Chronic myeloid leukemia and interferon-α: a study of complete cytogenetic responders

Blood ◽  
2001 ◽  
Vol 98 (10) ◽  
pp. 3074-3081 ◽  
Author(s):  
Francesca Bonifazi ◽  
Antonio de Vivo ◽  
Gianantonio Rosti ◽  
François Guilhot ◽  
Joëlle Guilhot ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Collaborative Study ◽  
Chronic Phase ◽  
Low Risk ◽  
Interferon Α ◽  
Term Survival ◽  
High Risk Patients ◽  
Risk Patients

Abstract Achieving a complete cytogenetic response (CCgR) is a major target in the treatment of chronic myeloid leukemia (CML) with interferon-α (IFN-α), but CCgRs are rare. The mean CCgR rate is 13%, in a range of 5% to 33%. A collaborative study of 9 European Union countries has led to the collection of data on 317 patients who were first seen between 1983 and 1997 and achieved CCgRs with IFN-α alone or in combination with hydroxyurea. The median time to first CCgR was 19 months (95% CI, 17-21; range, 3-84 months). At last contact, 212 patients were still alive and in continuous CCgR; 105 patients had lost CCgR, but 53% of them were still alive and in chronic phase. IFN-α treatment was discontinued permanently in 23 cases for response loss, in 36 cases for chronic toxicity (15 are still in unmaintained continuous CCgR), and in 8 cases because it was believed that treatment was no longer necessary (7 of these 8 patients are still in unmaintained continuous CCgR). The 10-year survival rate from first CCgR is 72% (95% CI, 62%-82%) and is related to the risk profile. High-risk patients lost CCgR more frequently and more rapidly and none survived more than 10 years. Low-risk patients survived much longer (10-year survival probability 89% for Sokal low risk and 81% for Euro low risk). These data point out that a substantial long-term survival in CCgRs is restricted mainly to low-risk and possibly intermediate-risk patients and occurs significantly less often in high-risk patients.

Changes in the dynamics of the excess mortality rate in chronic phase-chronic myeloid leukemia over 1990-2007: a population study

Blood ◽  
2011 ◽  
Vol 118 (16) ◽  
pp. 4331-4337 ◽  
Author(s):  
Selim Corm ◽  
Laurent Roche ◽  
Jean-Baptiste Micol ◽  
Valérie Coiteux ◽  
Nadine Bossard ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Myeloid Leukemia ◽  
Mortality Rate ◽  
Myeloid Leukemia ◽  
Excess Mortality ◽  
Chronic Phase ◽  
Relative Survival ◽  
High Risk Patients ◽  
Risk Patients ◽  
Sokal Score

Abstract Imatinib has transformed the prognosis and the management of chronic myeloid leukemia (CML) and has probably changed the patterns of mortality rates. We explored this change at each disease severity level (Sokal score) through a flexible statistical modeling of the effect of the year of diagnosis on the excess mortality rate. The study included 691 chronic-phase patients from Nord-Pas-de-Calais French CML registry diagnosed from 1990 to 2007. Imatinib was given to 93% of the patients diagnosed after 2000. Comparing the 1990-1994, 1995-1999, and 2000-2007 periods of diagnosis, the 5-year relative survival improved from 64% to 66% and 88%. The year of diagnosis was associated with a significant reduction of the excess mortality, but only in patients with intermediate to high Sokal scores. In high-risk patients diagnosed in the early 1990s, a peak of excess mortality was observed during the second year of follow-up. That peak decreased progressively over the years of diagnosis until disappearing in patients diagnosed after 2000. This study showed different effects according to Sokal scores of the use of imatinib on mortality in patients with chronic-phase CML and showed that since 2000 the pattern of mortality of high-risk patients became similar to that of intermediate-risk ones.

Long-Term Follow-Up of the Italian Trial of Interferon- Versus Conventional Chemotherapy in Chronic Myeloid Leukemia

Blood ◽  
1998 ◽  
Vol 92 (5) ◽  
pp. 1541-1548 ◽  
Author(s):  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Low Risk ◽  
Long Term Effects ◽  
Conventional Chemotherapy ◽  
Risk Patients ◽  
Cytogenetic Remission ◽  
Ifn Treatment

Abstract Several prospective randomized studies have shown that the treatment of chronic myeloid leukemia with interferon- (IFN-) prolongs the survival by comparison with conventional chemotherapy. However, although IFN- can induce cytogenetic responses, true complete remissions are rarely achieved and information on the long-term effects of IFN- treatment is limited. For that purpose, we updated and analyzed a prospective comparative trial of IFN- and conventional chemotherapy that was initiated in 1986. The first analysis of the trial was already published, and showed a survival advantage for IFN- (N Engl J Med 12:820, 1994). The observation period of living patients now ranges between 95 and 129 months and we examined the long-term effects of IFN- treatment, always by comparison with conventional chemotherapy and according to the intention-to-treat principle. The patients who were submitted to allogeneic bone marrow transplantation (BMT) in chronic phase (38 of 322 or 12%) were censored at the date of BMT. Seventy-three of the original 284 nontransplanted patients were alive, 56 (30%) in the IFN- arm and 17 (18%) in the chemotherapy arm. Forty-one patients overall (14%) were still receiving IFN-. In the IFN- arm 9 patients were in continuous complete cytogenetic remission and 11 were in major or minor cytogenetic remission. Median and 10-year survival of low-risk patients were 104 months (95% CI, 85 to 127 months) and 47% (95% CI, 36% to 59%) in IFN- arm versus 64 months (95% CI, 49 to 98 months) and 30% (95% CI, 16% to 44%) in chemotherapy arm (P = .03). Median and ten-year survival of non–low-risk patients were 69 months (95% CI, 56 to 76 months) and 16% (95% CI, 8% to 24%) in IFN- arm versus 46 months (95% CI, 39 to 61 months) and 5% (95% CI, 0% to 11%) in chemotherapy arm (P = .006). A low Sokal’s risk, hematologic response, and cytogenetic response were associated with a longer survival. No major or unusual side effects were recorded after the 5th year of IFN- treatment. Fourteen patients died in chronic phase, 9 (4%) in IFN- arm and 5 (5%) in chemotherapy arm, mainly of cardiovascular accidents (6 cases) and of other cancers (5 cases). We conclude that a policy of chronic treatment with IFN- maintained a significant survival advantage over conventional chemotherapy on a long-term basis and irrespective of the risk. However, the great majority of the long-term survivors were in the low-risk group. The question of treatment discontinuation was not addressed in this study. © 1998 by The American Society of Hematology.

The Rate of Individual BCR-ABL Decline As an Optimized Predictor of Tyrosine Kinase Inhibitors Treatment Outcome in Chronic Phase CML Patients, Comparison with CML Prognostic Scores and Early Molecular Response Achievement

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5150-5150 ◽  
Author(s):  
Mikhail Fominykh ◽  
Vasily Shuvaev ◽  
Irina Martynkevich ◽  
Grigory Tsaur ◽  
Natalya Bederak ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Phase ◽  
Low Risk ◽  
Prognostic Scores ◽  
Fisher Exact Test ◽  
Molecular Response ◽  
Optimal Response ◽  
High Risk Patients ◽  
Risk Patients ◽  
Sensitivity Specificity

Abstract Background. About 70% of chronic myeloid leukemia (CML) patients achieve early molecular response (BCR-ABLIS2 10% at 3-months) that lead to 5-years overall survival close to 95%. However, CML patients remain heterogeneous group and several studies in recent years were aimed to personalize treatment based on individual patients' characteristics. Our group previously put forward a hypothesis about the prognostic value of individual BCR-ABL declinerate in the first three months of CML therapy1,2. The ratio BCR-ABL at 3 months to baseline had chosen as 0.1 as best cut-off value to predict MMR at 12 months. The aims of this study were to validate our prognostic method in larger group of patients and compare these results according to CML prognostic scores. Patients and methods. Fifty-five patients (median age, 52 years; range 19-84; 24 male and 31 female) with chronic phase CML were included in the study. Patients' distribution for Sokal risk groups were as follows: low-30 / intermediate-15 / high-10. Six patients had EUTOS high-risk. Forty-two patients started treatment with Imatinib 400 mg/day, 12 patients started with Nilotinib 600 mg/day and 1 patient started with Dasatinib 100 mg/day. Median BCR-ABL transcript levels was 41.38% at diagnosis, range 3.39-3185.36% (IS). The ratio of BCR-ABL levels at 3 months to baseline for each patient was calculated. In addition, we calculated ratio of BCR-ABL levels at 3 months to BCR-ABL levels at 1 month for 13 patients. Comparison was made of the predictive sensitivity to achieve early molecular response at 3 months (10% by IS) and according to prognostic CML scores (Sokal and EUTOS). We also assessed positive likelihood ratio (LR) value for the probability of achieving MMR between patients' stratification methods. Statistical analysis was conducted with Fisher exact test and sensitivity-specificity analyses. Results. Twenty-six out of 34 patients (76.5%) with ratio of BCR-ABL levels at 3 months to baseline below than 0.1 achieved MMR at 12 months, while only 9 of 21 patients (42.9%) with ratio more than 0.1 had optimal response (LR = 1.86 (1.05 - 3.29); p=0.003). Ratio of BCR-ABL levels at 3 months to 1 month showed much better results with the same (0.1) cut-off value - 5 out of 6 patients (83.3%) with ratio BCR-ABL at 3 months to 1 month below than 0.1, while only 1 patient (14.3%) with ratio more than 0.1 achieved optimal response (LR = 5.83 (0.92 - 37.08); p=0.05), respectively. Application of early molecular response at 3 months (10% by IS) yielded worse discrimination results: 34 of 47 (72.3%) patients with BCR-ABL level ²10% at 3 months, whereas 2 of 8 (25%) patients with BCR-ABL >10% had MMR at 1 year (LR = 1.38 (1.01 - 1.89); p=0.78), respectively. CML prognostic scores results had the following sensitivity-specificity results: for Sokal - low-risk 23 of 30 (76.7%), intermediate-risk 9 of 15 (60%) and 3 of 10 (30%) high-risk patients achieved MMR at 1 year (LR (low+intermediate)/high = 1.41 (1.00 - 1.97); p=0.03); for EUTOS-score - low-risk 34 of 49 (69.4%) and only 1 of 6 (16.7%) high-risk patients had achieved MMR at 12 months (LR = 1.30 (1.00 - 1.68); p=0.02). Furthermore, application of our ratio cut-off value among patients with BCR-ABL level ²10% at 3 months allowed us to revealed additional 6 high-risk patients have not reached MMR at 1 year of therapy (Table 1). Conclusion. Our study showed that individual rates of BCR-ABL decline from baseline to 3 months and to 1 month had better LR than CML prognostic scores (Sokal, EUTOS) or early molecular response achievement (BCR-ABL levels ²10% at 3 months) and might be useful as an optimized predictors of outcome for CML patients (MMR at 1 year of treatment). 1 Fominykh M., ShuvaevV., Martynkevich I. et al. ELN Frontiers Meeting ÇWhere science meets clinical practiceÈ 16-19 October, 2014, Berlin, Germany. Abstract book: 11. 2 Shuvaev V., Fominykh M., Martynkevich I. et al. Blood (56th ASH Annual Meeting Abstracts), 2014; 124 (21): 5529. Figure 1. The patient numbers of achieving MMR at 12 months of therapy in various stratification groups with sensitivity-specificity characteristics Figure 1. The patient numbers of achieving MMR at 12 months of therapy in various stratification groups with sensitivity-specificity characteristics Disclosures Chelysheva: Novartis Pharma: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria. Turkina:Bristol Myers Squibb: Consultancy; Pfizer: Consultancy; Novartis Pharma: Consultancy.

Long-Term Follow-Up of the Italian Trial of Interferon- Versus Conventional Chemotherapy in Chronic Myeloid Leukemia

Blood ◽  
1998 ◽  
Vol 92 (5) ◽  
pp. 1541-1548 ◽  
Author(s):  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Low Risk ◽  
Long Term Effects ◽  
Conventional Chemotherapy ◽  
Risk Patients ◽  
Cytogenetic Remission ◽  
Ifn Treatment

Several prospective randomized studies have shown that the treatment of chronic myeloid leukemia with interferon- (IFN-) prolongs the survival by comparison with conventional chemotherapy. However, although IFN- can induce cytogenetic responses, true complete remissions are rarely achieved and information on the long-term effects of IFN- treatment is limited. For that purpose, we updated and analyzed a prospective comparative trial of IFN- and conventional chemotherapy that was initiated in 1986. The first analysis of the trial was already published, and showed a survival advantage for IFN- (N Engl J Med 12:820, 1994). The observation period of living patients now ranges between 95 and 129 months and we examined the long-term effects of IFN- treatment, always by comparison with conventional chemotherapy and according to the intention-to-treat principle. The patients who were submitted to allogeneic bone marrow transplantation (BMT) in chronic phase (38 of 322 or 12%) were censored at the date of BMT. Seventy-three of the original 284 nontransplanted patients were alive, 56 (30%) in the IFN- arm and 17 (18%) in the chemotherapy arm. Forty-one patients overall (14%) were still receiving IFN-. In the IFN- arm 9 patients were in continuous complete cytogenetic remission and 11 were in major or minor cytogenetic remission. Median and 10-year survival of low-risk patients were 104 months (95% CI, 85 to 127 months) and 47% (95% CI, 36% to 59%) in IFN- arm versus 64 months (95% CI, 49 to 98 months) and 30% (95% CI, 16% to 44%) in chemotherapy arm (P = .03). Median and ten-year survival of non–low-risk patients were 69 months (95% CI, 56 to 76 months) and 16% (95% CI, 8% to 24%) in IFN- arm versus 46 months (95% CI, 39 to 61 months) and 5% (95% CI, 0% to 11%) in chemotherapy arm (P = .006). A low Sokal’s risk, hematologic response, and cytogenetic response were associated with a longer survival. No major or unusual side effects were recorded after the 5th year of IFN- treatment. Fourteen patients died in chronic phase, 9 (4%) in IFN- arm and 5 (5%) in chemotherapy arm, mainly of cardiovascular accidents (6 cases) and of other cancers (5 cases). We conclude that a policy of chronic treatment with IFN- maintained a significant survival advantage over conventional chemotherapy on a long-term basis and irrespective of the risk. However, the great majority of the long-term survivors were in the low-risk group. The question of treatment discontinuation was not addressed in this study. © 1998 by The American Society of Hematology.

Should Hematopoietic Stem Cell Transplantation in First Complete Remission Be Restricted to High-Risk Patients in Childhood Acute Myeloid Leukemia?.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1094-1094
Author(s):  
Hideki Muramatsu ◽  
Nobuhiro Nishio ◽  
Asahito Hama ◽  
Hiroshi Yagasaki ◽  
Yoshiyuki Takahashi ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Chromosomal Abnormalities ◽  
Low Risk ◽  
Hematopoietic Stem ◽  
High Risk Patients ◽  
Risk Patients ◽  
Group A ◽  
Group B ◽  
First Complete Remission

Abstract Hematopoietic stem cell transplantation (HSCT) has been used as an effective consolidation therapy for children with acute myeloid leukemia (AML) in first complete remission (CR). Although it is effective in relapse prevention, often it causes severe late sequelae, such as short stature and infertility. There is a recent trend to restrict the use of HSCT in first CR for high-risk patients. However, there is no study comparing which strategy is better, risk-adapted or general recommendation for HSCT in AML children in first CR. In our institutes, all such children in first CR were recommended either allogeneic or autologous HSCT until 1997. After 1998, patients were classified into three risk-groups. Low-risk patients (t(8;21) and inv(16)) were not recommended to undergo HSCT. High-risk patients (−7, 5q-, Ph1, t(16;21) and remission failure) were recommended to undergo HSCT. Intermediate-risk (other karyotypes) patients received HSCT in first CR if a suitable donor was available. In this study, we retrospectively compared the prognosis of 66 patients who were diagnosed with de novo AML between 1991 and 1997 (group A; n=37) and between 1998 and 2003 (group B; n=29). AML with Down syndrome and AML-M3 were excluded. The median (range) age was five (0–15) years. FAB classifications were M0 (n = 1), M1 (n = 10), M2 (n = 22), M4 (n = 6), M4E (n = 5), M5 (n = 14), M6 (n = 0), and M7 (n = 8). Chromosome analysis data were t(8;21) (n = 18), inv(16) (n = 4), 11q23 (n = 10), other abnormalities (n = 14), normal karyotype (n = 14), and unknown (n = 6). Induction chemotherapy comprised VP-16, cytarabine, and mitoxantrone. Sixty-three of 66 patients (95.5%) achieved CR. HSCT in first CR was done in 24 patients (64.9%) in group A and seven patients (24.1%) in group B (p = 0.0044). Age, sex, WBC count at diagnosis, FAB classification and chromosomal abnormalities did not differ between the two groups. Fourteen (five in group A and nine in group B) patients relapsed. Six (three in group A and three in group B) of them were salvaged by HSCT. Both 5-year event-free survival (EFS) and overall survival (OS) were statistically higher in group A than in group B (5-year EFS: 83.8 ± 6.1% versus 62.1 ± 9.0%, p = 0.0404; 5-year OS: 91.6 ± 4.7% versus 71.6 ± 8.5%, p = 0.0364). Although intensified chemotherapy without HSCT for low-risk AML patients is desirable to avoid the late complications of HSCT, our analysis showed that the introduction of risk-stratified treatment strategy significantly worsened the chances of EFS and OS. Our risk stratification based on chromosomal abnormalities only may be insufficient to identify low-risk AML children. Development of more sophisticated risk classification, including molecular markers, may be required to identify true low-risk patients who should avoid HSCT in first CR.

Genetic biomarkers identify a subgroup of high-risk patients within low-risk NPM1-mutated acute myeloid leukemia

2020 ◽  
pp. 1-12
Author(s):  
Diego Carbonell ◽  
Julia Suárez-González ◽  
María Chicano ◽  
Cristina Andrés-Zayas ◽  
Miriam Díez-Díez ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Low Risk ◽  
High Risk Patients ◽  
Genetic Biomarkers ◽  
Risk Patients ◽  
Acute Myeloid

The EUTOS Survival Score Is Preferable over the Sokal Score for Prognosis of Long-Term Survival of Patients with Chronic Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 595-595 ◽  
Author(s):  
Markus Pfirrmann ◽  
Joerg Hasford ◽  
Susanne Saussele ◽  
Anna Turkina ◽  
Witold Prejzner ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Risk Group ◽  
Chronic Phase ◽  
Low Risk ◽  
Term Survival ◽  
Survival Score ◽  
Risk Patients ◽  
Sokal Score

Abstract Introduction: The in-study and out-study sections of the European Treatment and Outcome Study (EUTOS) registry comprise data on imatinib-treated adult patients with chronic myeloid leukemia (CML) who were prospectively enrolled in clinical studies or registries between 2002 and 2006. All patients diagnosed with chronic-phase Philadelphia chromosome-positive CML were eligible for analysis. The new EUTOS long-term survival (ELTS) score was developed in 2,205 in-study patients (Blood 2014; 124(21):153). Its purpose is the discrimination of three risk groups with clinically significantly different probabilities of dying from CML. The score was validated in 1,120 out-study patients. Aims: Up to now, many investigators still apply the Sokal score for the prognostic discrimination of CML-patients treated with tyrosine kinase inhibitors (TKIs). The Sokal score allocated more than 20% of chronic-phase patients to the high-risk group while it was 12% with the new ELTS score. Long-term outcome with tyrosine kinase inhibitors (TKIs) suggests that the allocation of more than 20% chronic-phase CML patients into a high-risk group is too pessimistic. The focus of this analysis was the comparison of risk group allocations and prognosis between the two scores. Methods: Survival time was calculated from the date of start of treatment to death or to the latest follow-up date. Survival was censored at the time of allogeneic stem cell transplantation in first chronic phase. Cumulative incidence probabilities (CIPs) of dying of CML were compared with the Gray test and overall survival probabilities with the log-rank test. As "death due to CML", only death after confirmed disease progression was regarded. Progression was defined in accordance with the recommendations of the ELN (Baccarani et al, Blood 2013). Level of significance was 0.05. Results: Both registries combined, the 3,325 patients had a median observation time of 6.1 years. Six-year overall survival probability was 91% (95% confidence interval (CI): 89-92%). Death was due to CML in 142 of 309 deceased patients (46%).The 6-year CIP of dying of CML was 4% (CI: 4-5%). From low to high risk groups, the Sokal score resulted in 6-year CIPs of 3% (n=1358 (41%), CI: 2-4%), 4% (n=1209 (36%), CI: 3-5%), and 8% (n=758 (23%), CI: 6-11%) and the ELTS score in 6-year CIPs of 2% (n=2030 (61%), CI: 2-3%), 6% (n=898 (27%), CI: 4-7%), and 13% (n=397 (12%), CI: 10-17%). Of the 758 patients allocated to high risk by the Sokal score, the ELTS score classified 165 (22%) as low risk and 265 (35%) as intermediate risk. Compared to the 328 high-risk patients (43%) according to both scores (6-year CIP of dying: 13%, CI: 9-17%), the CIPs of dying were significantly lower for the 165 low-risk patients (p=0.0062, 6-year CIP: 5%, CI: 2-9%) and for the 265 intermediate-risk patients (p=0.0050, 6-year CIP: 5%, CI: 3-9%). These 430 Sokal high but ELTS non-high-risk patients (6-year OS: 89%. CI: 86-92%) showed significantly higher OS probabilities than the 328 Sokal and ELTS high-risk patients (p=0.030, 6-year OS: 81%. CI: 76-85%). Of the 2030 patients identified as low risk by the ELTS score, the Sokal score allocated 603 (30%) to the intermediate- and 165 (8%) to the high-risk group. Without significant CIP differences to the latter group, at 6 years, the CIP of dying was 2% (CI: 1-3%) in the 1262 low-risk and also 2% in the 603 intermediate-risk patients (CI: 1-3%). The OS probabilities of the 768 non-low-risk patients according to the Sokal score (6-year OS: 93%. CI: 91-95%) were not significantly different from the 1262 classified as low-risk by both scores (6-year OS: 95%. CI: 93-96%). Conclusions: To be able to perform comparisons between the various prognostic groups suggested by the Sokal and the EUTOS survival score with a reasonable power, data of in- and out-study samples were combined. The Sokal score allocated an absolute difference of 12% (n=430) more patients to the high-risk groups than the EUTOS survival score. As these patients had significantly and clinically relevantly lower CIPs and higher OS probabilities, the allocation of the Sokal score was not appropriate. Contrarily, the long-term outcome of 768 patients assessed as low-risk by the ELTS and non-low-risk by the Sokal score was not different from the outcome of 1262 assesses as low-risk patients by both scores. For prognosis of long-term survival outcome, the use of the EUTOS survival score is recommended. Disclosures Pfirrmann: BMS: Consultancy, Honoraria; Novartis Pharma: Consultancy, Honoraria. Hasford:Novartis: Research Funding. Saussele:Novartis Pharma: Honoraria, Other: Travel grant, Research Funding; BMS: Honoraria, Other: Travel grant, Research Funding; ARIAD: Honoraria; Pfizer: Honoraria, Other: Travel grant. Turkina:Bristol Myers Squibb: Consultancy; Pfizer: Consultancy; Novartis Pharma: Consultancy. Prejzner:Novartis Pharma: Honoraria; BMS: Honoraria. Steegmann:Novartis Pharma: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Simonsson:Novartis Pharma: Research Funding. Zaritskey:University of Heidelberg: Research Funding; Novartis: Consultancy. Zackova:Novartis Pharma: Consultancy; Bristol Myers Squibb: Consultancy. Janssen:Novartis: Research Funding; Pfizer: Consultancy; Bristol Myers Squibb: Consultancy; ARIAD: Consultancy. Cervantes:Novartis: Consultancy, Speakers Bureau; Sanofi-Aventis: Consultancy; CTI-Baxter: Consultancy, Speakers Bureau. Hehlmann:Novartis Pharma: Research Funding; BMS: Consultancy. Baccarani:Novartis: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Speakers Bureau.

CML: Der Weg zur optimalen Therapieselektion

2020 ◽  
Vol 7 (4) ◽  
pp. 206-207
Author(s):  
Susanne Saußele
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Chronic Phase ◽  
Prognostic Scores ◽  
Term Survival ◽  
Long Term Survival ◽  
High Risk Patients ◽  
Risk Patients ◽  
Sokal Score

Prognostic scores support clinicians in selecting risk-adjusted treatments and in comparatively assessing different results. For patients with chronic-phase chronic myeloid leukemia (CML), four baseline prognostic scores are commonly used. Our aim was to compare the prognostic performance of the scores and to arrive at an evidence-based score recommendation. In 2949 patients not involved in any score development, higher hazard ratios and concordance indices in any comparison demonstrated the best discrimination of long-term survival with the ELTS score. In a second step, of 5154 patients analyzed to investigate risk group classification differences, 23% (n = 1197) were allocated to high-risk by the Sokal score. Of the 1197 Sokal high-risk patients, 56% were non-high-risk according to the ELTS score and had a significantly more favorable long-term survival prognosis than the 526 high-risk patients according to both scores. The Sokal score identified too many patients as high-risk and relatively few (40%) as low-risk (versus 60% with the ELTS score). Inappropriate risk classification jeopardizes optimal treatment selection. The ELTS score outperformed the Sokal score, the Euro, and the EUTOS score regarding risk group discrimination. The recent recommendation of the European LeukemiaNet for preferred use of the ELTS score was supported with significant statistical evidence.

scholarly journals Comparing the Prognostic Significance of Early Predictors of Survival in Chronic Myeloid Leukemia (CML) Treated with Imatinib - an Analysis of the Randomized CML-Study IV

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 156-156
Author(s):  
Benjamin Hanfstein ◽  
Michael Lauseker ◽  
Rüdiger Hehlmann ◽  
Susanne Saussele ◽  
Philipp Erben ◽  
...  
Keyword(s):  
High Risk ◽  
Chronic Myeloid Leukemia ◽  
Treatment Failure ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Treatment Intervention ◽  
High Risk Patients ◽  
Log Reduction ◽  
Risk Patients ◽  
Equity Ownership

Abstract Introduction: Early prediction of outcome using response-related predictive landmarks has become a major paradigm in the clinical management of chronic myeloid leukemia (CML). Several studies have shown the predictive impact of 10% BCR-ABLIS at 3 and 6 months for different tyrosine kinase inhibitors. The question, which landmark should define treatment failure and determine treatment intervention has been discussed vividly. However, an objective analysis of quality criteria for different early prognostic landmarks is lacking up to now. Here we compare sensitivity, specificity and the proportion of later disease progressions predicted by 3-month and 6-month landmarks in imatinib-treated patients of the CML-study IV. Methods: A total of 1,303 newly diagnosed patients were assigned to an imatinib-based treatment arm of CML-Study IV by April 2010. Median follow-up was 7.1 years. The number of molecular assessments was as follows: n=789 (at 6 months), n=692 (at 3 months) and n=301 (at 3 months and at diagnosis, without pretreatment). Gene expression levels were determined by quantitative RT-PCR. At 3 and 6 months, a BCR-ABL ratio was calculated using ABL as reference gene and standardized according to the international scale (BCR-ABLIS). In addition, at 3 months and at diagnosis a BCR-ABL ratio was calculated using beta-glucuronidase (GUS) as reference gene in order to ensure linearity of measurement at diagnosis. The log reduction at 3 months was calculated from the BCR-ABL ratio at 3 months and at diagnosis. Due to the time-dependent nature of censored survival data, the sensitivity and specificity at eight years were calculated using the method by Heagerty et al. (Biometrics 2000). Overall survival (OS) is defined by the absence of death from any reason, progression-free survival (PFS) is defined as survival in the absence of progression to accelerated or blastic phase. Landmark analyses were performed to compare survival outcomes according to Kaplan-Meier. Results:Comparing the 10% BCR-ABLIS landmark at 3 and 6 months, 8-year OS and PFS rates are equal or comparable (table). In contrast, sensitivity and specificity differ substantially with an advantage in favor of sensitivity for the 3-month landmark and in favor of specificity for the 6-month landmark. This difference is paralleled by a smaller proportion of high-risk patients and less progressions identified by the 6-month landmark. From a clinical point of view the 6-month landmark is not only less than half as sensitive, moreover a treatment intervention at 6 months might also prevent less progressions due to the delay of 3 months. The half-log reduction landmark at 3 months is as sensitive as 10% BCR-ABLIS at the same time. However, it shows improved specificity and defines the smallest proportion of high-risk patients. Conclusion: The 10% BCR-ABLIS landmark, which is currently defining treatment failure at 6 months according to European LeukemiaNet (ELN) criteria, fails to detect the majority of patients with later disease progression. Less than a half-log reduction of individual baseline BCR-ABL transcript levels at 3 months on treatment identifies patients with later progressions as sensitive but with higher specificity as compared to 10% BCR-ABLIS. Abstract 156. Table Prognostic landmark 8-year OS (%) 8-year PFS (%) P-value for PFS Sensitivity to predict progression (%) Specificity to predict progression (%) High-risk patients Disease progressions classified as high-risk / total 3 months (n=692) 10% BCR-ABLIS 88 vs. 96 82 vs. 90 0.001 41.1 74.6 191 (28%) 32/74 (43%) 6 months (n=789) 10% BCR-ABLIS 88 vs. 96 84 vs. 95 0.001 18.2 93.8 95 (12%) 17/74 (23%) 1% BCR-ABLIS 90 vs. 97 89 vs. 97 <0.001 39.6 68.6 291 (37%) 46/74 (62%) 3 months (n=301) 0.5-log reduction 81 vs. 95 75 vs. 94 <0.001 42.6 86.9 48 (16%) 10/24 (42%) Disclosures Hanfstein: Novartis: Research Funding; Bristol-Myers Squibb: Honoraria. Hehlmann:Novartis: Research Funding; Bristol-Myers Squibb: Research Funding. Saussele:Novartis: Honoraria, Research Funding, Travel Other; Bristol-Myers Squibb: Honoraria, Research Funding, Travel, Travel Other; Pfizer: Honoraria, Travel, Travel Other. Schnittger:MLL Munich Leukemia Laboratory: Equity Ownership. Neubauer:MedUpdate: Honoraria, Speakers Bureau. Kneba:Novartis: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Pfirrmann:Novartis: Consultancy; Bristol-Myers Squibb: Honoraria. Hochhaus:Novartis: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; ARIAD: Honoraria, Research Funding; Pfizer: Consultancy, Research Funding. Müller:Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; ARIAD: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding.

scholarly journals Evaluation of the Disease Risk Index on Outcomes Following Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2529-2529
Author(s):  
Fotios V. Michelis ◽  
Hans A. Messner ◽  
Jieun Uhm ◽  
Naheed Alam ◽  
David Loach ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Disease Risk ◽  
Risk Index ◽  
Low Risk ◽  
High Risk Patients ◽  
Risk Patients ◽  
Acute Myeloid

Abstract Allogeneic hematopoietic cell transplantation (HCT) is a curative treatment option when indicated for myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The Disease Risk Index (DRI, Armand et al, 2012) has been developed to predict overall survival and progression-free survival on the basis of differences in relapse risk. The purpose of this single-center study was to retrospectively investigate the prognostic value of the DRI on the outcome of 470 patients that underwent HCT for AML and MDS between 2000 and 2013. AML patients (n=381) underwent HCT in first and second complete remission and MDS patients (n=89) underwent HCT untreated or in remission. Median age at HCT was 51 (range 18-71), 219 (47%) patients were female. Myeloablative conditioning (MAC) was used in 304 (65%) patients, reduced-intensity (RIC) in 166 (35%) patients. Donors were related for 287 (61%) patients, unrelated for 183 (39%) patients. Grafts were peripheral blood stem cells (PBSC) in 377 (80%) patients and bone marrow in 93 (20%) patients. Median follow-up of patients alive was 44 months (range 1-134). In accordance with the DRI criteria, all 470 patients were in the low risk group concerning disease stage. Concerning disease biology characterized by cytogenetic risk, 11 patients were low risk, 396 patients were intermediate risk and 63 patients high risk. Based on the DRI overall risk stratification, 11, 396 and 63 patients were low, intermediate and high risk respectively. Univariate analysis demonstrated that the DRI was significantly prognostic for overall survival (OS) with a 3-year OS of 82%, 48% and 29% for low, intermediate and high risk patients respectively (p=0.005, Figure A). For cumulative incidence of relapse (CIR), DRI was again prognostic with 3-year CIR 0%, 21% and 30% for low, intermediate and high risk patients respectively (p<0.0001, Figure B). For non-relapse mortality (NRM), DRI did not demonstrate significant prognostic relevance with 3-year NRM 18%, 32% and 43% for low, intermediate and high risk patients respectively (p=0.14). Multivariable analysis for OS confirmed the prognostic significance of the DRI with hazard ratio (HR) 3.3 and 4.9 for intermediate and high risk respectively compared to low risk (p=0.01). For CIR, DRI was highly significant (p<0.0001) while for NRM, the DRI was not predictive (p=0.22). This study confirms the prognostic relevance of the DRI for OS and CIR in our cohort of patients undergoing HCT for AML and MDS. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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