scholarly journals High Levels of Wilms' Tumor Gene (wt1) mRNA in Acute Myeloid Leukemias Are Associated With a Worse Long-Term Outcome

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 1217-1225 ◽  
Author(s):  
Lothar Bergmann ◽  
Cornelius Miething ◽  
Ulrich Maurer ◽  
Jürgen Brieger ◽  
Tunca Karakas ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Wilms Tumor ◽  
Newly Diagnosed ◽  
Term Survival ◽  
Myeloid Leukemias ◽  
First Relapse ◽  
Tumor Gene ◽  
Acute Myeloid

Abstract The tumor suppressor gene wt1 (Wilms' tumor gene) encodes for a zinc finger DNA-binding protein with predominantly transcription repressing properties. Because wt1 has been shown to be expressed in the vast majority of patients with acute myeloid leukemias (AML), we investigated the relevance of wt-1 mRNA expression regarding prognosis and possible prediction of relapse during follow-up. Totally bone marrow-derived blasts of 139 AML patients (129 newly diagnosed AML patients, 22 AML patients again in first relapse, and 10 AML patients analyzed primarily in first relapse) were studied for wt1 mRNA expression. Seventy-seven patients were analyzed for wt1 mRNA expression during follow-up. wt1-specific reverse transcription-polymerase chain reaction (RT-PCR) was performed and the amplification product was visually classified as not, weakly, moderately, or strongly amplified, as described previously. PCR products were quantitated by competitive PCR using a shortened homologous wt1 construct standard in representative cases. The expression of wt1 transcripts was correlated to age, French-American-British (FAB) subtype, phenotype, karyotype, and long-term survival. wt1 mRNA was detectable in 124 of 161 (77%) samples at diagnosis and in first relapse. wt1 expression was independent from age, antecedent myelodysplastic syndrome or FAB subtype, with the exception of a significant difference in M5 leukemias showing wt1 transcripts in only 40% (P = .0025). There was no correlation between the level of wt1 mRNA and response to treatment or the prognostic groups defined by the karyotype. Concerning long-term survival, patients with high levels of wt1 had a significantly worse overall survival (OS) than those with not detectable or low levels. The 3-year OS for all newly diagnosed AMLs was 13% and 38% (P = .038), respectively, and 12% and 43% (P = .014) for de novo AMLs. The difference was more distinct in patients less than 60 years of age. During follow-up, all patients achieving complete remission became wt1 negative. Reoccurrence of wt1 transcripts predicted relapse. The data indicate that high expression of wt1 mRNA is associated with a worse long-term prognosis.

scholarly journals High Levels of Wilms' Tumor Gene (wt1) mRNA in Acute Myeloid Leukemias Are Associated With a Worse Long-Term Outcome

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 1217-1225 ◽  
Author(s):  
Lothar Bergmann ◽  
Cornelius Miething ◽  
Ulrich Maurer ◽  
Jürgen Brieger ◽  
Tunca Karakas ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Wilms Tumor ◽  
Newly Diagnosed ◽  
Term Survival ◽  
Myeloid Leukemias ◽  
First Relapse ◽  
Tumor Gene ◽  
Acute Myeloid

The tumor suppressor gene wt1 (Wilms' tumor gene) encodes for a zinc finger DNA-binding protein with predominantly transcription repressing properties. Because wt1 has been shown to be expressed in the vast majority of patients with acute myeloid leukemias (AML), we investigated the relevance of wt-1 mRNA expression regarding prognosis and possible prediction of relapse during follow-up. Totally bone marrow-derived blasts of 139 AML patients (129 newly diagnosed AML patients, 22 AML patients again in first relapse, and 10 AML patients analyzed primarily in first relapse) were studied for wt1 mRNA expression. Seventy-seven patients were analyzed for wt1 mRNA expression during follow-up. wt1-specific reverse transcription-polymerase chain reaction (RT-PCR) was performed and the amplification product was visually classified as not, weakly, moderately, or strongly amplified, as described previously. PCR products were quantitated by competitive PCR using a shortened homologous wt1 construct standard in representative cases. The expression of wt1 transcripts was correlated to age, French-American-British (FAB) subtype, phenotype, karyotype, and long-term survival. wt1 mRNA was detectable in 124 of 161 (77%) samples at diagnosis and in first relapse. wt1 expression was independent from age, antecedent myelodysplastic syndrome or FAB subtype, with the exception of a significant difference in M5 leukemias showing wt1 transcripts in only 40% (P = .0025). There was no correlation between the level of wt1 mRNA and response to treatment or the prognostic groups defined by the karyotype. Concerning long-term survival, patients with high levels of wt1 had a significantly worse overall survival (OS) than those with not detectable or low levels. The 3-year OS for all newly diagnosed AMLs was 13% and 38% (P = .038), respectively, and 12% and 43% (P = .014) for de novo AMLs. The difference was more distinct in patients less than 60 years of age. During follow-up, all patients achieving complete remission became wt1 negative. Reoccurrence of wt1 transcripts predicted relapse. The data indicate that high expression of wt1 mRNA is associated with a worse long-term prognosis.

Long-Term Follow-Up Confirms the Benefit of All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide (As2O3) as Front Line Therapy for Newly Diagnosed Acute Promyelocytic Leukemia (APL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 565-565 ◽  
Author(s):  
Yuan-Fang Liu ◽  
Yong-Mei Zhu ◽  
Zhan-Zhong Shi ◽  
Jun-Min Li ◽  
Li Wang ◽  
...  
Keyword(s):  
Remission Induction ◽  
Newly Diagnosed ◽  
Front Line ◽  
Current Group ◽  
Historical Cohort ◽  
Term Survival ◽  
Long Term Survival ◽  
Historical Group

Abstract PURPOSE: To further confirm the benifit of front-line use of all-trans retinoic acid (ATRA) combined with arsenic trioxide (As2O3) in patients with newly diagnosed acute promyelocytic leukemia (APL), we observed the long-term survival of the current group (median follow-up: 48 months) and compared it with our historical control. PATIENTS AND METHODS: There were two groups of patients with newly diagnosed APL enrolled in this analysis. The current cohort of patients includes 60 patients since April 2001. The historical cohort of patients included 56 patients from May 1998 to March 2001. No statistically significant differences were found between these two groups in terms of clinical characteristics including sex and age distribution or hematological data before treatment. For the current cohort of patients, all patients received 25mg/m2 ATRA orally and 0.16mg/kg As2O3 intravenously per day till CR. Once CR achieved, they were given 3 courses of consolidation chemotherapy and then 5 cycles of sequential treatment of ATRA, As2O3 and 6-MP/MTX. For the historical group, ATRA was given either 25mg/m2 daily till CR, chemotherapy was added in case of leukocytosis. The post-remission therapy consists of chemotherapy with or without ATRA. Quantitative real-time reverse transcription-polymerase chain reaction (RQ-RT-PCR) measurements of PML-RARa mRNA were retrospectively assessed before treatment, after CR, after consolidation, after maintenance and during follow-up period. The efficacy of these two protocol in terms of remission induction, molecular response and long-term survival were compared with our historical control. RESULT: In the current group, 56 (93.3%) patients achieved CR, and the median time to CR was 27 days. Compared with the historical group, the combined therapy induced an early hematological response. Till the last follow-up at April 2006, two patients underwent extramedullary relapse, one of them also relapsed in marrow thereafter, one patient died from CNS leukemia, and all the other patients were alive and remained in hematological remission. With a median follow-up of 48 months (25 to 60 months), the 4-year OS and EFS was estimated 98.1%±1.8% and 94.2%±3.3%. For the historical group, after a median follow-up of 56 months (12 to 79 months), the 4-year OS and EFS was estimated 83.4%±5.4% (P=0.012) and 45.6%±7.6% (P<0.00001). For the current group, PML-RARa normalized dose was more significantly decreased after remission induction and after consolidation as compared with the historical cohort. In the last follow-up, all of the available event-free patients of the current group remain in molecular remission (PML-RARa DoseN undetectable). CONCLUSION: These 4-year data of follow-up demonstated a benefit of front-line combination of ATRA and As2O3 regarding long-term survival (OS or EFS) of patients with newly diagnosed APL. With prolonged follow-up, we might be able to find a better chance of curing the disease.

Wilms Tumor Gene Expression in Acute Myeloid Leukemias

1997 ◽  
Vol 25 (5-6) ◽  
pp. 435-443 ◽  
Author(s):  
Lothar Bergmann ◽  
Ulrich Maurer ◽  
Eckhart Weidmann
Keyword(s):  
Gene Expression ◽  
Wilms Tumor ◽  
Wilms Tumor Gene ◽  
Myeloid Leukemias ◽  
Tumor Gene Expression ◽  
Tumor Gene ◽  
Acute Myeloid

scholarly journals Long-term survival after intensive chemotherapy or hypomethylating agents in AML patients aged 70 years and older: a large patient data set study from European registries

Leukemia ◽  
2021 ◽  
Author(s):  
Christian Récher ◽  
Christoph Röllig ◽  
Emilie Bérard ◽  
Sarah Bertoli ◽  
Pierre-Yves Dumas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Intensive Chemotherapy ◽  
Hypomethylating Agents ◽  
Term Survival ◽  
Acute Myeloid

AbstractThe outcome of acute myeloid leukemia patients aged 70 years or older is poor. Defining the best treatment option remains controversial especially when choosing between intensive chemotherapy and hypomethylating agents. We set up a multicentric European database collecting data of 3 700 newly diagnosed acute myeloid leukemia patients ≥70 years. The primary objective was to compare overall survival in patients selected for intensive chemotherapy (n = 1199) or hypomethylating agents (n = 1073). With a median follow-up of 49.5 months, the median overall survival was 10.9 (95% CI: 9.7–11.6) and 9.2 months (95% CI: 8.3–10.2) with chemotherapy and hypomethylating agents, respectively. Complete remission or complete remission with incomplete hematologic recovery was 56.1% and 19.7% with chemotherapy and hypomethylating agents, respectively (P < 0.0001). Treatment effect on overall survival was time-dependent. The Royston and Parmar model showed that patients treated with hypomethylating agents had a significantly lower risk of death before 1.5 months of follow-up; no significant difference between 1.5 and 4.0 months, whereas patients treated with intensive chemotherapy had a significantly better overall survival from four months after start of therapy. This study shows that intensive chemotherapy remains a valuable option associated with a better long-term survival in older AML patients.

Long-Term Analysis of the IFM 99 Trials for Myeloma: Cytogenetic Abnormalities [t(4;14), del(17p), 1q gains] Play a Major Role in Defining Long-Term Survival

2012 ◽  
Vol 30 (16) ◽  
pp. 1949-1952 ◽  
Author(s):  
Hervé Avet-Loiseau ◽  
Michel Attal ◽  
Loic Campion ◽  
Denis Caillot ◽  
Cyrille Hulin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Life Expectancy ◽  
Comprehensive Analysis ◽  
Newly Diagnosed ◽  
Term Survival ◽  
Risk Patients ◽  
Chromosomal Changes ◽  
Term Analysis

Purpose In multiple myeloma, many prognostic parameters have been proposed. However, all of these predict shorter survival. To identify patients with a longer life expectancy, we updated the data of patients treated in the IFM (Intergroupe Francophone du Myelome) 99-02 and 99-04 trials. Patients and Methods A series of 520 patients was analyzed. Median follow-up was 90.5 months. To perform a comprehensive analysis of the major prognostic factors, we reanalyzed all patients for 1q gains [in addition to updating del(13), t(4;14), and del(17p) analyses]. Results It was possible to identify a subgroup of patients (representing 20% of total patients) with an 8-year survival of 75%. These patients were defined by the absence of t(4;14), del(17p), and 1q gain and β2-microglobulin less than 5.5 mg/L. Conclusion We propose that all patients with newly diagnosed multiple myeloma be evaluated for these three chromosomal changes, not only to define high-risk patients but also to identify those with a longer life expectancy.

scholarly journals Long-term follow-up of a comparison of nonmyeloablative allografting with autografting for newly diagnosed myeloma

Blood ◽  
2011 ◽  
Vol 117 (24) ◽  
pp. 6721-6727 ◽  
Author(s):  
Luisa Giaccone ◽  
Barry Storer ◽  
Francesca Patriarca ◽  
Marcello Rotta ◽  
Roberto Sorasio ◽  
...  
Keyword(s):  
Complete Remission ◽  
New Drugs ◽  
High Dose ◽  
Newly Diagnosed ◽  
Term Survival ◽  
Free Survival ◽  
Long Term Follow Up ◽  
High Dose Melphalan

Abstract Before the introduction of new drugs, we designed a trial where treatment of newly diagnosed myeloma patients was based on the presence or absence of HLA-identical siblings. First-line treatments included a cytoreductive autograft followed by a nonmyeloablative allograft or a second melphalan-based autograft. Here, we report long-term clinical outcomes and discuss them in the light of the recent remarkable advancements in the treatment of myeloma. After a median follow-up of 7 years, median overall survival (OS) was not reached (P = .001) and event-free survival (EFS) was 2.8 years (P = .005) for 80 patients with HLA-identical siblings and 4.25 and 2.4 years for 82 without, respectively. Median OS was not reached (P = .02) and EFS was 39 months (P = .02) in the 58 patients who received a nonmyeloablative allograft whereas OS was 5.3 years and EFS 33 months in the 46 who received 2 high-dose melphalan autografts. Among patients who reached complete remission in these 2 cohorts, 53% and 19% are in continuous complete remission. Among relapsed patients rescued with “new drugs,” median OS from the start of salvage therapy was not reached and was 1.7 (P = .01) years, respectively. Allografting conferred a long-term survival and disease-free advantage over standard autografting in this comparative study.

scholarly journals Sorafenib or placebo in patients with newly diagnosed acute myeloid leukaemia: long-term follow-up of the randomized controlled SORAML trial

Leukemia ◽  
2021 ◽  
Author(s):  
Christoph Röllig ◽  
◽  
Hubert Serve ◽  
Richard Noppeney ◽  
Maher Hanoun ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Statistical Significance ◽  
Newly Diagnosed ◽  
Early Results ◽  
Significant Prolongation ◽  
Long Term Follow Up ◽  
Acute Myeloid

AbstractEarly results of the randomized placebo-controlled SORAML trial showed that, in patients with newly diagnosed acute myeloid leukaemia (AML), sorafenib led to a significant improvement in event-free (EFS) and relapse-free survival (RFS). In order to describe second-line treatments and their implications on overall survival (OS), we performed a study after a median follow-up time of 78 months. Newly diagnosed fit AML patients aged ≤60 years received sorafenib (n = 134) or placebo (n = 133) in addition to standard chemotherapy and as maintenance treatment. The 5-year EFS was 41 versus 27% (HR 0.68; p = 0.011) and 5-year RFS was 53 versus 36% (HR 0.64; p = 0.035). Allogeneic stem cell transplantation (allo SCT) was performed in 88% of the relapsed patients. Four years after salvage allo SCT, the cumulative incidence of relapse was 54 versus 35%, and OS was 32 versus 50%. The 5-year OS from randomization in all study patients was 61 versus 53% (HR 0.82; p = 0.282). In conclusion, the addition of sorafenib to chemotherapy led to a significant prolongation of EFS and RFS. Although the OS benefit did not reach statistical significance, these results confirm the antileukaemic activity of sorafenib.

scholarly journals Long Term Follow up from the NCRI AML17 Trial of Attenuated Arsenic Trioxide and ATRA Therapy for Newly Diagnosed and Relapsed Acute Promyelocytic Leukaemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 897-897
Author(s):  
Nigel H Russell ◽  
Alan K. Burnett ◽  
Robert K Hills ◽  
Sophie Betteridge ◽  
Michael Dennis ◽  
...  
Keyword(s):  
High Risk ◽  
Low Risk ◽  
Newly Diagnosed ◽  
Molecular Monitoring ◽  
Term Survival ◽  
Cns Disease ◽  
Significant Difference ◽  
Risk Of Relapse

Abstract Background: Two randomized studies have reported comparison of the "chemo-free" combination of ATO+ATRA with Anthracycline/ ATRA (AIDA) in APL. The GIMEMA-AMLSG-SAL trial, using a daily schedule improved both survival and relapse risk in patients with newly diagnosed, low or intermediate-risk APL. (Lo Coco et al., NEJM 2013; 369: 111-21). The NCRI AML17 trial using an attenuated dosing schedule in all risk groups resulted in a very low risk of relapse, significantly better EFS but no significant survival advantage Aims: The NCRI AML17 Trial compared AIDA vs the chemo-free combination of ATO (in an attenuated schedule) + ATRA. Here we present long term survival results for randomized patients and for 24 patients who received the same chemo-free schedule of ATO + ATRA after relapsing from the AIDA arm of the trial. Methods: From May 2009 to October 2013, 235 patients aged >16 who entered the AML17 trial with molecularly confirmed APL were randomized to either ATRA+ATO (8 week induction 0.3mg/kg d1-5 w1, 0.25mg/kgx2/w w2-8, followed by 4 consolidation courses of 0.3mg/kgx2 w1, 0.25mg/kgx2/ w2-4 (63 ATO doses) OR AIDA schedule: Idarubicin (Ida)12mg/m2 d2,4,6,8 + ATRA to d60) (induction) then Ida 5mg/m2 d1-4 + ATRA d1-15 (Course 2); Mitox. 10mg/m2 d1-4 + ATRA d1-15 (course 3); Ida 12mg/m2 d1 + ATRA d1-15 (Course 4). ATRA was 45mg/m2/d. Maintenance was not given. High risk patients could receive Gemtuzumab Ozogamicin (d1,6mg/m2). Another 70 patients were treated in AML17 with AIDA after closure of the randomization. 25/189 patients relapsed post AIDA and 24 were treated with a median of 4 cycles (range 1-5) of ATRA + ATO, 11/24 were later transplanted. Follow-up is complete to 1 January 2016. Results: The median age was 47y (16-77); 57 had WBC>10x109/L (27 AIDA, 30 ATRA+ATO) and 49 (24 AIDA, 25 ATRA+ATO) were >60y. The early results of the randomization for newly diagnosed patients have been reported (Burnett et al. Lancet Oncol. 2015, 16 (13):1295). 91% entered morphological CR with no significant difference in CR rate between the arms (Chemo-free 94%, Chemo 89%; OR 0.54 (0.21-1.34), p= 0.18). The OS at 4 years was 93% (Chemo-free) vs 89% (Chemo), HR 0.60 (0.26-1.42) p= 0.2, but EFS was significantly superior with ATRA+ATO (91% vs 70%, HR 0.35 (0.18-0.68) p=0.002). With a longer median follow-up of 53.4 months 5-year survival is now 93% (chemo-free) v 87% (chemo) (HR 0.61 (0.27-1.35) p=0.2). A significant reduction in relapse (2% vs 16% at 5 years, HR 0.19 (0.09-0.45) p=0.0005) translates to continuing significant RFS benefit for the chemo-free approach (96% vs 82%; HR 0.30 (0.13-0.67) p=0.004). This is seen both in low risk (95% vs 86% HR 0.45 (0.17-1.20) p=0.11) and high risk disease (100% vs 69% HR 0.10 (0.02-0.46) p=0.003), p=0.11 for heterogeneity. 25 patients relapsed following AIDA therapy, of whom 1 died in frank relapse before treatment could be initiated and 24 (5 with concomitant CNS involvement) were treated with the attenuated ATO + ATRA schedule. Of these 16 were treated at molecular relapse, reflecting the value of centralised MRD monitoring as part of the trial protocol. All 24 patients achieved molecular CR post ATO +ATRA. Eleven patients were transplanted (8 autograft, 3 allograft) including 4 of the 5 patients with CNS disease. 3 patients have had a second molecular relapse after ATO + ATRA salvage (1 transplanted and 2 not transplanted). The 3-year overall survival post-relapse is 96% with the only other death occurring post-transplant after 37 months. Summary/Conclusion: The combination of ATO + ATRA continues to show a very low risk of relapse irrespective of risk group resulting in significantly better RFS compared to AIDA and excellent survival but no survival benefit has emerged primarily because of effective salvage interventions for AIDA-treated patients with most patients treated at molecular relapse. Molecular monitoring for t(15;17) is therefore essential to optimize therapy with AIDA. For patients treated with frontline ATO+ATRA molecular monitoring is of questionable value once achievement of molecular CR has been documented, but molecular surveillance remains important in those with relapsed disease. The attenuated AML17 ATO dosing approach is effective both upfront and in patients relapsing post AIDA and these results question the role of transplantation as consolidation in patients achieving molecular CR2 with ATO + ATRA who do not have CNS disease at relapse. Disclosures Burnett: CTI Life Sciences, London: Employment. Hills:TEVA: Honoraria. Grimwade:TEVA: Research Funding.

scholarly journals Acute Myeloid Leukemia Patients Requiring Two Cycles of Intensive Induction for Attainment of Remission Experience Inferior Survival Compared with Patients Requiring a Single Course of Induction Chemotherapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3390-3390
Author(s):  
Gal Sharvit ◽  
Gabriel Heering ◽  
Maya Zlotnick ◽  
Arnon Nagler ◽  
Abraham Avigdor ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Risk Category ◽  
Intensive Chemotherapy ◽  
Single Cycle ◽  
Term Survival ◽  
Acute Myeloid

Abstract Background: Achievement of initial remission remains the most important clinical factor predicting long term survival in acute myeloid leukemia (AML) patients treated with intensive chemotherapy. Yet, whether the patient subset in need of a second cycle of intensive induction chemotherapy to reach remission experiences inferior outcomes compared to patients reaching remission after a single cycle of therapy, remains uncertain with previous publication showing diverging outcomes with respect to patient survival and the risk for disease relapse (Rowe et al. Cancer 2010; Othus et al. Leukemia 2016). In this analysis we aimed to readdress this important clinical question in a uniform cohort of recently treated patients. Patients and Methods: Retrospective analysis of 302 consecutive AML patients treated with intensive induction chemotherapy in our institution in 2007-2020. Univariate analyses were performed using T-Test for continuous variables, and Fisher's Exact test and Pearson's chi-squared for assessment of categorical variables. Overall survival was assessed using the Kaplan-Meier method, and the log-rank test was used to compare overall survival between groups. Multivariate analyses using logistic regression were performed using year of diagnosis, patient age, follow-up duration, patient gender, white blood cell (WBC) count at diagnosis, MRC cytogenetic risk category, FMS-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD) and nucleophosmin 1 (NPM1) status, and ELN 2017 risk category, as covariates. All tests were two-sided with the type I error rate set at 0.05 for the determination of factors associated with time-to-event outcomes. Results: Median patient age was 55 years with a median follow-up duration of 23 months. In terms of European LeukemiaNet (ELN) 2017 classification, 122 patients (40%) were designated as favorable risk disease, 108 patients (36%) were intermediate risk, and 71 patients (24%) were adverse risk. A hundred and seventy-seven patients (60%) attained remission following initial chemotherapy while 58 patients (20%) required an additional cycle of intensive chemotherapy for remission. Patients requiring two cycles to reach remission were less likely to be NPM1 mutated (33% versus 51%; p=0.025) or be in the ELN 2017 favorable risk category (25% versus 57%; p&lt;0.001). In multivariate analysis achievement of remission following 2 cycles of intensive compared with a single cycle resulted in significantly inferior survival [hazard ratio (HR)=1.68, 95% CI, 1.09-2.59; p=0.017] (figure 1) whereas leukemia-free survival was not significantly impacted (HR=1.26, 95% CI, 0.85-1.85) (p=0.23). Relapse rates also did not differ to a significant degree between groups (45% versus 47%, p=0.8). Conclusion: Our analysis reaffirms the indispensable clinical significance of attainment of an early remission following intensive induction chemotherapy for AML patients. The marked long term survival advantage conferred by an early remission speaks to the need to improve initial remission rates which with the recent introduction of novel targeted therapeutics seems to be an attainable goal. Figure 1 Figure 1. Disclosures Avigdor: Gilead: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; BMS: Research Funding; Janssen: Research Funding; Takeda: Consultancy, Honoraria.

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