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Introduction: Iron storage in patients (pts) with myelodysplastic syndromes at the time of diagnosis may vary from normal to iron overload. Even before the first blood transfusion, storage iron can be increased due to down-regulation of hepcidin and subsequent increase in duodenal iron uptake. Iron overload is known to worsen the prognosis of MDS patients, partly due to iron-related organ damage after long-term transfusion therapy, and partly due to an increased risk of infections. However, it is unclear whether increased storage iron at the time of diagnosis already has a prognostic influence. We assessed bone marrow iron stores at the time of MDS diagnosis and correlated them with clinical outcome. Methods: In a retrospective analysis of 3762 adult MDS patients from the Düsseldorf MDS Registry, Prussian blue staining of marrow smears was performed in our cytology lab to assess iron stores according to the following categories: normal or decreased iron stores versus increased iron stores versus iron overload. Patients were followed up for survival and AML evolution until June 2021. Median time of follow-up was 20 months. 67.4% of the patients died during the course of the disease. Results: The study included 3.762 adult patients who received their initial diagnosis of MDS between 1970 and 2021. 58% were diagnosed as non-blastic MDS ( MDS SLD (RS) (n=240), MDS MLD (RS) (n=350), MDSdel(5q) (n=107), and MDS-U (n=25). Iron stores were decreased in 8% of the patients, normal in 44%, increased in 41%, and strongly increased in 7% (massive iron overload). In 282 cases, histologic assessment of storage iron was available. When comparing cytologic and histologic assessment, we found a strong correlation (p The cumulative risk of AML evolution was not associated with the results of iron staining. Regarding survival, we found that patients with decreased or normal storage iron had a median survival of 31 months, whereas those with increased iron had a median survival of 28 months (p=0.007). Focusing on patients with non-blastic MDS, the difference was not significant (46 vs 44 ms). However, patients who presented as EB I (n=435), EBII (n=510), AML MRC (n=264), CMML I (n=254), or CMML II (n=77), showed a prognostic impact of storage iron; patients with increased iron had a median survival of 11 months, as compared to 16 months in patients with normal or decreased iron (p Conclusion: Increased tissue iron in the bone marrow at the time of diagnosis is associated with inferior survival in patients with MDS, primarily in patients with higher risk MDS. At diagnosis, patients are not yet transfusion-dependent. This suggests that increased iron reflects a prolonged period of increased duodenal iron uptake as a consequence of ineffective erythropoiesis. Therefore, increased marrow iron at the time of MDS diagnosis seems to be a surrogate parameter of hematopoietic insufficiency, which is the real cause of inferior prognosis. Disclosures Nachtkamp: Jazz: Honoraria; Bsh medical: Honoraria; Celgene: Other: Travel Support. Gattermann: Novartis: Honoraria; Takeda: Research Funding; Celgene: Honoraria. Germing: Jazz Pharmaceuticals: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria, Other: advisory activity, Research Funding; Janssen: Honoraria; Novartis: Honoraria, Research Funding.

Introduction: Infections are a well-recognized complication in patients (pts) with myelodysplastic syndromes (MDS) that contribute substantially to the morbidity and mortality particularly in pts suffering from neutropenia. Neutropenia and other immune defects including impaired neutrophil function have been reported to be predisposing factors for severe infections. Furthermore, some of the therapies may worsen neutropenia and lead to an additional risk factor to develop infectious episodes. Since infectious complications are no primary endpoint in clinical trials epidemiological data on infections in large cohorts of MDS pts is sparse. Methods: We performed a retrospective analysis of 3.787 MDS-patients from the Duesseldorf MDS Registry who were diagnosed between 1980 and 2018. Infectious complications were defined as clinical symptoms of infection associated with the need for antibiotic and/or antifungal therapy, and/or the isolation of a pathogen and/or an identifiable site of infection by physical examination. Infectious episodes were categorized as fever of unknown origin, microbiologically or clinically documented infection. Results: Amongst our study cohort, 42% of the pts suffered from at least one infectious complication of any type during the course of their disease. Most infectious diseases were of bacterial origin (34.7%) and in 17% a pathogen was isolated. Pneumonia was the most common site of infection (64%). Pts who experienced at least one infectious episode had a significant poorer overall survival (OS) than pts without such events (21 vs 37 months, p In univariate analyses comparing pts who had no infections versus those who had one or more, pts with older age (>65 years) tended to have a higher incidence of infectious episodes (p We found a highly significant negative correlation between the depth of cytopenia in all three myeloid lineages and the presence of infections (p Conclusion: The incidence of infections significantly increases in pts with advanced age. MDS-pts in general are more vulnerable for infection-related morbidity and mortality than non-MDS-pts. Low hemoglobin and platelet counts were both found to be associated with a worse prognosis compared to low neutrophil counts. The appearance of at least one infectious episode leads to an inferior Disclosures Nachtkamp: Jazz: Speakers Bureau; bsh medical: Speakers Bureau; Celgene: Other: Travel Support. Kobbe: Celgene: Research Funding. Gattermann: Celgene: Honoraria; Takeda: Research Funding; Novartis: Honoraria. Germing: Novartis: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria, Other: advisory activity, Research Funding; Janssen: Honoraria.

Introduction The effect of adherence to treatment guidelines has not yet been evaluated in myelodysplastic syndromes (MDS). Based on the large Düsseldorf MDS Registry, we explored adherence to European LeukemiaNet (ELN) guidelines as well as MDS expert recommendations in clinical routine. Methods In a preliminary retrospective analysis of 1658 patients documented in the Düsseldorf MDS registry, we reviewed if treatment was in accordance with the published ELN guidelines from 2014. The following treatments were considered: erythropoiesis stimulating agents (ESA), iron chelation, Lenalidomide, hypomethylating agents (HMA), intensive chemotherapy, and allogeneic stem cell transplantation (alloSCT). Since patients were diagnosed between 1982 and 2018, clinical decision-making could not be exclusively based on current guidelines. Therefore, we also performed a prospective analysis of 381 patients who received patient-tailored treatment recommendations, considering, IPSS-R, MDS-CI, HCT-CI, distance to our center, and ELN guidelines, with special attention to the above-mentioned treatment options. In addition, we conducted a matched-pair analysis, comparing patients who received a certain treatment with patients who, though eligible, did not receive it. Information regarding adherence to treatment recommendations was obtained by searching medical files and contacting primary care physicians. Probability of survival was estimated using the Kaplan-Meier method. Results The retrospective cohort was followed for a median of 22 months (1-500 months). Patients treated in accordance with the ELN guideline did not gain a significant survival benefit in the subgroups treated with ESA, iron chelation, Lenalidomide, HMA, and intensive chemotherapy, compared to patients who were eligible for the respective treatment but did not receive it. Solely the group of patients undergoing alloSCT derived a significant survival benefit compared to patients not receiving alloSCT despite qualifying for this treatment according to ELN criteria (30 vs 18 months, p=0.011, 95% CI 16.86; 25.14, fig. 1). The prospective cohort was followed for a median of 14 months (1-195 months). A median of four months elapsed before treatment was started. Non-adherence to patient-tailored therapeutic recommendations was found in 33% of the patients. The proportion of non-adherence was higher for intensive chemotherapy (47%) and lowest for patients receiving supportive treatment (13%) like ESA and chelation therapy. In the prospective group, the matched-pair study showed again that patients receiving ESA, iron chelation, Lenalidomide, HMA or intensive chemotherapy did not gain a significant survival benefit from adherence to the respective treatment recommendations. Again, survival only differed between patients adhering to and patients not adhering to a recommendation for alloSCT (median survival of 74 vs 28 months; 95% CI 7.5; 48.5, p=0.015). Conclusions According to current ELN guidelines, 33% of patients did not receive the treatment they were eligible for. Non-adherence to patient-tailored treatment recommendations from our tertiary referral center was found in 33% of the patients. Based on our two patient cohorts, supportive care regimens, Lenalidomide, HMA, as well as intensive chemotherapy do not appear to improve overall survival, whereas allogeneic stem cell transplantation provided a significant survival benefit in both groups. In summary, while adherence to MDS treatment guidelines and expert recommendations may influence survival in some of the patients, the overall effect appears to be limited, owing to the limited efficacy of the available treatment options, with the notable exception of alloSCT. However, we cannot exclude that adherence to treatment recommendations has an effect on other relevant outcomes such as quality of life or frequency of hospitalisations due to infections, bleeding and cardiovascular events. Finally, a systematic and standardized assessment of guideline-adherence, reasons for non-adherence, and impact on relevant outcomes would be desirable because it would support us in monitoring the quality of care of MDS patients and would allow comparisons to be made between different health economic environments. Disclosures Nachtkamp: Jazz Pharmaceuticals: Honoraria; Celgene: Other: Travel Support. Schroeder:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kobbe:Amgen: Honoraria, Other: Travel support, Research Funding; Neovii: Honoraria, Other: Travel support; Abbvie: Honoraria, Other: Travel support; Roche: Honoraria, Other: Travel support; Biotest: Honoraria, Other: Travel support; Celgene: Honoraria, Other: Travel support, Research Funding; Pfizer: Honoraria, Other: Travel support; Jazz: Honoraria, Other: Travel support; Takeda: Honoraria, Other: Travel support; Medac: Honoraria, Other: Travel support; MSD: Honoraria, Other: Travel support; Novartis: Honoraria, Other: Travel support. Kündgen:Otsuka: Honoraria; Takeda: Honoraria, Other: Travel Support; Novartis: Honoraria. Kaivers:Jazz Pharmaceuticals: Other: Travel Support. Rautenberg:Jazz Pharmaceuticals: Other: Travel Support; Celgene: Honoraria, Other: Travel Support. Gattermann:Novartis: Honoraria; Alexion: Research Funding; Takeda: Research Funding. Bonadies:Novartis: Other: financial support for travel, Research Funding; Roche: Other: financial support for travel, Research Funding; Amgen: Other: financial support for travel; Celgene: Other: financial support for travel, Research Funding; Sanofi Genzyme: Other: financial support for travel; Janssen: Other: financial support for travel. Germing:Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria; Amgen: Honoraria.