| 1. |
- Creignou, Maria, et al.
(författare)
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Early transfusion patterns improve the Molecular International Prognostic Scoring System (IPSS-M) prediction in myelodysplastic syndromes
- 2024
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Ingår i: Journal of Internal Medicine. - : WILEY. - 0954-6820 .- 1365-2796.
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Tidskriftsartikel (refereegranskat)abstract
- Background The Molecular International Prognostic Scoring System (IPSS-M) is the new gold standard for diagnostic outcome prediction in patients with myelodysplastic syndromes (MDS). This study was designed to assess the additive prognostic impact of dynamic transfusion parameters during early follow-up. Methods We retrieved complete transfusion data from 677 adult Swedish MDS patients included in the IPSS-M cohort. Time-dependent erythrocyte transfusion dependency (E-TD) was added to IPSS-M features and analyzed regarding overall survival and leukemic transformation (acute myeloid leukemia). A multistate Markov model was applied to assess the prognostic value of early changes in transfusion patterns. Results Specific clinical and genetic features were predicted for diagnostic and time-dependent transfusion patterns. Importantly, transfusion state both at diagnosis and within the first year strongly predicts outcomes in both lower (LR) and higher-risk (HR) MDSs. In multivariable analysis, 8-month landmark E-TD predicted shorter survival independently of IPSS-M (p < 0.001). A predictive model based on IPSS-M and 8-month landmark E-TD performed significantly better than a model including only IPSS-M. Similar trends were observed in an independent validation cohort (n = 218). Early transfusion patterns impacted both future transfusion requirements and outcomes in a multistate Markov model. Conclusion The transfusion requirement is a robust and available clinical parameter incorporating the effects of first-line management. In MDS, it provides dynamic risk information independently of diagnostic IPSS-M and, in particular, clinical guidance to LR MDS patients eligible for potentially curative therapeutic intervention.
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| 2. |
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| 3. |
- Larfors, Gunnar, et al.
(författare)
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Income, education and their impact on treatments and survival in patients with myelodysplastic syndromes
- 2021
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Ingår i: European Journal of Haematology. - : Munksgaard Forlag. - 0902-4441 .- 1600-0609. ; 107:2, s. 219-228
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 4. |
- Larfors, Gunnar, et al.
(författare)
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MDS-Comorbidity Index using register data has prognostic impact in Swedish MDS patients
- 2023
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Ingår i: Leukemia Research. - : Elsevier. - 0145-2126 .- 1873-5835. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- Comorbidities influence the mortality in patients with myelodysplastic syndromes, and a growing body of evidence suggest that comorbidity history should be used in addition to established prognostic indices. A comorbidity index specific for MDS, the MDS-CI, was introduced a decade ago. In this study we aim to construct an MDS-CI version based on diagnoses from register data only, to expand its use beyond the clinical setting to retrospective and register based studies. We further test this version on a Swedish population-based MDS cohort of 2947 patients, and compare its prognostic accuracy to that of Charlson Comorbidity Index. Our register based MDS-CI divided patients into three risk groups of similar proportions as have been published for the original MDS-CI. Compared to low risk patients, intermediate and high risk patients had 50 % and 70 % higher mortality, respectively. The prognostic value of MDS-CI was equal to that of Charlson comorbidity index. Adding MDS-CI to the established prognostic factors IPSS-R and age increased the prognostic accuracy. In summary, we demonstrate that MDS-CI can be adequately estimated from diagnoses recorded in registers only, and that it is a useful tool in any future study on myelodysplastic syndromes with a need to adjust for comorbidities.
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| 5. |
- Lindholm, C., et al.
(författare)
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Failure to reach hematopoietic allogenic stem cell transplantation in patients with myelodysplastic syndromes planned for transplantation : a population-based study
- 2022
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Ingår i: Bone Marrow Transplantation. - : Springer Nature. - 0268-3369 .- 1476-5365. ; 57, s. 598-606
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Tidskriftsartikel (refereegranskat)abstract
- The only potential cure for patients with myelodysplastic syndrome (MDS) is allogeneic hematopoietic stem cell transplantation (HCT). However, a proportion of patients who are HCT candidates do not finally get transplanted. This population-based study aimed to characterize HCT candidates were attempting to reach HCT fail and to identify causes and risk factors for failure. Data were collected from (1) the national Swedish registry, enrolling 291 transplant candidates between 2009-2018, and (2) Karolinska University Hospital, enrolling 131 transplantation candidates between 2000 and 2018. Twenty-five % (nation-wide) and 22% (Karolinska) failed to reach HCT. Reasons for failure to reach HCT were progressive and refractory disease (47%), no donor identified (22%), identification of comorbidity (18%), and infectious complications (14%). Factors associated with failure to reach HCT were IPSS-R cytogenetic risk-group very poor, mixed MDS/MPN disease, low blast count (0-4.9%), and low hemoglobin levels (<= 7.9 g/dL). Transplanted patients had a longer overall survival (OS) compared to patients who failed to reach transplantation (83 months versus 14 months; p < 0.001). The survival advantage was seen for the IPSS-R risk groups intermediate, high, and very high. This study demonstrated that a high proportion of HCT-candidates fail to reach HCT and underlines the difficulties associated with bridging MDS patients to HCT.
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| 6. |
- Moreno Berggren, Daniel
(författare)
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Population-based studies in Myelodysplastic syndromes : Prognostic scores, socioeconomic status, and therapy-related disease
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to expand the epidemiological knowledge of the haematological malignancy MDS and the related condition chronic myelomonocytic leukaemia (CMML). Using nationwide registers, the papers in this thesis address aspects of prognostication, comorbidity, socioeconomic status, and therapy-related disease, using a population-based approach.In paper I we validated the prognostic scoring systems WPSS, IPSS, and IPSS-R in a cohort of 1329 MDS patients. IPSS-R was the most effective scoring system, with the highest C-index of 0.74. The scoring systems were equally effective for therapy-related MDS (t-MDS) as they were for de novo MDS. In paper II we validated the scoring systems, IPSS-R, CPSS, MDAPS, and Mayo score and the comorbidity indices CCI, HCT-CI, and MDS-CI in a cohort of 337 patients with CMML. We concluded that CPSS is the most powerful scoring system. Among comorbidity indices, the CCI gave the most prognostic information. There was a strikingly high prevalence of autoimmune conditions affecting 25% of patients. In paper III we studied the effect of socioeconomic status in a cohort of 2945 patients with MDS. When adjusting for known prognostic factors, mortality was 50% higher in patients with the lowest income compared to those with the highest income and 40% higher among patients with the shortest education compared to those with the longest. Further, a lower socioeconomic status was associated with a reduced probability of receiving effective treatment and with a lower probability of a cytogenetic evaluation at diagnosis. In paper IV we studied t-MDS in a cohort of 2705 patients with MDS, of whom 16% had t-MDS. Patients with t-MDS had a shorter median survival as compared to de novo MDS (15.8 months versus 31.1 months). Previous treatment with either chemotherapy alone or in combination with radiation was associated with a shorter survival than treatment with radiation only. Having a non-malignant disease or a solid tumour as a primary disease was associated with a longer survival, compared with those with a haematological malignancy. IPSS-R and the WHO classification were effective in predicting survival in most subgroups of t-MDS. The t-MDS subgroup treated with radiation only was similar to patients with de novo MDS and should be regarded as having de novo MDS regarding prognostication and treatment.In summary, the findings in this thesis provide evidence for how to improve prognostication and expand knowledge on the patient and disease-specific characteristics leading to the diverse outcomes in MDS and CMML.
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| 7. |
- Moreno Berggren, Daniel, et al.
(författare)
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Prognostic scoring systems and comorbidities in chronic myelomonocytic leukaemia : a nationwide population-based study
- 2021
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Ingår i: British Journal of Haematology. - : John Wiley & Sons. - 0007-1048 .- 1365-2141. ; 192:3, s. 474-483
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Tidskriftsartikel (refereegranskat)abstract
- 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 center dot 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 center dot 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 center dot 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.
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| 8. |
- Moreno Berggren, Daniel, et al.
(författare)
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Therapy-related MDS dissected based on primary disease and treatment-a nationwide perspective
- 2023
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Ingår i: Leukemia. - : Springer. - 0887-6924 .- 1476-5551. ; 37:5, s. 1103-1112
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
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| 10. |
- Tobiasson, Magnus, et al.
(författare)
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Patient-Specific Measurable Residual Disease Markers Predict Outcome in Patients With Myelodysplastic Syndrome and Related Diseases After Hematopoietic Stem-Cell Transplantation
- 2024
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 42:12, s. 1378-1390
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Clinical relapse is the major threat for patients with myelodysplastic syndrome (MDS) undergoing hematopoietic stem-cell transplantation (HSCT). Early detection of measurable residual disease (MRD) would enable preemptive treatment and potentially reduced relapse risk.METHODS: Patients with MDS planned for HSCT were enrolled in a prospective, observational study evaluating the association between MRD and clinical outcome. We collected bone marrow (BM) and peripheral blood samples until relapse, death, or end of study 24 months after HSCT. Patient-specific mutations were identified with targeted next-generation sequencing (NGS) panel and traced using droplet digital polymerase chain reaction (ddPCR).RESULTS: Of 266 included patients, estimated relapse-free survival (RFS) and overall survival (OS) rates 3 years after HSCT were 59% and 64%, respectively. MRD results were available for 221 patients. Relapse was preceded by positive BM MRD in 42/44 relapses with complete MRD data, by a median of 71 (23-283) days. Of 137 patients in continuous complete remission, 93 were consistently MRD-negative, 39 reverted from MRD+ to MRD-, and five were MRD+ at last sampling. Estimated 1 year-RFS after first positive MRD was 49%, 39%, and 30%, using cutoff levels of 0.1%, 0.3%, and 0.5%, respectively. In a multivariate Cox model, MRD (hazard ratio [HR], 7.99), WHO subgroup AML (HR, 4.87), TP53 multi-hit (HR, 2.38), NRAS (HR, 3.55), and acute GVHD grade III-IV (HR, 4.13) were associated with shorter RFS. MRD+ was also independently associated with shorter OS (HR, 2.65). In a subgroup analysis of 100 MRD+ patients, presence of chronic GVHD was associated with longer RFS (HR, 0.32).CONCLUSION: Assessment of individualized MRD using NGS + ddPCR is feasible and can be used for early detection of relapse. Positive MRD is associated with shorter RFS and OS (ClinicalTrials.gov identifier: NCT02872662).
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