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119 UPDATE ON THE MULTICENTER MDS BIOREGISTRY PROJECT OF THE “KREBSHILFE-VERBUNDFORSCHUNGSPROJEKT MDS” OF THE GERMAN MDS STUDY GROUP
Poster Presentations – 13th International Symposium on Myelodyspastic Syndromes / Leukemia Research 39 S1 (2015) S1–S166
Overall safety data were consistent with the known safety profile of lenalidomide. These data suggest lenalidomide can be safely and effectively used in this patient population. 118 A PHASE 2 STUDY OF AZACITIDINE AND EPOETIN-BETA IN UNTREATED RBC-TRANSFUSION DEPENDENT LOWER-RISK MDS PATIENTS G. Sanz1, R. de Paz2, T. Bernal3, J. Bargay4, P. Montesinos1, M. Diez-Campelo5, C. del Cañizo5, on behalf of GESMD and PETHEMA cooperative groups6 1 Hematology Department, Hospital Universitario y Politecnico La Fe, Valencia, Spain; 2Hematology Department, Hospital Universitario La Paz, Madrid, Spain; 3Hematology Department, Hospital Universitario Central de Asturias, Oviedo, Spain; 4Hematology Department, Hospital Son Llatzer, Palma de Mallorca, Spain; 5Hematology Department, Hospital Universitario de Salamanca, Salamanca, Spain; 6Spain The aim of this phase-2 multicenter, non-randomized, open-label, clinical trial was to assess the efficacy and safety of a combination of azacitidine (AZA) and epoetin B (EPO) in untreated RBCtransfusion dependent (TD) lower-risk (low or intermediate-1risk IPSS) MDS patients. RBC-TD was defined as having received ≥1 unit of RBCs every 8 weeks for a minimum of 16 weeks. Patients were required to have ≥1x109 PMN/L and ≥50 x109 platelets/L and adequate renal and hepatic function. Treatment consisted of 6 cycles of AZA (50 mg/m2/d subcutaneously x 5 d every 28 d) and EPO (60,000 IU subcutaneously on days 1, 8, 15, and 22 of cycles 1 – 3 and 30,000 IU on cycles 4 – 6) administered over 24 weeks. Patients showing erythroid improvement were entered into a 24-weeks (6 additional cycles) extension phase with both drugs administered as in cycles 4 – 6. The main efficacy endpoint was RBC-transfusion independence (TI; no RBC transfusion for >8 weeks) at 24 weeks. Secondary endpoints included erythroid, PMN, and platelet improvement by IWG 2006 response criteria. Adverse events were graded by NCI CTAE v3.0 criteria. Sixteen patients were included. Median age was 74 yr (range, 54–89), 9 (56%) were males, 7 patients had RA, 4 RARS, and 5 AREB according to FAB, 5 patients were low- (31%) and 11 intermediate-1-risk (69%) by IPSS, median number of RBC units in previous 8 weeks was 6 (range, 3–18), and endogenous EPO level was >200 IU/L (>500) in 6/13 (5/13) patients. Six patients discontinued before week 24 (toxicity, 3; progression 2; withdraw consent, 1). By intention-totreat analysis, 8 patients (50%) attained RBC-TI and 9 (56%) had an erythroid improvement at week 24 (median Hb increase, 3.1 g/dL). One additional patient had RBC-TI at week 48. RBC-TI was observed in 4/5 low- and 5/11 intermediate-1-risk patients and in 4/7 and 3/6 [3/5] with EPO <200 IU/L and >200 [500] IU/L, respectively. Median RBC-TI duration was 288 days (range, 73410+; maintained at week 48 in 5 patients). Neutropenia (94%; grades 3-4, 56%), thrombocytopenia (50%; grades 3-4, 25%), and respiratory tract infections (56%, grades 3-4, 25%) were the most common adverse events. The combination of AZA and EPO yields a high rate of RBC-TI in untreated RBC-TD lower-risk MDS patients but is associated with substantial hematological toxicity. The rate of RBC-TI observed with this combination in patients with EPO level >200 UI/L is encouraging and merits further study.
119 UPDATE ON THE MULTICENTER MDS BIOREGISTRY PROJECT OF THE “KREBSHILFE-VERBUNDFORSCHUNGSPROJEKT MDS” OF THE GERMAN MDS STUDY GROUP J. Schemenau1, C. Strupp1, M. Wulfert1, T. Schroeder1, B. Xicoy2, A. Nusch3, W. Langer3, N. Kalhori3, D. Haase4, T. Brümmendorf5,
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J. Schütte6, A. Ganser7, S. Parmentier8, K. Schulte9, D. Plewe10, C. Losem10, E. Biekmann11, W. Hoffmann12, L. Hahn13, M. Neise14, A. Lollert14, C. Maintz15, C. Hinske15, F. Weißinger16, D. Heudobler17, E. Rodermann18, H. Culmann19, T. Kretschmar20, T. Steinmetz21, A. Giagounidis22, G. Meckenstock23, V. Runde24, R. Haas1, U. Germing1, W.K. Hofmann25, N. Gattermann1 1 Department of Hematology and Oncology, Heinrich-HeineUniversität Düsseldorf, Düsseldorf, Germany; 2Department of Hematology, Hospital Germans Trias i Pujol, Barcelona, Spain; 3 Hematology, Private Practice, Ratingen, Germany; 4Department of Hematology, Georg-August-University Göttingen, Göttingen, Germany; 5Department of Hematology, University Aachen, Aachen, Germany; 6Hematology, Private Practice, Düsseldorf, Germany; 7Department of Hematology, Medizinische Hochschule Hannover, Hannover, Germany; 8Department of Hematology, Rems-Murr-Kliniken, Winnenden, Germany; 9Department of Hematology, Kliniken Köln Holweide, Köln, Germany; 10Hematology, Private Practice, Neuss, Germany; 11Department of Hematology, Evangelisches Krankenhaus Herne, Herne, Germany; 12Department of Hematology, St. Anna Krankenhaus Herne, Herne, Germany; 13 Hematology, Private Practice, Herne, Germany; 14Hematology, Private Practice, Krefeld, Germany; 15Hematology, Private Practice, Würselen, Germany; 16Department of Hematology, Evangelisches Krankenhaus Bielefeld, Bielefeld, Germany; 17Department of Hematology, University Hospital Regensburg, Regensburg, Germany; 18Hematology, Private Practice, Troisdorf, Germany; 19 Hematology, Private Practice, Bergisch-Gladbach, Germany; 20 Department of Internal Medicine, Kreiskrankenhaus Dormagen, Dormagen, Germany; 21Hematology, Private Practice, Köln, Germany; 22 Department of Hematology, Marienhospital Düsseldorf, Düsseldorf, Germany; 23Department of Hematology, St. Josef-Hospital, Gelsenkirchen, Germany; 24Department of Hematology, WilhelmAnton-Hospital, Goch, Germany; 25Department of Hematology and Oncology, University of Mannheim, Mannheim, Germany Introduction: In October 2013 the German MDS study group started a multicenter MDS Bioregistry supported by the Deutsche Krebshilfe as a part of the „Verbundforschungsprojekt MDS“ (speaker: W.K. Hofmann, Mannheim; deputy: U. Germing, Düsseldorf). Methods: After informed consent, blood and marrow samples of MDS patients are processed and stored in the Biobank of the University Cancer Center in Düsseldorf. A detailed protocol defines a selection of CD34+, CD71+, CD15+, and CD61+ cells, prior to standardized extraction of nucleic acids. To obtain nonclonal DNA, T cells are isolated from blood. Cytomorphologic review according to the WHO 2008 classification is performed in Düsseldorf. A well defined data set is employed to characterize each specimen including WHO type, prognostic scores, treatment, follow-up, and progression. Results: 528 samples (248 blood, 71 marrow, 209 both) were collected since the project´s initiation by 24 participating MDS centers. 26.7% of all samples were taken at first diagnosis, all other specimens were collected at first or second progression (8.2%), during the course of the disease without any clinical changes (60.1%), at the time of relapse (0.9%) or during remission (0.2%). At the time of last follow-up on 31st December 2014, 93.6% of all patients were still alive, 0.6% were lost to follow-up and 3.6% had already died. According to the WHO 2008 classification, 37.3% of our patients were classified as RCMD, 12.9% as RARS, 4.9% as MDS del(5q). High risk MDS, such as RAEB I (13.7%) and RAEB II (9.2%) occurred as well as CMML I (7.7%) and CMML II (4.3%). IPSS-R risk groups were distributed as in the following: 34.5% very low, 14.0% low, 10.9% intermediate, 5.6% high and 2.8% very high (n=362).
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Poster Presentations – 13th International Symposium on Myelodyspastic Syndromes / Leukemia Research 39 S1 (2015) S1–S166
52.8% presented with a normal karyotype, MDS del(5q) was found in 10.4%, trisomy 8 and -y were present in 6.3% each. Monosomy 7 occurred in 3.8% of all karyotypes analysed. MDS treatment comprised several therapeutic options and implied best supportive care (31.8%), cytokines (EPO, G-CSF: 10.1%), Vidaza (9.8%) and iron chelation (7.8%), predominantly. Allogeneic stem cell transplantation was performed in 0.2% of all cases. 31.8% did not receive any therapy at all. Conclusions: Biomaterial is combined with a clinical data set, providing a useful basis for scientific projects in the cooperating centers. Since the aim is to collect material from 500 patients per year, we are grateful to a number of collaborating colleagues, who support the research acitivities by actively contributing patients` samples.
120 RESULTS OF THE MULTICENTER, PHASE II STUDY OF THE SAFETY OF LENALIDOMIDE MONOTHERAPY IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES (MDS) ASSOCIATED WITH AN ISOLATED DEL(5Q) E. Schuler1, J. Schemenau1, A. Giagounidis2, D. Haase3, G. Büsche4, U. Platzbecker5, F. Nolte6, K. Götze7, R.F. Schlenk8, A. Ganser9, A. Letsch10, M. Lübbert11, P. Schafhausen12, G. Bug13, U. Germing1 1 Department of Hematology and Oncology, Heinrich-HeineUniversität, Düsseldorf, Germany; 2Department of Hematology Oncology and Palliative Care, Marienhospital Düsseldorf, Düsseldorf, Germany; 3Department of Hematology and Oncology, University Hospital Göttingen, Göttingen, Germany; 4Institute of Pathology, Medizinische Hochschule Hannover, Hannover, Germany; 5 Department of Hematology, University Hospital Dresden, Dresden, Germany; 6Department of Internal Medicine, University Hospital Mannheim, Mannheim, Germany; 7Department of Internal Medicine, Klinikum Rechts der Isar, München, Germany; 8Department of Internal Medicine, University Hospital Ulm, Ulm, Germany; 9 Department of Hematology Haemostaseology and Stem Cell Transplantation, Medizinische Hochschule Hannover, Hannover, Germany; 10Department of Hematology and Oncology, Charité Benjamin Franklin University, Berlin, Germany; 11Department of Internal Medicine, University Hospital Freiburg, Freiburg, Germany; 12 Department of Internal Medicine, University Hospital Hamburg Eppendorf, Hamburg, Germany; 13Department of Internal Medicine, University Hospital Frankfurt, Frankfurt, Germany Lenalidomide (Len) has been successfully used in patients (pts) with MDS with del (5q). A small proportion of patients with MDS and del(5q) develop leukemia while treated with len. Therefore we aimed at identifying predictive factors for disease progression in pts with MDS and an isolated deletion del(5q) and blast count <5%, undergoing treatment with len. LE-MON 5 is an open-label, nonrandomized, single-arm multicenter, phase II study investigating the safety of len monotherapy. Screening procedure included centralized bone marrow histology, cytology, and cytogenetic examination. 147 pts were screened, 91 pts did fulfill the inclusion criteria, 89 were included into trial and treated. 56 pts (38%) were screening-failures because of following reasons: >5% blasts in cytology (40%), >5% blasts in histology (31%) or not fulfilling the cytogenetic criterion, i.e. presence of additional cytgenetic aberration or lack of del(5q) (60%). In 3 pts all 3 criteria were not matching and in 8 pts 2 criteria were not matching. Treatment was scheduled 4 month (mo) Len 10mg d1-21. Patients who did not gain transfusion independency were excluded as non-responders after 4 cycles. Patients, who responded, were on Len until disease progression, if no side effect occurred or pts wished to discontinue. Median age at inclusion was 68.3 years [40-87], 70 pts were female (78.7%),
time from diagnosis was 21.3 mo [1-180.7]. 69 patients (77.5%) were not pre-treated before entering study. Median cycles on drug were 12 months [1-48]. 47/78 (60.3%) patients maintained the dose until the end of the study. By average, patients were treated for 14.0 months and received 14.8 cycles with lenalidomide. For 60 (67.4%) patients, transfusion independence was documented; median time to transfusion independence starting from the first day of study medication was estimated as 35 days; duration of transfusion-independent period was estimated 9 months. Disease progression meaning increasing medullary blast count or progression/relapse following erythroid hematologic improvement or neutrophil or platelet hematologic improvement was found in 27 (30.3%) patients. Median time to progression starting from the first day of study medication was estimated as 44.5 months. 9 (10.1%) patients with AML transformation were found. 3 Patients developed AML or RAEB while on treatment. Until the end of the current observation period, 15 (16.9%) patients have died. On the basis of this data we state that it is safe to use len in MDS with isolated del 5q and that disease progression in treated patients is comparable to untreated patients.
121 PERIPHERAL BLOOD (PB) WILMS’ TUMOR 1 (WT1) EXPRESSION QUANTIFIED BY A STANDARDIZED EUROPEAN LEUKEMIA NET (ELN)-CERTIFIED ASSAY AS PROGNOSTIC AND MINIMAL RESIDUAL DISEASE (MRD) MARKER IN MDS T. Schroeder1, S. Pechtel1, M. Lamers1, A. Dienst1, E. Schuler1, E. Rachlis1, N. Wegener1, A. Kündgen1, M. Kondakci1, R. Fenk1, R. Haas1, U. Germing1, G. Kobbe1 1 Department of Hematology Oncology and Clinical Immunology, University Hospital Duesseldorf Medical Faculty, Düsseldorf, Germany Measurement of PB WT1 mRNA expression is an established method for MRD monitoring in de-novo AML. WT1 overexpression has also been reported in a proportion of MDS patients suggesting its potential use as prognostic and MRD marker. However, so far WT1 has been not established as prognostic or MRD marker in MDS due to limited patients numbers, differing sample sources and the use of non-standardized in-house methods. This prompted us to measure PB WT1-expression of 106 newlydiagnosed MDS patients with all WHO subtypes using the Ipsogen® WT1 ProfileQuant® Kit (Qiagen, Germany) for correlation with disease characteristics and to determine its’ prognostic impact. Furthermore, we investigated its’ value as MRD marker after alloHSCT and impact for guiding salvage therapy with Azacitidine and donor lymphocyte infusions (DLI). Using the validated PB cut-off level of 50 WT1 copies/104 ABL copies, WT1 overexpression was detected in 58/106 MDS patients (55%) and significantly discriminated between MDS and healthy controls (0/12, 0%, p=0.0003) as well as between MDS and nonMDS cytopenias (0/18, 0%, p<0.0001). WT1 expression positively correlated with advanced WHO categories as depicted not only by the frequency of WT1-overexpressing patients, but also by absolute WT1 levels (p<0.0001). Accordingly, there was a clear association between WT1 expression and IPSS (p=0.042) as well as IPSS-R stage (p=0.10). Furthermore, in IPSS low or intermediate-1 patients, but also IPSS-R low or intermediate WT1 overexpression was identified as prognostic factor for progression-free survival by multivariate analysis. Monitoring of WT1-expression in 21 patients revealed a clear correlation between WT1 levels and disease burden after alloHSCT. After a rapid decline below normal threshold in all patients, 12 patients exhibited low and stable WT1 levels and remained in
Overall safety data were consistent with the known safety profile of lenalidomide. These data suggest lenalidomide can be safely and effectively used in this patient population. 118 A PHASE 2 STUDY OF AZACITIDINE AND EPOETIN-BETA IN UNTREATED RBC-TRANSFUSION DEPENDENT LOWER-RISK MDS PATIENTS G. Sanz1, R. de Paz2, T. Bernal3, J. Bargay4, P. Montesinos1, M. Diez-Campelo5, C. del Cañizo5, on behalf of GESMD and PETHEMA cooperative groups6 1 Hematology Department, Hospital Universitario y Politecnico La Fe, Valencia, Spain; 2Hematology Department, Hospital Universitario La Paz, Madrid, Spain; 3Hematology Department, Hospital Universitario Central de Asturias, Oviedo, Spain; 4Hematology Department, Hospital Son Llatzer, Palma de Mallorca, Spain; 5Hematology Department, Hospital Universitario de Salamanca, Salamanca, Spain; 6Spain The aim of this phase-2 multicenter, non-randomized, open-label, clinical trial was to assess the efficacy and safety of a combination of azacitidine (AZA) and epoetin B (EPO) in untreated RBCtransfusion dependent (TD) lower-risk (low or intermediate-1risk IPSS) MDS patients. RBC-TD was defined as having received ≥1 unit of RBCs every 8 weeks for a minimum of 16 weeks. Patients were required to have ≥1x109 PMN/L and ≥50 x109 platelets/L and adequate renal and hepatic function. Treatment consisted of 6 cycles of AZA (50 mg/m2/d subcutaneously x 5 d every 28 d) and EPO (60,000 IU subcutaneously on days 1, 8, 15, and 22 of cycles 1 – 3 and 30,000 IU on cycles 4 – 6) administered over 24 weeks. Patients showing erythroid improvement were entered into a 24-weeks (6 additional cycles) extension phase with both drugs administered as in cycles 4 – 6. The main efficacy endpoint was RBC-transfusion independence (TI; no RBC transfusion for >8 weeks) at 24 weeks. Secondary endpoints included erythroid, PMN, and platelet improvement by IWG 2006 response criteria. Adverse events were graded by NCI CTAE v3.0 criteria. Sixteen patients were included. Median age was 74 yr (range, 54–89), 9 (56%) were males, 7 patients had RA, 4 RARS, and 5 AREB according to FAB, 5 patients were low- (31%) and 11 intermediate-1-risk (69%) by IPSS, median number of RBC units in previous 8 weeks was 6 (range, 3–18), and endogenous EPO level was >200 IU/L (>500) in 6/13 (5/13) patients. Six patients discontinued before week 24 (toxicity, 3; progression 2; withdraw consent, 1). By intention-totreat analysis, 8 patients (50%) attained RBC-TI and 9 (56%) had an erythroid improvement at week 24 (median Hb increase, 3.1 g/dL). One additional patient had RBC-TI at week 48. RBC-TI was observed in 4/5 low- and 5/11 intermediate-1-risk patients and in 4/7 and 3/6 [3/5] with EPO <200 IU/L and >200 [500] IU/L, respectively. Median RBC-TI duration was 288 days (range, 73410+; maintained at week 48 in 5 patients). Neutropenia (94%; grades 3-4, 56%), thrombocytopenia (50%; grades 3-4, 25%), and respiratory tract infections (56%, grades 3-4, 25%) were the most common adverse events. The combination of AZA and EPO yields a high rate of RBC-TI in untreated RBC-TD lower-risk MDS patients but is associated with substantial hematological toxicity. The rate of RBC-TI observed with this combination in patients with EPO level >200 UI/L is encouraging and merits further study.
119 UPDATE ON THE MULTICENTER MDS BIOREGISTRY PROJECT OF THE “KREBSHILFE-VERBUNDFORSCHUNGSPROJEKT MDS” OF THE GERMAN MDS STUDY GROUP J. Schemenau1, C. Strupp1, M. Wulfert1, T. Schroeder1, B. Xicoy2, A. Nusch3, W. Langer3, N. Kalhori3, D. Haase4, T. Brümmendorf5,
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J. Schütte6, A. Ganser7, S. Parmentier8, K. Schulte9, D. Plewe10, C. Losem10, E. Biekmann11, W. Hoffmann12, L. Hahn13, M. Neise14, A. Lollert14, C. Maintz15, C. Hinske15, F. Weißinger16, D. Heudobler17, E. Rodermann18, H. Culmann19, T. Kretschmar20, T. Steinmetz21, A. Giagounidis22, G. Meckenstock23, V. Runde24, R. Haas1, U. Germing1, W.K. Hofmann25, N. Gattermann1 1 Department of Hematology and Oncology, Heinrich-HeineUniversität Düsseldorf, Düsseldorf, Germany; 2Department of Hematology, Hospital Germans Trias i Pujol, Barcelona, Spain; 3 Hematology, Private Practice, Ratingen, Germany; 4Department of Hematology, Georg-August-University Göttingen, Göttingen, Germany; 5Department of Hematology, University Aachen, Aachen, Germany; 6Hematology, Private Practice, Düsseldorf, Germany; 7Department of Hematology, Medizinische Hochschule Hannover, Hannover, Germany; 8Department of Hematology, Rems-Murr-Kliniken, Winnenden, Germany; 9Department of Hematology, Kliniken Köln Holweide, Köln, Germany; 10Hematology, Private Practice, Neuss, Germany; 11Department of Hematology, Evangelisches Krankenhaus Herne, Herne, Germany; 12Department of Hematology, St. Anna Krankenhaus Herne, Herne, Germany; 13 Hematology, Private Practice, Herne, Germany; 14Hematology, Private Practice, Krefeld, Germany; 15Hematology, Private Practice, Würselen, Germany; 16Department of Hematology, Evangelisches Krankenhaus Bielefeld, Bielefeld, Germany; 17Department of Hematology, University Hospital Regensburg, Regensburg, Germany; 18Hematology, Private Practice, Troisdorf, Germany; 19 Hematology, Private Practice, Bergisch-Gladbach, Germany; 20 Department of Internal Medicine, Kreiskrankenhaus Dormagen, Dormagen, Germany; 21Hematology, Private Practice, Köln, Germany; 22 Department of Hematology, Marienhospital Düsseldorf, Düsseldorf, Germany; 23Department of Hematology, St. Josef-Hospital, Gelsenkirchen, Germany; 24Department of Hematology, WilhelmAnton-Hospital, Goch, Germany; 25Department of Hematology and Oncology, University of Mannheim, Mannheim, Germany Introduction: In October 2013 the German MDS study group started a multicenter MDS Bioregistry supported by the Deutsche Krebshilfe as a part of the „Verbundforschungsprojekt MDS“ (speaker: W.K. Hofmann, Mannheim; deputy: U. Germing, Düsseldorf). Methods: After informed consent, blood and marrow samples of MDS patients are processed and stored in the Biobank of the University Cancer Center in Düsseldorf. A detailed protocol defines a selection of CD34+, CD71+, CD15+, and CD61+ cells, prior to standardized extraction of nucleic acids. To obtain nonclonal DNA, T cells are isolated from blood. Cytomorphologic review according to the WHO 2008 classification is performed in Düsseldorf. A well defined data set is employed to characterize each specimen including WHO type, prognostic scores, treatment, follow-up, and progression. Results: 528 samples (248 blood, 71 marrow, 209 both) were collected since the project´s initiation by 24 participating MDS centers. 26.7% of all samples were taken at first diagnosis, all other specimens were collected at first or second progression (8.2%), during the course of the disease without any clinical changes (60.1%), at the time of relapse (0.9%) or during remission (0.2%). At the time of last follow-up on 31st December 2014, 93.6% of all patients were still alive, 0.6% were lost to follow-up and 3.6% had already died. According to the WHO 2008 classification, 37.3% of our patients were classified as RCMD, 12.9% as RARS, 4.9% as MDS del(5q). High risk MDS, such as RAEB I (13.7%) and RAEB II (9.2%) occurred as well as CMML I (7.7%) and CMML II (4.3%). IPSS-R risk groups were distributed as in the following: 34.5% very low, 14.0% low, 10.9% intermediate, 5.6% high and 2.8% very high (n=362).
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Poster Presentations – 13th International Symposium on Myelodyspastic Syndromes / Leukemia Research 39 S1 (2015) S1–S166
52.8% presented with a normal karyotype, MDS del(5q) was found in 10.4%, trisomy 8 and -y were present in 6.3% each. Monosomy 7 occurred in 3.8% of all karyotypes analysed. MDS treatment comprised several therapeutic options and implied best supportive care (31.8%), cytokines (EPO, G-CSF: 10.1%), Vidaza (9.8%) and iron chelation (7.8%), predominantly. Allogeneic stem cell transplantation was performed in 0.2% of all cases. 31.8% did not receive any therapy at all. Conclusions: Biomaterial is combined with a clinical data set, providing a useful basis for scientific projects in the cooperating centers. Since the aim is to collect material from 500 patients per year, we are grateful to a number of collaborating colleagues, who support the research acitivities by actively contributing patients` samples.
120 RESULTS OF THE MULTICENTER, PHASE II STUDY OF THE SAFETY OF LENALIDOMIDE MONOTHERAPY IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES (MDS) ASSOCIATED WITH AN ISOLATED DEL(5Q) E. Schuler1, J. Schemenau1, A. Giagounidis2, D. Haase3, G. Büsche4, U. Platzbecker5, F. Nolte6, K. Götze7, R.F. Schlenk8, A. Ganser9, A. Letsch10, M. Lübbert11, P. Schafhausen12, G. Bug13, U. Germing1 1 Department of Hematology and Oncology, Heinrich-HeineUniversität, Düsseldorf, Germany; 2Department of Hematology Oncology and Palliative Care, Marienhospital Düsseldorf, Düsseldorf, Germany; 3Department of Hematology and Oncology, University Hospital Göttingen, Göttingen, Germany; 4Institute of Pathology, Medizinische Hochschule Hannover, Hannover, Germany; 5 Department of Hematology, University Hospital Dresden, Dresden, Germany; 6Department of Internal Medicine, University Hospital Mannheim, Mannheim, Germany; 7Department of Internal Medicine, Klinikum Rechts der Isar, München, Germany; 8Department of Internal Medicine, University Hospital Ulm, Ulm, Germany; 9 Department of Hematology Haemostaseology and Stem Cell Transplantation, Medizinische Hochschule Hannover, Hannover, Germany; 10Department of Hematology and Oncology, Charité Benjamin Franklin University, Berlin, Germany; 11Department of Internal Medicine, University Hospital Freiburg, Freiburg, Germany; 12 Department of Internal Medicine, University Hospital Hamburg Eppendorf, Hamburg, Germany; 13Department of Internal Medicine, University Hospital Frankfurt, Frankfurt, Germany Lenalidomide (Len) has been successfully used in patients (pts) with MDS with del (5q). A small proportion of patients with MDS and del(5q) develop leukemia while treated with len. Therefore we aimed at identifying predictive factors for disease progression in pts with MDS and an isolated deletion del(5q) and blast count <5%, undergoing treatment with len. LE-MON 5 is an open-label, nonrandomized, single-arm multicenter, phase II study investigating the safety of len monotherapy. Screening procedure included centralized bone marrow histology, cytology, and cytogenetic examination. 147 pts were screened, 91 pts did fulfill the inclusion criteria, 89 were included into trial and treated. 56 pts (38%) were screening-failures because of following reasons: >5% blasts in cytology (40%), >5% blasts in histology (31%) or not fulfilling the cytogenetic criterion, i.e. presence of additional cytgenetic aberration or lack of del(5q) (60%). In 3 pts all 3 criteria were not matching and in 8 pts 2 criteria were not matching. Treatment was scheduled 4 month (mo) Len 10mg d1-21. Patients who did not gain transfusion independency were excluded as non-responders after 4 cycles. Patients, who responded, were on Len until disease progression, if no side effect occurred or pts wished to discontinue. Median age at inclusion was 68.3 years [40-87], 70 pts were female (78.7%),
time from diagnosis was 21.3 mo [1-180.7]. 69 patients (77.5%) were not pre-treated before entering study. Median cycles on drug were 12 months [1-48]. 47/78 (60.3%) patients maintained the dose until the end of the study. By average, patients were treated for 14.0 months and received 14.8 cycles with lenalidomide. For 60 (67.4%) patients, transfusion independence was documented; median time to transfusion independence starting from the first day of study medication was estimated as 35 days; duration of transfusion-independent period was estimated 9 months. Disease progression meaning increasing medullary blast count or progression/relapse following erythroid hematologic improvement or neutrophil or platelet hematologic improvement was found in 27 (30.3%) patients. Median time to progression starting from the first day of study medication was estimated as 44.5 months. 9 (10.1%) patients with AML transformation were found. 3 Patients developed AML or RAEB while on treatment. Until the end of the current observation period, 15 (16.9%) patients have died. On the basis of this data we state that it is safe to use len in MDS with isolated del 5q and that disease progression in treated patients is comparable to untreated patients.
121 PERIPHERAL BLOOD (PB) WILMS’ TUMOR 1 (WT1) EXPRESSION QUANTIFIED BY A STANDARDIZED EUROPEAN LEUKEMIA NET (ELN)-CERTIFIED ASSAY AS PROGNOSTIC AND MINIMAL RESIDUAL DISEASE (MRD) MARKER IN MDS T. Schroeder1, S. Pechtel1, M. Lamers1, A. Dienst1, E. Schuler1, E. Rachlis1, N. Wegener1, A. Kündgen1, M. Kondakci1, R. Fenk1, R. Haas1, U. Germing1, G. Kobbe1 1 Department of Hematology Oncology and Clinical Immunology, University Hospital Duesseldorf Medical Faculty, Düsseldorf, Germany Measurement of PB WT1 mRNA expression is an established method for MRD monitoring in de-novo AML. WT1 overexpression has also been reported in a proportion of MDS patients suggesting its potential use as prognostic and MRD marker. However, so far WT1 has been not established as prognostic or MRD marker in MDS due to limited patients numbers, differing sample sources and the use of non-standardized in-house methods. This prompted us to measure PB WT1-expression of 106 newlydiagnosed MDS patients with all WHO subtypes using the Ipsogen® WT1 ProfileQuant® Kit (Qiagen, Germany) for correlation with disease characteristics and to determine its’ prognostic impact. Furthermore, we investigated its’ value as MRD marker after alloHSCT and impact for guiding salvage therapy with Azacitidine and donor lymphocyte infusions (DLI). Using the validated PB cut-off level of 50 WT1 copies/104 ABL copies, WT1 overexpression was detected in 58/106 MDS patients (55%) and significantly discriminated between MDS and healthy controls (0/12, 0%, p=0.0003) as well as between MDS and nonMDS cytopenias (0/18, 0%, p<0.0001). WT1 expression positively correlated with advanced WHO categories as depicted not only by the frequency of WT1-overexpressing patients, but also by absolute WT1 levels (p<0.0001). Accordingly, there was a clear association between WT1 expression and IPSS (p=0.042) as well as IPSS-R stage (p=0.10). Furthermore, in IPSS low or intermediate-1 patients, but also IPSS-R low or intermediate WT1 overexpression was identified as prognostic factor for progression-free survival by multivariate analysis. Monitoring of WT1-expression in 21 patients revealed a clear correlation between WT1 levels and disease burden after alloHSCT. After a rapid decline below normal threshold in all patients, 12 patients exhibited low and stable WT1 levels and remained in