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Background: Measurable residual disease (MRD) is an important biomarker in acute myeloid leukemia (AML). Among patients who achieve remission after standard chemotherapy, detection of MRD (MRD+) after two cycles of intensive chemotherapy, at the end of consolidation and before allogeneic stem cell transplantation (alloHSCT) is a strong prognostic factor for relapse and shorter overall survival (OS) (Short NJ, JAMA Oncol. 2020). The optimal time-points to asses MRD, and MRD cut-offs as well as whether eliminating of MRD due to further chemotherapy improves an outcome still remain open questions. PALG-AML1/2016 study aims to compare the safety and efficacy of two commonly used induction and salvage regimens in AML (NCT03257241). This is also the first international randomized trial in AML induction to prospectively evaluate the impact of MRD on overall survival, using multi-modality testing (flow-cytometry, FC; next-generation sequencing, NGS) of serial samples. Study Design: In this study, 582 adult patients with newly-diagnosed AML will be randomized to DA-90 or DAC induction. Patients with complete remission (CR) or CR with incomplete hematologic recovery (CRi) receive further post-remission therapy adjusted to predefined risk group. The serial samples for multimodal MRD evaluation are collected at D14 (MRD-1), at time of CR/CRi after single or two induction cycles (MRD-2), and after each consolidation cycle (MRD-3, -4, -5). Material and Methods. The aim of this preliminary analysis was to evaluate the prognostic value of bone marrow assessment at D14 both cytological and by FC (MRD-1) as well as the kinetics of MRD during post-remission treatment. Multivariable logistic regression models were developed with significant variables from univariate analyses, including MRD and blast count. The predictive power of the MRD level and blasts percentage at D14 was evaluated by receiver operating characteristics (ROC) and area under the curve (AUC) analysis to determine the ability of the biomarkers to accurately predict response to the induction treatment. Results: The study group consisted of 284 patients (mean age: 47.1 ± 10.9) recruited until the end of May 2021. MRD-1 by FC was reported in 225 patients. CR and CRi either after single or double induction were achieved in 175 (61.6%) and 48 (16.9%) patients, respectively leading to an overall CR/CRi rate 78.5%. In univariate analyses, the factors significantly associated with achieving CR/CRi were: ELN high-risk group (OR 0.12, 95% CI: 0.05-0.33, p MRD-3 at the end of consolidation 1 was reported in 182 patients: MRD+ in 99 (54.4%) and MRD- in 83 (45.6%) patients. Results of MRD-4 at the end of consolidation 2 were available in 114 patients with 49 (43.0%) being MRD+ and 65 (57.0%) MRD-. Fifty-eight patients (35 MRD-2+ and 23 MRD-2-) were evaluated for MRD kinetics from the end of induction until the end of consolidation 3. Conversion rate from MRD- to MRD+ was 13% (n=3) and from MRD+ to MRD- 34%(n=12), respectively (p=0.038). Conclusions: Our preliminary results suggest that flow cytometric bone marrow assessment on D14 has a predictive value for CR/CRi achievement and a potential prognostic utility for overall survival. The kinetics of MRD during consolidation requires further studies to better evaluate its prognostic significance. References Short NJ, JAMA Oncol. 2020; Zhou S, Fu C, et al. Association of Measurable Residual Disease with Survival Outcomes in Patients with Acute Myeloid Leukemia: A Systematic Review and Meta-analysis. 6(12):1890-1899. Disclosures Wierzbowska: Celgene/BMS: Consultancy; Jazz: Research Funding; Novartis: Consultancy; Abbvie: Consultancy; Astellas: Consultancy; Janssen: Consultancy. Libura: Novartis: Consultancy, Research Funding. Giebel: Pfizer: Consultancy, Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau. Czemerska: Novartis: Honoraria; Takeda: Honoraria. Sobas: Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Wróbel: Takeda: Honoraria, Speakers Bureau; BMS: Honoraria; Novartis: Honoraria, Speakers Bureau; BeiGene: Honoraria; Janssen: Honoraria, Speakers Bureau; Roche: Honoraria, Research Funding, Speakers Bureau. Patkowska: Bristol-Myers Squibb: Other: Travel fees; Angelini Pharma: Honoraria, Other: Travel fees; Jazz Pharmaceuticals: Other: Travel fees; Pfizer: Other: Travel fees; Astellas Pharma, Inc.: Consultancy, Other: Travel fees; Servier: Honoraria, Other: Travel fees; KCR US, Inc.: Consultancy; Novartis: Honoraria, Other: Travel fees; AMGEN: Honoraria. Desai: Kura Oncology: Consultancy; Astex: Research Funding; Agios: Consultancy; Takeda: Consultancy; Bristol Myers Squibb: Consultancy; Janssen R&D: Research Funding. Lee: Innate: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pin Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees. Ritchie: Astellas: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; ARIAD Pharmaceuticals: Ended employment in the past 24 months, Speakers Bureau; Jazz: Consultancy, Research Funding; Takeda: Consultancy, Honoraria; Celgene/BMS: Consultancy, Other: travel support, Speakers Bureau; NS Pharma: Research Funding; Abbvie: Consultancy, Honoraria; Protaganist: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding. Guzman: SeqRx: Consultancy; BridgeMedicines: Consultancy; Cellectis: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees. Roboz: Actinium: Consultancy; Novartis: Consultancy; Astellas: Consultancy; Amgen: Consultancy; Otsuka: Consultancy; Jazz: Consultancy; Agios: Consultancy; Jasper Therapeutics: Consultancy; AbbVie: Consultancy; Astex: Consultancy; Helsinn: Consultancy; Glaxo SmithKline: Consultancy; Daiichi Sankyo: Consultancy; Celgene: Consultancy; Blueprint Medicines: Consultancy; Bayer: Consultancy; MEI Pharma - IDMC Chair: Consultancy; Mesoblast: Consultancy; AstraZeneca: Consultancy; Bristol Myers Squibb: Consultancy; Janssen: Consultancy; Janssen: Research Funding; Pfizer: Consultancy; Roche/Genentech: Consultancy. OffLabel Disclosure: cladribine in the induction chemotherapy

Objectives:Cytogenetics is one of the most important prognostic factors in acute myeloid leukemia (AML). Two major, partially overlapping cytogenetic subsets of AML associated with an adverse prognosis, are AML with complex karyotype (CK) and AML with monosomal karyotype (MK). MK has been shown to constitute a cytogenetic feature that identifies AML patients (pts) with very poor outcomes when treated with currently available therapy. CK-AML pts are very heterogeneous cytogenetically, and treatment outcomes of these subsets are also influenced by TP53 alterations, complexity of the karyotype or presence of residual normal metaphases. However, impact of all these variables on outcome of CK-AML patients was so far analyzed separately. The aim of our study was to assess treatment outcome of CK-AML patients with or without MK regarding some cytogenetic and clinical features. Materials and methods: One hundred twenty five newly diagnosed AML patients with CK treated between January 2007 and January 2013 with PALG protocols (Holowiecki et al., JCO 2012) were included into the study. Cytogenetic analysis was performed on metaphases from bone marrow aspirates taken at diagnosis using standard banding techniques. Karyotypes were reported in accordance with the ISCN 2009. CK was defined as a presence of ≥ 3 unrelated abnormalities. MK was defined by the presence of an autosomal monosomy in conjunction with at least one other autosomal monosomy or structural abnormality in the absence of t(8;21), inv(16), t(15;17) (Breems et al., JCO 2008). FISH method was used to verify MK in all cases with monosomy as well as to assess 17p13 (TP53) deletion. Results:Clinical characteristics. The median age of all pts was 60 years (range 19-85 years). FISH verification proved the MK karyotype (MK+) in 75 out of 125 (60%) pts with CK-AML. Remaining pts had non-monosomal CK (MK-). Sixty six (55%) pts received intensive induction chemotherapy (IC) according to PALG protocols and 59 pts received non-intensive treatment with low-dose cytarabine (LDAC) or best supportive care (BSC). Baseline characteristics were generally balanced between MK+ and MK- groups in terms of age, WBC and PLT counts, hemoglobin level, percentage of bone marrow blasts at diagnosis and presence of residual normal metaphases in the karyotype. Higher proportions of MK+ pts had deletion of 17p13 (TP53) (47,9% vs. 20,4% of MK-; p=0.0017) as well as ≥5 cytogenetic aberrations (93,3% vs. 74%; p=0.004). Furthermore, there were no differences in the proportion of IC, LDAC and BSC strategies between both groups. Treatment Response and Outcome. With the median time of follow-up 7,7 months (mos), median OS in MK- pts was significantly longer compared to MK+ group (4,5 mos vs. 2,0 mos; p=0.0075). 66/125 CK-AML pts received standard IC according to PALG AML protocols (DA-36 pts; DAC-27 pts and DAF-3 pts). Only 7 pts underwent allogeneic stem cell transplantation (allo-SCT). In intensively treated pts the overall CR rate in MK- was about twice as high as in MK+ group (62,1% vs 32,4%; p=0.013). The median OS in MK- pts was longer compared to MK+ group (6,8 mos vs. 2,7 mos; p=0.016). Probability of 1-year OS in MK+ vs. MK- group was 14% vs. 30%. In multivariate analysis we have found that WBC >20 G/l, MK and ≥5 chromosomal abnormalities were independent prognostic factors associated with significantly shorter OS (Table 1). In contrast, allo-SCT was associated with survival benefit. Furthermore, we analyzed the impact of purine analogue containing induction regimens on treatment outcome. We found that addition of cladribine to the standard DA regimen improves OS in MK- but not in MK+ group (Figure 1). Conclusions: Monosomal karyotype, high WBC count and high complexity of the karyotype (≥5 aberrations) are associated with more aggressive clinical course and short survival in high-risk CK-AML. Cladribine added to standard DA induction regimen prolongs survival of pts with complex but not monosomal karyotype. *AW and EW equally contributed to the study. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Abstract 4848 Background Myelodysplastic syndrome(MDS) belong to the most common hematological diseases however epidemiological data on MDS are sparse. Until 2008 there were no data about epidemiology of MDS in Poland. Methods From 03.2008-05.2009 we have registered 966 patients in Polish MDS Registry. We have included only alive patients of various time of diagnosis. Patients from 22 centers were diagnosed according to WHO 2001 criteria. Results There were 508(53%)males and 458(47%) females. Median age at diagnosis was 70(range 19-99). Under 50 were 83(9%) cases with preponderance of females- 51 cases( males 32cases), between 50-70 there were 353(41%) cases, half of the patients-432(50%) were above 70( 247 males and 185 females).Prior chemotherapy and/or radiotherapy had 37((3,8%) patients. Distribution of MDS subtypes was as follows: RA-170(20%) cases, RARS-58(7%), RCMD-244(28%), RCMD-RS-18(2%), RAEB-1-120(14%), RAEB-2-169(19,5%), 5q- -40(4,6%), MDS-U-44(5%).In 103(10%) subtype was not done. Karyotype was available in 276(28%) cases. Cytogenetic risk groups were: low risk-182(68%), intermediate-52(20%) and high risk-33(12%). The most frequent cytogenetic results were: normal karyotype 44%, isolated 5q deletion 19%, complex karyotype 6%, 5q deletion + another one change 3% and 5q deletion with at least 2 changes 3%. According to IPSS risk groups low risk was found in 61( 22%) of cases, intermediate-1 -130(48%), intermediate-2-47(17%) and high risk in 31(11,5%). Median values of Hb was 9,1 g/dL, plts 129 G/L, ANC 1,7 G/L. RBC transfusion dependent were 429(44%) patients and platelet transfusion dependent were 100( 11%) pts. At least 2 U/month RBC transfusion requirement was 140(14%) patients. Serum ferritin level was assessed in 530 cases-171 of them( 32%) had higher than 1000μg/L level. Conclusions We have observed predominance of females among MDS patients under 50. Half of the patients had RA or RCMD subtype. Isolated 5 q deletion was the most frequent cytogenetic abnormality. Forty four percentage of patients was RBC transfusion dependant. Serum ferritin level was significantly elevated in 32% of assessed patients at the moment of MDS diagnosis. Disclosures No relevant conflicts of interest to declare.