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.

scholarly journals A Retrospective Cohort Study of Upfront Nilotinib in Chronic Myeloid Leukemia: A Single-Center Experience

2021 ◽  
Author(s):  
Reema Singh ◽  
Jyotsna Kapoor ◽  
Rayaz Ahmed ◽  
Pallavi Mehta ◽  
Vishvdeep Khushoo ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Elevated Serum ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Female Ratio ◽  
Single Center Experience ◽  
Male To Female

Abstract Context Nilotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia (CML). Aims We aim to evaluate the responses and safety of upfront Nilotinib therapy in Indian CML patients. Setting and Design We retrospectively reviewed the medical records of CML patients who received Nilotinib as an upfront treatment at our center between January 1, 2011 and October 15, 2019.The follow-up was taken till March 31, 2020. Results Forty One patients (n = 36 chronic phase and five accelerated-phase CML) received frontline Nilotinib. Median age was 39 years (21–63) with male-to-female ratio of 1.1: 1. At 3 months, 96.9% patients achieved BCR-ABL of ≤10% at international scale. By the end of 12 months, 71.5% patients achieved major molecular response (BCR-ABL ≤0.1%) and 91.4% patients achieved complete cytogenetic response assessed by BCR-ABL polymerase chain reaction of ≤1%. Common toxicities observed were weight gain, thrombocytopenia, corrected QT prolongation, and elevated serum amylase in 14 (34.1%), 7(17.07%), 4(9.7%), and 4(9.7%) patients, respectively. Overall, five patients had loss of response with further progression and death in three patients. At a median of 43.7 months, 38 patients survived with estimated 3 year event-free survival and overall survival of 65 ± 9 and 93 ± 5%. Conclusion This study showed remarkable good response with upfront Nilotinib in Indian patients with 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?

scholarly journals A Rare t(9;22;16)(q34;q11;q24) Translocation in Chronic Myeloid Leukemia for Which Imatinib Mesylate Was Effective: A Case Report

2011 ◽  
Vol 2011 ◽  
pp. 1-3
Author(s):  
Masahiro Manabe ◽  
Yumi Yoshii ◽  
Satoru Mukai ◽  
Erina Sakamoto ◽  
Hiroshi Kanashima ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Normal Karyotype ◽  
Cytogenetic Response ◽  
Imatinib Therapy ◽  
Molecular Response ◽  
Trisomy 8 ◽  
Additional Chromosome

The t(9;22)(q34;q11) translocation is found in about 90% of chronic myeloid leukemia (CML) patients. About 5–10% of CML patients have complex variant translocations involving a third chromosome in addition to chromosomes 9 and 22. Herein, we describe a CML-chronic phase male with a complex translocation involving chromosome 16, t(9;22;16)(q34;q11;q24). First, he was treated with interferon-alpha and intermittent hydroxyurea, but only a partial cytogenetic response was attained. Subsequently, the patient was treated with imatinib mesylate because of an additional chromosome abnormality, trisomy 8. A major molecular response was obtained after one year's imatinib therapy, and the follow-up chromosomal analysis performed 4 years and 3 months after the initiation of imatinib therapy displayed a normal karyotype of 46,XY.

scholarly journals Efficacy of nilotinib in a patient relapse after 9 years of imatinib treatment and in stable complete cytogenetic response

2015 ◽  
Vol 5 (3S) ◽  
pp. 7-11
Author(s):  
Marzia Defina
Keyword(s):  
Target Therapy ◽  
Clonal Evolution ◽  
Peptide Vaccine ◽  
Chronic Phase ◽  
Transcript Level ◽  
Cytogenetic Response ◽  
Kinase Domain ◽  
Molecular Response ◽  
Imatinib Treatment ◽  
Complete Cytogenetic Response

We report a case of a patient with chronic myeloid leukemia in chronic phase who was treated with interferon-alpha plus low dose of cytarabine for 5 years, achieving a partial cytogenetic response. In 2000, he started imatinib at 400 mg/day obtaining rapidly a complete cytogenetic response (CCyR) (after 6 months of treatment) and a “near” major molecular response (MMolR) with BCR-ABL transcript level waving from 0.13 to 0.15% (BCR-ABL/ABL%) during molecular follow-up performed in the subsequent 6 years. To further improve his molecular response, we associated to TKI an immune target therapy with a BCR-ABL derived peptide vaccine developed by us, obtaining a MMolR, confirmed during the following 12 months from the beginning of the vaccinations. Surprisingly, at 9 years from starting imatinib, we documented the loss of MMolR and CCyR. Clonal evolution, kinase domain mutations and reduced drug intake were excluded, thus the patient switched to nilotinb at 400 mg/BID: after 3 months of treatment he achieved CCyR and MMolR and after 6 months we documented also a complete molecular response (CMolR).

Imatinib Mesylate Dose Escalation Improves Disease Response in Chronic-Phase Chronic Myeloid Leukaemia Patients after Cytogenetic or Molecular Suboptimal Responses to Standard Doses of Imatinib.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1052-1052 ◽  
Author(s):  
Delphine Rea ◽  
Gabriel Etienne ◽  
Selim Corm ◽  
Pascale Cony-Makhoul ◽  
Martine Gardembas ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Median Duration ◽  
Dose Escalation ◽  
Standard Dose ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
High Dose ◽  
Molecular Response ◽  
Dose Increase

Abstract In chronic phase-chronic myeloid leukemia (CP-CML), a complete cytogenetic response (CCR) along with a major molecular response (MMR) on imatinib mesylate (IM) at 400mg/d represents a strong factor predicting survival. Suboptimal cytogenetic responders (minimal or minor CR (mCR) by 6 months or partial CR (pCR) by 12 months, ELN) have a probability of further achievement of CCR of only 50%. Suboptimal molecular responders (CCR without MMR by 18 months, ELN) have a decreased probability of remaining event-free survivors when compared to optimal responders. Since non-randomized trials suggest that high-dose IM at CML diagnosis produces high rates of optimal responses, dose escalation can be recommended for suboptimal responders to standard dose of IM, but this strategy has not been yet evaluated. Here, we present the results from a series of 24 CP-CML patients who experienced IM-dose escalation for cytogenetic or molecular suboptimal response to standard doses of IM. Suboptimal cytogenetic responders (n=10) included 9 males, median age was 51.3 years-old (27.7–64.2), all were in early CP. Sokal scores were low (n=5), int (n=2), high (n=2) and unknown (n=1). All patients were treated with IM frontline at 400mg/d (n=9) or 600mg/d (n=1) and 2 received PEGIFN associated with IM at 400mg/d (withdrawn after 3 months for intolerance in 1). Prior to dose escalation, 7 patients were in pCR at 12 months and 3 in mCR at 6 months. The search for BCR-ABL mutations was negative in 6 patients tested. IM was increased to 600mg/d (n=7) or 800mg/d (n=3) after a median time of 13.7 months (5.6–15.2) on initial IM treatment. Median follow-up from IM at standard and escalated doses were respectively 28 (16.1–79.1) and 14.9 months (2.2–73.5). Of 9 patients with cytogenetic evaluation, 100% obtained CCR after a median duration of high-dose IM of 6.2 months (2.4–12.6). Five patients (50%) achieved a MMR after a median duration of high-dose IM of 9.7 months (2.9–45). Only one patient treated with PEGIFN and IM increased to 600mg/d obtained a complete molecular response (CMR) 19.9 months after high-dose IM. Suboptimal molecular responders (n=14) included 11 males, median age was 38.2 years-old (20.9–63.2), 9 were in early CP and 5 in late CP. Six had previously received IFN for a median of 4 months (4–53). Sokal scores were low (n=5), int (n=5), high (n=3) and unknown (n=1). All patients had received IM at 400mg/d, for a median duration of 27.3 months (16.7–73.3). BCR-ABL mutations were detected in 2/8 patients tested (M244V and Q252R). IM was increased to 600mg/d (n=13) or to 800mg/d (n=1). Median BCR-ABL prior to dose increase was 0.79% (0.15–3.06). Median follow-up from standard and escalated doses of IM were respectively 45.2 (26.9–85.9) and 12.5 months (3.3–38.1). Six patients (43%) obtained a MMR after a median of 6.7 months (2–25.4) of high-dose IM, including 1 with the M244V mutation. None achieved a CMR. To conclude, IM-dose escalation is beneficial to suboptimal cytogenetic responders with a rate of achievement of CCR and MMR of respectively 100 and 50%. Regarding molecular suboptimal responders, the rate of MMR after dose increase in only 43% and other strategies should be considered.

Serum Erythropoietin Dose Not Participate in Anemia That Persists in CML Patients after MMR Achievement by Imatinib Mesylate Therapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4274-4274
Author(s):  
Maho Ishikawa ◽  
Fumiharu Yagasaki ◽  
Daisuke Okamura ◽  
Tomoya Maeda ◽  
Naoki Takahashi ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Regression Line ◽  
Chronic Phase ◽  
Serum Levels ◽  
Cytogenetic Response ◽  
Deficiency Anemia ◽  
Molecular Response ◽  
Moderate Anemia ◽  
Grade 3 ◽  
Serum Erythropoietin

Abstract Serum Erythropoietin dose not Participate in Anemia that Persists in CML Patients after MMR Achievement by Imatinib Mesylate Therapy The IRIS study revealed that imatinib mesylate (IM) has resulted in durable responses in patients with CML in early chronic phase. Overall, 86% of patients on IM achieved complete hematologic response (CHR) by 3 months and 78% achieved complete cytogenetic response (CCR) by 18 months. According to the European LeukemiaNet guidelines, CHR is defined without evaluation of anemia. In the IRIS study, grade 3 or 4 of anemia was reported as 4% after 5 years of therapy, however, we found most patients remain mild to moderate anemia even after achievement of major molecular response (MMR). Persistent anemia sometimes deteriorates patients’ quality of life and is thought to be clinically important. Here, we investigated frequency and severity of anemia, and participation of serum erythropoietin (EPO) among 23 patients, who have achieved MMR by IM at doses in excess of 300mg for more than 2 years. At diagnosis, the median age was 53 years (range 20–87) and 14 were male. 20 patients were in chronic, and 3 in accelerated phase. Median leukocyte count was 31.6 × 109/L (range 4.1–216.3 × 109), median hemoglobin (Hb) was 13.1 g/dl (range 6.2–16.2), and median platelet count was 629 × 109/L (176–1640). The cumulative rate of CHR by 3 months was 100% and that of CCR by 12 months was 77.3%. Among 18 patients who had MMR, hematologic adverse events were assessed. After reaching MMR, leukocytopenia was observed in 3 (16.6%) patients (grade 2; 2pts, grade 3;1pt), anemia was in 13 (72.2%) patients (grade 1; 10pts, grade 2; 2pts, grade 3; 1pt), and thrombocytopenia was in 3 (16.6%) patients (grade 1; 2pts, grade 2; 1pt). Mild to moderate anemia tends to persist at high rates as compared with other cytopenias. In anemic group, median MCV, MCHC, and reticulocyte was 99.4fL (range 91.6–113.1), 33.3% (range 30.4–35.2), and 53691/micro L (range 30450–72324), respectively, and serum urea and creatinine were normal. To reveal mechanism of persistent anemia, EPO levels were measured by a radioimmunoassay (normal range 9.1–32.8 mIU/ml). For control, we used the formula: log[EPO]=3.436–0.1675[Hb], which was led by 58 iron deficiency anemia (IDA) patients and had been previously reported (Toyoda A, et al. Exp Hematol21:1085, 1993). The EPO corresponding to each Hb level from the formula was defined as the expected value. The median serum EPO level of CML patients with anemia was 46.0 mIU/ml (range 23.9–188.1). Comparison of the observed EPO with the expected EPO levels showed no significant differences (p=0.557). The equation of regression line for the observed EPO was y=−21.07x+284.2 (Figure 1. solid line, r=−0.732, p=0.0008), and that of the expected EPO was y=−22.65x+296.3 (Figure 1. dashed line, r=−0.939, p&lt;0.0001). In addition, serial EPO measurement could be performed in one patient treated with IM. At the diagnosis of CML, Hb was 11.0g/dl and EPO was 47.7mIU/ml. He developed anemia with Hb of 7.8g/dl due to gastrointestinal bleeding, and EPO was 183.6 mIU/ml. After discontinuation of IM for 7days, Hb was 8.4g/dl and EPO was 64.9mIU/ml. These data show that IM has little influence on the serum EPO levels. In conclusion, grades 1–2 anemia frequently persist in CML patients after MMR achievement. The EPO response does not concern about the condition of persistent anemia, and IM have little influence on the serum levels of EPO. Figure 1. Correlation between erythropoietin and hemoglobin. Figure 1. Correlation between erythropoietin and hemoglobin.

CML and Imatinib Mesylate: Response Related to Karyotype.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4866-4866
Author(s):  
Araceli Rubio-Martinez ◽  
Valle Recasens ◽  
Maria D. Odero ◽  
Daniel Rubio-Felix ◽  
Maria J. Calasanz ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Cytogenetic Study ◽  
Specific Inhibitor ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Rt Pcr ◽  
Group A ◽  
Group B ◽  
Mean Time

Abstract Background: Imatinib mesylate (STI571), as a specific inhibitor for tyrosine kinase product of oncoprotein Bcr/Abl. Efficacy of Imatinib is questioned when other cytogenetics abnormalities associated to t(9;22) are present. We describe our experience in CML patients treated with Imatinib in one centre, evaluating hematological (HR) and cytogenetic response (CR) related to kariotype. Patients and methods: 28 patients diagnosed as having CML, 1990–2005, Imatinib 400–800 mg/d, were stratified according to cytogenetic abnormalities: Group A: t(9;22) typical in 19 patients, Group B: patients with t(9;22) and different genomic rearrangement associated: 9. At diagnosis were classified in stages Kantarjian score and the cytogenetic study (kariotype, % metaphases Ph, FISH and PCR/RT-PCR in bone marrow (BM) and peripheral blood (PB)). HR was evaluated monthly and CR in BM every 3–6 months. In patient with complete cytogenetic response (CCR) we performed follow-up in PB by RT-PCR every 3 months and a cytogenetic study in BM once a year. Cytogenetic response (CR) was quantified by n° metaphases Ph in BM: 0% CCR, 1–35% partial (PCR), 36–95% minor (MCR) and &gt; 95% failure (F). Molecular response (MR): normal kariotype (Bcr/Abl negative and RT-PCR&lt;5 copies). Statistical analysis: Chi-cuadrado and Kaplan-Meier survival test. Results: 18 M /10 F (2 died by blast crisis), mean age 50 (range 30–72), Kantarjian score: A group (4: 2pts, 3: 5pts, 2: 5pts, 1: 7 pts). Mean time on therapy: 26.46 m (1–51 ). Previous therapy: α-interferon 7, α-interferon/pegilated 1, α-interferon/α-interferon+citarabine 3, α-interferon+citarabine 6. Imatinib as first line: 11. When Imatinib started: accelerated phase 3, chronic phase 23 and chronic phase post-blast crisis2. The results of therapy are in table I. We have not observed statistically significant differences (s.s.d) in MR (p=.577) and in OS (p=.581) between group A and B with the same doses. Two patients that had started therapy with Imatinib 800 mg/day (group A) reached MR three months later. In group B one patient 12 months after got MR surprisingly developed a ALL Ph’, he received chemotherapy plus Imatinib 800 mg/day and 6 months later he is in CCR. Conclusions: Three months after Imatinib therapy HR was 100% in both groups. One year undergoing therapy CR response was higher in A group (81% vs 50%). Nevertheless the n° of MR obtained in patients with complex karyotypes receiving Imatinib 400 mg/day has been high (33.3%) and without s.s.d.with those with classical translocation. Hematological and Cytogenetic response to Imatinib Months N.E.P. A Group (19) N.E.P. B Group (9) 1 19 HR : 100% 9 HR :78% 3 10 HR:100%. CR 7 (70%): 4CCR(2MR), 2PRC, 1MRC, 3F. 3 HR: 100%. CR 2 (67%): 2MCR, 1F 6 16 HR: 94%. CR: 12 (75%), 7CCR (3MR), 3PRC, 2MCR, 4F 6 HR: 86%. CR 4 (67%): 3CCR, 1MCR, 2F 12 16 HR: 94%. CR 13 (81%): 11CCR (6MR), 2PRC, 3 F 4 HR: 100%. CR 2 (50%): 2CCR (1MR), 2F 18 13 HR: 100%. CR 12 (92%): 10CCR (6MR), 2PRC, 1F 5 HR: 80%. CR 3(60%): 3CCR (2 MR), 2F 24 13 HR: 93%. CR 12 (92%): 10CCR (7MR), 2PRC, 1F 6 HR: 83%. CR : 4 (67%): 3CCR (3 MR*), 1PRC, 2F 36 4 HR: 100%. CR 3 (75%): 2CCR (1MR), 1PRC, 1F 5 HR: 60%. CR 2 (40%): 2CCR (2MR), 3F 48 2 HR: 100%. CR 1 (50%): 1 PRC,1F 0 MR:N 10 (52,6%). Mean time : 12 m (3–24 m). Imatinib : 488,88 mg/d, Months in MR : mean 15.8 (9–21m) 3 (33.3%). Mean time : 18 months (12–26 m). Imatinib : 400 mg/day. Months in MR : mean 18 (12–26 m)

High Efficacy and Particular Safety Profile of Imatinib Mesylate (Glivec®) in Elderly Patients with CML in Chronic Phase: Results of the AFR04 Prospective Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1039-1039
Author(s):  
Philippe Rousselot ◽  
Franck Nicolini ◽  
François Xavier Mahon ◽  
Delphine Réa ◽  
Jérome Jaubert ◽  
...  
Keyword(s):  
High Risk ◽  
Elderly Patients ◽  
Prospective Study ◽  
Imatinib Mesylate ◽  
Cardiac Failure ◽  
Cumulative Incidence ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Level 3

Abstract The reported median age of the chronic myelogenous leukaemia (CML) patients (pts) enrolled in the pivotal IRIS trial was 50y. Subgroup analysis have been already published focusing on pts over 60y with the conclusion that imatinib is efficient and well tolerated. We report here the first prospective study dedicated to imatinib in elderly pts with CML in chronic phase (CP). Patients aged 70y and over were eligible if they were diagnosed with CP CML for less than 12 months. The Cumulative Illness Rating Scale for Geriatrics (CIRS-G) comorbidity index was calculated for all pts. Hydroxyurea was the only treatment accepted before inclusion. Imatinib mesylate (IM, Novartis Pharma) was administered at the dosage of 400 mg QD. Cytogenetic response was assessed for each patient every 6 months during 2 years and every year thereafter. BCR-ABL analysis were performed in reference laboratories every 3 months and results expressed according to the ENL recommendations. Thirty pts with newly diagnosed CP CML were enrolled from March 2002 to October 2004. Median age was 74.8 years (70 to 90). Sex ratio (M/F) was 1.72. Thirty percent of the pts were classified as high risk, 35% intermediate risk and 35% low risk according to the Sokal score stratification. The mean severity CIRS-G index value was 1.47. Two pts had categories at level 3 (cardiopathy and nephropathy). Interval between diagnosis and imatinib initiation was 51 days (13 to 312). Median follow up was 45 months. Grade 2 to 3 neutropenia was observed in 22% of the patients (one patient received G-CSF). Grade 2 to 3 anemia was noted in 31.8% of the pts, 86% of them received rHU-EPO with a complete resolution of anemia. The most commonly reported extra haematological toxicity was oedema (71%, only one grade 3) followed by gastrointestinal symptoms (38%). Of note, 65% of the pts had cardiovascular comorbidities. The 2 pts who presented a cardiac failure episode were those with a CIRS-G cardiac categorie at level 3. Three pts stopped IM (2 already mentioned for cardiac intolerance and one for cutaneous intolerance). The median daily dose of IM was 392 mg (256 to 445), as calculated from the patients records. A transient or permanent dosage reduction was noted in 52.3% of the patients. Cumulative incidence of complete cytogenetic response (CCR) was 71.4% and 77% at 12 and 24 months respectively. One patient lost CCR after imatinib discontinuation. The cumulative incidence of major molecular response (MMR) was 25%, 56% and 59% at months 12, 24 and 36 respectively. Among pts in MMR at month 36, 25% were in complete molecular response. There was no correlation between the CIRS-G score or index and response. Among the 3 pts who stopped the treatment, 2 had CIRS-G categories at level 3. In conclusion, the toxicity of imatinib mesylate appeared more pronounced on the red cell lineage in elderly patients that reported in younger patients. Oedema are also very common but easily treated with diuretics. We observed 2 cases of cardiac failure in this cohort of high risk patients in the 2 patients with a previous level 3 CIRS-G category, suggesting a non favourable benefit/risk ratio in patients with severe comorbidity. For all other elderly patients, a high level of sustained cytogenetic and molecular responses was observed irrespective of age.

Does BCR-ABL transcript type predict cytogenetic response to imatinib mesylate in chronic phase, chronic myeloid leukemia patients?

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7043-7043
Author(s):  
P. Sharma ◽  
L. Kumar ◽  
S. Mohanty ◽  
S. Bose ◽  
V. Kochupillai
Keyword(s):  
Imatinib Mesylate ◽  
Median Time ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Interferon Alfa ◽  
Molecular Response ◽  
Previously Treated ◽  
The Mean ◽  
Pre Treatment ◽  
Transcript Type

7043 Background: We prospectively studied BCR-ABL transcript type (b2a2, b3a2, e1a2 and e19a2 in 100 CML-CP patients treated with Imatinib mesylate therapy and studied their correlation with the cytogenetics responses. Methods: Between Aug, 2004 and Sep, 2006, 100 CML –CP patients (median age was 32 years, range, 11 to 62 years, M: F: 2.5: 1) were treated prospectively with imatinib mesylate 400 mg daily on outpatients. 70 patients were pre-treated with interferon Alfa. The mean duration of Gleevec treatment was 24 months (range 3 to 38 months). Patients were monitored closely for clinical, hematological, cytogenetic & molecular response as per standard guidelines. Bone marrow was studied at 3, 6, 9 then 4–6 months interval for cytogenetic response (CGR) and also for the presence of BCR-ABL transcript types by multiplex and nested RT-PCR technique. Results: 96% of patients achieved complete hematological remission (CHR); median time being 21 days, ranging from 7 to 110 days. 60% of patients achieved Major CGR (complete 32, partial CGR-28); median time 8 months, ranging from 6 to 22 months. Previously untreated patients had higher major (70% vs 55.7%) and complete (46.6% vs 25.7%) CGR compared to patients previously treated with interferon alfa. Analysis for BCR-ABL transcript type revealed - b2a2 in 38%, b3a2 -54% and both in 8% of patients. 28 of 38(74%) patients with b2a2 type acieved Major CGR compared to 24 of 54 (44%) patients with b3a2 transcript, p<0.002. Of remaining 40 patients with minor or no CGR, 10(25%) had b2a2 compared to 30 (75 %) b3a2 type, p<.002. However, there was no significant correlation between transcript type and pre-treatment characteristics e.g. spleen size (in cm), Hb (G/dl), WBC & platelets counts. Conclusions: Present study suggests that site of breakpoint in major breakpoint cluster region might be predictive of cytogenetic responses to Imatinib Mesylate in CML patients. No significant financial relationships to disclose.

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