EUTOS Score Is Predictive of Event-Free Survival, but Not for Progression-Free and Overall Survival in Patients with Early Chronic Phase Chronic Myeloid Leukemia Treated with Imatinib: A Single Institution Experience

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1681-1681 ◽  
Author(s):  
Katia B. Pagnano ◽  
Irene Lorand-Metze ◽  
Eliana C M Miranda ◽  
Vagner O Duarte ◽  
Marcia T Delamain ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Low Risk ◽  
Event Free Survival ◽  
Free Survival ◽  
Sokal Score ◽  
Eutos Score

Abstract Abstract 1681 Recently the European LeukemiaNet has developed a new scoring system (European Treatment and Outcome Study [EUTOS] score) for newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP) treated with imatinib. The EUTOS score classifies patients in high or low risk on the basis of the percentage of basophils in the peripheral blood and the spleen size at diagnosis, with significant correlations with the achievement of an 18-month complete cytogenetic response (CCyR) and progression-free survival (PFS). The aim of this work was to evaluate EUTOS score in CML-CP treated in our center with imatinib as a predictive factor for overall survival (OS), event-free survival (EFS) and PFS. Patients and methods: Between February 2003 and May 2012 consecutive patients with newly diagnosed CML-CP were treated with imatinib 400 mg daily (n= 144) or imatinib 600–800 mg daily (n= 14) were included in the analysis. The criteria recommended by European LeukemiaNet (ELN) were used for the definitions of CCyR and the progression to accelerated phase (AP) or blast phase (BP). The EUTOS score was defined by (7×basophils) plus (4×spleen size) at diagnostic. A EUTOS score of more than 87 indicates high risk, and less than or equal to 87 low risk. EFS was measured from the start of imatinib treatment to the date of any of the following events: death from any cause at any time, loss of complete hematologic response, loss of CCyR, or progression to AP or BP. PFS was measured from the start of treatment to the date progression to AP or BP, last follow-up, or death from any cause. Survival probabilities were estimated by the Kaplan-Meier method and compared by the log-rank test whereas it was applied cumulative incidence for the probability to achieve CCyR. Results: A total of 158 patients were treated, 94 (59.5%) male. The median age at Imatinib was 47 years (17–86 years). The median time from diagnosis to TKI therapy was 2 (0–6) months, with 153 (96.8%) receiving previous treatment with Hydrea. The median follow-up was 29 (1–110) months. The median splenomegaly size was 4 (0–29) cm and the median basophil percentage was 2.5% (0–18%). According to the Sokal score, 43 (34,4%) patients, 46 (36,8%), and 36 (28,8%) were in low, intermediate, and high Sokal score category, respectively (33 not available). Concerning the Hasford score, 60 (48,3%), 50 (40,4%) and 14 (11,3%) were in low, intermediate and high risk categories (34 NA). A total of 137 (86,8%) patients were in the low EUTOS score category and 21 (13,2%) in the high risk category. The cumulative probability of achieving a CCyR and MMR at 36 months for all patients was 78% and 64%, respectively. Patients who had not achieved CCyR after 6 months (51/153 – 33%) had a 2% risk of subsequent progression, which increased to 12% after 12 months, 14% in 18 months and 19% after 24 months. EFS, PFS, and OS rates for the whole group were 60%, 89%, and 92%, respectively. Patients with a low EUTOS score had higher rates of cumulative CCyR compared with patients with high EUTOS score (82% vs. 53%, p= 0.06) (figure 1). There were no differences in the cumulative CCyR rates in patients stratified by Sokal or Hasford scores (and 0.21 and P=0.82, respectively). Patients with CCyR at 18 months had a higher EFS (81% vs. 18%, p< 0.0001) and PFS rates (96% vs. 82%, p= 0.03). There was no difference in PFS (figure 2) and OS rates between patients with low and high EUTOS score. However, patients with high and intermediate Sokal score had an inferior PFS rates in comparison with low risk group (77%, 84% and 100%, respectively, p= 0.02). There was a superior EFS rates in low risk in comparison with high EUTOS score (63% vs. 36%, p= 0.01) (figure 3), whereas the overall survival there was no difference (91% vs. 100%). Sokal scores EFS rates were 68%, 60% and 40% for low, intermediate and high risk groups respectively (p= 0.03). In conclusion, similarly to the original report, EUTOS score seems to predict CCyR, but not PFS in our population. However, EFS was significantly better in the low than high risk group. The score can discriminate patients with poor outcome, with lower probability of achieving responses to first line imatinib therapy. Disclosures: No relevant conflicts of interest to declare.

Evaluation of the Imatinib Treatment of Patients with Chronic Myeloid Leukemia (CML). a Retrospective Study from Algerian Working Group on CML (GAT-LMC)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5454-5454
Author(s):  
K Djouadi ◽  
A Bouchakour ◽  
S Taoussi ◽  
MT Abad ◽  
Z Ouchenane ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Progression Free Survival ◽  
Molecular Response ◽  
Imatinib Treatment ◽  
Free Survival ◽  
Sokal Score ◽  
Eutos Score

Abstract Introduction: The advent of anti-tyrosine kinase has revolutionized the treatment of chronic myeloid leukemia. Indeed, from 2000, the IMATINIB has become internationally the gold standard of treatment for CML chronic phase, while the allogeneic bone marrow transplant was previously, the 1st intention choice, when an HLA-matched donor is available. The aim of this study is to evaluate the efficiency and the toxicity of a treatment with Imatinib(copy), drug used in Algeria to treat patients with a CML chronic phase. The main objective is to evaluate the overall survival and the progression-free survival to these patients. Materials and methods: This is a longitudinal study, National, multicenter, retrospective, which included Algerian patients with chronic phase CML and treated with Imatinib between January 2007 and December 2013. A technical form was established and distributed to different hematology services nationwide, to collect and analysis the following data: Patient's general characteristics, disease circumstances of discovery, clinical and para-clinical examinations at diagnosis (blood count, blood smear, bone marrow aspiration, karyotype, molecular biology, Sokal prognostic classification score and Eutos score). The treatment: Imatinib 400 mg / d, a therapeutic assessment is made according to the ELN recommendations adapted to our conditions and capabilities in Algeria: The complete hematologic response (CHR) at 03 months and molecular response and / or cytogenetic and / or Fish at 03, 06.12, 18.24 months and more according to capabilities. At 03mois and / or 6 months we search a bcr / abl rate <10%. At 12 months we research a major molecular response (MMR), defined by a bcr / abl ratio lower than 0, 1% according to the ELN. A ratio between 0.1 to 1% is considered a good response according to GAT-LMC (the CML study Algerian group) so the Imatinib treatment is continued. The median follow-up of patients in December 2014 is 48 months (12-84 months). Overall survival and progression-free survival are determined by using the Kaplan-Meier method. The descriptive analysis of the quantitative variables by calculating averages, medians and the qualitative variables, by using percentages and 95% confidence interval. The Chi2 test is used to compare between two variables. Results: From 1024 collated sheets, 1007 are assessable; the median age of patients was 45.7 years (06-87 years), it's about 516 men and 491 women with a sex ratio M / F 1.05. The Diagnosis of CML is done by cytogenetic examination in 337 patients (33%), by Fish 214 patients (21%) and by molecular biology in 401 patients (39%). The prognostic classification (PC), according to the Sokal score, found a low risk in 18.7%, 55.5% as intermediate and a high risk in 25.8%. The Eutos score is less than 87 in 97% and more than 87 in 03%. A CHR at 03mois was found in 907 patients (90.1%). There is no correlation between the RHC at 03 months and the SOKAL PC (p = 0.23), by cons we found a significant correlation with the Eutos score (p <10-3). Molecular assessment at 03 and 06 months is performed in 222 patients and a bcr / abl ratio <10% was found in 66.5%. A molecular evaluation at 12 months showed an MMR in 55.4%. Cytogenetic evaluation (FISH) has found a 28.6% CCyR at 3 months, 45% at 6 months, 64.2% at 12 months (IRIS = 68%), 75.7% at 18 months (IRIS = 76.2%) and 85% at 24 months. Overall survival was 84% at 08 years and it is significantly correlated to Sokal score (p <10-6). A failure to TRT was found in 11.5% of the cases and a 10, 1% relapse rate, related to non-adherence to TRT in 50% of the cases and a lack of monitoring by a regular molecular control in the other half of the cases. Event-free survival at 08 years was 76%. A good clinical and biological tolerance is noted in 90% of the cases. Only 8% of patients were switched to a 2nd generation TKIs because of intolerance. A non-adherence to TRT was found in 14.4%. Conclusion: Imatinib, used in Algeria, is a very interesting molecule both efficiency side and tolerance level. However, we must ensure a molecular monitoring for a patients optimal follow up, and an adequate patient education for a better adherence. Disclosures No relevant conflicts of interest to declare.

The EUTOS Score Is Highly Predictive for Clinical Outcome and Survival in Asian Patients with Early Chronic Phase Chronic Myeloid Leukemia Treated with Imatinib

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3758-3758 ◽  
Author(s):  
Hein Than ◽  
Lingyee Kuan ◽  
Chiu Hong Seow ◽  
Wenyun Li ◽  
John C Allen ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Risk Group ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
High Risk Group ◽  
Low Risk ◽  
Free Survival ◽  
Asian Patients ◽  
Eutos Score

Abstract Abstract 3758 Background: The EUTOS score has been proposed by the European LeukemiaNet (ELN) as a new scoring system which is predictive for 18-month (mth) complete cytogenetic response (CCyR) and 5-year (yr) progression-free survival (PFS) in chronic phase (CP) chronic myeloid leukemia (CML) patients treated with first-line imatinib (IM) (Hasford et al, Blood 2011). The score is calculated using spleen size and basophil percentage and divides patients into low risk and high risk groups. However the EUTOS score was not validated in two studies, one which determined 8-yr overall survival (OS), PFS, CCyR and major molecular remission (MMR) (Marin et al, J Clin Oncol 2011); and in another which analysed 3-yr event-free survival, transformation-free survival and OS and overall CCyR and MMR (Kantarjian H et al, Blood 2012). Recent reports have suggested that Asian CML patients may have clinical and genetic differences compared to Causcasians, e.g. younger median age at presentation (Au et al, Int J Hem 2009) and genetic polymorphism leading to IM resistance (Pan et al, Nat Med 2012). Although a different disease, splenomegaly was also reported to be less frequent in Chinese patients with myelofibrosis (Xiao et al, Blood 2012). Given these differences, we sought to determine if the EUTOS score was predictive for clinical outcome and survival in Asian CP-CML patients treated with IM. Methods: A retrospective analysis was undertaken of CP-CML patients followed up in our institution from 2000–2012. All patients were treated with IM 400 mg within one year of diagnosis. The rates of 6-mth major cytogenetic response (MCyR), 12-mth CCyR, 18-mth CCyR, 12-mth MMR and 18-mth MMR were evaluated. MMR was defined as BCR-ABL transcript levels ≤ 0.1% by the International Scale. The probability of OS, PFS and failure-free survival (FFS) at 5 and 8 years was also determined. Progression was defined as transformation to accelerated or blast phase (AP/BP) or death from any reason. Failure was defined according to the 2009 ELN criteria or as an increase in dose of IM, change of therapy, transformation to AP/BP or death. Results: A total of 139 patients were included in the analysis. The median age at presentation of CML was 45 yrs (range 16–88) with 64% Chinese, 17% Malays and 8% Indians. There was 69% in the low risk EUTOS group. Cytogenetic responses were significantly better in the low risk group compared to the high risk group with 6-mth MCyR rates of 82% vs 48% (p<0.001), 12-mth CCyR rates of 68% vs 39% (p=0.008) and 18-mth CCyR rates of 73% vs 36% (p=0.003). MMR rates were also higher in the low risk group at 12 mth (42% vs 14%, p=0.026) and at 18 mth (56% vs 21%, p=0.009). The probability of PFS was significantly higher in the low risk group compared to the high risk group at 5 yrs (93% vs 83%, p=0.032) and at 8 yrs (92% vs 70%, p=0.032). The low risk group also had a significantly higher FFS at 5 yrs (64% vs 20%, p<0.001) and at 8 yrs (61% vs 20%, p<0.001). (Figure 1) There was a trend towards a better overall survival in the low risk group at 5 and 8 yrs but this did not reach statistical significance (95% vs 92% and 94% vs 83% respectively, p=0.084). Conclusion: Our analysis confirms that the EUTOS score is a valid tool in predicting 18-mth CCyR and 5-yr PFS in Asian patients with early CP-CML treated with IM. In addition, we have shown that the EUTOS score was highly predictive for cytogenetic and molecular responses at earlier time points and long-term PFS and FFS. Disclosures: Chuah: Novartis, Bristol Myers-Squibb: Honoraria.

Real World Efficacy Evaluation of Branded and Copy Imatinib in Chronic Myeloid Leukemia: A Retrospective Multicentric Study from Argentina

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 36-37
Author(s):  
Ana Ines Varela ◽  
Georgina Bendek ◽  
Carolina Pavlovsky ◽  
Maria Josefina Freitas ◽  
Veronica Ventriglia ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Myeloid Leukemia ◽  
Molecular Response ◽  
Advisory Committees ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Kaplan Meier ◽  
Sokal Score

Background: Data on the safety and efficacy of copy drugs is usually unavailable. Imatinib mesylate is used to treat chronic myeloid leukemia (CML) patients in Argentina since 2002. During the last decade more than ten different imatinib copies are marketed by the different health-care systems in the country, usually for cost issues. In spite of the undoubted benefit of this tyrosine-kinase inhibitor indication in CML, there is no solid evidence that supports copy drug equivalent outcomes for this patient population. Aim: To compare the clinical presentation, treatment response and outcome of a chronic phase (CP) CML patient cohort treated with branded and copy imatinib in the real-life setting. Methods: Multicentric, retrospective trial based on data obtained from medical charts of adult CP CML patients treated with imatinib in 9 centers in Argentina from 2002 to 2020.We analyzed demographic characteristics and clinical characteristics described for branded and copy imatinib treated cohorts. Frequency of complete cytogenetic response (CCyR) at 12 months, Major molecular response or better(≥MMR) at 12, 18 and 24 months and overall MR4.0, MR4.5 and deep molecular response (MR4.0 +MR4.5 IS) were analyzed. Event was defined as failure, progression or CML related death. Kaplan Meier comparison of event free, progression free and overall survival. Statistics: IBM SPSS version 1. Results: A total of 568 CP CML adult patients (pt) treated with imatinib were included. Mean age at diagnosis: 45.7 years (range 18 - 85). Male 55.6% (316/568). Sokal Score was recorded in 471 pt: 57% (269/471) low, 26% (122/471) intermediate and 17% (80/471) high-risk. Median follow-up 107 months (RIQ: 36-149). Branded imatinib treatment 330 (58%) and imatinib copies 238 (42%). For branded and copy imatinib cohorts mean age 46,1 (18-85) and 45.3(18-80), male 53% (175/330) and 59% (141/238), median follow up 102 (RIQ 101-130) and 61 (RIQ 62-146) respectively. Sokal score low 58% (164/284) and 56% (105/187), intermediate 27% (77/284) and 24% (45/187) and high 15% (43/284) and19% (37/187). Frequency of CCyR at 12 months 71% (67/94) and 69% (41/59), ≥MMR at 12 months 57% (79/138) and 43% (39/89), ≥MMR 18m 66 % (61/92) and 71% (43/60), ≥MMR 24m 65% (96/147) and 79% (58/73). Overall MR4, MR 4.5 and Deep MR with branded imatinib 62.4% (186/298), 42% (118/276) and 63% (189/300), compared to 45(97/214), 24% (50/207) and 46% (99/215) with copies. Difference in evaluation throughout the treatment periods with loss of data did not allow response rate statistical comparison in predetermined timepoints. Kaplan Meier Event free survival median 229 months vs 75 months p 0.001, Progression free survival mean 318 months vs 208 pt 0.034 and Overall Survival mean 275 months vs 206 months for branded and copy imatinib respectively. Discussion: Several case reports have shown poor outcomes in patients treated with imatinib copy drugs, including loss of responses previously attained with branded imatinib. This study reports data from a large cohort of CP CML patients treated in daily practice during a long period of time. Treatment results at determined timepoints is comparable. Although management and treatment decisions were performed in different time periods, results show different outcomes in EFS and PFS between patients treated with branded vs copy imatinib. Overall survival in both cohorts is comparable. As studies assesing the safety and efficacy of the copy drugs compared with branded imatinib will hardly be performed this evidence calls for careful attention and strict follow up measures when managing CML patients with copy imatinib. Figure Disclosures Varela: Novartis: Consultancy, Speakers Bureau. Pavlovsky:Pint Pharma: Speakers Bureau; Pfizer: Speakers Bureau; BMS: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Freitas:Pfizer: Consultancy, Other: Advisory Board. Pavlovsky:Varifarma: Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel grants, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau. Moiraghi:Novartis: Speakers Bureau; BMS: Speakers Bureau.

scholarly journals Plasma imatinib levels and ABCB1 polymorphism influences early molecular response and failure-free survival in newly diagnosed chronic phase CML patients

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Bharathi M. Rajamani ◽  
Esther Sathya Bama Benjamin ◽  
Aby Abraham ◽  
Sukanya Ganesan ◽  
Kavitha M. Lakshmi ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Target Genes ◽  
Chronic Phase ◽  
Predictive Biomarkers ◽  
Imatinib Therapy ◽  
Molecular Response ◽  
Event Free Survival ◽  
Free Survival ◽  
Dosing Algorithm ◽  
Sokal Score

AbstractAchieving early molecular response (EMR) has been shown to be associated with better event free survival in patients with chronic phase chronic myeloid leukemia (CP-CML) on Imatinib therapy. We prospectively evaluated the factors influencing the 2-year failure free survival (FFS) and EMR to imatinib therapy in these patients including day29 plasma Imatinib levels, genetic variants and the gene expression of target genes in imatinib transport and biotransformation. Patients with low and intermediate Sokal score had better 2-year FFS compared to those with high Sokal Score (p = 0.02). Patients carrying ABCB1-C1236T variants had high day29 plasma imatinib levels (P = 0.005), increased EMR at 3 months (P = 0.044) and a better 2 year FFS (P = 0.003) when compared to those with wild type genotype. This translates to patients with lower ABCB1 mRNA expression having a significantly higher intracellular imatinib levels (P = 0.029). Higher day29 plasma imatinib levels was found to be strongly associated with patients achieving EMR at 3 months (P = 0.022), MMR at 12 months (P = 0.041) which essentially resulted in better 2-year FFS (p = 0.05). Also, patients who achieved EMR at 3 months, 6 months and MMR at 12 months had better FFS when compared to those who did not. This study suggests the incorporation of these variables in to the imatinib dosing algorithm as predictive biomarkers of response to Imatinib therapy.

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

Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 6014-6017 ◽  
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.

scholarly journals Comparative analysis of the Sokal, Euro and European Treatment and Outcome Study score in prognostication of Indian chronic myeloid leukemia-chronic phase patients on imatinib

2018 ◽  
Vol 07 (04) ◽  
pp. 258-262 ◽  
Author(s):  
Sunita Chhikara ◽  
Sudha Sazawal ◽  
Kanwaljeet Singh ◽  
Rekha Chaubey ◽  
Haraprasad Pati ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Prognostic Score ◽  
Chronic Phase ◽  
Risk Scores ◽  
Outcome Study ◽  
Appropriate Treatment ◽  
Sokal Score ◽  
Eutos Score

Abstract Introduction: The ultimate goal for CML management is risk stratification of the patients to design the appropriate treatment approach. The Sokal, Euro and EUTOS risk scores were established to prognosticate the patients on therapy. Aim: To perform a comparative assessment of the Sokal, Euro and EUTOS prognostic score in Indian CML-CP patients on imatinib. Methods: This is a retrospective study performed in 260 Ph+ CML-CP patients who were administered oral imatinib (400 mg/day). Results: 166/260 were males and 94/260 were females (M: F::1.6:1) with median age 35 years (range 20-70). 92 (35.38%), 125 (48.07%) and 43 (16.5%) patients were divided into low, intermediate and high risk Sokal score respectively. 102 (39.23%), 106 (40.76%) and 52 (20%) patients were discriminated into low, intermediate and high risk Euro score respectively. 210 (80.7%) and 50 (19.2%) patients were divided into low and high risk EUTOS score. Cumulative incidence of MMR for low, intermediate and high-risk Sokal score was 87%, 76% and 84% respectively (P = 0.016). Incidence of MMR in low, intermediate and high-risk Euro score was 93%, 85% and 68% respectively (P = 0.001). Incidence of MMR was 80 % and 81% for low and high risk EUTOS score (P = 0.764). Both EFS and OS are significantly correlated with Sokal score (P = 0.004, P = 0.007) and Euro score (P = 0.009, P = 0.001) but not with EUTOS score (P = 0.581, P = 0.927). Conclusion: The present study highlights the significant prognostic role of Sokal and Euro score in predicting the treatment outcome of the CML- CP patients on imatinib.

scholarly journals The Impact of EUTOS Long-Term Survival (ELTS) Score on Predicting Progression and Survival Among Turkish Patients with Chronic Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4600-4600
Author(s):  
Mert Bektaş ◽  
Tuğrul Elverdi ◽  
Ayşe Salihoğlu ◽  
Muhlis Cem Ar ◽  
Şeniz Öngören ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Roc Analysis ◽  
Risk Groups ◽  
Low Risk ◽  
Term Survival ◽  
Hazard Ratios ◽  
Sokal Score

Abstract Introduction and Objectives: For patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP), four baseline prognostic scores are commonly used including the Sokal score and the most recently introduced EUTOS long-term survival (ELTS) score. The ELTS score was shown to be superior to the Sokal score for predicting survival. The aim of the study is to evaluate the value of ELTS score on predicting disease progression and survival in Turkish pts with CML-CP. Material and Method: Demographic, laboratory and clinical features, disease responses to tyrosine kinase inhibitor (TKI) therapy and survival of CML-CP pts, who received upfront imatinib (IM) between 2003 and 2018 were analyzed retrospectively. Treatment responses were reevaluated according to European LeukemiaNet 2013 recommendations. Risk groups analysis, discrimination and hazard ratios (HRs) were evaluated with Cox regression and Kaplan-Meier survival analysis. Receiver operating characteristic (ROC) analysis was performed to examine the effects of scores on predicting overall survival (OS) and progression-free survival (PFS). Results: A total of 185 pts were included, of which 103 (55.7%) were male and median age was 47 years (range, 16 - 81 years) (Table 1). The percentages of pts with low-, intermediate-, and high-risk ELTS scores were 60.5%, 25.9%, and 13.5%, respectively. For the Sokal score, these percentages were 37.3%, 40.5%, and 22.2% respectively. For Sokal high-risk pts, only 46.3% were classified as high-risk according to the ELTS score. Similarly, 44% of pts with intermediate Sokal risk had low-risk ELTS score (Fig. 1). Seventy-seven pts (41.6%) had at least one comorbidity, and the most common comorbidities were hypertension (21.6%), diabetes mellitus (13%), and ischemic heart disease (12.4%) (Table 1). The median durations of IM therapy and follow-up were 2728 (range, 14 - 6320 days) and 3473 (range, 71 - 6320 days) days, respectively. Complete hematologic and early molecular (BCR-ABL1 IS &lt;10% at 3 months) responses at 3 months were 95.6% and 75.9%, respectively. Complete cytogenetic and major molecular response rates at 6 and 12 months were 72.3% and 86.1% and 45.4% and 54%, respectively. Thirty-five pts (18.9%) switched to second-generation TKI therapy and 6 pts (3.2%) progressed to advanced-phase disease during the follow-up (Table 1). For PFS, with reference to the low-risk Sokal score, the HR of high-risk groups was 9.301 (95% CI: 1.086-79.656, p=0.042) (Fig. 2A). Similarly, with reference to the low-risk ELTS score, the HR of intermediate- and high-risk groups were 4.744 (95% CI: 0.43-52.314, p=0.204) and 14.642 (95% CI: 1.523-140.791, p=0.020) (Fig. 2B). Regarding OS, with reference to the low-risk Sokal score, the HR of the intermediate- and high-risk groups were 1.835 (95% CI: 0.564-5.964, p=0.313) and 6.412 (95% CI: 2.11-19.489, p=0.001), respectively (Fig. 2C). With reference to the low-risk ELTS score, the HR of the intermediate- and high-risk groups were, 3.263 (95% CI: 1.242-8.576, p=0.016) and 7.258 (95% CI: 2.762-19.074, p&lt;0.001) respectively (Fig. 2D). In the ROC analysis, the ELTS score was superior than the Sokal risk score for both predicting PFS (AUC=0.820 vs. AUC=0.818) and OS (AUC=0.762 vs. AUC=0.744). During the follow-up, 27 (14.6%) pts died, of which 6 died due to CML progression and causes of death were unrelated to CML in 21. Conclusion: In our study, we showed that the ELTS score could successfully predict high-risk pts compatible with the literature. With higher hazard ratios and better risk group stratifications, the ELTS score outperformed the Sokal score. The ELTS score can help clinicians to better discriminate poor prognostic pts and can promote optimal treatment strategies for these pts with potentially worse prognosis. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Long-Term Follow-up of Chronic Phase Chronic Myeloid Leukemia Patients Who Failed Interferon Alpha and Switched to Imatinib

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3742-3742
Author(s):  
Massimo Breccia ◽  
Giuseppina Loglisci ◽  
Adriano Salaroli ◽  
Alessandra Serrao ◽  
Irene Zacheo ◽  
...  
Keyword(s):  
Survival Rate ◽  
High Risk ◽  
Interferon Alpha ◽  
Low Risk ◽  
Long Term Outcome ◽  
Free Survival ◽  
Blastic Phase ◽  
Eutos Score

Abstract Abstract 3742 Few data were reported about the long-term outcome of patients treated with imatinib after interferon-alpha (IFN) failure. Recently, MDACC group reported a 10-year survival rate of 68%. We report here the outcome of 134 adult Ph+ CML patients who switched to imatinib after IFN failure. Response criteria used are in accordance to ELN guidelines; survival was calculated from start of imatinib until death for any cause, progression-free survival (PFS) was calculated from start of imatinib to advent of accelerated/blastic phase or death for any cause and event-free survival (EFS) was calculated from start of therapy to development of any event leading patient to discontinue the drug. There were 74 males and 60 females, median age was 47 years. Median follow-up was 96 months. Sokal score identified 66 patients as low risk, 49 patients as intermediate and 17 as high risk, whereas Eutos score identified 107 patients as low risk and 10 patients as high risk. Overall, 103 patients (76.8%) achieved a CCyR as their best cytogenetic response and 68 (51%) achieved a MMR, after a median time of 52 months. Complete molecular remission (CMR, undetectable transcript according to ELN recommendations) was achieved as the best response in 60 patients after a median follow-up of 76 months. The estimated 9-year overall survival rate was 74%, the PFS rate was 71% and the EFS was 54%. Progression to accelerated/blastic phase was detected in 19 patients. Due to resistance or intolerance to imatinib, 22 patients switched to dasatinib (12 patients for cytogenetic resistance, 5 patients for intolerance, 2 for molecular resistance and 3 for BC) and 17 patients switched to nilotinib (11 patients for cytogenetic resistance and 6 for molecular resistance): 18 patients (64%) achieved or maintained CCyR and 11 patients (35%) achieved MMR. Achieving at 12 months a CCyR or an MMR was associated with a significant better OS in the long-term (82%) as compared to less than PCyR (70%) or only CHR (12%). Baseline factors that correlated with a poor OS were clonal cytogenetic evolution, higher percentage of basophils and blast cells in peripheral blood, high Sokal and Eutos score, whereas age did not correlate with a worse OS. The results of our study support the validity of rescuing with imatinib patients failing IFN, with an estimated 9-year survival rate of 74% that is similar to that reported in other recent studies. Disclosures: No relevant conflicts of interest to declare.

Validation of the Low Risk Prognostic Scoring System (LR-PSS) in Patients with VERY Low, Low and Intermediate Risk IPSS-R Myelodysplastic Syndrome. Results from a Single Center

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2902-2902 ◽  
Author(s):  
Helena Pomares ◽  
Isabel Sánchez-Ortega ◽  
Esther Alonso ◽  
Javier Grau ◽  
Rafael F. Duarte ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Myeloid Leukemia ◽  
Low Risk ◽  
Prognostic Impact ◽  
Score System ◽  
Free Survival ◽  
Kaplan Meier ◽  
Acute Myeloid

Abstract Background: Myelodysplastic syndrome (MDS) therapeutic decisions have been traditionally based on the IPSS; however, this score system does not allow the identification of patients with low risk disease (low or intermediate-1 IPSS) but a poor prognosis, who could benefit from an early intervention. Garcia-Manero et al (Leukemia 2008) described a specific prognostic scoring system for this subgroup of patients (LR-PSS) based on age ≥60 years, hemoglobin <10g/dl, platelet count <50k/uL or 50-200k/uL, bone marrow blasts ≥4% and unfavorable cytogenetics (non-del(5q), non-diploid). This LR-PSS score system enables the stratification of low risk MDS patients into 3 different risk categories; interestingly, the third category identifies a subgroup of patients with a median overall survival (OS) similar to that of patients classified as intermediate-2 and high risk IPSS. Besides, the IPSS-R described by Greenberg et al (Blood 2012) has demonstrated a strong prognostic value for OS and LFS as compared to the IPSS when applied to different independent series of MDS patients. The prognostic impact of the LR-PSS has not been analyzed in MDS patients with very low-, low- and intermediate IPSS-R scores. Aim: To analyze the prognostic impact according to OS and leukemia free survival of the LR-PSS when applied to a population MDS patients with very low, low and intermediate IPSS-R. Methods: A total of 789 consecutive patients diagnosed with MDS (01/1992-12/2014) at the Catalan Institute of Oncology of Barcelona were included in the study. 413 (52%) had available cytogenetics and therefore, IPSS-R was calculated. Overall, 371 (89%) patients were classified as very low, low and intermediate IPSS-R and included in the study. Results: 123 (30%) patients were classified as very low, 182 (44%) low and 66 (16%) intermediated IPSS-R risk MDS; median age 72 years (range 32-101) and 258 (69%) male. 1.4 % CRDU, 7.6 % RA, 41.6 % RCMD, 16.2 % RAEB‐1, 4.1 % RAEB‐2, 25.9 % CMML and 3.2 % MDS‐U with isolated 5q deletion according to the 2008 WHO classification. At diagnosis, median hemoglobin, platelet and bone marrow blast were 11.8 g/dL (5.5-17.1), 152 x109/L (1-1492) and 3 % (0-17), respectively and fifty-three (14.3 %) patients had unfavorable LR-PSS cytogenetics. For the whole population, median follow up was 6.6 years (range 6-7.7). At the time of last follow up, 48.2 % (179) had died and only 49 (13%) had progressed to acute myeloid leukemia. When the LR-PSS was applied to the very low, low and intermediate IPSS-R subgroups three well-differentiated prognostic categories could be identified: 58 patients (15.6%) category 1, scores 0-2; 277 (74.6%) patients category 2, scores 3-4 and 36 (9.8%) patients category 3, scores 5-7 with significantly different overall survival and leukemia free survival. Median OS for categories 1 (9.4 years; 95% CI 6.7-12), 2 (6 years; 95% CI 5-7.1) and 3 (2.6 years; 95% CI 2.1-3) were significantly different (p<0.001; Figure 1). Moreover, the rate of progression to acute myeloid leukemia was 5% (3/58), 13% (37/277) and 25% (9/36) for categories 1, 2 and 3, respectively. Summary/Conclusion: When applied to a low risk (very low, low and intermediate) IPSS-R cohort of MDS population, the LR-PSS identifies a subgroup of patients with a significantly worse prognosis who could benefit from an early intervention. Further studies are warranted. Fig 1. Kaplan-Meier survival for patients with very low-, low- and intermediate IPSS-R risk assigned to categories 1 to 3 by LR-PSS. Fig 1. Kaplan-Meier survival for patients with very low-, low- and intermediate IPSS-R risk assigned to categories 1 to 3 by LR-PSS. Disclosures Sureda: Takeda: Consultancy, Speakers Bureau.

5 Year Experience in Chronic Phase-Chronic Myeloid Leukemia Treated with Imatinib Copy Drugs in a Peruvian Hospital

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4449-4449
Author(s):  
Aimee Torres ◽  
Juan Ramon Navarro ◽  
Jose Untama ◽  
Mariela Moreno ◽  
Sergio Murillo
Keyword(s):  
Overall Survival ◽  
Chronic Myeloid Leukemia ◽  
Median Time ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Progression Free Survival ◽  
Cytogenetic Response ◽  
Event Free Survival ◽  
Free Survival ◽  
Hasford Score

Abstract Abstract 4449 BACKGROUND AND OBJECTIVES: In our Hospital patients with Chronic Myeloid Leukemia (CML) in chronic phase (CP) were treated with imatinib (Glivec) 400 mg qd from june 2001 to june 2006. Since july 2006, only imatinib copy drugs (brand names: Zeite, Imatec, Imatib, Millatus and Celonib, all of Indian origin) are being used to treat this disease at the Rebagliati Hospital in Lima Peru. We present here the efficacy, security, event-free survival, progression free survival, overall survival of patients treated with imatinib copy drugs. METHODS Retrospective and descriptive analysis of CP-CML patients treated only with imatinib since july 2006. They all initiated the treatment with 400 mg qd. Five year experience is presented here. RESULTS We analyzed data from 51 patients (pts) with CP-CML. Median age at diagnosis was 45.1 years (15–90), 49% female and 51% male, all patients were Chromosome Philadelphia positive. Low, Intermediate and High Hasford Score were 32%, 48% and 20%, respectively. Median time from diagnosis to start of imatinib was 7.6 months (0–123). Five patients (9.8%) began treatment more than six months after diagnosis. All patients had at least a 3 month cytogenetic monitoring. Thirty five (68.6%) and 39 patients (76.4%) achieved Complete Cytogenetic Response (CCyR) and Mayor Cytogenetic Response (MCyR), respectively. Median time to CCyR was 7.6 months and 71.4% of these patients achieved it during the first six months of treatment. CCyR and MCyR were 38% and 67% at 3 months, 57% and 70% at 6 months, 63% and 83% at 12 monhts, 78% and 91% at 18 months, respectively. Quantitative RT-PCR was performed in 22 patients with CCyR and 18 pts (81.8%) had Mayor Molecular Response (MMR) in five years of follow up. Four pts (7.8%) progressed to Blastic Phase and all of them had Low Hasford Risk at diagnosis. Eight pts (15.6%) changed to 2nd line treatment. Two pts (3.9%) abandoned treatment. Only 1 pt (1.9%) had both anemias 3–4. Eighteen pts (35.2%) had neutropenia-3, 8 pts (15.6%) had neutropenia-4, 7 pts (13.7%) had thrombocytopenia-3 and 4 pts (7.8%) had thrombocytopenia-4. Neutropenias 3–4 were managed with filgrastim, as treatment and as prophylaxis. At 5 years, Event Free Survival (EFS), Progression Free Survival (PFS) and Overall Survival (OS) were 82%, 89% and 91%, respectively (Figure 1, 2 and 3). CONCLUSIONS In our hospital, CP-CML patients treated with imatinib copy drugs obtained important cytogenetic and molecular responses with prolonged EFS, PFS and OS and an acceptable safety profile. Hasford Score was not a good prognosis predictor. Treatment with Imatinib copy drugs has proven to be an acceptable treatment in CML patients in our hospital. Disclosures: Torres: Bristol Myers Squibb: Speakers Bureau.

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