numbers of patients who are resistant to the therapy of imatinib are also upregulated, resulting in a dissatisfactory prognosis.…”

Section: Introductionmentioning

confidence: 99%

Salidroside enhances the anti-cancerous effect of imatinib on human acute monocytic leukemia via the induction of autophagy-related apoptosis through AMPK activation

Zhang

Feng

2019

RSC Adv.

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As the typical tyrosine kinase inhibitor, imatinib has been the first-line antineoplastic agent for both chronic myeloid leukemia and acute lymphoblastic leukemia. However, a large number of patients are still resistant to the benefits of imatinib, and they have a dissatisfactory prognosis. Salidroside, a compound that is extracted from natural plants, has been reported to have an excellent anticancer effect and few side effects. In the present study, we have developed a new combination therapy strategy of salidroside and imatinib for combating the growth of acute lymphoblastic leukemia. As demonstrated by the anti-proliferation assay, salidroside exhibited excellent cytotoxicity against myeloid leukemia cells. Moreover, cells treated by the combination therapy of salidroside and imatinib displayed a clear lower growth rate than cells only treated by imatinib, indicating that salidroside has a positive effect on enhancing the cytotoxicity of imatinib against leukemia cells. Subsequently, the underlying mechanisms were investigated. The results revealed that autophagy marker proteins in leukemia cells, including LC3, p62, and Beclin1, displayed a significant expression change after treating them with salidroside plus imatinib, with the levels of LC3 and Beclin1 dramatically increasing while the expression of p62 was significantly decreased. Moreover, an obvious downregulation of p-PI3K, p-AKT and p-mTOR expression levels in leukemia cells after treatment with salidroside plus imatinib suggested that the PI3K/mTOR pathway plays an important role in the process of cell apoptosis induced by salidroside or imatinib. Further studies showed that pre-incubating the cells with an autophagy inhibitor dramatically inhibited the ability of imatinib to induce autophagy, but did not inhibit the ability of salidroside. The underlying causes were subsequently explored and the results showed that silencing AMPKa1, the most important regulator of autophagy, dramatically attenuates the ability of salidroside to induce cell apoptosis. These results together indicated that salidroside enhances the cytotoxicity of imatinib on acute monocytic leukemia via the induction of autophagy-related apoptosis through AMPK activation. The unique advantages of combination therapy were further confirmed by in vivo experiments, with the tumor-bearing cells treated with salidroside plus imatinib achieving the best anti-tumor effect. Fig. 1 Cell viabilities of THP-1 and U937 cells after receiving therapy with salidroside, imatinib, or the combination therapy strategy. (A) Salidroside exists in Rhodiola rosea, and the molecular structure is shown. THP-1 and U937 cells were treated with different concentrations of imatinib (B) and salidroside (C) for 48 h, and the cell viability was detected by a CCK-8 assay. For further determination of the ratio of salidroside and imatinib in the combination therapy strategy, both THP-1 and U937 cells were treated by various combination therapy strategies: 2 mM salidroside + 10 mM imatinib (D), 2 mM salidroside + 20 m...

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“…Although a few studies have been performed in India with a greater number of patients, the patients' molecular responses were not assessed consistently. [25] Four patients were absent from school for more than 6 months and missed 1 year of schooling, whereas older children could cope with their schooling despite frequent absences. However, all our patients were eager to study, with the primary aim of supporting their families in the future.…”

Section: Discussionmentioning

confidence: 93%

Profile of Pediatric Chronic Myeloid Leukemia in the Era of Imatinib: A Study from South India

Bernard

Suman

Rajendran

et al. 2019

Indian Journal of Medical and Paediatric Oncology

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Introduction: Chronic myeloid leukemia (CML), a chronic hematologic malignancy, is rare in pediatric patients. Studies of the tyrosine kinase inhibitor imatinib are required so that uniform guidelines may focus on disease therapy and follow-up for children. We analyzed the clinicohematologic features of the disease, treatment response to imatinib, follow-up measures, and the impact of the disease on the patients and their family. Materials and Methods: All pediatric patients diagnosed with CML and treated and followed-up were studied regarding demographics, clinical features at presentation, and diagnostic profile, including laboratory parameters, peripheral blood smear test, fluorescent in situ hybridization and karyotyping, and reverse-transcriptase polymerase chain reaction for the BCR-ABL fusion gene. Treatment modalities, adverse reactions, remedial measures, assessment at every follow-up visit, patient's education, parents' socioeconomic status, and economic and psychological stresses were also evaluated. Results: Six patients were administered upfront therapy with a standard dose of imatinib. Hematological and biochemical parameters were monitored after the drug administration. We assessed the treatment response using molecular detection of the BCR-ABL transcripts. All patients who complied with drug therapy showed a complete molecular response and minimal toxic symptoms. However, parents found it difficult to cope socially and economically. Conclusion: Imatinib mesylate is effective and has a good molecular response, minimal toxicity, and good patient compliance. However, due to its cost, families reacquire financial debt, and the disease creates uncertainty about the child's future, thereby necessitating psychosocioeconomic support for parents. Changes in the policies of cancer support groups are urgently needed to provide lifelong, lifesaving drugs free of cost.

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Treatment of Chronic Phase Chronic Myeloid Leukemia with Imatinib

Abstract: Imatinib is a reasonable first line therapy in pediatric CML-CP, which is effective and well tolerated. Outcomes are comparable to those reported from the West. Availability of second line agents and increased access to stem cell transplantation could further improve outcomes.

Cited by 6 publications

References 17 publications

Chronic Myeloid Leukemia in India

Chronic Myeloid Leukemia in India

Salidroside enhances the anti-cancerous effect of imatinib on human acute monocytic leukemia via the induction of autophagy-related apoptosis through AMPK activation

Profile of Pediatric Chronic Myeloid Leukemia in the Era of Imatinib: A Study from South India

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