Monitoring of BCR-ABL levels in chronic myeloid leukemia patients treated with imatinib in the chronic phase

Machado, Melissa Pereira; Tomaz, Juarez Pires; Lorand-Metze, Irene; Souza, Cármino Antônio de; Vigorito, Afonso Celso; Delamain, Márcia Torresan; Bendit, Israel; Pereira, Noemi F.; Pagnano, Kátia Bórgia Barbosa

doi:10.5581/1516-8484.20110056

Cited by 16 publications

(9 citation statements)

References 11 publications

(13 reference statements)

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“…This result was approximately closed to data reported from Patan hospital in India where optimal hematological response rate was 78% [18], but lower than those reported in Asia including China, Hong Kong, India and Southern Korea with 98%, 100%, 96%, and 100% optimal hematological response respectively [19], and lower than data reported from Brazil (95%) [20], Portugal (95.4%) [21], Malaysia (93.2%) [22], and Tanzania (91.3%) [23]. where optimal hematological response reached at the end of three months following starting therapy.…”

Section: Discussionsupporting

confidence: 50%

Chronic Myeloid Leukemia in South Yemen

Abdul-Rahman¹,

Ga²,

Nasher³

2018

Int J Biopharm Sci

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Objectives: There is no any published chronic myeloid leukemia epidemiology and evaluation of the hematological and molecular response of chronic myeloid leukemia patients. Material and Methods: This is a descriptive study conducted at National Oncology Center-Aden, South Yemen from September 2014-March 2016. Results: 50 patients were studied, 22 of them were males and 28 were females, the age is ranged between 20-71 years old with a mean age 41.9 years. The most common complaint was fatigability 86%, followed by fever and abdominal distension 78%, 76% respectively while in 82% of patients splenomegaly was the prominent sign detected during the examination. Most patients were anemic at diagnosis with a mean hemoglobin 10.2 g/ dl, leukocytosis was observed in 90% of patients ranging from 4.6 × 10 9 up to 290 × 10 9 with a mean WBC count about 40.0 × 10 9. The dramatic hematological improvement was observed with the achievement of CHR in 84% of patients which considered as an optimal response. Monitoring early molecular response after three months of starting imatinib revealed an achievement of optimal response in 60% of patients (≥ 1 log reduction of standardized baseline value which is 72.2% in our study), suboptimal or warning response is observed in 22%, (<1 log reduction but >standardized baseline value), and failure to response in 18% (6% didn't show any molecular response but still in chronic phase, 8% progress to blast crisis, 4% drug intolerance). Conclusions: 1) Chronic myeloid leukemia found to be more common in patients within 4 th-5 th decades in our study, with slight female predominance (0.8:1 M:F ratio). 2) Early molecular response is significant and optimal early molecular response was achieved by 60% of patients, 22% showed a suboptimal response while only 18% failed to show any molecular response.

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Section: Discussionsupporting

confidence: 50%

Chronic Myeloid Leukemia in South Yemen

Abdul-Rahman¹,

Ga²,

Nasher³

2018

Int J Biopharm Sci

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“…BCR-ABL1 transcripts were measured in the peripheral blood by real-time quantitative polymerase chain reaction (RQ-PCR) at baseline and then every 3 months using procedures described elsewhere with some modifications 11 . First, cDNA was amplified using the ABI 7300 sequence detection system (Applied Biosystems) and TAQMAN Universal Master Mix in a final reaction volume of 25 μL according to the instructions recommended by the manufacturer.…”

Section: Methodsmentioning

confidence: 99%

Treatment with dasatinib or nilotinib in chronic myeloid leukemia patients who failed to respond to two previously administered tyrosine kinase inhibitors – a single center experience

Ribeiro¹,

Miranda²,

Albuquerque³

et al. 2015

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OBJECTIVE:To evaluate hematological, cytogenetic and molecular responses as well as the overall, progression-free and event-free survivals of chronic myeloid leukemia patients treated with a third tyrosine kinase inhibitor after failing to respond to imatinib and nilotinib/dasatinib.METHODS:Bone marrow karyotyping and real-time quantitative polymerase chain reaction were performed at baseline and at 3, 6, 12 and 18 months after the initiation of treatment with a third tyrosine kinase inhibitor. Hematologic, cytogenetic and molecular responses were defined according to the European LeukemiaNet recommendations. BCR-ABL1 mutations were analyzed by Sanger sequencing.RESULTS:We evaluated 25 chronic myeloid leukemia patients who had been previously treated with imatinib and a second tyrosine kinase inhibitor. Nine patients were switched to dasatinib, and 16 patients were switched to nilotinib as a third-line therapy. Of the chronic phase patients (n=18), 89% achieved a complete hematologic response, 13% achieved a complete cytogenetic response and 24% achieved a major molecular response. The following BCR-ABL1 mutations were detected in 6/14 (43%) chronic phase patients: E255V, Y253H, M244V, F317L (2) and F359V. M351T mutation was found in one patient in the accelerated phase of the disease. The five-year overall, progression-free and event-free survivals were 86, 54 and 22% (p<0.0001), respectively, for chronic phase patients and 66%, 66% and 0% (p<0.0001), respectively, for accelerated phase patients. All blast crisis patients died within 6 months of treatment. Fifty-six percent of the chronic phase patients lost their hematologic response within a median of 23 months.CONCLUSIONS:Although the responses achieved by the third tyrosine kinase inhibitor were not sustainable, a third tyrosine kinase inhibitor may be an option for improving patient status until a donor becomes available for transplant. Because the long-term outcome for these patients is poor, the development of new therapies for resistant chronic myeloid leukemia patients is necessary.

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“… 4 De Lavallade et al, Silveira and Machado et al found this level of response in 39.0%, 37.1% and 40% of patients, respectively. 15 , 16 , 17 In the prospective and sequential study of de Lavallade et al, patients achieved MMR between two and 73 months (median: 15.7 months) after starting treatment. 15 MMR was achieved with a median time of 18 months (6–78 months) according to Silveira, but his study included too few patients with molecular assessments ( n = 39).…”

Section: Discussionmentioning

confidence: 99%

“…16 Machado et al found this response level between 0.4 and 31 months of treatment (median: 8.5 months). 17 In this time interval, 31.7% (26/82) were included in the warning signs group ( BCR - ABL1 IS >0.1 and ≤1%), and 23.2% (19/82) in the treatment failure group as the number of transcripts >1% according to the ELN criteria. 5 …”

Section: Discussionmentioning

confidence: 99%

Molecular response to imatinib mesylate of Brazilian patients with chronic myeloid leukemia

Vieira-Mion

Pereira

Funke

et al. 2017

Revista Brasileira de Hematologia e Hemoterapia

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BackgroundImatinib mesylate has revolutionized the treatment of chronic myeloid leukemia leading to significant reductions of BCR-ABL1 transcript levels in peripheral blood.ObjectiveTo evaluate the response to imatinib mesylate treatment (400 mg/day) in Brazilian patients in the chronic phase of chronic myeloid leukemia monitored by quantitative real time polymerase chain reaction.MethodsBetween October 2002 and October 2010, 3169 peripheral blood samples were collected from 1403 patients from 3 to 5 months, 6 to 11 months, 12 to 17 months, 18 to 23 months and ≥24 months after beginning imatinib treatment. Eighty-two patients had samples available and analyzed for all time intervals. BCR-ABL1 quantification was performed by quantitative real time polymerase chain reaction using the ABL1 gene as the control. Results of the BCR-ABL1 ratio as a percentage were reported by the international scale (IS) using the laboratory conversion factor (0.51).ResultsIn the first interval, 80.8% of patients achieved the optimal response (BCR-ABL1IS ≤ 10%). In the second period, 69.1% achieved optimal response (BCR-ABL1IS ≤ 1%) and, between 12 and 17 months, 47.3% achieved major molecular response (BCR-ABL1IS ≤ 0.1%).ConclusionsThe results of this retrospective study show that the response to imatinib treatment (400 mg/day) of Brazilian patients in the chronic phase of chronic myeloid leukemia is within the expected profile when compared to patients reported in international prospective randomized studies.

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Monitoring of BCR-ABL levels in chronic myeloid leukemia patients treated with imatinib in the chronic phase

Cited by 16 publications

References 11 publications

Chronic Myeloid Leukemia in South Yemen

Chronic Myeloid Leukemia in South Yemen

Treatment with dasatinib or nilotinib in chronic myeloid leukemia patients who failed to respond to two previously administered tyrosine kinase inhibitors – a single center experience

Molecular response to imatinib mesylate of Brazilian patients with chronic myeloid leukemia

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