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Purpose Guidelines recommend a structured symptom screening (SC) for especially advanced cancer patients (CPs). The aim of this multicenter German prospective quality assurance project KeSBa (Kennzahl Symptom- und Belastungserfassung) was to gain knowledge on SC procedures in Oncology Centers (OCs) for advanced cancer patients and a first impression on the consequences of SC. Methods The KeSBa project consisted of three phases: pilot, 3 months screening and feedback phase. Participating OCs decided to use either the Minimal Documentation System (MIDOS) or the Integrated Palliative care Outcome Scale (IPOS) and defined the cutoff values for positive screening results. Results Out of 172 certified German OCs, 40 (23%) participated in the KeSBa pilot phase, 29 (16.8%) in the 3 months screening phase using MIDOS (n = 18, 58.6%) or IPOS (n = 11, 41.3%) and in the feedback round. 25/29 performed paper-based screening (86.2%). 2.963 CPs were screened. Results were documented for 1255 (42.2%, SC +) positive and 874 (29.5%, SC–) negative screenings depending on the center´s schedules: 452 SC + CPs (28.4%) and 42 SC– CPs (2.6%) had contact to specialized palliative care or other supportive specialist teams afterwards, 458 SC + CPs (28.8%) and 605 SC– CPs (38.1%) remained in standard oncology care. In the feedback round missing resources (personal and IT) and improved communication were mentioned most often. Conclusion Routine SC is feasible in advanced CPs treated in OCs but associated with considerable workload. In 42.2% of CPs SC was classified as positive, indicating the need of further diagnostics or professional judgment. SC requires staff and IT resources.

AIMS: Maintaining quality of life (QoL) in patients with cancer has gathered significant interest, but little is known about its major determinants. We sought to identify determinants of QoL in patients undergoing cancer treatment as well as in treatment-naïve patients about to commence such therapy. METHODS AND RESULTS: QoL was assessed in 283 patients with cancer using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 questionnaire. All patients underwent a battery of tests including physical examination, resting electrocardiogram, hand grip strength, and biochemistry assessment. Using multivariable logistic regression, we found that age [odds ratio (OR) 0.954, 95% confidence interval (CI) 0.916-0.994], resting heart rate (OR 1.036, 95% CI 1.004-1.068), hand grip strength (OR 0.932, 95% CI 0.878-0.990), and the presence of cachexia (OR 4.334, 95% CI 1.767-10.631) and dyspnoea (OR 3.725, 95% CI 1.540-9.010; all P

In this single center retrospective analysis 76 patients with high-risk (HR) myelodysplastic syndrome (MDS) treated with azacitidine (AZA) were reviewed for response, especially cytogenetic response (cyR) using repeated chromosome banding analyses (CBA) of bone marrow (bm) metaphases and frequent sequential Fluorescence-in-situ Hybridization (FISH) analyses of immunomagnetically enriched CD34 + circulating peripheral blood cells (CD34 +pb-FISH). In total, 526 CD34 +pb-FISH analyses and 236 CBA were examined. Median observation time was 8.45 months, median number of AZA cycles applied was 8, median overall survival (OS) was 14.9 months, 42.1 % of patients responded to therapy according to IWG criteria: 5 complete response (CR), 0 partial response (PR), 12 bmCR, 15 stable disease with hematologic improvement (HI). HI was reached in 36.8 % of patients, 31.5 % became transfusion-independent. By CBA or CD34 +pb-FISH 20.4 % and 31.6 % of patients showed cyR, respectively. HI rate was significantly higher in cytogenetic responders than in non-responders, but there was no impact on OS or leukemia-free-survival. Cytogenetic responders showed significantly better OS than non-responders. Patients with ≥ 6 AZA cycles had significantly better OS than patients with 6 cycles applied. Karyotype evolution (KE) as a manifestation of cytogenetic progression was diagnosed in 29.5 % and 17.1 % of patients by CBA and CD34 +pb-FISH, respectively. KE was associated with significantly poorer OS and leukemia-free-survival.

Standard first-line therapy for younger patients with peripheral T-cell lymphoma consists of six courses of CHOP or CHOEP consolidated by high-dose therapy and autologous stem cell transplantation (AutoSCT). We hypothesized that consolidative allogeneic transplantation (AlloSCT) could improve outcome. 104 patients with nodal peripheral T-cell lymphoma except ALK+ ALCL, 18 to 60 years of age, all stages and IPI scores except stage 1 and aaIPI 0, were randomized to receive 4 x CHOEP and 1 x DHAP followed by high-dose therapy and AutoSCT or myeloablative conditioning and AlloSCT. The primary endpoint was event-free survival (EFS) at three years. After a median follow-up of 42 months, 3-year EFS of patients undergoing AlloSCT was 43% (95% confidence interval [CI]: 29%; 57%) as compared to 38% (95% CI: 25%; 52%) after AutoSCT. Overall survival at 3 years was 57% (95% CI: 43%; 71%) versus 70% (95% CI: 57%; 82%) after AlloSCT or AutoSCT, without significant differences between treatment arms. None of 21 responding patients proceeding to AlloSCT as opposed to 13 of 36 patients (36%) proceeding to AutoSCT relapsed. Eight of 26 patients (31%) and none of 41 patients died due to transplant-related toxicity after allogeneic and autologous transplantation, respectively. In younger patients with T-cell lymphoma standard chemotherapy consolidated by autologous or allogeneic transplantation results in comparable survival. The strong graft-versus-lymphoma effect after AlloSCT was counterbalanced by transplant-related mortality. CHO(E)P followed by AutoSCT remains the preferred treatment option for transplant-eligible patients. AlloSCT is the treatment of choice for relapsing patients also after AutoSCT.

Therapeutic regimens in chronic lymphocyte leukemia/small lymphocytic lymphoma (CLL/SLL) are undergoing tremendous changes. In 2014, the Bruton tyrosine kinase inhibitor (TKI) ibrutinib was approve...

Background Myeloid sarcoma (MS), also known as chloroma, is an extramedullary manifestation of malignant primitive myeloid cells. Previously, only small studies investigated clinical and imaging features of MS. The purpose of this study was to elucidate clinical and imaging features of MS based upon a multicenter patient sample. Methods Patient records of radiological databases of 4 German university hospitals were retrospectively screened for MS in the time period 01/2001 and 06/2019. Overall, 151 cases/76 females (50.3%) with a mean age of 55.5 ± 15.1 years and 183 histopathological confirmation or clinically suspicious lesions of MS were included into this study. The underlying hematological disease, localizations, and clinical symptoms as well as imaging features on CT and MRI were investigated. Results In 15 patients (9.9% of all 151 cases) the manifestation of MS preceded the systemic hematological disease. In 43 cases (28.4%), first presentation of MS occurred simultaneously with the initial diagnosis of leukemia, and 92 (60.9%) patients presented MS after the initial diagnosis. In 37 patients (24.5%), the diagnosis was made incidentally by imaging. Clinically, cutaneous lesions were detected in 35 of 151 cases (23.2%). Other leading symptoms were pain (n = 28/151, 18.5%), neurological deficit (n = 27/151, 17.9%), swelling (n = 14/151, 9.3%) and dysfunction of the affected organ (n = 10/151, 6.0%). Most commonly, skin was affected (n = 30/151, 16.6%), followed by bone (n = 29/151, 16.0%) and lymphatic tissue (n = 21/151, 11.4%). Other localizations were rare. On CT, most lesions were homogenous. On T2-weighted imaging, most of the lesions were hyperintense. On T1-weighted images, MS was hypointense in n = 22/54 (40.7%) and isointense in n = 30/54 (55.6%). A diffusion restriction was identified in most cases with a mean ADC value of 0.76 ± 0.19 × 10− 3 mm2/s. Conclusions The present study shows clinical and imaging features of MS based upon a large patient sample in a multicenter design. MS occurs in most cases meta-chronous to the hematological disease and most commonly affects the cutis. One fourth of cases were identified incidentally on imaging, which needs awareness of the radiologists for possible diagnosis of MS.

Clonal cytogenetic evolution (CE) (i.e., acquisition of new chromosomal aberrations over time) is relevant for the progression of myelodysplastic syndromes (MDS). We performed detailed analysis of CE in 729 patients with MDS and related disorders. Patients with CE showed shorter survival (median OS 18.0 versus 53.9 months; P P P P P = 0.020) and del (17p) (P = 0.002) were especially unfavorable. Extending the evolution patterns from Tricot et al. (1985) forming five subgroups, prognosis was best (median OS not reached) in patients with “transient clones/changing clone size”, whereas those with “CE at diagnosis” showed very poor outcomes (P

We genetically analyzed a group of high risk MDS/AML patients treated by a combination of azacitidine and lenalidomide. In our cohort, the extent of genetic rearrangements was associated with outcome and response to treatment. The size of total genomic aberrations as defined by molecular karyotyping (SNP-array analysis) was a predictive marker for overall survival. TP53 mutations were associated with therapy refractoriness only if accompanied by heavily rearranged chromosomes. This study suggests a potential value of molecular karyotyping as a method to objectivate comprehensively the extent of genetic alterations in high risk patients with complex karyotypes, especially if the clinical value of the size of total genomic aberrations and the fragmentation status of single chromosomes could be evaluated in larger therapy trials.

Loss of the Y-chromosome (LOY) is described as both a normal age-related event and a marker of a neoplastic clone in hematologic diseases. To assess the significance of LOY in myelodysplastic syndromes (MDS), we determined the percentage of LOY in clonal CD34+ peripheral blood cells in comparison to normal CD3+ T-cells of 27 MDS patients using fluorescence in situ hybridization (FISH) analysis. Results were compared with the percentage of LOY in CD34+ and CD3+ cells of 32 elderly men without hematologic diseases and in 25 young blood donors. While LOY could not be detected in CD3+ cells of young men, it was observed in CD3+ cells of elderly men without hematologic diseases (2.5% LOY) as well as in CD3+ cells of elderly MDS patients (5.8% LOY). The percentage of CD34+ cells affected by LOY was significantly higher in MDS patients compared to elderly men without hematologic diseases (43.3% vs. 13.2%, P = 0.005), indicating that LOY has an age-related basis but is also associated with MDS. Furthermore, we aimed to define a threshold between age- and disease-associated LOY in MDS. Statistical analysis revealed that a value of 21.5% LOY in CD34+ peripheral blood cells provided the best threshold to discriminate between these two conditions in MDS. We conclude that LOY is clonal in a substantial number of MDS based on an age-related predisposition.

In myelodysplastic syndromes (MDS), deletion of the short arm of chromosome 12 (del(12p)) is usually a small abnormality, rarely detected as a single aberration by chromosome banding analysis (CBA) of bone marrow metaphases. Del(12p) has been described in 0.6 to 5% of MDS patients at initial diagnosis and is associated with a good to intermediate prognosis as a sole anomaly according to current scoring systems. Here, we present the results of a systematic del(12p) testing in a German prospective diagnostic study (clinicaltrials.gov: NCT01355913) on 367 MDS patients in whom CD34+ peripheral blood cells were analysed for the presence of del(12p) by sequential fluorescence in situ hybridization (FISH) analyses. A cohort of 2,902 previously published MDS patients diagnosed by CBA served as control. We demonstrate that, using a sensitive FISH technique, 12p deletion occurs significantly more frequently in MDS than previously described (7.6% by CD34+ PB-FISH vs. 1.6% by CBA, P < 0.001) and is often associated with other aberrations (93% by CD34+ PB-FISH vs. 60% by CBA). Additionally, the detection rate can be increased by repeated analyses in a patient over time which is important for the patient´s prognosis to distinguish a sole anomaly from double or complex aberrations. To our knowledge, this is the first study to screen for 12p deletions with a suitable probe for ETV6/TEL in 12p13. Our data suggest that the supplement of a probe for the detection of a 12p deletion to common FISH probe panels helps to avoid missing a del(12p), especially as part of more complex aberrations.

Transfusion-dependent patients with low- or intermediate-1-risk myelodysplastic syndrome

International Prognostic Scoring Systems are used to determine the individual risk profile of myelodysplastic syndrome patients. For the assessment of International Prognostic Scoring Systems, an adequate chromosome banding analysis of the bone marrow is essential. Cytogenetic information is not available for a substantial number of patients (5%-20%) with dry marrow or an insufficient number of metaphase cells. For these patients, a valid risk classification is impossible. In the study presented here, the International Prognostic Scoring Systems were validated based on fluorescence in situ hybridization analyses using extended probe panels applied to cluster of differentiation 34 positive (CD34(+)) peripheral blood cells of 328 MDS patients of our prospective multicenter German diagnostic study and compared to chromosome banding results of 2902 previously published patients with myelodysplastic syndromes. For cytogenetic risk classification by fluorescence in situ hybridization analyses of CD34(+) peripheral blood cells, the groups differed significantly for overall and leukemia-free survival by uni- and multivariate analyses without discrepancies between treated and untreated patients. Including cytogenetic data of fluorescence in situ hybridization analyses of peripheral CD34(+) blood cells (instead of bone marrow banding analysis) into the complete International Prognostic Scoring System assessment, the prognostic risk groups separated significantly for overall and leukemia-free survival. Our data show that a reliable stratification to the risk groups of the International Prognostic Scoring Systems is possible from peripheral blood in patients with missing chromosome banding analysis by using a comprehensive probe panel (clinicaltrials.gov identifier:01355913). peerReviewed

Introduction For patients (pts) with aggressive B-cell lymphoma immunochemotherapy with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone) represents the standard of care with curative intention. For elderly pts a dose-reduced R-mini-CHOP protocol is feasible. No standard of care exists for frail or very old (>80 yrs) pts not eligible for CHOP-like treatment. Here we present the final results of the prospective DSHNHL-phase-2 trial for old or frail pts receiving Rituximab/Bendamustine (RB) for 1st-line treatment of aggressive B-cell lymphoma. Our goal was to determine feasibility, toxicity of the BR regimen in this pt cohort, and to determine which pts groups might potentially benefit from this reduced-intensity approach. Methods The open-label, multicenter, prospective, non-randomized phase-II trial "Subcutaneous Rituximab and Intravenous Bendamustine in very Elderly Patients or Elderly Medically Non Fit Patients ("Slow Go") with Aggressive CD20-positive B-cell Lymphoma" (B-R-ENDA, DSHNHL 2010-1, EudraCT 2010-024004-98) included all pts aged ≥81 yrs or 61-80 yrs and elevated CIRS >6, not qualifying for R- CHOP, with histologically confirmed CD20+aggressive lymphoma of any Ann Arbor-stage and IPI score, and ECOG 80 yr cohort), and treatment-associated deaths, frequency of grade 3/4 adverse events and SAEs, adherence to the protocol, complete and partial remission rate, rate of primary progression and relapse, and quality of life assessed by geriatric assessment and EORTC-QLQ-C30 for feasibility. Results: From 2012 to 2016, 68 pts (22 male, 46 female) were recruited in 24 centers into the trial and included into this intent-to-treat analysis (ITT). The median age was 81 yrs with 21% of pts older than 85 yrs. The median CIRS score was 8 and 72% had a CIRS >6. The IPI was >2 in 59% of pts. The patient population was per protocol divided into two subgroups: pts 61 to 80 yrs old and medically non-fit (29 pts) and pts older than 80 yrs (39 pts). For the 61 to 80 yrs old medically non-fit patients median age was 77 yrs (64-80), median CIRS score was 10 (2-22), IPI was > 2 in 76% of pts, 66% of pts had stage 3 or 4 disease, and ECOG was >1 in 52% of pts. For the subgroup of pts > 80 yrs, median age was 84 yrs (81-95), median CIRS score was 7 (1-17), IPI was > 2 in 46% of pts, 51% of pts had stage 3 or 4 disease, and ECOG was >1 in 23% of pts. 49% of pts received the complete treatment as planned (61-80 yrs: 38%; >80 yrs: 56%). Reasons for early termination of treatment were PD in 15% (17%; 13%) and toxicity in 24% (24%; 23%) of pts. 29% 95% Confidence interval 19-42% of pts (38%; 23%) had grade 3-5 infections. Treatment related mortality was 15% (17%; 13%). Overall response rate (ORR) was 41% (28%; 51%) with 31% CR (10%; 46%). Median observation time was 29 months for EFS, PFS and OS. 2-yrs EFS was 23% (10%; 37%), PFS was 40% (32%; 45%), OS was 42% (37%; 46%). In a multivariate analysis adjusted for IPI factors elevated LDH and ECOG >1 constituted the most significant risk factors for poor outcome. Conclusions: We describe a frail patient cohort with a median CIRS score of 8, with 72% pts with a CIRS >6, considerable comorbidities and a high percentage of high-risk IPI. The primary efficacy endpoint (2 yr PFS > 80 yrs 45%) was met; for R-mini-CHOP, this was reported at 47% (Peyrade et al., Lancet Haemat, 2011). The IPI predicts outcome in the >80 yrs cohort reliably. The RB regimen is active even in very elderly and frail pts up to 90 yrs of age. Therefore, in pts not eligible for full- or reduced dose R-CHOP treatment, it represents a tolerable and efficient alternative, albeit with a limited curative potential preferably in IPI low/intermediate-risk pts. Biomarker, comorbidity and QoL data will be analysed subsequently. Disclosures Zettl: Roche: Other: travel grants, Research Funding; Mundipharma: Research Funding. Viardot:Kite/Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees. Korfel:Mundipharma: Consultancy, Research Funding. Dreyling:Janssen: Consultancy, Other: scientific advisory board, Research Funding, Speakers Bureau; Novartis: Other: scientific advisory board; Gilead: Consultancy, Other: scientific advisory board, Speakers Bureau; Sandoz: Other: scientific advisory board; Acerta: Other: scientific advisory board; Celgene: Consultancy, Other: scientific advisory board, Research Funding, Speakers Bureau; Mundipharma: Consultancy, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: scientific advisory board, Research Funding, Speakers Bureau; Bayer: Consultancy, Other: scientific advisory board, Speakers Bureau. Illmer:Roche: Other: travel support. Schmitz:Novartis: Honoraria; Gilead: Honoraria; Celgene: Equity Ownership; Riemser: Consultancy, Honoraria. Klapper:Roche, Takeda, Amgen, Regeneron: Honoraria, Research Funding. Poeschel:Hexal: Speakers Bureau; Roche: Other: Travel support; Amgen: Other: Travel support; Abbvie: Other: Travel support; Astra Zeneca: Other: Travel support. Truemper:Takeda: Consultancy, Research Funding; Roche: Research Funding; Seattle Genetics, Inc.: Research Funding; Mundipharma: Research Funding; Janssen Oncology: Consultancy; Nordic Nanovector: Consultancy.

Introduction: Complex aberrant karyotypes (CK, ≥3 cytogenetic aberrations, CA) are associated with an unfavorable prognosis and an increased AML transformation rate in MDS. However, even MDS with CK (CK-MDS) are heterogeneous in terms of genetic profile and prognosis. Recently, we demonstrated that a high number of CA as well as mutations in TP53 (TP53mut) are associated with increased risk in CK-MDS (Haase et al, 2019). However, as there is a strong association between CK-MDS and TP53mut, it is still a matter of debate whether the karyotype and TP53mut are prognostically independent genetic markers. Furthermore, loss of heterozygosity (LOH) of 17p13 (TP53LOH), due to loss of genetic material or to copy number neutral LOH (CN-LOH), is also associated with a poor prognosis. We here aimed to characterize TP53mut andTP53LOH in CK-MDS and to elucidate the impact of cytogenetics, TP53mut and TP53LOH on the outcome of CK-MDS. Methods: We included 178 pts with MDS (N=138), CMML (N=5) and secondary AML after MDS (AML with myelodysplasia-related changes, N=35), all with CK. The median precentage of bone marrow (bm) blasts was 11% (range: 0-90%). The median age was 72 yrs (range: 30-95 yrs). The male:female ratio was 1.23:1. The number of CA was determined by banding analysis in all cases. The karyotype was confirmed by multicolor FISH in 134 cases. TP53LOH was verified by FISH analysis of the TP53 locus in 17p13 (146 analyses) and/or molecular karyotyping (MK, 41 analyses). In 144 cases further FISH probes in addition to TP53 were used. TP53mut was identified by NGS (54 cases) or Sanger sequencing (124 cases). Follow-up data for survival analyses were available for 127 pts with MDS and oligoblastic AML with less than 30% bm blasts. Results: The median number of CA was 7 (range: 3-46), 98/178 pts (55%) showed a TP53mut (median VAF: 34%, range: 8-93%) and 64/178 (36%) a TP53LOH (median FISH clone size: 65%, range: 6-99%), including 9 pts with a CN-LOH in 17p13. The CN-LOH was either identified by MK (5/41 pts (12%) where MK was available showed a CN-LOH, 4/5 with TP53mut) or by NGS (4/54 pts (7%) where NGS was available showed a VAF >70% and normal TP53-FISH). In total, a TP53mut and/or a TP53LOH was identified in 116/178 pts (65%). Overall survival (OS) did not significantly differ between CK-MDS with TP53mut only, TP53LOH only, and TP53mut+TP53LOH (Fig.1). Therefore, we merged TP53mut and TP53LOH to TP53altered in all further analyses. Regarding the cytogenetic characterization of pts with TP53altered, the number of CA was significantly higher in pts with TP53altered than in pts with normal TP53 (median 9 CA (range: 3-46) vs 5 CA (range: 3-24), P The number of CA as well as the TP53 status contributed significantly to OS (Fig.2). The presence of anemia (Hb Conclusions: The presence of ≥5 CA is associated with reduced OS in CK-MDS. A TP53mut as well as a TP53LOH both further segregate outcome. The impact of the clone size of TP53mut and TP53LOH on survival is currently being evaluated. Our data imply that the TP53 status (TP53mut and/or TP53LOH) and the complexity of the karyotype are independent prognostic markers. Based on the presence of anemia, the TP53 status (TP53mut and/or TP53LOH), and the number of CA, the individual risk of CK-MDS can be estimated more accurately. This will allow to better tailor treatment decisions for individual pts with CA. Funding (FS): 2017 SGR 288-GRC Disclosures Germing: Jazz Pharmaceuticals: Honoraria; Novartis: Honoraria, Research Funding; Amgen: Honoraria; Celgene: Honoraria, Research Funding. Kaivers:Jazz Pharmaceuticals: Other: Travel Support. Kröger:Celgene: Honoraria, Research Funding; DKMS: Research Funding; JAZZ: Honoraria; Medac: Honoraria; Neovii: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Riemser: Research Funding; Sanofi-Aventis: Research Funding. Hertenstein:RS Media: Research Funding. Döhner:Daiichi: Honoraria; Jazz: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; CTI Biopharma: Consultancy, Honoraria. Bug:Hexal: Membership on an entity's Board of Directors or advisory committees; Celgene Neovii: Other: travel grant; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Sanofi: Other: travel grants; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; Jazz Pharmaceuticals: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees. Nickelsen:Roche Pharma AG: Membership on an entity's Board of Directors or advisory committees, Other: Travel Grants; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant; Janssen: Membership on an entity's Board of Directors or advisory committees. Platzbecker:Celgene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

Results of a multicenter prospective phase II trial investigating the safety and efficacy of lenalidomide in patients with myelodysplastic syndromes with isolated del(5q) (LE-MON 5)

The gold standard of cytogenetic analysis in myelodysplastic syndromes (MDS) is conventional chromosome banding (CCB) analysis of bone marrow (BM) metaphases. Most aberrations can also be detected by fluorescence-in situ-hybridization (FISH). For this prospective multicenter German diagnostic study (www.clinicaltrials.gov: #NCT01355913) 360 patients, as yet, were followed up to 3 years by sequential FISH analyses of immunomagnetically enriched CD34+ peripheral blood (PB) cells using comprehensive FISH probe panels, resulting in a total number of 19,516 FISH analyses. We demonstrate that CD34+ PB FISH correlates significantly with CCB analysis and represents a feasible method for a reliable non-invasive cytogenetic monitoring from PB.

Sequential combination of azacitidine and lenalidomide in del(5q) higher-risk myelodysplastic syndromes or acute myeloid leukemia: a phase I study

BACKGROUND In previous work, a single administration of anticarcinoembryonic antigen (anti-CEA) 131I-labetuzumab radioimmunotherapy (RIT) after complete resection of colorectal liver metastases was well tolerated and significantly improved survival compared with controls. In the current phase 2 trial, the authors studied repeated RIT in the same setting, examining safety, feasibility, and efficacy. METHODS Sixty-three patients (median age, 64.5 years) received RIT at 40 to 50 millicuries/m2 per dose. Before the receipt of RIT, restaging was performed with computed tomography/magnetic resonance imaging and 18F-fluorodeoxyglucose–positron emission to confirm that patients were “truly adjuvant.” Patients who had elevated serum CEA levels or radiographically inconclusive new lesions were classified as “possibly nonadjuvant,” but they also received RIT. Time to progression (TTP), overall survival (OS), and cause-specific survival (CSS) were calculated. The median follow-up was 54 months. RESULTS After the first course of RIT, 14 of 63 patients experienced National Cancer Institute Common Toxicity Criteria grade 4 hematotoxicity; 19 patients did not receive the second course of RIT because of impaired performance status (N = 5) or relapse (N = 14). After the second course of RIT, 9 of 44 patients experienced National Cancer Institute Common Toxicity Criteria grade 4 hematotoxicity. Five patients developed myelodysplastic syndrome (MDS) from 22 to 55 months after their last RIT. The median TTP, OS, and CSS for all patients were 16, 55, and 60 months, respectively. The “truly adjuvant” patients (N = 39) had an improved median TTP (not reached vs 6.1 months; hazard ratio, 0.12; P

Background Few data are available on therapy-related myelodysplastic syndromes and acute myeloid leukemia developing after radioiodine treatment. Design and methods We retrospectively analyzed 39 patients with myeloid neoplasms following radioiodine treatment, whose data were reported to the Duesseldorf Myelodysplastic Syndromes Register (8 of 3814 patients) and five other German Myelodysplastic Syndromes centers (n=31) between 1982 and 2011. These data were compared with those from 165 patients from our Myelodysplastic Syndromes Register with therapy-related myeloid neoplasms following chemotherapy (n=90), radiation (n=30), or radiochemotherapy (n=45). Results With a median latency of 79 months, 18 patients developed therapy-related acute myeloid leukemia and 21 presented with therapy-related myelodysplastic syndromes (8 refractory anemia with excess blasts I/II, 6 refractory anemia with multilineage dysplasia, 3 myelodysplastic syndromes with del(5q), 1 refractory anemia, 1 refractory anemia with ring sideroblasts, 1 chronic myelomonocytic leukemia II, 1 myelodysplastic/myeloproliferative neoplasm unclassifiable). Risk assessment according to the International Prognostic Scoring System was low-risk in 23%, intermediate-1 in 29%, intermediate-2 in 35%, and high-risk in 13%. Karyotype was abnormal in 68%, with chromosomes 7 (30%), 5 (26%), 8 (26%) and 3 (17%) being most frequently affected. No differences in the distribution of gender, World Health Organization subtype, acute myeloid leukemia progression, International Prognostic Scoring System score, and cytogenetic risk were observed between patients with therapy-related myeloid neoplasms following radioiodine or other treatment modalities. Of 17 patients who received induction chemotherapy, 71% were refractory to this treatment or died from treatment-related toxicity. The median overall survival in the entire group was 21.7 months (95%-CI 10.5-33 months) and did not differ significantly in comparison to the survival of patients with therapy-related myeloid neoplasms following other cytotoxic treatments. Patients with therapy-related acute myeloid leukemia had significantly inferior overall survival (12.4 versus 28.7 months, P=0.002). Conclusions Patients developing a therapy-related myeloid neoplasm after radioiodine treatment usually present with biological characteristics similar to those seen in patients with therapy-related myeloid neoplasms following other cytotoxic treatment modalities, associated with a low response rate to induction chemotherapy and poor prognosis.

Introduction: Loss of the Y-chromosome (LOY) is frequent in myelodysplastic syndromes (MDS) and observed as a single aberration in 3-4% of male MDS patients (pts). It is often clonal and not only age associated and confers a very good prognosis and a very low risk for leukemic transformation (Greenberg et al, Blood 2012; Schanz et al, JCO 2012). But LOY does not prove a hematologic disease per se (Arber et al, Blood 2016). To facilitate a better discrimination between age-related and clonal LOY, the aim of this study was to identify molecular mutations and cytomorphological features which might be characteristic for MDS with isolated LOY. Methods: We included 291 pts in our analysis. The cohort comprised 199 pts with normal karyotype (NK) and morphologically proven MDS (excess blasts (EB) in 77/199 (38%) pts) and 92 pts with LOY. NK was defined by 20 normal metaphases or at least 10 normal metaphases and normal fluorescence in situ hybridization (FISH, Tab.1). Results from mutational analysis were available for all pts with NK and for 61 pts with LOY as single cytogenetic aberration in ≥3 metaphases. Seventeen core genes (Tab.2) were sequenced in all 260 pts by Sanger and/or next generation sequencing (NGS). In 134 pts further 28 genes (Tab.2) were analyzed using one of two NGS panels. In addition to these myeloid genes, the second NGS panel covered single nucleotide polymorphisms on the Y-chromosome which enabled determination of the LOY clone size. Detailed cytomorphology for the evaluation of dysplasia was performed by two experts (UG, UB) as previously described (Germing et al, Leuk Res 2012) in 41 pts, including pts with small LOY clones and with cytogenetic sub-clones. Results: Sequencing of 40 pts with LOY and morphologically proven dysplasia showed higher frequencies of mutations in TET2 (epigenetic regulator), ZRSR2 (splicing factor, located at Xp22.2), and CBL (kinase signaling) compared to MDS with NK (Fig.1). Amongst others, mutations in IDH1/2 (epigenetic regulators) and RUNX1 (transcription factor) were rare in MDS with LOY (Fig.1). The total number of mutated core genes did not significantly differ between MDS with LOY and MDS with NK and no EB (p=0.54), but it was significantly higher in MDS with NK and EB (p=0.014, Fig.2). To distinguish between LOY as ancestral or secondary mutation we sequenced 12 pts with MDS and cases we included as clonal cytopenia of undetermined significance (CCUS, pts with cytopenia(s) and molecular mutation and/or LOY≥75% of metaphases) (Wiktor et al, GCC 2000) using the second NGS panel that allowed determination of LOY clone size and detection of molecular mutations. Thereby, we identified four pts where LOY was most likely the founder aberration, two pts with LOY as secondary aberration in addition to ancestral molecular mutations, and six pts with co-dominance of LOY and a molecular mutation (Fig.3). Finally, we aimed to evaluate if the cut off of LOY≥75% (Wiktor et al, GCC 2000) can distinguish between age-related and clonal LOY in our cohort. In 41 pts analyzed in more detail, peripheral blood counts (hemoglobin: mean 10.4 vs. 9.7 g/dL; white blood count: 4.9 vs. 6.0x10(9)/L, platelets: 163 vs. 198x10(9)/L) and dysplasia of the individual cell lines (erythro-, granulo-, megakaryopoesis) did not differ significantly between LOY≥75% and Conclusions: Cytopenia with isolated LOY seems to comprise a heterogeneous mixture of cytomorphologic and molecular subtypes. We identified pts where LOY definitely is part of the MDS clone that also harbors molecular mutations, indicating that LOY is not only age-associated in these cases. The low total number of mutated genes corresponds to the previously described favorable prognosis of isolated LOY (Schanz et al, JCO 2012; Greenberg et al, Blood 2012). Our data support the current guidelines that LOY does not prove a hematologic disease in the absence of diagnostic morphologic features. In these cases LOY might fulfill the requirements of a clonal mutation as described for clonal hematopoiesis of indeterminate potential (CHIP) or CCUS. In summary, our data suggest that MDS with LOY shows a characteristic molecular mutation profile. Disclosures Germing: Janssen: Honoraria; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

In myelodysplastic syndromes (MDS), deletion of the short arm of chromosome 12 (del(12p)) is usually a small abnormality, rarely detected as a single aberration by chromosome banding analysis (CBA) of bone marrow metaphases. Del(12p) has been described in 0.6 to 5% of MDS patients at initial diagnosis and is associated with a good to intermediate prognosis as a sole anomaly according to current scoring systems. Here, we present the results of a systematic del(12p) testing in a German prospective diagnostic study (clinicaltrials.gov: NCT01355913) on 367 MDS patients in whom CD34+ peripheral blood cells were analysed for the presence of del(12p) by sequential fluorescence in situ hybridization (FISH) analyses. A cohort of 2,902 previously published MDS patients diagnosed by CBA served as control. We demonstrate that, using a sensitive FISH technique, 12p deletion occurs significantly more frequently in MDS than previously described (7.6% by CD34+ PB-FISH vs. 1.6% by CBA, P0.001) and is often associated with other aberrations (93% by CD34+ PB-FISH vs. 60% by CBA). Additionally, the detection rate can be increased by repeated analyses in a patient over time which is important for the patient´s prognosis to distinguish a sole anomaly from double or complex aberrations. To our knowledge, this is the first study to screen for 12p deletions with a suitable probe for ETV6/TEL in 12p13. Our data suggest that the supplement of a probe for the detection of a 12p deletion to common FISH probe panels helps to avoid missing a del(12p), especially as part of more complex aberrations.

Loss of the Y-chromosome (LOY) is described as both a normal age-related event and a marker of a neoplastic clone in hematologic diseases. To assess the significance of LOY in myelodysplastic syndromes (MDS), we determined the percentage of LOY in clonal CD34+ peripheral blood cells in comparison to normal CD3+ T-cells of 27 MDS patients using fluorescence in situ hybridization (FISH) analysis. Results were compared with the percentage of LOY in CD34+ and CD3+ cells of 32 elderly men without hematologic diseases and in 25 young blood donors. While LOY could not be detected in CD3+ cells of young men, it was observed in CD3+ cells of elderly men without hematologic diseases (2.5% LOY) as well as in CD3+ cells of elderly MDS patients (5.8% LOY). The percentage of CD34+ cells affected by LOY was significantly higher in MDS patients compared to elderly men without hematologic diseases (43.3% vs. 13.2%, P = 0.005), indicating that LOY has an age-related basis but is also associated with MDS. Furthermore, we aimed to define a threshold between age- and disease-associated LOY in MDS. Statistical analysis revealed that a value of 21.5% LOY in CD34+ peripheral blood cells provided the best threshold to discriminate between these two conditions in MDS. We conclude that LOY is clonal in a substantial number of MDS based on an age-related predisposition.

A 67 year old patient was diagnosed with grade I extranodal follicular lymphoma of the parotid gland. She suffered from a painless swelling of the right parotid gland. No other symptoms, especially no B-symptoms were present on admission. The physical examination as well as the laboratory study was all normal. Histological, immunhistochemical and molecular genetic workup of the parotid gland showed an infiltration by a population of small CD20and CD10-positive clonal B-cells, consistent with an extranodal follicular Non Hodgkin Lymphoma (FL), grade I. The staging examinations (CAT scan, bone marrow trephine) showed no further lymphoma involvement apart from multiple hypoattenuating lesions in the spleen suspicious of a splenic infiltration of the lymphoma (Figure 1, white arrow). Since the treatment approach for a limited stage IEA (FLIPI 1) FL is curative, whereas a more extensive Ann Arbor stage [1] IIIEA (FLIPI 2) with spleen involvement is palliative, splenectomy was performed to define the exact stage of the disease. The histological workup showed multiple anastomosing neovascular channels lined by cells which have endothelial and histocytic (CD 68) properties, indicative of a littoral cell angioma (LCA) of the spleen (Figure 2 white arrow) beneath physiological lymphoid follicles (Figure 2, black arrow). The LCA is a rare splenic vascular tumor that derives from littoral cells which cover the splenic sinus channels of the red pulp. It was first described in 1991, normally shows a benign behavior and can be associated with solid and haematological neoplasias. Characteristic, but not specific CAT-findings are multiple defects in the spleen with low contrast. To exclude malignant primary splenic entities such as an angiosarcoma, splenic metastases, or, as suspected here, a lymphoma infiltration, a splenectomy is advisable in most cases [2]. In our patient, a splenic involvement of the spleen could be ruled out, and she underwent an involved field radiation and is still in remission 5 years later.

7500Background: Standard treatment in pTNHL pts is unsatisfactory due to a high rate of early progression. Alemtuzumab (A), a monoclonal anti-CD52 antibody, has demonstrated efficacy in relapsed pTNHL pts, and phase II trials have shown feasibility of concomitant A+CHOP application. We report the final analysis of the international ACT-2 phase III randomized trial in elderly pts comparing standard CHOP to A-CHOP. Methods: Between 2007 and 2013, 116 pts from 52 centers were randomized to receive either 6 cycles of CHOP or A-CHOP at 14-day intervals with G-CSF support. Pts were to receive a total of 360 mgs A (until pt 39) or 120 mg. The protocol demanded stringent CMV / EBV monitoring and anti-infective prophylaxis. The study was powered to detect a 15% increase in EFS with the addition of A to CHOP. Results: 116 pts (median age 69 yrs, 58% male) were randomized (58/58). Histologies were 41% AITL, 39% pTNHL NOS , 6% ALCL , 14% other subtypes. Complete treatment as planned was applied in 79% (CHOP) resp 57%...

Trough total imatinib (t-IM) concentrations have been reported to be associated with therapeutic and toxic responses in patients with chronic myelogenous leukemia (CML) and gastrointestinal stromal tumor (GIST). Little is known about the relationships between effects and concentrations of either unbound imatinib (f-IM) or imatinib's major metabolite, N-desmethyl imatinib (NDI). In part, this is because of the lack of a single, validated, well-described clinically useful assay for these measurements. The authors report the development and application of such an assay.A single liquid-chromatography tandem-mass-spectrometry assay was used to monitor t-IM, f-IM, and t-NDI concentrations in CML and GIST patients treated at a tertiary German teaching hospital. The assay was also validated for measuring other kinase inhibitors, including t-nilotinib, sunitinib, and erlotinib. Ultrafiltration assays were validated and used to measure f-IM and to compare free fractions to plasma α1-acid glycoprotein concentrations (AGP).The assays were linear over a working range (in micrograms per liter) of 8.4-8370, 8.3-4165, and 1.0-250 and had within- and between-run coefficient of variance of7%,12%, and9% for t-IM, t-NDI, and f-IM, respectively. The f-IM assay was reproducible despite high (25.2%-31.6%) but concentration-independent binding to ultrafiltration devices. Clinically relevant results, such as nondetectable (ND) t-IM (8.4 μg/L) in non-responders and1500 μg/L in patients with major toxicity, were found. Of 156 total samples from 68 adult CML patients and 127 total samples from 42 adult GIST, only 48 samples from 22 CML patients and 40 samples from 20 GIST patients were trough samples with adequate dosing and collection information. More than half (27 of 48 CML and 24 of 40 GIST) had t-IM concentrations ≥10% below recommended target concentrations (1002 μg/L for CML and 1100 μg/L for GIST). Concentrations50% over targets were also found in 6 of 48 CML and 4 of 40 GIST samples. Wide variations in concentrations of t-IM (range, ND to 2973 μg/L), t-NDI (range, ND to 659 μg/L), f-IM (range, 8.3-262 μg/L), and t-IM:f-IM ratios (range, 2.6%-14%) were found both between and within patients. A statistically significant association (Spearman correlation coefficient and P value for all samples, r = 0.290 and P = 0.023; for trough only, r = -0.585 and P = 0.028) was found between AGP and f-IM concentrations but wide interpatient and intrapatient variations made individual predictions unreliable.The liquid-chromatography tandem-mass-spectrometry methods developed provided information useful to understand individual responses to therapy even though necessary sampling and dosing information was often not available. Wide unpredictable variations in t-IM, t-NDI, and f-IM were found. Clinical outcome trials are needed to examine whether f-IM or NDI monitoring can improve the ability to predict individual responses.

Cytogenetic aberrations are major markers in pathogenesis, diagnosis, and prognosis of patients with myelodysplastic syndromes (MDS). Their relevance for an individualized therapy in selected patients with MDS is increasing. Using conventional chromosomal banding analysis, aberrations are detectable in about 50% of patients. The application of additional methods like fluorescence in situ hybridization (FISH)-techniques improves the detection rate and diagnostic accuracy. In spite of the cytogenetic heterogeneity of MDS patients, the prognostic impact of the most frequent chromosomal changes is known and the understanding of rare abnormalities, independent clones, and double and complex aberrations is increasing. Future research will also focus on karyotype evolution, as it could give notice of disease progression and thus affect therapy decisions. International cooperations facilitate to unravel the remaining challenges for cytogenetics in MDS.

In myelodysplastic syndromes (MDS) chromosomal anomalies can be identified in 50-80% of patients. They have a diagnostic and prognostic impact and are increasingly considered for therapeutic decisions. Cytomorphology and cytogenetic analyses of bone marrow (bm) cells define the goldstandard to diagnose MDS patients and to document treatment response. We present a novel method using peripheral blood (pb) for frequent cytogenetic monitoring: after immunomagnetic cell separation circulating CD34+ cells were analysed by fluorescence in situ hybridization (FISH). We compared FISH analyses of enriched and non-enriched pb and bm cells with conventional chromosome banding analyses of bm metaphases: analysing circulating CD34+ cells by FISH is a sensitive, reliable method to measure the abnormal cell clones in pb. This method is practicable, non-invasive, representative for the clonal situation in the bm, and has a predictive value. Its feasibility was proven in a cohort of 27 MDS patients.

Introduction: Total (-7) or partial (7q-) monosomy 7 is the second frequent abnormality in MDS, occurring in around 12% of MDS/AML and up to 40% of therapy-associated MDS/AML. The present study was designed to analyze clinical features, prognosis and response to different therapeutic strategies in patients with -7 or del(7q) in a multicentric, retrospective cohort study. Patients and Methods: 471 patients with MDS/AML following MDS and monosomy 7 were registered and retrospectively analyzed. The median observation time was 3.6 years. Inclusion criteria were defined as follows: Morphologic diagnosis of MDS/AML following MDS, bone marrow blast count Results: 147 patients (31.2%) showed 7q-, 313 (66.5%) -7 and 11 (2.3) patients showed both abnormalities at the first cytogenetic examination. The abnormality was detected by CBA±FISH in 440 (93.4%) and by FISH only in 31 (6.6%). In the latter cases, the CBA was either unsuccessful or showed a normal karyotype. In 182 (38.6%) patients, -7/del7q was detected as a single abnormality, 77 (16.3%) showed two abnormalities and 184 (39.1%) showed a complex karyotype involving -7/7q-. As previously described (Schanz et al., 2012), untreated patients with an isolated 7q- as compared to an isolated -7 show a better prognosis regarding OS (median: 4.0 vs. 0.7 years; p Conclusions: To our knowledge, the study describes the largest patient cohort with MDS/AML and monosomy 7 published to date. Further data regarding the clinical characteristics of this subgroup of patients and the treatment regimes applied will be presented in detail. The study was supported by research funding from Celgene Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Schanz: Celgene: Honoraria, Research Funding, Travel grants: Celgene, Novartis, Lilly Other. Götze:Celgene Corp, Novartis Pharma: Honoraria. Nolte:Celgene, Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel grants Other.

Introduction Total (-7) or partial (7q-) monosomy 7 is frequent in malignant myeloid disorders, observed in around 12% of MDS/AML and up to 40% of therapy-associated MDS/AML. Monosomy 7 is associated with poor outcome, high susceptibility to infections and poor response to chemotherapy. A therapeutic benefit for 5-azacytidine was previously described (Fenaux et al., 2009). The present study was designed to analyze clinical features, prognosis and response to different therapeutic strategies in patients with monosomy 7 in a multicentric, retrospective German cohort study. Patients and methods Currently, 231 patients with MDS/AML following MDS and monosomy 7 were included. Inclusion criteria were defined as follows: Morphologic diagnosis of MDS/AML following MDS, age ≥18 years, bone marrow blast count ≤30% and presence of -7 or 7q-. The data was assembled from centers in Düsseldorf, (n=120; 52%), Cologne (n=38; 17%), Freiburg (n=31; 13%), Göttingen (n=14; 6%), Munich (n=13; 6%), Dresden (n=11; 5%) and Mannheim (n=4; 2%). The median age in the study cohort was 67 years, 65% of patients were males. 29/231 patients (13%) were diagnosed as AML following MDS. MDS/AML was therapy-associated in 24 patients (11%). Regarding IPSS, 38 (19%) were classified as low/intermediate 1 risk and 165 (81%) as intermediate-2/high-risk. According to IPSS-R, 2 (1%) were assigned to the very-low/low risk group, 31 (16%) to the intermediate group, 52 (27%) to the high-risk group and 107 (56%) to the very high risk group. The treatment was classified as follows: Best supportive care (BSC), low-dose Chemotherapy (LDC), high-dose chemotherapy (HDC), demethylating agents (DMA; either 5-azacytidine or decitabine), and others. Results A best supportive care regimen was chosen in nearly half of the patients (49%). The remaining patients received 1-4 sequential therapies (1: 29%; 2: 11%; 3: 10%; 4: 1%). As the first line therapy, 64 patients (54%) received DMA, 24 (20%) an allo-Tx, 9 (8%) HDC, 5 (4%) LDC, and 16 (14%) were treated with other therapies. The best prognosis was observed in patients eligible for allo-Tx: The median OS in transplanted patients was 924 days as compared to 361 days (p Conclusions Patients with MDS, partial or total monosomy 7 and a high risk according to IPSS or a very high risk according to IPSS-R show a pronounced benefit when treated with DMA, regarding overall- as well as AML-free survival. Further results from the ongoing data analysis will be presented in detail. The study was supported by research funding from Celgene. Disclosures: Schanz: Celgene: Research Funding. Braulke:Celgene: Research Funding. Germing:Celgene: Honoraria, Research Funding. Schmitz:Novartis: Research Funding; Celegene: Consultancy, Research Funding, Speakers Bureau. Götze:Celgene: Honoraria. Platzbecker:Celgene: Honoraria, Research Funding. Haase:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

Abstract 3816 Background Conventional chromosome banding (CCB) analyses of bone marrow (bm) metaphases represent the gold standard of cytogenetic diagnostics in myelodysplastic syndromes (MDS), but they are not suitable for frequent follow-up analyses. Most aberrations can also be detected by fluorescence in situ hybridisation (FISH), and they are provable in CD34+ cells from peripheral blood (pb). In our prospective multicenter German diagnostic study “Screening and genetic monitoring of patients with MDS under different treatment modalities by cytogenetic analyses of circulating CD34+cells” (ClinicalTrails.gov NCT01355913) we followed MDS pts by sequential FISH analyses. Methods CD34+ pb cells were enriched by immunomagnetic cell sorting (MACS®) and analysed by FISH using a “Superpanel” (D7/CEP7, EGR1, CEP8, CEP XY, D20, TP53, IGH/BCL2, TEL/AML1, RB1, MLL, 1p36/1q25, CSF1R, all Abbott® Products) at initial screening, every 12 months during follow-up and in case of suspected disease progression and a “Standardpanel” (EGR1, D7/CEP7, CEP8, TP53, D20, TEL/AML1, CEP XY, plus -if necessary- another informative probe) every 2 months in the 1st and every 3 months in the 2nd and 3rd year. If bm aspirate was available, additional CCB and FISH analysis of CD34+ and native bm cells were performed. Cut-off values for each FISH probe were evaluated in our lab. Cytogenetics, bm morphology, clinical course and therapies were documented in a database. All pts gave their written informed consent. The study was approved by all local ethic committees. Results After 3 years of study time, 361 patients (25 AZALE (University of Dresden), 110 LEMON5 (University of Duesseldorf), 226 CD34+FISH) have been included in the study, resulting in a total number of 19,516 FISH analyses: Median age, gender distribution and MDS subtypes were typical for the disease, median follow-up at the time of analysis was 8.2 (1–36) months. Chromosomal aberrations could be detected by FISH of CD34+ pb cells in 71.5% of pts (55% of CD34+FISH-cohort, 99% of LEMON5-trial pts, 100% of AZALE-trial pts). FISH and CCB were highly correlated: p Discussion Our interim results demonstrate that FISH analysis of circulating CD34+ pb cells provides relevant cytogenetic informations. It is a reliable novel method for screening and cytogenetic monitoring of MDS pts during the course of disease and under different therapies, and helps in cases where a bm biopsy is not possible or not successful. Disclosures: Braulke: Celgene: This study was supported by Celgene. Other. Götze:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Bug:Celgene: Honoraria, travel support, advisory board Other; Novartis: Honoraria, travel support, advisory board, travel support, advisory board Other; Boehringer Ingelheim: Honoraria, travel support, advisory board, travel support, advisory board Other. Schafhausen:Novartis: Honoraria, travel support Other; BMS: Honoraria, travel support, travel support Other; Roche: Honoraria, travel support, travel support Other; Celgene: Honoraria, travel support, travel support Other; Alexion: Honoraria, travel support Other. Haase:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.