The myelodysplastic syndromes (MDS) have highly variable outcomes and prognostic scoring systems are important tools for risk assessment and to guide therapeutic decisions. However, few population-based studies have compared the value of the different scoring systems. With data from the nationwide Swedish population-based MDS register we validated the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R) and the World Health Organization (WHO) Classification-based Prognostic Scoring System (WPSS). We also present population-based data on incidence, clinical characteristics including detailed cytogenetics and outcome from the register. The study encompassed 1329 patients reported to the register between 2009 and 2013, 14% of these had therapy-related MDS (t-MDS). Based on the MDS register, the yearly crude incidence of MDS in Sweden was 2·9 per 100 000 inhabitants. IPSS-R had a significantly better prognostic power than IPSS (P < 0·001). There was a trend for better prognostic power of IPSS-R compared to WPSS (P = 0·05) and for WPSS compared to IPSS (P = 0·07). IPSS-R was superior to both IPSS and WPSS for patients aged ≤70 years. Patients with t-MDS had a worse outcome compared to de novo MDS (d-MDS), however, the validity of the prognostic scoring systems was comparable for d-MDS and t-MDS. In conclusion, population-based studies are important to validate prognostic scores in a 'real-world' setting. In our nationwide cohort, the IPSS-R showed the best predictive power.

Summary Outcomes in chronic myelomonocytic leukaemia (CMML) are highly variable and may be affected by comorbidity. Therefore, prognostic models and comorbidity indices are important tools to estimate survival and to guide clinicians in individualising treatment. In this nationwide population‐based study, we assess comorbidities and for the first time validate comorbidity indices in CMML. We also compare the prognostic power of: the revised International Prognostic Scoring System (IPSS‐R), CMML‐specific prognostic scoring system (CPSS), MD Anderson Prognostic Scoring System (MDAPS) and Mayo score. In this cohort of 337 patients with CMML, diagnosed between 2009 and 2015, the median overall survival was 21·3 months. Autoimmune conditions were present in 25% of the patients, with polymyalgia rheumatica and Hashimoto’s thyroiditis being most common. Of the tested comorbidity indices: the Charlson Comorbidity Index (CCI), Haematopoietic cell transplantation‐specific Comorbidity Index (HCT‐CI) and Myelodysplastic Syndrome‐Specific Comorbidity Index (MDS‐CI), CCI had the highest C‐index (0·62) and was the only comorbidity index independently associated with survival in multivariable analyses. When comparing the prognostic power of the scoring systems, the CPSS had the highest C‐index (0·69). In conclusion, using ‘real‐world’ data we found that the CCI and CPSS have the best prognostic power and that autoimmune conditions are overrepresented in CMML.

Objectives To assess whether socioeconomic indices such as income and educational level can explain part of the variation in survival among patients with myelodysplastic syndromes, and further to assess whether these factors influence care and treatment decisions. Methods Population‐based cohort study on 2945 Swedish patients diagnosed between 2009 and 2018 and included in the Swedish MDS Register. Relative mortality was assessed by Cox regression, whereas treatment differences were assessed by Poisson regression. Regarding mortality, patients were also compared to a matched comparison group from the general population. Results Mortality was 50% higher among patients in the lowest income category compared to the highest and 40% higher in patients with mandatory school education only compared to those with college or university education. Treatment with hypomethylating agents and allogeneic stem cell transplantation, as well as investigation with cytogenetic diagnostics were also linked to income and education. The findings were not explained by differences in risk class or comorbidity at the time of diagnosis. Conclusions Income and education are linked to survival among patients with myelodysplastic syndromes. Socioeconomic status also seems to influence treatment intensity as patients with less income and education to a lesser degree receive hypomethylating agents and transplants.

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In this population-based study, we aimed to characterize and compare subgroups of therapy-related Myelodysplastic syndromes (t-MDS) and define the implications of type of previous treatment and primary disease. We combined data from MDS patients, diagnosed between 2009 and 2017 (n = 2705), in the nationwide Swedish MDS register, with several health registers. Furthermore, using matched population controls, we investigated the prevalence of antecedent malignancies in MDS patients in comparison with the general population. This first ever nationwide study on t-MDS confirms a shorter median survival for t-MDS compared to de novo MDS (15.8 months vs 31.1 months, p < 0.001). T-MDS patients previously treated with radiation only had disease characteristics with a striking resemblance to de novo-MDS, in sharp contrast to patients treated with chemotherapy who had a significantly higher risk profile. IPSS-R and the WHO classification differentiated t-MDS into different risk groups. As compared with controls, MDS patients had a six-fold increased prevalence of a previous hematological malignancy but only a 34% increased prevalence of a previous solid tumor. T-MDS patients with a previous hematological malignancy had a dismal prognosis, due both to mortality related to their primary disease and to high-risk MDS.

A decade ago reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT) was successfully introduced to facilitate transplantation in patients with co-morbidities. In contrast to myeloablative conditioning regimens RIC transplants are associated with less toxicity and thus preferred in the elderly population. However, there are also disadvantages with RIC such as the increased risk of graft failure caused by rejection by remnant recipient T-cells at transplant, which often results in mixed chimerism during the first months post-transplant. Here, we present risk factors for graft failure in all first RIC allo-HSCTs performed at our center from 1995 to mid-2010 (n=357). Graft failure was defined as >95% recipient T-cells any time after engraftment or reinfusion of donor cells due to >50% recipient cells with no clinical or laboratory signs of relapse. Thirty-six patients (10%) experienced graft failure. The median age of the patients was 51 and 57% were males. In univariate analysis, graft failure was 3-fold increased in male compared to female patients (15% versus 4%; P<0.01). Furthermore, patients with non-malignant disorders (26% versus 2%; P<0.01) and solid tumors (20% vs. 2%; P<0.01) had an increased risk of graft failure when compared to acute leukemia. Graft versus host disease (GVHD) prophylaxis using cyclosporine A (CSA) in combination with mycophenolate mofetil (MMF) resulted in increased numbers of graft failure when compared to our standard regimen with CSA and methotrexate (18% vs. 5%; P<0.01). The graft failure rate was the lowest among HLA-identical sibling donors (6%), slightly higher in 8/8 matched unrelated donors (10%), and the highest in 6/6 matched unrelated donors (18%; P<0.01). Total nucleated cell (TNC) dose was also important with less graft failures when the TNC dose was >10 x 108/kg, whereas CD34+ cell dose had no impact on graft failure (P=0.15). Moreover, in univariate analyses year of transplant, donor sex, cell source, CMV mismatch, ABO mismatch, or pre-planned G-CSF did not influence graft failure rates (P>0.05). In multivariate analysis (Table 1), solid tumors were associated with markedly increased risk of graft failure (RR=10.95; P=0.03), whereas there was a tendency towards increased graft failure risk in non-malignant disorders (RR=8.01; P=0.05). Graft failures were also increased in male recipients (RR=3.27; P<0.01), in grafts with a TNC dose less than 10 x 108/kg (RR=2.17; P=0.03), when using MMF containing GVHD prophylaxis (RR=3.61; P<0.01), and in transplants with HLA match less than 8/8 (RR=4.94; P<0.01). In conclusion, graft failure is augmented in male recipients, and associated with diseases which usually do not receive high-dose chemotherapy pre-transplant such as solid tumors. HLA mismatch as well as TNC dose and GVHD prophylaxis were also important risk factors for graft failure in the present study.Table 1Multivariate analysis of risk factors for graft failure in reduced intensity conditioning allo-HSCT.CharacteristicsNRR95% CIP-valueNo of patients357Recipient sexFemale1531Male2043.271.35-7.93<0.01DiseaseAcute leukemiaa661CML276.810.70-66.310.10CLL225.380.55-52.630.15Lymphoma361.540.10-24.830.76MDS324.260.38-47.190.24MPD187.400.67-82.360.10Multiple myeloma2300-82.361Aplastic anemia382.540.25-26.210.43Non-malignant disorders348.010.96-66.800.05Solid tumors6110.951.34-89.170.03HLA matchHLA-identical sibling1561Unrelated donor 6/6454.941.84-13.24<0.01Unrelated donor 8/81232.160.90-5.180.09Other matched300-13.241Other mismatched303.301.18-9.240.02Total nucleated cell dose (x108/kg)0-58615-10920.540.24-1.220.1410-14870.370.15-0.940.04>14870.240.08-0.750.01GVHD profylaxisCSA+MTX2401CSA+Pred142.160.63-7.400.22CSA+MMF403.611.38-9.44<0.01Fk 506 +Rapamune451.320.43-4.080.63Other176.242.27-17.16<0.01aAML (n=60) and ALL (n=6). Disclosures: No relevant conflicts of interest to declare.