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.
Blood-level testing; chronic myeloid leukemia; imatinib; pharmacodynamics; pharmacokinetics; tyrosine kinase inhibitors
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.
Chronic myeloid leukemia; India; Indian cooperative oncology network; mylestone
All India Institute of Medical Sciences is an Apex Institute and caters more than 1.5 million out-patients and 80,000 in-patients every year. In this study, they have presented interesting results of patients treated with interferon, interferon plus cytarabine and then with imatinib plus cytarabine. They 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.
CML; Interferon; Imatinib
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.
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.
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.
Chronic myeloid leukemia; chronic phase; Glivec; veenat
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.
Chronic myeloid leukemia; chronic phase; veenat; Glivec
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.
Chronic myeloid leukemia; chronic phase; Indira Gandhi Institute of Medical Sciences
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.
Chronic myeloid leukemia; chronic phase; Institute of Hematology and Transfusion Medicine
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.
Chronic myeloid leukemia; chronic phase; Jaipur
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.
Chronic myeloid leukemia; Jaipur; SEAROC
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.
Chronic myeloid leukemia; Delhi; Imatinib
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.
Chronic myeloid leukemia; chronic phase; Post Graduate Institute
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%.
Chronic myeloid leukemia; Gujarat cancer and research institute; imatinib
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.
Chronic myeloid leukemia; Imatinib; Sterling Hospitals
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.
Bangalore; chronic myeloid leukemia; chronic phase
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.
Chronic myeloid leukemia; cytogenetic response; imatinib mesylate; India; molecular response; toxicity
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.
Chronic myeloid leukemia; chronic phase; Omega Hospitals
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.
Chennai; chronic myeloid leukemia; Women India Association
Nizam's Institute of Medical Science is a premier institute of Hyderabad, established in 1980. The Medical Oncology Unit is the 1st 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.
Chronic myeloid leukemia; chronic phase; imatinib
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.
Bangalore; chronic myeloid leukemia; chronic phase
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.
Chronic myeloid leukemia; imatinib; kinase domain mutations
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.
Chronic myeloid leukemia; imatinib; kinase domain mutations and responses