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Indian Journal of Medical and Paediatric Oncology
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   2013| July-September  | Volume 34 | Issue 3  
    Online since December 26, 2013

 
 
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ORIGINAL ARTICLES
Imatinib mesylate resistance and mutations: An Indian experience
Shweta Srivastava, Sarjana Dutt
July-September 2013, 34(3):213-220
DOI:10.4103/0971-5851.123748  PMID:24516315
The treatment of chronic myeloid leukemia (CML) has been revolutionized by the small molecule selective kinase inhibitor imatinib mesylate. Imanitib was the first BCR-ABL targeted agent approved for the treatment of CML patients and confers significant response in most patients; however, a substantial number of patients are initially refractory to the drug or may develop resistance during the course of treatment. Point mutations in the kinase domain (KD) of BCR-ABL that impact drug binding have been identified as one of the major mechanisms of resistance. We present here an overview of the current practice in monitoring for such mutations, including the methods used, criteria for investigating and guidelines for reporting the mutations. We further present and discuss the experience of our own laboratory in studying the KD mutations in Indian CML patients on imatinib treatment.
  2,084 402 3
Therapeutic drug monitoring for imatinib: Current status and Indian experience
Brijesh Arora, Vikram Gota, Hari Menon, Manju Sengar, Reena Nair, Pankaj Patial, SD Banavali
July-September 2013, 34(3):224-228
DOI:10.4103/0971-5851.123752  PMID:24516317
Imatinib is the current gold standard for treatment of chronic myeloid leukemia (CML). Recent pharmacokinetic studies have shown considerable variability in trough concentrations of imatinib due to variations in its metabolism, poor compliance, or drug-drug interactions and highlighted its impact on clinical response. A trough level close to 1000 ng/mL, appears to be correlated with better cytogenetic and molecular responses. Therapeutic Drug Monitoring (TDM) for imatinib may provide useful added information on efficacy, safety and compliance than clinical assessment alone and help in clinical decision making. It may be particularly helpful in patients with suboptimal response to treatment or treatment failure, severe or rare adverse events, possible drug interactions, or suspected nonadherence. Further prospective studies are needed to confirm relationship between imatinib plasma concentrations with response, and to define effective plasma concentrations in different patient populations.
  1,665 429 1
COMMENTARY
Chronic myeloid leukemia data from India
Shweta Bansal, Kumar Prabhash, Purvish Parikh
July-September 2013, 34(3):154-158
PMID:24516297
In an effort to collaborate the data of chronic myeloid leukemia (CML) patient from all over India,meeting was conceived by ICON ( Indian Cooperative Oncology Network) in 2010. This article presents the summarized picture of the data presented in the meeting. In the meeting 8115 patients data was presented and 18 centres submitted their manuscripts comprising of 6677 patients. This data represents large series of patients from all over the country treated on day to day clinical practice and presents the actual outcomes of CML patients in India. The compilation of data confirms the younger age at presentation, increased incidence of resistance and poor outcomes in patients with late chronic phase. It also addresses the issues like Glivec versus Generic drug outcomes, safety of Imatinib during pregnancy and mutational analysis among resistant patients. It concludes that survival and quality of life of CML patients in India has improved over the years especially when treated in early chronic phase. The generic drug is a good option where original is unable to reach the patient due to various reasons. Hopefully, this effort will provide a platform to conduct systematic studies in learning the best treatment options among CML patients in Indian settings.
  1,667 376 -
EDITORIAL COMMENTARIES
Chronic myeloid leukemia: Review of our Indian experience
Abhay A Bhave
July-September 2013, 34(3):149-150
DOI:10.4103/0971-5851.123703  PMID:24516295
  1,682 239 -
ORIGINAL ARTICLES
Report of chronic myeloid leukemia in chronic phase from Tata Memorial Hospital, Mumbai, 2002-2008
Purvish Parikh
July-September 2013, 34(3):164-167
DOI:10.4103/0971-5851.123716  PMID:24516299
Background: Chronic myeloid leukemia (CML) is the commonest hematological malignancy in India. This manuscript is a single center analysis CML in chronic phase (CP). Materials and Methods: We did retrospective analysis of almost 1000 patients registered as chronic myeloid leukemia over a period of 6 years at Tata Memorial Hospital. Results: We found striking difference in cytogenetic response among patients presenting in late chronic phase (CP) compared with the patients in early CP. The rate of complete cytogenetic response among patients in late CP was 60% while in early CP it was 80%, which was statistically significant (P = 0.0001). The overall survival was 86%, at a median follow-up of 51 months. Innovator glivec was taken by 671 patients among which complete cytogenetic response (CCyR) was seen in 72% whereas generic veenat was taken by 237 patients and CCyR was seen in 75% of them. Conclusion: Availability of imatinib has dramatically changed the outlook for CML in India. The response was identical for those treated with innovator brand of imatinib as compared to the generic brand. Hence quality generics provide a cost effective solution, which is particularly relevant in the current global scenario.
  1,660 234 4
Report of chronic myeloid leukemia from All India Institute of Medical Sciences, 1990-2010
Pravas Mishra, Tulika Seth, Sudha Sazawal, Manoranjan Mahapatra, Renu Saxena
July-September 2013, 34(3):159-163
DOI:10.4103/0971-5851.123712  PMID:24516298
All India Institute of Medical Sciences, New Delhi is an Apex Institute and caters to more than 1.5 million out-patients and 80,000 in-patients every year. In this study, we have presented data of patients over a period of 20 years. This encompasses our initial experience with hydroxyurea, then interferon alone or with cytarabine and finally imatinib. We have presented data of 525 patients treated on imatinib alone. Imatinib dose was increased in 56 (10.6%) patients and regain of complete hematological response was seen in 26 patients. A total of 14 patients were transplanted for different indications of chronic myeloid leukemia and out of which 12 patients are doing well, while two died due to Grade IV gut graft-versus-host disease.
  1,533 274 -
A short report on chronic myeloid leukemia from Post Graduate Institute of Medical Education and Research, Chandigarh
Pankaj Malhotra, Neelam Varma, Subhash Varma
July-September 2013, 34(3):186-188
DOI:10.4103/0971-5851.123728  PMID:24516306
Post Graduate Institute (PGI) Chandigarh is a premier institute of North India. There are approximately 70,000 admissions per year. The adult clinical hematology department sees more than 2000 new patients per year. A preliminary analysis of 299 chronic myeloid leukemia patients registered from January 2001 until December 2007 was done. Out of these, 256 (86%) patients were in chronic phase (CP). The median age at presentation was 40 years. At 6 months of follow-up 95% of patients who were started on Imatinib mesylate based therapy remained in CP. Partial cytogenetic remission was seen in 69% of patients while complete cytogenetic response was seen in only 20% of patients at 6 months on Imatinib mesylate.
  1,339 219 3
Report of chronic myeloid leukemia SMS Medical College Hospital, Jaipur
Hemant Malhotra, Rajesh Sharma, Yogender Singh, Hemant Chaturvedi
July-September 2013, 34(3):177-179
DOI:10.4103/0971-5851.123723  PMID:24516303
This is a retrospective analysis of patients of chronic myeloid leukemia (CML) registered and under treatment at the Leukemia Lymphoma Clinic at the Birla Cancer Center, SMS Medical College Hospital, Jaipur. Approximately, two-thirds of the patients are getting imatinib mesylate (IM) through the Glivec International Patient Assistance Program while the rest are on generic IM. In addition to comparison of hematological and molecular responses in the Glivec versus the genetic group, in this analysis, an attempt is also made to assess the socio-economic (SE) status of the patients and its effect on the response rates. Of the 213 patients studied, most (28.6%) are in the age group between 30 years and 40 years and the mean age of the patients in 39 years, a good decade younger that in the west. There is a suggestion that patients in lower SE class present with higher Sokal scores and with more disease burden. Possibly hematological responses are similar with both Glivec and generic IM. No comment can be made with regards to molecular response between the two groups as a significant number of patients in the Glivec arm (42%) do not have molecular assessment because of economic reasons. CML is a common and challenging disease in the developing world with patients presenting at an earlier age with more advanced disease. SE factors play a significant role in therapy and disease monitoring decision making and may impact on response rates and prognosis.
  1,308 218 -
Report of chronic myeloid leukemia in chronic phase from Ashirwad Hematology Centre, Mumbai, 2002-2009
MB Agarwal, Usha M Agarwal, Shonali S Rathi, Sangeeta Masurkar, Bindi Zaveri
July-September 2013, 34(3):199-203
DOI:10.4103/0971-5851.123741  PMID:24516310
We have analyzed our experience regarding use of tyrosine kinase inhibitors especially imatinib mesylate in patients of chronic myeloid leukemia-chronic phase over last 7 years at our center (2002-2009). The object was to report long-term efficacy (hematological, cytogenetic and molecular) and toxicity. Overall, 775 patients were treated. Out of these, 576 were analyzable with a median follow-up of 3.6 years. The median age was 42 years. Complete cytogenetic response (CCyR) was achieved in 351/576 patients, i.e., 62.1%. Grade 3/4 adverse effects were observed in 36 patients, i.e., 6.25%. Age under 40 years, low Sokal score, complete hematological response and CCyR were significant predictive factors for event free survival (EFS) on univariate analysis while low Sokal score and early chronic phase were significant predictive factors for EFS on multivariate analysis. Our results are almost similar to those reported from various studies from western population.
  1,344 168 1
EDITORIAL COMMENTARIES
Chronic myeloid leukemia in India
John M Goldman
July-September 2013, 34(3):147-148
DOI:10.4103/0971-5851.123700  PMID:24516294
  1,078 258 2
ORIGINAL ARTICLES
Kinase domain mutations and responses to dose escalation in chronic myeloid leukemia resistant to standard dose imatinib mesylate
Senthil Rajappa, Krishna Mohan Mallavarapu, Sadashivudu Gundeti, Tara Roshni Paul, Rachel Thomas Jacob, Raghunadharao Digumarti
July-September 2013, 34(3):221-223
DOI:10.4103/0971-5851.123750  PMID:24516316
Imatinib has shown unprecendeted success in the treatment of chronic myeloid leukemia (CML). However, over few years there have been reports regarding the primary and secondary resistance to Imatinib dampening the overall outcome in CML patients. In this study we have tried to assess the effect of dose escalation in patients resistant to standard dose of Imatinib and correlate it with presence of ABL kinase domain (KD) mutations. There were 90 patients resistant to imatinib, out which 29 patients were identified with KD mutations. The most common mutation was T315I , 9 out of 29 patients had it. 35 (38%) responded to dose escalation and had 67% event free survival (EFS) at estimated 2 years. Our results showed that dose escalation can over come resistance in some patients especially those in cytogenetic failure.
  1,038 220 2
Report of chronic myeloid leukemia in chronic phase from Dr. Senthil Rajappa, 2002-2009
Senthil Rajappa, Lalit Varadpande, Tara Roshni Paul, Rachel Thomas Jacob, Raghunadharao Digumarti
July-September 2013, 34(3):208-210
DOI:10.4103/0971-5851.123745  PMID:24516313
Nizam's Institute of Medical Science is a premier institute of Hyderabad, established in 1980. The Medical Oncology Unit is the 1 st comprehensive cancer center established for the state of Andhra Pradesh. The department has presented a data of total 201 patients with the median age of 32 at diagnosis. Among these 66 (33%) patients belonged to low Hasford risk group. Complete hematologic response was seen in 195 (97%) of patients. The progression free survival (PFS) was 77% for all patients while those who achieved complete cytogenetic response, PFS was 88% at 29 months.
  1,082 151 -
Chronic myeloid leukemia treatment with Imatinib: An experience from a private tertiary care hospital
DC Doval, Ullas Batra, Sumit Goyal, Ajay Sharma, Saud Azam, Rashmi Shirali
July-September 2013, 34(3):182-185
DOI:10.4103/0971-5851.123725  PMID:24516305
The data presents 75 chronic myeloid leukemia patients diagnosed over a period 6 years i.e. from 2002 to 2008. The most common presentation was splenomegaly and 97% achieved complete hematological response at median duration of 4.3 weeks. The uniqueness of this study is follow-up with molecular response monitoring. Nearly, 30% patients achieved major molecular response (MMoR) by 12 months. 70% of patients achieved MMoR by median time of 60 months. Only 10% of the patient who achieved MMoR by 18 months had lost their responses subsequently.
  993 197 -
Report of chronic myeloid leukemia in chronic phase from Omega Hospital and Indo-American Centre, Hyderabad, 2004-2010
PS Dattatreya, SS Nirni
July-September 2013, 34(3):204-205
DOI:10.4103/0971-5851.123742  PMID:24516311
Omega hospital and Indo-American Center from Hyderabad presented a data of 55 patients with chronic myeloid leukemia 87% (48) patients were in chronic phase. 5% (3) patients had primary resistance, while 64% (36) had shown good response to imatinib. At a median follow-up of 36 months 73% (40) of patients were in chronic phase.
  1,049 140 -
Report of chronic myeloid leukemia in chronic phase from Eastern India, Institute of Hematology and Transfusion Medicine, Kolkata, 2001-2009
Siddhartha Sankar Ray, Prantar Chakraborty, Utpal Chaudhuri, Ganesh
July-September 2013, 34(3):175-176
DOI:10.4103/0971-5851.123721  PMID:24516302
The data 192 patients from Eastern India, Kolkata center was presented in Indian cooperative oncology network meeting, out of which 97% patients were diagnosed in the chronic phase. Complete hematological response was seen in 70.5% among patients and 86% of patients were in clinical and hematological remission over 5 years with a median follow-up of 4.85 years.
  1,004 172 -
GUEST EDITORIAL
Chronic myeloid leukemia in the Imatinib era - Compilation of Indian data from 22 centers involving 8115 patients
Purvish Parikh, Shweta Bansal
July-September 2013, 34(3):145-146
DOI:10.4103/0971-5851.123699  PMID:24516293
  873 274 -
EDITORIAL COMMENTARIES
Will kinase domain mutations dictate the terms…
MB Agarwal, Shyam A Rathi
July-September 2013, 34(3):151-153
DOI:10.4103/0971-5851.123707  PMID:24516296
  958 176 1
ORIGINAL ARTICLES
Report of patients with chronic myeloid leukemia, from hematology clinic, Ahmedabad, Gujarat 2000-2010 at 1 st myelostone meeting: Indian evidence of chronic myelogenous leukemia
Uday R Deotare, Urmish Chudgar, Eva Bhagat
July-September 2013, 34(3):193-195
DOI:10.4103/0971-5851.123734  PMID:24516308
The data of 156 patients was presented from Hematology clinic, Ahmedabad. This hematology clinic caters large number of the population from Gujarat as well as from neighboring states such as Rajasthan and Madhya Pradesh. Out of 156 patients, 146 (94%) patients were in chronic phase. Complete hematological response was seen in 90% of patients and overall survival was 82% at 5 years.
  907 200 -
The treatment of chronic myeloid leukemia, data from Gujarat Cancer and Research Institute, Ahmedabad
Sandip A Shah
July-September 2013, 34(3):189-192
DOI:10.4103/0971-5851.123729  PMID:24516307
Gujarat Cancer and Research Institute, Ahmedabad presented data of total 840 patients, out of which 775 (90%) were in chronic phase. Complete hematological response (CHR) was seen in 96% of patients and median time to achieve (CHR) was 2 months. Complete cytogenetic response was seen in 36%.
  906 180 -
Report of chronic myeloid leukemia in chronic phase from Cancer Institute (Women India Association), Chennai, 2002-2009
Prasanth Ganesan, R Rejiv, N Manjunath, C Sanju, TG Sagar
July-September 2013, 34(3):206-207
DOI:10.4103/0971-5851.123744  PMID:24516312
Cancer Institute Chennai is the first Institute of Oncological sciences to be established in the country. In ICON meeting, they presented the data of 516 patients, of which 91% patients achieved complete hematological response. The overall survival was 88% and event free survival was 65% at 5 years.
  924 148 -
Report of chronic myelogenous leukemia in chronic phase from, Asian Institute of Oncology, Mumbai, 2002-2010
Shweta Bansal, SH Advani
July-September 2013, 34(3):168-171
DOI:10.4103/0971-5851.123717  PMID:24516300
Chronic myeloid leukemia (CML) has paradigm shift in its treatment modality after the discovery of targeted therapy Imatinib. At our centre we collected data of 100 consecutive patients over a period of 8 years. The interesting finding in our study was difference in the survival of patients presenting in early chronic phase (81%) versus late chronic phase (16%). Also the patients with primary resistance did poorly compared to the patients who developed secondary resistance to Imatinib.
  882 157 -
Report of chronic myeloid leukemia from Indira Gandhi Institute of Medical Sciences, Regional Cancer Center, 2002-2009
Rajiv Ranjan Prasad, Pritanjali Singh
July-September 2013, 34(3):172-174
DOI:10.4103/0971-5851.123719  PMID:24516301
Indira Gandhi Institute of Medical Sciences, Regional Cancer Center was established in 1993. It's one of the main Health-Care Institution in the state of Bihar. The data of 205 patients was presented in the ICON meeting and 98% of patients were diagnosed in chronic phase. Complete hematological response was seen in 91% of patients in 3 months. A total of 197 (96%) patients were alive at the time of analysis of which 179 (87%) were still in chronic phase with hematological remission.
  788 163 -
Report of patients with chronic myeloid leukemia Kidwai Memorial Institute of Oncology, Bangalore over 15 years
Govind Babu
July-September 2013, 34(3):196-198
DOI:10.4103/0971-5851.123736  PMID:24516309
Kidwai Memorial Institute of Bangalore is one of the most comprehensive and major regional cancer center. It was established in 1974 and caters population not only from Karnataka, but also from Tamil Nadu, Andhra Pradesh. They presented the data of 540 patients out of which 95% patients were in chronic phase. Complete hematological response was seen in 98.45 of patients. Overall survival at 5 years was 86.5%.101 patients has suboptimal response were considered for and underwent mutational analysis, out of which 27 patients showed various mutations and are mentioned elaborately in the article.
  796 143 -
Epidemiological and clinical profile of patients with chronic myeloid leukemia at Health-Care Global, Bangalore Institute of Oncology
KG Srinivas, Shekar Patil, Shashidhara
July-September 2013, 34(3):211-212
DOI:10.4103/0971-5851.123746  PMID:24516314
Health-Care Global, Bangalore Institute of Oncology is a cancer care center, which provides comprehensive care for cancer patients. Here, we present data of 350 patients diagnosed as cases of chronic myeloid leukemia over a period of 10 years. In our patient population, there was male predominance and majority of patients lied between the age group of 40 and 50 years. 90% patients were initially started on 400 mg dose of imatinib. About 30% of patient population required dose excalation due to inadequate response while 10% required dose descalation due to myelosuppression. 60% of patients had complete response by 3 months and 52% of patients had major molecular response by 1 year.
  737 171 -
Report of chronic myeloid leukemia from SEAROC experience, Jaipur over a period of 9 years
Anish Maru
July-September 2013, 34(3):180-181
DOI:10.4103/0971-5851.123724  PMID:24516304
SEAROC cancer center presented the data 387 patients from the city of Jaipur. This oncology center caters large number of population from Jaipur as well as from neighboring states. Out of the 387 patients, 334 (86%) patients were in chronic phase. Complete hematological response was seen in 368 (95%) of patients and no response in 5 patients. Among these patients, 33 (8.5%) progressed to blast crisis.
  724 129 -
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