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Validation of a New Clinically Based Classification System for Stratification of Prognosis in Patients with CMML
Poster Presentations – 14th International Symposium on Myelodysplastic Syndromes / Leukemia Research 55 S1 (2017) S45–S167
The cumulative incidence (CI) of first infection, with death as competitive risk, was higher in patients who received ≥2 PRBC/ month (CI at 12 months: 59.6% versus 30.7%; Grays ś test p = 0.011). Treatment with AZA shows a tendency to lower CI of infection (CI 12 months 49.6 versus 38.9%, Graýs test p = 0.06). No differences were observed with other variables. In multivariant logistical regression only AZA treatment (HR 0.20; p = 0.001) and PRBC/month (HR 1.14; p = 0.033) showed prognostic impact on risk of infection. Table 1:
S149
elevated LDH predicting poor OS in MD/MP-CMML ( p = 0.0015). Cummulative risk for AML evolution after 2 years was 10%, 12% and 14% respectively ( p = n.s.) Conclusion: This retrospective analysis validates data presented by Onida et al. showing that their 3-grouped classification schema allows stratification of survival in CMML pts. However in our cohort it was not capable to predict AML progression, probably because parameters associated with disease progression like cytogenetics and medullary blast count were not taken into account in this schema.
NeutroInfection
Ferritin #
TSI #
AZA
phil
Hemo-
Platelets
(x10^9/
globin
(x10^9/
#
#
#
(n)
Age#
Sex: M/F
(µg/L)
(%)
the-rapy
L)
(g/L)
NO: 54
74
31/23
238
41.9
29 (54%)
2.85
93.7
106
YES: 58
77
33/25
333
35.6
12 (21%)
1.95
96.5
72
<0.001
0.21
p Value*
0.22
0.22
0.19
0.19
0.69
L)
0.24
PRBC/ month
#
0.94 2.18 0.006
*Mann-Whitney test or Fisher´s test. # Median.
Conclusion: PRBC/month and treatment with AZA should be considered when evaluating the infections risk in hematological patients.
259 VALIDATION OF A NEW CLINICALLY BASED CLASSIFICATION SYSTEM FOR STRATIFICATION OF PROGNOSIS IN PATIENTS WITH CMML C. Rautenberg1, E. Schuler1, K. Nachtkamp1, T. Schroeder1, S. Blum2, C. Aul1, R. Haas1, U. Germing1 1 Department of Hematology- Oncology and Clinical Immunology, University Hospital Duesseldorf, Duesseldorf, Germany; 2Department of Hematology, University Lausanne, Lausanne, Switzerland Introduction: CMML is a myeloid neoplasm characterized by dysplastic and proliferative aspects. According to FAB classification it is divided into a dysplastic and proliferative subgroup depending on WBC count (below or above 13 × 103/µL). To allow a more informative stratification for prognosis of CMML pts Onida et al. developed a 3-group classification schema which was shown to independently stratify prognosis very well (ASH 2016, abstract no. 4320). Herein, we validate this system and evaluate whether it also allows prediction of disease progression. Methods: Data of 337 patients from the Düsseldorf MDS registry between 1972 and 2015 were analysed. As described by Onida et al. patients ( pts) were divided into three clinically based subgroups depending on (1) WBC count, (2) PB-IMC count and (3) evidence of splenomegaly or none. Pearson-c2 test was conducted for comparison of categorical characteristics. For estimation of overall survival (OS) and cumulative risk of progression Kaplan-Meier method was applied and log rank test was used for comparison of curves. Results: 90 (27%), 135 (40%) and 112 (31%) pts were included in the three subcategories of MD-, MD/MP-, and MP-CMML, respectively. Within the MD/MP-CMML subgroup 183 (54%) pts had WBC < 13 × 103/µL corresponding to MD-CMML and 154 (46%) pts showed WBC >13 × 103/µL equivalent to MP-CMML according to FAB criteria. 67 pts (about 50%) within the MD/MP-CMML subgroup had WBC <10 × 10^3/microL, but either showed peripheral blasts or splenomegaly indicating proliferative character of disease. Median overall survival in MD-, MD/MP- and MP-CMML subcategories was 41, 20, and 15 months, respectively ( p < 0.001). As a unique variable distinctly governing a subgroups’ prognosis, we only identified
260 PERIPHERAL BLOOD WT1 EXPRESSION REFINES PROGNOSTIC INFORMATION FOR MDS PATIENTS WITHIN THE IPSS-R RISK CATEGORIES VERY LOW, LOW AND INTERMEDIATE C. Rautenberg1, S. Pechtel1, S. Geyh1, P. Jäger1, R. Haas1, U. Germing1, G. Kobbe1, T. Schroeder1 1 Department of Hematology- Oncology and Clinical Immunology, University Hospital of Duesseldorf, Duesseldorf, Germany Introduction: Currently the IPSS-R represents the standard to estimate prognosis of MDS patients. Given the recent discovery of several gene mutations, the major research issue is to refine IPSS-R by integration of molecular information. This may be hampered by limited incidence of individual mutations, limited access for testing and optionally the need for biopsy. The unmutated Wilms’ Tumour (WT1) gene is overexpressed at mRNA level in about 50% of MDS patients and is measureable in PB. Aim of the current analysis was to determine whether PB WT1 expression offers prognostic information in MDS patients. Methods: We measured PB WT1 mRNA expression in 89 MDS patients at diagnosis using the Ipsogen® WT1 ProfileQuant® Kit, offering a validated PB cut-off level of 50 WT1 copies/104 ABL copies to distinguish between normal and overexpression of WT1. Based on this, patients were dichotomized into those with WT1 overexpression and those with normal WT1 expression. Subsequently, we tested whether WT1 expression correlated with clinical parameters and outcome. Results: WT1 was overexpressed in 49 patients (55%) and significantly correlated with WHO disease category indicated both by frequency of WT1-overexpressing patients and by absolute WT1 levels of the respective MDS subtypes ( p = 0.0281). WT1 expression also correlated with IPSS-R categories. We then tested whether WT1 expression refines the prognostic information of IPSS-R. In the IPSS-R high and very high risk group, no prognostic impact of WT1 status was found in these categories. Within the IPSS-R very low/low risk group as well as within the IPSS-R intermediate group PFS significantly differed between patients with normal and elevated WT1 level (IPSS-R very low/low: median PFS WT1 high 33,5 months vs. WT1 normal not reached, p = 0.0382; IPSS-R intermediate: median PFS WT1 high 17,7 months vs. WT1 normal 64,6 months, p = 0.0058. OS also significantly differed depending on WT1 status in very low/low risk group (median OS WT1 high 55 months vs. WT1 normal not reached, p = 0.0487) and by trend in the intermediate risk group (median OS WT1 high 120,8 months vs. WT1 normal not reached, p = 0.0894). Differences in PFS retained in multivariate analysis after adjusting for IPSS-R (HR 0,306; 95% CI 0,156–0,598, p = 0.001) Conclusion: These findings suggest that PB WT1 expression offers additional information refining prognosis of patients within the IPSS-R very low, low and intermediate risk group and may help to identify patients being at risk for early progression.
The cumulative incidence (CI) of first infection, with death as competitive risk, was higher in patients who received ≥2 PRBC/ month (CI at 12 months: 59.6% versus 30.7%; Grays ś test p = 0.011). Treatment with AZA shows a tendency to lower CI of infection (CI 12 months 49.6 versus 38.9%, Graýs test p = 0.06). No differences were observed with other variables. In multivariant logistical regression only AZA treatment (HR 0.20; p = 0.001) and PRBC/month (HR 1.14; p = 0.033) showed prognostic impact on risk of infection. Table 1:
S149
elevated LDH predicting poor OS in MD/MP-CMML ( p = 0.0015). Cummulative risk for AML evolution after 2 years was 10%, 12% and 14% respectively ( p = n.s.) Conclusion: This retrospective analysis validates data presented by Onida et al. showing that their 3-grouped classification schema allows stratification of survival in CMML pts. However in our cohort it was not capable to predict AML progression, probably because parameters associated with disease progression like cytogenetics and medullary blast count were not taken into account in this schema.
NeutroInfection
Ferritin #
TSI #
AZA
phil
Hemo-
Platelets
(x10^9/
globin
(x10^9/
#
#
#
(n)
Age#
Sex: M/F
(µg/L)
(%)
the-rapy
L)
(g/L)
NO: 54
74
31/23
238
41.9
29 (54%)
2.85
93.7
106
YES: 58
77
33/25
333
35.6
12 (21%)
1.95
96.5
72
<0.001
0.21
p Value*
0.22
0.22
0.19
0.19
0.69
L)
0.24
PRBC/ month
#
0.94 2.18 0.006
*Mann-Whitney test or Fisher´s test. # Median.
Conclusion: PRBC/month and treatment with AZA should be considered when evaluating the infections risk in hematological patients.
259 VALIDATION OF A NEW CLINICALLY BASED CLASSIFICATION SYSTEM FOR STRATIFICATION OF PROGNOSIS IN PATIENTS WITH CMML C. Rautenberg1, E. Schuler1, K. Nachtkamp1, T. Schroeder1, S. Blum2, C. Aul1, R. Haas1, U. Germing1 1 Department of Hematology- Oncology and Clinical Immunology, University Hospital Duesseldorf, Duesseldorf, Germany; 2Department of Hematology, University Lausanne, Lausanne, Switzerland Introduction: CMML is a myeloid neoplasm characterized by dysplastic and proliferative aspects. According to FAB classification it is divided into a dysplastic and proliferative subgroup depending on WBC count (below or above 13 × 103/µL). To allow a more informative stratification for prognosis of CMML pts Onida et al. developed a 3-group classification schema which was shown to independently stratify prognosis very well (ASH 2016, abstract no. 4320). Herein, we validate this system and evaluate whether it also allows prediction of disease progression. Methods: Data of 337 patients from the Düsseldorf MDS registry between 1972 and 2015 were analysed. As described by Onida et al. patients ( pts) were divided into three clinically based subgroups depending on (1) WBC count, (2) PB-IMC count and (3) evidence of splenomegaly or none. Pearson-c2 test was conducted for comparison of categorical characteristics. For estimation of overall survival (OS) and cumulative risk of progression Kaplan-Meier method was applied and log rank test was used for comparison of curves. Results: 90 (27%), 135 (40%) and 112 (31%) pts were included in the three subcategories of MD-, MD/MP-, and MP-CMML, respectively. Within the MD/MP-CMML subgroup 183 (54%) pts had WBC < 13 × 103/µL corresponding to MD-CMML and 154 (46%) pts showed WBC >13 × 103/µL equivalent to MP-CMML according to FAB criteria. 67 pts (about 50%) within the MD/MP-CMML subgroup had WBC <10 × 10^3/microL, but either showed peripheral blasts or splenomegaly indicating proliferative character of disease. Median overall survival in MD-, MD/MP- and MP-CMML subcategories was 41, 20, and 15 months, respectively ( p < 0.001). As a unique variable distinctly governing a subgroups’ prognosis, we only identified
260 PERIPHERAL BLOOD WT1 EXPRESSION REFINES PROGNOSTIC INFORMATION FOR MDS PATIENTS WITHIN THE IPSS-R RISK CATEGORIES VERY LOW, LOW AND INTERMEDIATE C. Rautenberg1, S. Pechtel1, S. Geyh1, P. Jäger1, R. Haas1, U. Germing1, G. Kobbe1, T. Schroeder1 1 Department of Hematology- Oncology and Clinical Immunology, University Hospital of Duesseldorf, Duesseldorf, Germany Introduction: Currently the IPSS-R represents the standard to estimate prognosis of MDS patients. Given the recent discovery of several gene mutations, the major research issue is to refine IPSS-R by integration of molecular information. This may be hampered by limited incidence of individual mutations, limited access for testing and optionally the need for biopsy. The unmutated Wilms’ Tumour (WT1) gene is overexpressed at mRNA level in about 50% of MDS patients and is measureable in PB. Aim of the current analysis was to determine whether PB WT1 expression offers prognostic information in MDS patients. Methods: We measured PB WT1 mRNA expression in 89 MDS patients at diagnosis using the Ipsogen® WT1 ProfileQuant® Kit, offering a validated PB cut-off level of 50 WT1 copies/104 ABL copies to distinguish between normal and overexpression of WT1. Based on this, patients were dichotomized into those with WT1 overexpression and those with normal WT1 expression. Subsequently, we tested whether WT1 expression correlated with clinical parameters and outcome. Results: WT1 was overexpressed in 49 patients (55%) and significantly correlated with WHO disease category indicated both by frequency of WT1-overexpressing patients and by absolute WT1 levels of the respective MDS subtypes ( p = 0.0281). WT1 expression also correlated with IPSS-R categories. We then tested whether WT1 expression refines the prognostic information of IPSS-R. In the IPSS-R high and very high risk group, no prognostic impact of WT1 status was found in these categories. Within the IPSS-R very low/low risk group as well as within the IPSS-R intermediate group PFS significantly differed between patients with normal and elevated WT1 level (IPSS-R very low/low: median PFS WT1 high 33,5 months vs. WT1 normal not reached, p = 0.0382; IPSS-R intermediate: median PFS WT1 high 17,7 months vs. WT1 normal 64,6 months, p = 0.0058. OS also significantly differed depending on WT1 status in very low/low risk group (median OS WT1 high 55 months vs. WT1 normal not reached, p = 0.0487) and by trend in the intermediate risk group (median OS WT1 high 120,8 months vs. WT1 normal not reached, p = 0.0894). Differences in PFS retained in multivariate analysis after adjusting for IPSS-R (HR 0,306; 95% CI 0,156–0,598, p = 0.001) Conclusion: These findings suggest that PB WT1 expression offers additional information refining prognosis of patients within the IPSS-R very low, low and intermediate risk group and may help to identify patients being at risk for early progression.