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 » Results
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  Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 3  |  Page : 305-307
 

Hematologic, liver enzymes and electrolytes changes in chronic myeloid leukemia after Imatinib medication


1 Department of Internal Medicine, Arak University of Medical Sciences, Arak, Iran
2 Department of Hematology and Oncology, Isfahan University of Medical Sciences, Isfahan, Iran
3 Department of Cardiac Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
4 Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
5 Department of Epidemiology and Biostatistics, Health Policy and Promotion Research Center, Qom University of Medical Sciences, Qom, Iran

Date of Web Publication18-Feb-2016

Correspondence Address:
A Mohammadbeigi
Department of Epidemiology and Biostatistics, Health Policy and Promotion Research Center, Qom University of Medical Sciences, Qom
Iran
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Source of Support: Arak University of Medical Sciences, Arak, Iran, Conflict of Interest: None


DOI: 10.4103/0019-509X.176715

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 » Abstract 

Background: Chronic myeloid leukemia (CML), is the first malignancy that related to the chromosomal abnormality and include 15-20% of all adulthood leukemia. AIMS: This study aimed to compare the hematologic, breakpoint cluster region-abelson (BCR-ABL) and liver function enzymes changes during treatment period of Imatinib. Settings And Design: A noncurrent clinical trial study. Materials And Methods: New incident CML patients received Iranian made or Indian-made Imatinib after baseline measurement. Hematologic, BCR-ABL, electrolytes and liver function enzymes measured again after 24 weeks. Statistical Analysis Used: Paired t-test and independent t-test was used to assess the effect of treatment in within and between groups, respectively. Results: Imatinib has a decreasing impact on white blood cells and placates. While an increasing effect on hemoglobin concentration. Iranian made and Indian-made Imatinib has a same effect on improvement of hematologic, BCR-ABL, electrolytes in CML patients. However, the liver changes of Imatinib were not clinically significant. Conclusion: The Iranian-made Imatinib can be used as a replacement for Indian made ones without any statistical and clinical significant difference on Improvement of CML patients.


Keywords: Cancer, chronic myeloid leukemia, Imatinib, leukemia, neoplasm


How to cite this article:
Moshfeghi K, Nazemizadeh N, Mehrzad V, Hajiannejad A, Esmaeili F, Mohammadbeigi A. Hematologic, liver enzymes and electrolytes changes in chronic myeloid leukemia after Imatinib medication. Indian J Cancer 2015;52:305-7

How to cite this URL:
Moshfeghi K, Nazemizadeh N, Mehrzad V, Hajiannejad A, Esmaeili F, Mohammadbeigi A. Hematologic, liver enzymes and electrolytes changes in chronic myeloid leukemia after Imatinib medication. Indian J Cancer [serial online] 2015 [cited 2019 Jun 26];52:305-7. Available from: http://www.indianjcancer.com/text.asp?2015/52/3/305/176715



 » Introduction Top


Leukemia is the most prevalent type of cancer in children and including 32% of all pediatric cancers.[1] Myeloid leukemia is a subtype of leukemia and divided in two type of acute and chronic disease.[2] Although, the acute myeloid leukemia is a rare and infrequent diseases,[2] but the chronic myeloid leukemia (CML), is the first malignancy that related to the chromosomal abnormality [3] and include 15-20% of all adulthood leukemia.[4] The median age of diagnosis of CML is between 64 and 68 years in different population.[5],[6] Moreover, the standardized incidence rates of CML varied between 0.6 and 2.0 cases per 100,000 people.[6]

CML is characterized by production of a breakpoint cluster region-abelson (BCR-ABL) fusion protein with ABL kinase activity. This is due to reciprocal translocation between chromosomes 9 and 22.[7] The CML cytogenetically is detectable with shortened chromosome 22.[7],[8] Imatinib mesylate (Gleevec or Glivec–formerly STI571), an ABL kinase inhibitor, which has revolutionized the CML therapy,[9],[10] is a selective tyrosine kinase inhibitor, which contests with ATP in binding the BCR-ABL (and ABL) protein kinase. It produces sustained complete hematologic responses in CML patients.[8],[9],[11]

Pre-clinical studies were demonstrated the effect of Imatinib in CML patients, but the results of recent clinical trials exceeded expectations.[3],[7],[9],[10],[12],[13],[14] Furthermore, the sequence and timing of morphologic and cytogenetic changes in CML patients during therapy in a long-time has not been described. Also, platelet count, blood percentage of blasts, basophils and other hematologic elements are the prognostic factors for CML treatment failure.[15] However, we aimed to determine and compare the changes of hematologic, BCR-ABL and liver function enzymes as well as electrolytes during treatment time period.


 » Materials and Methods Top


In a noncurrent clinical trial study, new diagnosed cases of CML who referred to two hematology clinics – Khansari hospital (Arak-Iran) and Seyed-o-Shohada (Isfahan-Iran)- participated into study from January to June 2011. Hematologic, BCR-ABL, liver function enzymes and electrolytes of participants measured at baseline and after treatment with Indian-made or Iranian-made Imatinib in 24th week. CML patients who treated with Indian-made Imatinib were considered as control group. Treatment group selected based on consecutive sampling method. For controlling the confounding variables (age and sex), restriction method was used to two groups be comparable. All the patients signed the informed consent and the study protocol approved by the Ethical Committee of Arak University of Medical Sciences.

Diagnosis of patients was based on the clinical suspicious followed by exterior blood and bone marrow examinations. Also, the confirmed diagnosis conducted by genetic studies for detection the translocation between chromosomes 9 and 22 as well as reverse transcription polymerase chain reaction (RT-PCR) for BCR-ABL gene. During the study each groups including 43 CML patients. The treatment regime for each patient started with 400 mg/day and increase to 800 mg daily, if it tolerated by the patients. More details about the inclusion and exclusion criteria and treatment consideration is published in another article.[12]

Molecular response and hematologic changes measured by RT-PCR and complete blood count, respectively. Data entered to SPSS software (Version 16, Chicago, IL) and paired t-test was used to assess the effect of treatment in each group. Furthermore, independent sample t-test was used to compare the changes of outcomes between Iranian and Indian-made Imatinib treated groups. Significant level considered at 0.05 levels.


 » Results Top


Baseline measurement showed that two groups are comparable. The mean age of participants was 60 years and did not observe any statistical difference between two groups (P > 0.05). From all the participants 52 (60.5%) were male. Also, sex ratio was not significant between two groups (P > 0.05). Based on our results, white blood cells and plackets showed a significant decreasing trend and hemoglobin showed an increasing trend since starting treatment in two groups. The hematologic response due to Imatinib calculated as 86% for all and each treatment group. The molecular change according to decreasing in BCR-ABL gene was 45.3% in overall and 46.6% and 44.2% for Iranian and Indian Imatinib, respectively.

The results in [Table 1] showed that aspartate aminotransferase (AST), alanine aminotransferase (ALT) and BCR-ABL gene have a significant difference during the time of treatment period as all these three factors have a decreasing trend between baseline and after medication (P < 0.05). However, the treatment type did not show different impact on changes of alkaptinase and bilirubin (P > 0.05)
Table 1: Changes in liver enzymes and BCR-ABL gene during treatment period in two study groups

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Our results [Table 2] showed that there was an increasing trend in blood urea nitrogen (BUN) and creatinine of Iranian made Imatinib but, there was not any difference in the baseline and 24th week in Na, K, calcium and phosphor in Iranian made Imatinib. Moreover, the changes in, creatinine and electrolytes during treatment period have not any statistical differences after using Indian made Imatinib. Moreover, our study showed that BUN is different between two groups and the BUN value is higher in Iranian-made Imatinib (P < 0.05).
Table 2: Changes in BUN, creatinine and electrolytes during treatment period in two study groups

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 » Discussion Top


The results of current study showed the hematologic, liver enzymes and electrolytes effects of Imatinib on CML patients. Also, the impact of Imatinib on molecular changes founded. Based on the results there were no significant difference in Indian-made and Iranian-made Imatinib on the hematologic, liver enzymes and electrolytes as well as BCR-ABL changes. In addition, the treatment period has been improved the patients problems. Our recent study was showed that the safety and effectiveness of the Indian-made and Iranian-made Imatinib are the same in CML patients.[12] Moreover, in Moshfeghi et al. study, did not observe significant adverse effects between two groups.[12]

The sex ratio in the current study was 1.5 and the mean age of CML diagnosis was 60 years. Based on the other studies the mean age of disease in Iran is higher than of other clinical studies in developed countries, which varied between 47 and 60 years.[5],[6] Although, the mean age of diagnosis based on the cancer registry centers in developed countries is higher than 60 years.[6] However, another study in low and middle income countries showed the mean age of diagnosis is 38.5 years. according to that study Asians were youngest (38.3 years) patients, Africans (39.5 years), then Southern/Eastern Europeans (41.1 years) and oldest age of diagnosis related to Latin Americans with 41.3 years.[5] The sex ratio in our study was as the same of Mendizabal study.[5] However, based on epidemiological studies the morbidity rate in males is higher than females.[2],[5],[6]

The decreasing effect of Imatinib on BCR-ABL in two types of drug was similar and calculated as 46.6% and 44.2% for Iranian and Indian-made Imatinib. This finding is in concordant with other clinical trials.[3],[7],[8],[12],[16],[17],[18] In a way that, in Zaker et al. study,[3] complete molecular response calculated in 46.7% and in Moshfeghi et al. study,[12] this response was 46.5%. based on these results we can recommended the Iranian made Imatinib for treatment of CML to preservation of money and have good and rapid access to the care. However, a review article or meta-analysis study feels to be necessary for the effectiveness and safety of Imatinib on CML. Moreover, The ALT and AST changes in liver enzymes were not clinically significant besides that the changes in these enzymes were statistically significant.


 » Conclusion Top


Indian and Iranian made Imatinib is a well-tolerated with significant anti-leukemic activity in patients with CML at chronic phase. This equivalent study showed the same effect of Imatinib upon improvement of liver enzymes, BCR-ABL gene and electrolytes changes in CML patients. Therefore, Iranian made Imatinib can be used or replaced with Indian ones for treatment in CML patients.


 » Acknowledgments Top


The authors are grateful for all patient patients who participated in study. Also, we are very thankful for research vice-chancellor of Arak University of medical Sciences for financial support of this work.

 
 » References Top

1.
Amir AH, Soheil Z, Mehran K, Esmaeil K, Abolfazl M. Survival rate of childhood leukemia in Shiraz, Southern Iran. Iran J Pediatr 2013;23:53-8.  Back to cited text no. 1
    
2.
Deschler B, Lübbert M. Acute myeloid leukemia: Epidemiology and etiology. Cancer 2006;107:2099-107.  Back to cited text no. 2
    
3.
Razmkhah, F, Razavi M, Zaker F, Kazemi A, Negari SH, Rasighaemi P, et al. Hematologic and molecular responses to generic imatinib in patients with chronic myeloid leukemia. Lab Medicine 2010; 41: 547-550.  Back to cited text no. 3
    
4.
Cervantes F, Mauro M. Practical management of patients with chronic myeloid leukemia. Cancer 2011;117:4343-54.  Back to cited text no. 4
    
5.
Mendizabal AM, Garcia-Gonzalez P, Levine PH. Regional variations in age at diagnosis and overall survival among patients with chronic myeloid leukemia from low and middle income countries. Cancer Epidemiol 2013;37:247-54.  Back to cited text no. 5
    
6.
Rohrbacher M, Hasford J. Epidemiology of chronic myeloid leukaemia (CML). Best Pract Res Clin Haematol 2009;22:295-302.  Back to cited text no. 6
    
7.
Braziel RM, Launder TM, Druker BJ, Olson SB, Magenis RE, Mauro MJ, et al. Hematopathologic and cytogenetic findings in Imatinib mesylate-treated chronic myelogenous leukemia patients: 14 months' experience. Blood 2002;100:435-41.  Back to cited text no. 7
    
8.
Crossman LC, O'Brien S. Clinical results with Imatinib in chronic myeloid leukaemia. Leuk Res 2004;28 Suppl 1:S3-9.  Back to cited text no. 8
    
9.
Deininger M, Buchdunger E, Druker BJ. The development of Imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 2005;105:2640-53.  Back to cited text no. 9
    
10.
Breccia M, Efficace F, Alimena G. Imatinib treatment in chronic myelogenous leukemia: What have we learned so far? Cancer Lett 2011;300:115-21.  Back to cited text no. 10
    
11.
Breccia M, Alimena G. The significance of early, major and stable molecular responses in chronic myeloid leukemia in the Imatinib era. Crit Rev Oncol Hematol 2011;79:135-43.  Back to cited text no. 11
    
12.
Moshfeghi K, Nazemzadeh N, Mehrzad V, Hajiannejad A, Esmaili F. Comparison of effectiveness and safety of Iranian-made versus Indian-made imatinib in treatment of chronic myeloid leukemia. Adv Biomed Res 2013;2:17.  Back to cited text no. 12
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Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med 2006;354:166-78.  Back to cited text no. 13
    
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Hehlmann R. Introduction: CML in the Imatinib era. Best Pract Res Clin Haematol 2009;22:283-4.  Back to cited text no. 14
    
15.
Hernández-Boluda JC, Cervantes F. Prognostic factors in chronic myeloid leukaemia. Best Pract Res Clin Haematol 2009;22:343-53.  Back to cited text no. 15
    
16.
Cilloni D, Saglio G. CML: A model for targeted therapy. Best Pract Res Clin Haematol 2009;22:285-94.  Back to cited text no. 16
    
17.
Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001;344:1031-7.  Back to cited text no. 17
    
18.
O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003;348:994-1004.  Back to cited text no. 18
    



 
 
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