scholarly journals Haematological and cytogenetic changes in CML patients treated with imatinib mesylate in Western Libya

2019 ◽  
Vol 7 (3) ◽  
Author(s):  
Jbireal JM ◽  
Azab Elsayed Azab ◽  
Alzahani S ◽  
Elshareef M
Keyword(s):  
Imatinib Mesylate ◽  
White Blood Cells ◽  
Chronic Phase ◽  
Significant Negative Correlation ◽  
Cytogenetic Response ◽  
P Value ◽  
Normal Range ◽  
Long Time ◽  
Cytogenetic Changes ◽  
Males And Females

Background: Chronic myeloid leukemia (CML) is a clonal myeloid proliferative disorder of primitive haemopoietic progenitor cells. The incidence of CML ranges between 10 and 15 cases/106 /year without any major geographic or ethnic differences. Imatinib mesylate provides good results in the treatment of CML. Early studies demonstrated that Imatinib mesylate can produce clear hematologic and cytogenetic response when used as a treatment of CML patients with positive BCR-ABL gene. Nevertheless, some patient with different stages of CML (chronic, accelerated, or acute phases) either relapse or stay unchanged for a long time after initial doses of treatment. This phenomenon led to the fact that we must explore the possible changes expected to appear if we make some changes in the treatment strategy. Objectives: The present study aimed to evaluate hematologic and molecular responses of CML patients to Imatinib mesylate treatment. Methods: Eighteen CML patients in chronic phase aged (24–65 years) males and females were treated with Imatinib mesylate (400, 500 or 600 mg/day) for sixteen months. Hematologic and cytogenetic changes were analyzed periodically. Results: Overall 18 cases, hematologic response of 14 cases was complete white blood cells (WBCs) decrease to normal range within 4 months) with P value of less than 0.0001 whereas in 4 cases WBCs were decreased slowly (after 8 months). A major cytogenetic response was noticed in 4 cases while in others the response was partially or in minor range. The major hematologic and cytogenetic response was noticed when using 600mg/day of Imatinib mesylate. The correlation appeared as a significant positive correlation between the treatment doses and Hb, hematocrit, MCV, MCH, esinophils%, and monocytes %. And a significant negative correlation between the treatment doses and RDW %, platelets count, WBCs count, and basophils %. On the other hand, no correlation between the treatment doses and RBCs Count, MCHC, Neutrophil % and BCR/APL ratio % Conclusion: It can be concluded that treatment of CML patients with Imatinib mesylate caused complete WBCs decrease to normal range. The major hematologic and cytogenetic response was noticed when using a higher dose of Imatinib mesylate.

Hematopathologic and cytogenetic findings in imatinib mesylate–treated chronic myelogenous leukemia patients: 14 months' experience

Blood ◽  
2002 ◽  
Vol 100 (2) ◽  
pp. 435-441 ◽  
Author(s):  
Rita M. Braziel ◽  
Teresa M. Launder ◽  
Brian J. Druker ◽  
Susan B. Olson ◽  
R. Ellen Magenis ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Treatment Interruption ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Cytogenetic Changes ◽  
Polymerase Chain

Abstract Imatinib mesylate, an Abl kinase inhibitor, produces sustained complete hematologic responses (CHRs) in chronic myelogenous leukemia (CML) patients, but the sequence and timing of morphologic and cytogenetic changes in CML patients during prolonged imatinib mesylate treatment has not been described. In this report, we document sequential hematologic and bone marrow findings in 19 interferon-refractory/interferon-intolerant chronic phase CML patients on imatinib mesylate for at least 14 months. Patients treated at an effective oral dose (300 to 600 mg per day) were followed with peripheral blood (PB) counts, marrow examination, and cytogenetic studies at 0, 2, 5, 8, 11, and 14 months. By 2 months, 17 of 19 patients achieved CHR; 1 reached CHR by 5 months, and 1 at 11 months. Five of 19 patients developed cytopenias requiring treatment interruption and/or dose reduction, but all were able to continue in CHR on study. In contrast to interferon-alfa treatment, imatinib mesylate–treated CML patients achieved not only CHR but complete morphologic marrow response. Normalization of marrow lagged behind PB response; however, by 8 months, all marrows showed normal or reduced cellularity without morphologic evidence of CML. Eighteen of 19 patients continued in CHR and morphologic marrow remission at 14 months; 1 patient relapsed with chronic phase CML. Although hematologic and marrow responses were uniform, cytogenetic responses were variable. Complete cytogenetic responses occurred in 6 patients, with 4 also in remission by fluorescent in situ hybridization and/or reverse-transcription–polymerase chain reaction. Six of 19 had partial and 7 of 19 no cytogenetic response. Several patients acquired additional clonal cytogenetic abnormalities during therapy, a finding with significant implications for prognosis and laboratory monitoring in imatinib mesylate–treated CML patients.

scholarly journals Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia

Blood ◽  
2002 ◽  
Vol 100 (5) ◽  
pp. 1590-1595 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Susan O'Brien ◽  
Jorge E. Cortes ◽  
Sergio A. Giralt ◽  
Mary Beth Rios ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Imatinib Mesylate ◽  
Allogeneic Stem Cell Transplantation ◽  
Response Rate ◽  
Chronic Phase ◽  
Complete Response ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Blastic Phase

Twenty-eight adults with chronic myelogenous leukemia (CML) that had relapsed after allogeneic stem cell transplantation (SCT) received imatinib mesylate (400-1000 mg/d). Disease was in chronic phase in 5 patients, accelerated in 15, and blastic in 8 (7 medullary, 1 extramedullary); median time from transplantation to relapse was 9 months (range, 1-137 months). Thirteen patients had undergone salvage donor lymphocyte infusion (DLI) (median time from DLI to imatinib mesylate therapy, 4 months [range, 2-39 months]). The overall response rate was 79% (22 of 28 patients); the complete hematologic response (CHR) rate was 74% (17 of 23 patients), and the cytogenetic response rate was 58% (15 of 26 patients; complete response in 9 [35%] patients). CHR rates were 100% for chronic phase, 83% for accelerated phase, and 43% for blastic phase. The patient with extramedullary blastic disease achieved complete response. Cytogenetic response rates were 63% (12 of 19 patients) for chronic or accelerated phases (complete cytogenetic response in 8) and 43% for blastic phase (3 of 7 patients). At median follow-up of 15 months, 19 patients were alive, 9 with no evidence of disease. The 1-year estimated survival rate was 74%. Five patients had recurrence of grade 3 (3 patients) or grades 1 to 2 (2 patients) graft-versus-host disease (GVHD). Severe granulocytopenia developed in 43% of patients and thrombocytopenia in 27%; both conditions reversed with dose adjustments of imatinib mesylate. We conclude that imatinib mesylate effectively controlled CML that recurred after allogeneic SCT, but it was associated with side effects including myelosuppression and recurrence of severe GVHD.

Favorable long-term follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukemia after failure of interferon-α treatment

Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1039-1043 ◽  
Author(s):  
Andreas Hochhaus ◽  
Brian Druker ◽  
Charles Sawyers ◽  
Francois Guilhot ◽  
Charles A. Schiffer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Interferon Α ◽  
Imatinib Treatment ◽  
Serious Adverse Events ◽  
Response Level

Abstract Imatinib mesylate, a targeted inhibitor of BCR-ABL tyrosine kinase, is the standard of care for chronic myeloid leukemia (CML). A phase 2 trial of imatinib in late chronic-phase (CP) CML after interferon-α (IFNα) failure enrolled 532 patients, 454 with a confirmed diagnosis of CP CML. Median time from diagnosis was 34 months; median duration of imatinib treatment was 65 months. Cumulative best rates of major cytogenetic response (MCyR) and complete cytogenetic response (CCyR) were 67% and 57%, respectively. At the 5-year landmark, 184 (41%) of the 454 patients are in CCyR. At more than 6 years, 199 (44%) of the 454 patients remain on imatinib. Most responses occurred within 12 months of starting imatinib; however, some patients achieved initial MCyR and CCyR more than 5 years after imatinib initiation. Estimated rates of freedom from progression to accelerated phase (AP) and blastic phase (BP) and overall survival at 6 years were 61% and 76%, respectively. Both freedom from progression to AP/BP and overall survival (OS) were associated with cytogenetic response level at 12 months. No increase in rates of serious adverse events was observed with continuous use of imatinib for up to 6.5 years, compared with earlier time points. Imatinib continues to be an effective and safe therapy for patients with CP CML after failure of IFN.

The Time to Cytogenetic Response Determines Survival in CML Patients (Pts) Receiving Second-Line Tyrosine Kinase Inhibitors, and Allows Early Identification of Pts Destined To Fail Therapy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1931-1931
Author(s):  
Constantine S. Tam ◽  
Hagop Kantarjian ◽  
Gautam Borthakur ◽  
William Wierda ◽  
Farhad Ravandi ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Early Identification ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Cumulative Probability ◽  
P Value ◽  
Second Line ◽  
Term Survival

Abstract Background: Novel Tyrosine Kinase Inhibitors (TKIs) are used in the treatment of CML pts who fail imatinib. However, more than half of chronic phase (CP) pts will not achieve complete cytogenetic response (CCyR), and the criteria for when to consider alternate therapy among such pts are not well defined. Methods: We analyzed the pattern of cytogenetic response in 113 pts with CML in CP receiving nilotinib (n=43, 38%) or dasatinib (n=70, 62%) after imatinib failure in order to determine which milestones are important for long-term survival, and to develop a predictive model for the early identification of poor-risk pts. Pts (n=26, 23%) with clonal evolution with no other criteria for accelerated phase were included in the analysis. The previous best response to imatinib was CCyR in 24%, major cytogenetic response (MCyR, 1–35% Ph+) in 20%, minor cytogenetic response (mCyR, 36–95% Ph+) in 15%, complete hematological response (CHR) in 39%, and no response (NR) in 3%. Results: Median follow-up was 27 months. The cumulative probability of CCyR was 35%, 42% and 48% after 3, 6 and 12 months of 2nd TKI therapy. The achievement of MCyR or better by 12 months (12MMCyR) was an important milestone in determining future survival: 1-year survival from the 12 month landmark was 97% for the pts who achieved 12MMCyR, compared with 84% for those who did not (p=0.01). In contrast, no protection was conferred by lesser responses, with comparable survival for pts in mCyR, CHR and NR (86%, 83% and 88% respectively, p=0.78). The one year risk of progression to accelerated or blast phase, loss of hematologic response or death was 3% for pts in 12MMCyR, and 17% for those in mCyR or CHR (p=0.003). Early cytogenetic response was predictive of eventual 12MMCyR, with pts not achieving any degree of cytogenetic response by 3 to 6 months being unlikely to reach MCyR or better by 12 months (Table). Significant (p<0.05) univariate associations of 12MMyCR included age, time from diagnosis, more than one previous therapy, previous cytogenetic response to imatinib, low hemoglobin, high white cell count, blood blast percentage and platelet count; of these, only previous cytogenetic response to imatinib (p<0.001) and hemoglobin (p=0.003) remained independent in a multivariate analysis. If the three month response was added to the multivariate model, it emerged as the only significant factor suggesting that early response is the most important determinant of 12MMCyR. Conclusion: Achieving 12MMCyR was associated with superior survival and decreased risk of disease progression in pts receiving second-line TKI therapy. Since pts not achieving any degree of cytogenetic response by 3 to 6 months are unlikely (<10%) to reach 12MMCyR, this milestone may be a reasonable indication for considering alternative therapy. Assessment Response 12MMCyR(%) P-Value Three Months Minor CyR 10/15 (67%) <0.001 Three Months No CyR 3/42 (7%) Six Months Minor CyR 8/16 (50%) <0.001 Six Months No CyR 1/38 (3)

Impact of Prior Therapy with Imatinib Mesylate on the Outcome of Hematopoietic Cell Transplantation (HCT) for Chronic Myeloiod Leukemia (CML).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 738-738 ◽  
Author(s):  
Stephanie Lee ◽  
Richard Maziarz ◽  
Manisha Kukreja ◽  
Tao Wang ◽  
Sergio Giralt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Imatinib Mesylate ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Phase ◽  
Marrow Transplant ◽  
P Value ◽  
Prior Therapy ◽  
First Line Therapy ◽  
Using Data ◽  
Reported Data

Abstract Imatinib mesylate (IM, Gleevec®) has largely supplanted allogeneic HCT as first line therapy for CML. Nevertheless, many persons with CML eventually undergo HCT raising the question of whether prior IM-therapy impacts HCT outcome. The effect of IM on HCT outcomes is unknown. Using data from the Center for International Blood and Marrow Transplant Research (CIBMTR) on 409 subjects treated with IM pretransplant (IM+) and 900 subjects who did not (IM-), we evaluated transplant-related mortality (TRM), acute graft-vs.-host disease (GVHD), leukemia relapse (defined as hematologic), leukemia-free survival (LFS) and survival. Transplants occurred from 1999–2003. Only data from centers that reported data on at least 80% of IM+ subjects which also concurrently treated IM- subjects were included to minimize potential bias. Because of population differences, results are presented separately for 1st chronic phase (CP1) and all other phases (> CP1). In both groups, IM+ subjects were transplanted more recently, had a longer interval from diagnosis to transplant, were more likely to receive peripheral blood than bone marrow, and to have unrelated donors. Within the CP1 group, 52% had planned to undergo transplant regardless of response to IM, while transplant was prompted by IM failure or no response in 37% and by IM intolerance in 9%. 52% of CP1 subjects received IM within a month of transplant. In CP1 subjects, IM-therapy prior to HCT was associated with better survival. Other significant factors associated with better survival in CP1 patients were better matched donor (p<0.0001), use of bone marrow (RR 0.66; p=0.002), and transplants < 1 year from diagnosis (RR 0.68; p=0.002). There was also a trend towards less TRM and more relapses; LFS was similar. Because of concern about possible selection biases, a matched-pairs analysis considering interval from diagnosis to HCT (+/− 3 mos), HLA-match, graft-type and sex-match was performed with 143 IM+ CP1 subjects and 236 IM- controls. Results confirmed a higher survival rate and less TRM in IM+ subjects. In subjects > CP1, use of IM before HCT was not associated with TRM, relapse, LFS or survival. Acute GVHD rates were similar between IM+ and IM- subjects regardless of leukemia phase. In summary, treatment with IM before HCT while in CP1 is associated with higher survival and trends towards less TRM and more hematologic relapses after transplant. In subjects > CP1, prior treatment with IM was associated with similar outcomes seen in patients not receiving IM before HCT. These results should be reassuring to patients receiving IM or CP1 patients contemplating a trial of IM before HCT. Stage Outcome RR 95% CI p-value CP1 Survival 0.63 0.46–0.88 0.006 LFS 0.89 0.68–1.15 0.36 TRM 0.70 0.49–0.98 0.04 Hematologic Relapse 1.54 1.02–2.35 0.04 Beyond CP1 Survival 0.93 0.74–1.18 0.57 LFS 1.05 0.84–1.32 0.67 TRM 0.87 0.64–1.18 0.35 Hematologic Relapse 1.35 0.95–1.89 0.09

Imatinib mesylate therapy in newly diagnosed patients with Philadelphia chromosome–positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses

Blood ◽  
2003 ◽  
Vol 101 (1) ◽  
pp. 97-100 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Jorge E. Cortes ◽  
Susan O'Brien ◽  
Francis Giles ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Interferon Α ◽  
Combination Regimens ◽  
Philadelphia Chromosome Positive

Abstract Fifty patients with Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML) in early chronic phase received imatinib mesylate, 400 mg orally daily. After a median follow-up of 9 months, 49 patients (98%) achieved a complete hematologic response and 45 patients (90%) achieved a major cytogenetic response, complete in 36 patients (72%). Compared with similar patients who received interferon-α with or without hydroxyurea or other interferon-α combination regimens, those receiving imatinib mesylate had higher incidences of complete and major (Ph &lt; 35%) cytogenetic responses at 3 months (34% and 74% versus 1%-4% and 9%-24%, respectively), 6 months (52% and 80% versus 3%-7% and 11%-28%, respectively), and 9 months (60% and 77% versus 5%-11% and 14%-30%, respectively; P &lt; .001). Competitive quantitative polymerase chain reaction (QPCR) studies at 9 months showed a median QPCR value (ratio of BCR-ABL/ABL transcripts × 100) of 0.59% overall and of 0.24% (range, 0.001%-29.5%) for complete cytogenetic response.

Type of BCR-ABL Transcript Predicts Response to Imatinib Mesylate.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4848-4848
Author(s):  
Pratibha Sharma ◽  
Lalit Kumar ◽  
Vinod Kochupillai ◽  
Sujata Mohanty ◽  
Atul Sharma ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Target Therapy ◽  
Chronic Phase ◽  
Bone Marrow Examination ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Female Ratio ◽  
Time Period ◽  
Significant Probability ◽  
Male To Female

Abstract Imatinib Mesylate, a molecular target therapy is the first line treatment for all CML patients. We prospectively studied 50 CML patients (37 pre-treated with interferon Alfa) for response to Imatinib. Patients median age was 32 years, range, 11 to 62 years with male to female ratio being 2.5: 1. All patients were in chronic phase and received 400 mg imatinib daily for a mean time period of 18 months (range 3 to 38 months). Patients were monitored closely for clinical, hematological, cytogenetic & molecular response. Bone marrow examination was done at 3, 6, 9 then 4–6 months interval for cytogenetic response (CGR) and also for presence of BCR-ABL transcript types (b2a2, b3a2, e1a2 and e19a2) by multiplex and nested RT-PCR technique. All patients achieved complete hematological remission with in 3 months of starting Imatinib. 20/50 patients achieved Major CGR (complete -8, Partial CGR-12). Of these, 12/20(60%) patients had b2a2 transcript, 3/20 (15%) b3a2 transcript and 5/20 (25%) had both the transcripts. 24/50 had minor CGR (b2a2-10/24 (41.6%), b3a2-14/24 (58.3%). Remaining 6 patients had no Cytogenetic response (4/6-b3a2, 2/6-b2a2). Patients with BCR-ABL transcript b2a2 had a significant probability of achieving Major cytogenetic response 12/50(24%) compared with b3a2 transcripts, 3/50 (6%), p<0.001. However, there was no significant correlation between transcript type and spleen size, Hb, WBC, platelets counts. These initial observations are very provocative and suggest that site of breakpoint in major breakpoint cluster region might be predictive of cytogenetic responses to Imatinib Mesylate. We are continuing to accrue more patients in this study to confirm these results.

Cytogenetic Response in Relation to the Adherence to Treatment with Imatinib Mesylate: A Case Control Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4553-4553 ◽  
Author(s):  
Carlos Doti ◽  
German Stemmelin ◽  
Claudia Shanley ◽  
Jose Ceresetto ◽  
Oscar Rabinovich ◽  
...  
Keyword(s):  
Adverse Events ◽  
Imatinib Mesylate ◽  
Case Control Study ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Case Control ◽  
Control Group ◽  
Hematological Response ◽  
Control Study

Abstract Introduction: The treatment of chronic myeloid leukemia (CML) suffered a dramatic change with the introduction of Imatinib mesylate. This drug has become the choice for first line treatment of CML. However, it has been shown that the effectiveness of the treatment requires a high compliance with the prescribed dose for a long period of time, and sub-dosing has been associated with a delay in achieving cytogenetic response and development of resistance. We conducted a prospective case-control study, in order to analyze how a better compliance affects the cytogenetic response to Imatinib. Materials and Methods: Between January and June 2006, 24 patients with newly diagnosed Phi (+) chronic phase CML were recruited and followed for the next 12 months. Patients were put on 400mg of Imatinib and were asked to note down all taken doses, and reasons for non-compliance. During each of the monthly visits, the dosing schedules were revised, non-adherence reasons were discussed and the medication was counted. All adverse events were noted and graded according to the NCI CTCAE (VERSION 3.0) code. Reductions or interruptions in the schedule were only allowed for related adverse events with a CTC score ≥3. All other events were treated accordingly, without modifications in the Imatinib dosing. As a control group, we matched each case with a chronic phase Phi (+) CML patient from our data base (controls were matched for sex, age, and hematological response). Only patients who received treatment with Imatinib and with complete information about dosing and adverse events were acceptable as controls. Compliance was measured as: mg taken /mg prescribed x 100 during the study period. Cytogenetic response was reported as the percentage of t(9;22) negative metaphases. Results: Twenty-four patients, 14 males with median age 55 yo (range: 23–82) were included in the study; three were lost to follow up, leaving only twenty-one for analysis of compliance. At the end of the year of follow up, all patients have achieved a complete hematological response. Compliance during the 12 months was 96.1 ± 9% 1SD for the cases group, which is clearly superior to the 80% reported in the setting of clinical trials. As for one year cytogenetic response, 60 ± 25% of the control group achieved a mayor response (Phi < 35%), while 89.9 ± 20% of the cases achieved that same response. This difference is statistically significant with a p=0.027. The incidence of adverse events was similar for both groups, being nausea, vomiting, peripheral edema and skin rash the most common ones. As for hematological toxicity, CTC grade 1–2 leucopenia (11%) and thrombocytopenia (17%) were the more frequent. However, although moderate, these were the main reasons for interruption or reduction of Imatinib dosage in the control group. Conclusions: This study shows that improving compliance is associated with a better cytogenetic response. As this response is the ultimate goal in the treatment of CML patients, physicians should make an effort to assure the best adherence to the treatment and avoid sub-dosing. Doing this will help patients obtain a better cytogenetic response which has already proved to be essential for long term survival in CML.

High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome–positive chronic phase chronic myeloid leukemia

Blood ◽  
2004 ◽  
Vol 103 (8) ◽  
pp. 2873-2878 ◽  
Author(s):  
Hagop Kantarjian ◽  
Moshe Talpaz ◽  
Susan O'Brien ◽  
Guillermo Garcia-Manero ◽  
Srdan Verstovsek ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Quantitative Polymerase Chain Reaction ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Complete Cytogenetic Response

Abstract Imatinib mesylate (STI571) is effective in chronic phase chronic myelogenous leukemia (CML). However, most patients treated with 400 mg imatinib daily have variable levels of residual molecular disease. We treated 114 patients with newly diagnosed chronic phase CML with 400 mg imatinib twice daily. Overall, 109 patients (96%) had a major cytogenetic response (Philadelphia chromosome [Ph] &lt; 35%), and 103 (90%) had a complete response (Ph 0%). With a median follow-up of 15 months, no patient has progressed to accelerated or blastic phase. The estimated 2-year survival rate was 94%. By quantitative polymerase chain reaction (QPCR) studies, 71 (63%) of 112 patients showed BCR-ABL/ABL percentage ratios decrease to less than 0.05%, and 31 (28%) to undetectable levels. Compared with standard-dose imatinib, high-dose imatinib was associated with significantly better complete cytogenetic response (P = .0005), major molecular response (QPRC &lt; 0.05%; P = .00001), and complete molecular response (undetectable BCR-ABL; P = .001). High-dose imatinib was well tolerated but resulted in more frequent myelosuppression; 82% of patients continue to receive 600 mg or more of imatinib daily. In conclusion, high-dose imatinib induced higher rates of complete cytogenetic response and of molecular response in patients with newly diagnosed chronic phase CML. (Blood. 2004; 103:2873-2878)

Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: when is this a safe option to consider?

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 184-188 ◽  
Author(s):  
Kendra Sweet ◽  
Vivian Oehler
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Deep Level ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Response To Therapy ◽  
Molecular Response ◽  
Rt Pcr

Abstract Mrs G is a 54-year-old woman with a diagnosis of chronic-phase chronic myeloid leukemia dating back 8 years. She had a low-risk Sokal score at diagnosis and was started on imatinib mesylate at 400 mg orally daily within one month of her diagnosis. Her 3-month evaluation revealed a molecular response measured by quantitative RT-PCR of 1.2% by the International Scale. Within 6 months of therapy, she achieved a complete cytogenetic response, and by 18 months, her BCR-ABL1 transcript levels were undetectable using a quantitative RT-PCR assay with a sensitivity of ≥ 4.5 logs. She has maintained this deep level of response for the past 6.5 years. Despite her excellent response to therapy, she continues to complain of fatigue, intermittent nausea, and weight gain. She is asking to discontinue imatinib mesylate and is not interested in second-line therapy. Is this a safe and reasonable option for this patient?

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