Determinants of Overall and Progression-Free Survival of Nigerian Patients with Philadelphia-Positive Chronic Myeloid Leukemia

Objective. The tyrosine kinase inhibitors have markedly changed the disease course for patients with Ph+and/orBCR-ABL1+chronic myeloid leukemia (CML). This study was embarked upon to assess the long-term effects of imatinib therapy on survival in adult Nigerian patients with CML.Methods. All adult patients on imatinib (400–600 mg) seen from July 2003 to December 2010 were assessed. Male/female distribution was 171/101, with a median age of 38 (range, 20–75) years. Overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan-Meier techniques.Results. Of all the 272 patients, 205 were in chronic phase, 54 in accelerated phase, and five in blastic phase, at commencement of imatinib. As at December 2010, 222 were alive. OS at 1 and 5 years was 94% and 63%, while PFS was 89% and 54%, respectively. Similarly, amongst the 205 patients in chronic phase, OS at 1 and 5 years was 97% and 68%, while PFS was 92% and 57%.Conclusion. Imatinib’s place as first-line therapy in the treatment of CML has further been reinforced in our patients, with improved survival and reduced morbidity, comparable with outcomes in other populations.

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Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure

Blood ◽

10.1182/blood-2011-11-390120 ◽

2012 ◽

Vol 119 (15) ◽

pp. 3403-3412 ◽

Cited By ~ 191

Author(s):

H. Jean Khoury ◽

Jorge E. Cortes ◽

Hagop M. Kantarjian ◽

Carlo Gambacorti-Passerini ◽

Michele Baccarani ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Adverse Events ◽

Myeloid Leukemia ◽

Kinase Inhibitor ◽

Phase 1 ◽

Chronic Phase ◽

Progression Free Survival ◽

Cytogenetic Response ◽

Abl Tyrosine Kinase ◽

Kaplan Meier

Bosutinib, a dual Src/Abl tyrosine kinase inhibitor (TKI), has shown potent activity against chronic myeloid leukemia (CML). This phase 1/2 study evaluated the efficacy and safety of once-daily bosutinib 500 mg in leukemia patients after resistance/intolerance to imatinib. The current analysis included 118 patients with chronic-phase CML who had been pretreated with imatinib followed by dasatinib and/or nilotinib, with a median follow-up of 28.5 months. In this subpopulation, major cytogenetic response was attained by 32% of patients; complete cytogenetic response was attained by 24%, including in one of 3 patients treated with 3 prior TKIs. Complete hematologic response was achieved/maintained in 73% of patients. On-treatment transformation to accelerated/blast phase occurred in 5 patients. At 2 years, Kaplan-Meier–estimated progression-free survival was 73% and estimated overall survival was 83%. Responses were seen across Bcr-Abl mutations, including those associated with dasatinib and nilotinib resistance, except T315I. Bosutinib had an acceptable safety profile; treatment-emergent adverse events were primarily manageable grade 1/2 gastrointestinal events and rash. Grade 3/4 nonhematologic adverse events (> 2% of patients) included diarrhea (8%) and rash (4%). Bosutinib may offer a new treatment option for patients with chronic-phase CML after treatment with multiple TKIs. This trial was registered at www.clinicaltrials.gov as NCT00261846.

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Real-world study of imatinib treatment patterns and outcomes among veteran patients with chronic myeloid leukemia.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.6600 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 6600-6600

Author(s):

Lizheng Shi ◽

Lei Chen ◽

Hari Sharma ◽

Maryna Marynchenko ◽

Eric Q. Wu ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Disease Progression ◽

Myeloid Leukemia ◽

Chronic Phase ◽

Treatment Patterns ◽

Imatinib Treatment ◽

Dose Increase ◽

First Line Therapy ◽

Diagnosis Codes ◽

Kaplan Meier

6600 Background: Imatinib (IM) is the most commonly used drug in the treatment of chronic myeloid leukemia-chronic phase (CML-CP) patients (pts). This study investigated the treatment patterns and outcomes for veteran CML-CP pts initiated on IM. Methods: Pts (age >18 yrs) with >1 CML diagnosis codes documented (ICD-9 CM: 205.1x) between 1/1/2000 and 12/31/2010 were identified from the VISN 16 data warehouse. Pts were required to have initiated IM as the first-line therapy in CML-CP. Accelerated and blastic phases (A/BP) were identified based on WHO classification using CBC information. IM dose adjustments were assessed as dose increase from <400 mg to >600mg or from 400-600mg to >800 mg daily. Rates of IM discontinuation (no use of IM for >60 days) and switching to other drug therapy (dasatinib/nilotinib (DS/NL), hydroxyurea, and interferon-alpha) were estimated. Time to discontinuation, progression to A/BP, and survival were assessed using Kaplan-Meier analysis (K-M). Overall survival was measured from IM initiation while survival among pts with disease progression was measured from the date of progression. Results: Among the 137 pts selected, average age was 64.8 yrs and follow-up time was 4.0 yrs. 16.8% of pts had dose increase from <400mg to >600mg and 21.7% of these pts switched to other therapy after dose increase. 13.1% of pts had dose increase from 400-600mg to >800 mg with 22.2% of these pts switching to other therapy later. During the study, 83.8% of the 74 pts who discontinued IM did not use other drug therapies; and 16.2% (12 pts) switched, among which 9 pts took DS/NL. K-M showed that 25.6% and 42.4% pts discontinued IM treatment by year 1 and 2 and 8.1% and 16.0% pts experienced disease progression by year 1 and 2, respectively. Among the 28 patients who had disease progression, 32.1% continued IM use after progression and only 7.1% switched to other therapies (50% switching to DS/NL). The mortality rates were 3.0% and 9.5% by year 1 and 2 after IM initiation, and 21.7% and 42.7% by year 1 and 2 after disease progression, respectively. Conclusions: The majority of IM-treated patients, including patients with disease progression, discontinued IM use without switching to other effective therapies.

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Comparison of allogeneic stem cell transplantations in chronic myeloid leukemia before and after the era of tyrosine kinase inhibitors.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.7038 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 7038-7038

Author(s):

Muhit Ozcan ◽

Bengi Ozturk ◽

Mehmet Ozen ◽

Pervin Topcuoglu ◽

Mutlu Arat ◽

...

Keyword(s):

Overall Survival ◽

Myeloid Leukemia ◽

Kinase Inhibitors ◽

Progression Free Survival ◽

Donor Lymphocyte Infusion ◽

First Year ◽

Free Survival ◽

New Era ◽

Blastic Phase ◽

Before And After

7038 Background: In this retrospective study we aimed to evaluate the rates and the clinical outcomes of allo-HSCT in CML following the advent of TKIs. Methods: We compared the transplantations (Txs) performed prior to 2002 (old era), the first year of TKIs, with the Txs during and after 2002 (new era). Results: Between 1989 and 2012 inour Tx unit a total of 189 allo-HSCTs were performed in 185 CML patients (second Tx for 4 patients). The ratio of Tx for CML among the whole Tx group decreased from 40 % to 12 % after 2002. The ratio also dropped to less than 5 % after 2008 and increased again to 15% in 2012. Time from diagnosis to Tx was longer in the old era than in the new era (9.2 months vs 15.4 months, p<.0001). The ratio of patients with advanced disease (accelerated or blastic phase) was higher in the new era. Although the progression free survival (PFS) was shorter in the new era than in the old era (median 13.8 months vs 37.1 months, p=0.09), overall survival, Tx outcomes and survival curves did not change. Conclusions: AlloHSCT rates sharply decreased after the TKIs, but a slight increase in recent years have been observed compatible with the TKI’s failure in years. Despite the fact that patients who underwent allo HSCT in the new era had more challenging disease biologically, overall survival was not affected possibly due to post-Tx interventions such as use of TKI alone or with donor lymphocyte infusion. [Table: see text]

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Outcomes of Chronic Phase Chronic Myeloid Leukemia after Treatment with Multiple Tyrosine Kinase Inhibitors

Journal of Clinical Medicine ◽

10.3390/jcm9051542 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1542

Author(s):

Jee Hyun Kong ◽

Elliott F. Winton ◽

Leonard T. Heffner ◽

Manila Gaddh ◽

Brittany Hill ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Myeloid Leukemia ◽

Kinase Inhibitors ◽

Chronic Phase ◽

Molecular Response ◽

Line Treatment ◽

First Line ◽

Blastic Phase

We sought to evaluate the outcomes of chronic phase (CP) chronic myeloid leukemia (CML) in an era where five tyrosine kinase inhibitors (TKIs) are commercially available for the treatment of CML. Records of patients diagnosed with CP CML, treated with TKIs and referred to our center were reviewed. Between January 2005 and April 2016, 206 patients were followed for a median of 48.8 (1.4–190.1) months. A total of 76 (37%) patients received one TKI, 73 (35%) received two TKIs and 57 (28%) were exposed to >3 TKIs (3 TKIs, n = 33; 4 TKIs, n = 17; 5 TKIs, n = 7). Nineteen (9.2%) patients progressed to advanced phases of CML (accelerated phase, n = 6; myeloid blastic phase, n = 4; lymphoid blastic phase, n = 9). One third (n = 69) achieved complete molecular response (CMR) at first-line treatment. An additional 55 patients achieved CMR after second-line treatment. Twenty-five patients (12.1%) attempted TKI discontinuation and 14 (6.8%) stopped TKIs for a median of 6.3 months (range 1–53.4). The 10-year progression-free survival and overall survival (OS) rates were 81% and 87%, respectively. OS after 10-years, based on TKI exposure, was 100% (1 TKI), 82% (2 TKIs), 87% (3 TKIs), 75% (4 TKIs) and 55% (5 TKIs). The best OS was observed in patients tolerating and responding to first line TKI, but multiple TKIs led patients to gain treatment-free remission.

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Prediction of Response to Imatinib by Prospective Quantitation of BCR-ABL Transcript in Late Chronic Phase Chronic Myeloid Leukemia PatientsBy GIMEMA Working Party on CML.

Blood ◽

10.1182/blood.v104.11.4672.4672 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4672-4672

Author(s):

Giovanni Martinelli ◽

Gianantonio Rosti ◽

Fabrizio Pane ◽

Marilina Amabile ◽

Simona Bassi ◽

...

Keyword(s):

Bone Marrow ◽

Chronic Myeloid Leukemia ◽

Peripheral Blood ◽

Myeloid Leukemia ◽

Chronic Phase ◽

Working Party ◽

Progression Free Survival ◽

Prediction Of Response ◽

Free Survival ◽

Blood Samples

Abstract Imatinib mesylate (STI571), a specific Bcr-Abl inhibitor, has shown a potent antileukemic activity in clinical studies of chronic myeloid leukemia (CML) patients. Early prediction of response to imatinib cannot be anticipated. We used a standardized quantitative reverse-transcriptase polymerase chain reaction (QRT-PCR) for bcr-abl transcripts on 191 out of 200 late-chronic phase CML patients enrolled in a phase II clinical trial with imatinib 400 mg/day. Bone marrow samples were collected before treatment, after 3, 6 and 12 months or at the end of study treatment (12 months) while peripheral blood samples were obtained after 2, 3, 6, 10, 14, 20 and 52 weeks of therapy. The amount of Bcr-Abl transcript was expressed as the ratio of Bcr-Abl to β2-microglobulin (β2M). We show that, following initiation of imatinib, the early Bcr-Abl level trends in both bone marrow and peripheral blood samples made it possible to predict the subsequent cytogenetic outcome after 6 and 12 months of treatment, and that these early trends were also predictive of progression-free survival.

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Clinical Significance of Deeper Molecular Responses with Four Modalities of Tyrosine Kinase Inhibitors As Frontline Therapy for Chronic Myeloid Leukemia

Blood ◽

10.1182/blood.v120.21.164.164 ◽

2012 ◽

Vol 120 (21) ◽

pp. 164-164 ◽

Cited By ~ 3

Author(s):

Lorenzo Falchi ◽

Hagop M. Kantarjian ◽

Alfonso Quintas-Cardama ◽

Susan O'Brien ◽

Elias J. Jabbour ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Clinical Significance ◽

Myeloid Leukemia ◽

Research Funding ◽

Kinase Inhibitors ◽

Chronic Phase ◽

Cytogenetic Response ◽

Initial Therapy ◽

Molecular Responses ◽

Free Survival

Abstract Abstract 164 Background: The achievement of a major molecular remission (MMR) after imatinib therapy in pts with chronic myeloid leukemia (CML) in chronic phase (CP) predicts for decreased risk of events, but has little impact in overall survival (OS) among patients with complete cytogenetic response (CCyR). Deeper molecular responses (MR), including undetectable transcripts, are frequently sought in patients with CML treated with tyrosine kinase inhibitors (TKI), but the prognostic significance of these responses is not known. Objectives: To determine the long-term clinical significance of achieving deeper level of MR achieved after therapy with TKI for CML in CP. Methods: Pts were included in clinical trials for initial therapy for CML with one of the following modalities: imatinib 400mg/day (IM400), imatinib 800mg/day (IM800), nilotinib (NILO) and dasatinib (DASA). We defined the level of MR as MMR, MR4, MR4.5 and undetectable transcripts (UND), corresponding to an ABL/BCR-ABL ratio (International Scale) of ≤0.1%, ≤0.01%, ≤0.0032%, and undetectable transcripts (minimum sensitivity 4.5-log), respectively. Results: A total of 495 pts were treated: 83 pts with IM400, 204 with IM800, 106 with NILO and 102 with DASA. At presentation leukocyte counts were higher in the NILO group (41.5 vs 22.2, 27.5 and 27×109/L for IM400, IM800 and DASA pts). All other patient characteristics were equally distributed across the 4 treatment groups. After a median follow-up of 73 months (2 to 142), complete cytogenetic response (CCyR) was achieved in 88%. CCyR rates for IM400, IM800, NILO and DASA pts were 82%, 88%, 90% and 90%, respectively. Best level of MR for the entire population was: <MMR in 17% of pts, MMR in 13%, MR4 in 5%, MR4.5 in 19%, UND in 44%. In IM400 pts MR was <MMR in 28% of pts, MMR in 10%, MR4 in 8%, MR4.5 in 14%, UND in 40%. In IM800 pts MR was <MMR in 14% of pts, MMR in 8%, MR4 in 5%, MR4.5 in 19%, UND in 54%. In NILO pts MR was <MMR in 18% of pts, MMR in 20%, MR4 in 7%, MR4.5 in 22%, UND in 33%. In DASA pts MR was <MMR in 18% of pts, MMR in 18%, MR4 in 7%, MR4.5 in 23%, UND in 39%. There was a trend for earlier achievement of MR with NILO: median times to MMR, MR4, MR4.5 and UND were 12, 17.4, 17.9 and 25.1 months, respectively, for IM400 pts; 5.8, 8.7, 11.8 and 23.7 months, respectively, for IM800 pts; 5.7, 7, 8.3 and 16.4 months, respectively, for NILO pts; 5.7, 8.8, 17.4 and 27.2 months, respectively, for DASA pts. To analyze the relationship between the degree of MR and clinical outcome we excluded pts not achieving a CCyR as their best response since the clinical significance of CCyR is well known. For the remaining 438 pts, the depth of molecular remission was inversely correlated with the risk of losing CCyR (19%, 16%, 11%, 7%, 2% in pts with <MMR, MMR, MR4, MR4.5 and UND, respectively) or losing MMR (31%, 42%, 24%, 2%, respectively), as well as the risk of events (22%, 20%, 15%, 12%, 3%, respectively), transformation (3%, 5%, 0%, 1%, 0%, respectively), or death (25%, 11%, 8%, 6%, 4%, respectively). The 6-year OS for pts with <MMR, MMR, MR4, MR4.5 and UND is 74%, 84%, 95%, 96% and 99%, respectively (p<.0001); transformation-free survival (TFS) is 95%, 93%, 100%, 99% and 100%, respectively (p<.014); event-free survival (EFS) is 74%, 74%, 86%, 89% and 99%, respectively (p<.0001). To adjust for the lead-time to achieve deeper responses, we then calculated OS, TFS and EFS rates at 6 years according to the depth of molecular response at 18 or 24 months. Results are summarized in table 1. Conclusion: Most patients treated with TKI as initial therapy for early CP CML achieve a MR during the course of treatment. BCR-ABL transcripts become undetectable in a significant fraction of them. Achieving a MMR or better at 18 months or 24 months is associated with significantly superior 6-years OS, TFS and EFS. These result suggest that deeper molecular responses (MMR and beyond) are associated with clinical benefit, with a particularly good outcome for those achieving undetectable transcript levels. Disclosures: Off Label Use: Imatinib, dasatinib and nilotinib frontline for chronic phase chronic myeloid leukemia on clinical trial. Kantarjian:Bristol-Myers Squibb: Research Funding; Ariad: Research Funding; Pfizer: Research Funding; Novartis: Research Funding. Jabbour:Pfizer: Honoraria; Novartis: Honoraria; Bristol-Myers Squibb: Honoraria. Ravandi:Bristol-Myers-Squibb: Research Funding. Cortes:Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding.

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Efficacy Of Different Therapeutic Approaches In Blastic Phase Of Chronic Myeloid Leukemia: Single Centre Experience

Blood ◽

10.1182/blood.v122.21.5173.5173 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5173-5173

Author(s):

Elza Lomaia ◽

Ekaterina Romanova ◽

Larisa Girshova ◽

Yulia Alexeeva ◽

Eugenia Sbityakova ◽

...

Keyword(s):

Overall Survival ◽

Chronic Myeloid Leukemia ◽

Median Time ◽

Myeloid Leukemia ◽

Kinase Inhibitors ◽

Chronic Phase ◽

Molecular Response ◽

Line Therapy ◽

Advanced Phase ◽

Blastic Phase

Abstract Dramatic changes in overall survival of patients (pts) with chronic myeloid leukemia (CML) in chronic phase (CP) have occurred since tyrosine kinase inhibitors (TKIs) were implemented in the treatment strategy. But there are still many issues in therapy of advanced phase disease, especially in blastic phase (BP). Allogeneic stem cell transplantation (alloSCT) is still the only curative option for CML BP, so all efforts should be focused on bringing pts to alloSCT. Thus optimal approach to obtain at least stable hematologic response before alloSCT is needed. Since 2008, 14 pts (4 more pts with isolated extramedullary BP were not included) with CML BP were admitted to our clinic. These were 8 males and 6 females with a median age of 44 years (range; 21-63) at the time of BP. The types of BP were: biphenotypic (n=1), undifferentiated (n=1), myeloid (n=8) and lymphoid (n=4). All pts except 2 (1 with BP and 1 with accelerated phase) were initially diagnosed as CP. Median time from diagnosis to BP was 37 months (range; 0-83). Before BP all pts except 2 were pretreated with imatinib and 6 of them, after failing imatinib, received one or more new TKIs. First line therapy in BP was monotherapy with new TKI (n=5) or chemotherapy (“7+3”, “RACOP”, low doses of Ara-C, “Hyper-CVAD”, “Dexa+VCR”) with or w/o TKI (n=9). Responses are specified in table 1. FLAG regimen was subsequently given to 5 pts as second or more line therapy after failure of previous monoTKI (n=1) or Rx + TKI (n=4). Median time from BP to FLAG was 3,5 months (range; 1,5-21). The best response to FLAG therapy was complete hematologic (n=1), complete cytogenetic with (n=1) or w/o (n=1) major molecular response. There were no responses in 2 cases. All responders maintain their response after median follow up (FU) of 2 months (range; 1,5-5). All patients treated with FLAG are alive (2 after alloSCT, 3 pending alloSCT). Only 1 ptn reached alloSCT w/o any Rx after monoTKI. AlloSCT was successful in 4/5. Median FU time for patients alive after alloSCT is 12 months (range; 3,5-25). For whole group after a median FU of 14 months, 7/14 (50%) pts are alive, including 4 pts after alloSCT. Estimated 3-year overall survival for all pts is 54% (fig. 1). Conclusion All CML BP patients treated with TKIs alone lost their response in a short time. Responses were much more durable in pts treated with Rx +/- TKIs. FLAG regimen was effective even in pts with failure to previous Rx+TKIs. The majority of pts after alloSCT are alive. Chemotherapy, including FLAG with concomitant or subsequent TKIs, had advantage over monoTKI both in overall and progression free survival in CML BP. Disclosures: Lomaia: Novartis: Honoraria, Travel grants Other; Bristol-Myers Squibb: Honoraria, Travel grants, Travel grants Other. Zaritskey:University of Heidelberg: Research Funding.

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BCR-ABL1 Transcript Levels at 3 and 6 Months Are Better for Identifying Chronic Myeloid Leukemia Patients with Poor Outcome in Response to Second-Line Second-Generation Tyrosine Kinase Inhibitors after Imatinib Failure: A Report from a Single Institution

Acta Haematologica ◽

10.1159/000430835 ◽

2015 ◽

Vol 134 (4) ◽

pp. 248-254 ◽

Cited By ~ 4

Author(s):

Beatriz Felicio Ribeiro ◽

Bruna Rocha Vergílio ◽

Eliana Cristina Martins Miranda ◽

Maria Helena Almeida ◽

Marcia Torresan Delamain ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Kinase Inhibitors ◽

Chronic Phase ◽

Second Line ◽

Second Line Therapy ◽

Free Survival ◽

Transcript Levels ◽

Real Time Quantitative Pcr ◽

Better Than

Early reduction of BCR-ABL1 transcript levels has been associated with improved outcome in chronic myeloid leukemia (CML) treatment. We evaluated 54 chronic-phase CML patients treated with imatinib who switched therapy to dasatinib (n = 33) or nilotinib (n = 21). BCR-ABL1 transcript levels were measured in peripheral blood using real-time quantitative PCR (RQ-PCR) every 3 months from the start of second-line treatment. Patients with BCR-ABL transcript levels >10% at 3 months and >1% at 6 months had significantly inferior progression-free (PFS) and event-free survival (EFS) than patients with RQ-PCR <10% at 3 months and <1% at 6 months (66 vs. 100%, p = 0.01, and 33 vs. 73%, p = 0.02, respectively). Patients with RQ-PCR <10% at 3 months and >1% at 6 months also had inferior PFS and EFS than patients with RQ-PCR <10% at 3 months and <1% at 6 months (48 vs. 100%, p = 0.002, and 25 vs. 73%, p < 0.0001, respectively). Two measurements of BCR-ABL levels were better than a single one to stratify chronic-phase CML patients as failure after second-line therapy.

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EUTOS score is not predictive for survival and outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors: a single institution experience

Blood ◽

10.1182/blood-2011-10-388967 ◽

2012 ◽

Vol 119 (19) ◽

pp. 4524-4526 ◽

Cited By ~ 41

Author(s):

Elias Jabbour ◽

Jorge Cortes ◽

Aziz Nazha ◽

Susan O'Brien ◽

Alfonso Quintas-Cardama ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Myeloid Leukemia ◽

Kinase Inhibitors ◽

Chronic Phase ◽

Molecular Response ◽

Major Molecular Response ◽

Free Survival ◽

Eutos Score

Abstract To validate the recently reported European Treatment and Outcomes Study (EUTOS) score, we applied it to 465 patients with early chronic phase chronic myeloid leukemia treated with standard-dose imatinib (n = 71), high-dose imatinib (n = 208), or second-generation tyrosine kinase inhibitors (n = 186), and assessed its ability to predict event-free survival (EFS), transformation-free survival (TFS), and overall survival (OS). The median follow-up was 69 months. The overall complete cytogenetic response and major molecular response rates were 92% and 85%, respectively. The 3-year EFS, TFS, and OS rates were 86%, 95%, and 97%, respectively. Of the 465 patients, 427 (92%) were in low EUTOS score category. There was no difference in the major molecular response, TFS, EFS, and OS rates between patients with low and high EUTOS score, overall and within specific therapies. In conclusion, 8% of patients with chronic phase chronic myeloid leukemia treated at our institution are in the high EUTOS score; in this population, the EUTOS score was not predictive for outcome.

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EVI-1 oncogene expression predicts survival in chronic-phase CML patients resistant to imatinib treated with second-generation tyrosine kinase inhibitors

Blood ◽

10.1182/blood-2010-01-264234 ◽

2010 ◽

Vol 116 (26) ◽

pp. 6014-6017 ◽

Cited By ~ 20

Author(s):

Mustafa Daghistani ◽

David Marin ◽

Jamshid Sorouri Khorashad ◽

Lihui Wang ◽

Philippa C. May ◽

...

Keyword(s):

Overall Survival ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Myeloid Leukemia ◽

Second Generation ◽

Kinase Inhibitors ◽

Chronic Phase ◽

Progression Free Survival ◽

Event Free Survival ◽

Free Survival

Abstract Activation of the EVI-1 oncogene has been reported in acute myeloid leukemia, chronic myeloid leukemia (CML) in blast crisis, and less commonly, in chronic-phase CML patients. We screened an unselected cohort of 75 chronic-phase CML patients who had failed imatinib for expression of EVI-1 and sought a correlation with subsequent outcome on the second-generation tyrosine kinase inhibitors dasatinib (n = 61) or nilotinib (n = 14). The 8 patients (10.7%) who expressed EVI-1 transcripts detectable by real-time polymerase chain reaction had significantly lower event-free survival, progression-free survival, and overall survival than patients with undetectable transcript. The predictive value of EVI-1 expression was validated in an independent cohort. In a multivariate analysis, EVI-1 expression status and the best cytogenetic response obtained on imatinib were the only independent predictors for overall survival, progression-free survival, and event-free survival. Our data suggest that screening for EVI-1 expression at the time of imatinib failure may predict for response to second-line TKI therapy and consequently aid clinical management.

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