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Article ; Online: Malignancy-associated hemophagocytic lymphohistiocytosis in Sweden: incidence, clinical characteristics, and survival.

Löfstedt, Alexandra / Jädersten, Martin / Meeths, Marie / Henter, Jan-Inge

2023 Volume 143, Issue 3, Page(s) 233–242

Abstract: Abstract: We evaluated malignancy-associated hemophagocytic lymphohistiocytosis (mal-HLH) in Sweden regarding population-based incidence, clinical features, and survival. From 1997 to 2018, we identified 307 adults (≥18 years old) and 9 children (209 ... ...

Abstract	Abstract: We evaluated malignancy-associated hemophagocytic lymphohistiocytosis (mal-HLH) in Sweden regarding population-based incidence, clinical features, and survival. From 1997 to 2018, we identified 307 adults (≥18 years old) and 9 children (209 males, 107 females; P < .001) with both an HLH-related diagnosis and malignant disease, corresponding to 0.19 per 100 000 adults annually (0.15/100 000 for the entire population), increasing from 0.026 (1997-2007) to 0.34 (2008-2018) (P < .001). In the latest 7-year period (2012-2018), the annual incidence was 0.45 per 100 000 adults (n = 246). This incidence varied between the 6 health care regions in Sweden, from 0.18 to 0.71 (Region Stockholm) per 100 000 adults annually (P < .001), likely due to variable awareness. Mal-HLH was reported in 0.6% of all hematological malignancies, with the highest proportion (2.5%) in young males. Among the 316 patients, the 1-month probability of survival, likely representing the HLH episode, increased significantly from 52% (95% confidence interval [CI], 40-63) (1997-2007) to 71% (95% CI, 65-76) (2008-2018), whereas 2-year survival remained poor (25%; 95% CI, 20-30). Altogether, 52% were lymphomas, 29% leukemias, 8% other hematological malignancies, and 11% solid tumors. Males were more affected than females by mal-HLH, also taking the over-representation of males with hematological malignancies into account (P = .0012). Validation by medical-file reviews revealed 13% over-reporting of HLH. We conclude that the annual mal-HLH incidence has increased 10-fold and was at least 0.71 per 100 000 adults from 2012 to 2018, that is, 0.62 per 100 000 adults considering 13% estimated HLH over-reporting, and that early survival improved significantly, likely due to increased awareness and more HLH-directed therapy.
MeSH term(s)	Adult ; Male ; Child ; Female ; Humans ; Adolescent ; Lymphohistiocytosis, Hemophagocytic/diagnosis ; Sweden/epidemiology ; Incidence ; Neoplasms/complications ; Neoplasms/epidemiology ; Hematologic Neoplasms/complications ; Hematologic Neoplasms/epidemiology ; Hematologic Neoplasms/drug therapy ; Retrospective Studies
Language	English
Publishing date	2023-08-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2023020715
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Article ; Online: Omalizumab alleviates pruritus in myeloproliferative neoplasms.

Landtblom, Anna Ravn / Ungerstedt, Johanna / Hedlund, Anette / Tobiasson, Magnus / Deneberg, Stefan / Jädersten, Martin

Haematologica

2023 Volume 108, Issue 7, Page(s) 1968–1971

MeSH term(s)	Humans ; Omalizumab/therapeutic use ; Neoplasms ; Pruritus/drug therapy ; Pruritus/etiology ; Myeloproliferative Disorders/complications ; Myeloproliferative Disorders/drug therapy ; Myeloproliferative Disorders/genetics
Chemical Substances	Omalizumab (2P471X1Z11)
Language	English
Publishing date	2023-07-01
Publishing country	Italy
Document type	Case Reports
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2022.281639
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Article ; Online: Pathophysiology and treatment of the myelodysplastic syndrome with isolated 5q deletion.

Jädersten, Martin

Haematologica

2010 Volume 95, Issue 3, Page(s) 348–351

MeSH term(s)	Chromosome Deletion ; Chromosomes, Human, Pair 5/genetics ; Humans ; Myelodysplastic Syndromes/drug therapy ; Myelodysplastic Syndromes/genetics ; Myelodysplastic Syndromes/physiopathology ; Thalidomide/analogs & derivatives ; Thalidomide/therapeutic use
Chemical Substances	Thalidomide (4Z8R6ORS6L) ; lenalidomide (F0P408N6V4)
Language	English
Publishing date	2010-03
Publishing country	Italy
Document type	Editorial
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2009.019141
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Article ; Online: Therapy-related MDS dissected based on primary disease and treatment-a nationwide perspective.

Moreno Berggren, Daniel / Garelius, Hege / Willner Hjelm, Petter / Nilsson, Lars / Rasmussen, Bengt / Weibull, Caroline E / Lambe, Mats / Lehmann, Sören / Hellström-Lindberg, Eva / Jädersten, Martin / Ejerblad, Elisabeth

Leukemia

2023 Volume 37, Issue 5, Page(s) 1103–1112

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, ... ...

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.
MeSH term(s)	Humans ; Leukemia, Myeloid, Acute/diagnosis ; Prognosis ; Neoplasms, Second Primary/epidemiology ; Neoplasms, Second Primary/etiology ; Neoplasms, Second Primary/diagnosis ; Risk Factors ; Hematologic Neoplasms
Language	English
Publishing date	2023-03-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-023-01864-6
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Article ; Online: Limited benefit in patients with MDS receiving venetoclax and azacitidine as a bridge to allogeneic stem cell transplantation.

Jädersten, Martin / Boriskina, Ksenia / Lindholm, Carolin / Weström, Simone / Cavelier, Lucia / Hellström-Lindberg, Eva / Mielke, Stephan / Tobiasson, Magnus

Leukemia & lymphoma

2021 Volume 63, Issue 3, Page(s) 755–758

MeSH term(s)	Azacitidine/therapeutic use ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Sulfonamides/therapeutic use
Chemical Substances	Bridged Bicyclo Compounds, Heterocyclic ; Sulfonamides ; Azacitidine (M801H13NRU) ; venetoclax (N54AIC43PW)
Language	English
Publishing date	2021-11-15
Publishing country	United States
Document type	Letter
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2021.2002319
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Article ; Online: Characterization of therapy-related acute myeloid leukemia: increasing incidence and prognostic implications.

Nilsson, Christer / Linde, Fredrika / Hulegårdh, Erik / Garelius, Hege / Lazarevic, Vladimir / Antunovic, Petar / Cammenga, Jörg / Deneberg, Stefan / Eriksson, Anna / Jädersten, Martin / Björkvall, Cecilia Kämpe / Möllgård, Lars / Wennström, Lovisa / Ölander, Emma / Höglund, Martin / Juliusson, Gunnar / Lehmann, Sören

Haematologica

2023 Volume 108, Issue 4, Page(s) 1015–1025

Abstract: Studies of therapy-related AML (t-AML) are usually performed in selected cohorts and reliable incidence rates are lacking. In this study, we characterized, defined the incidence over time and studied prognostic implications in all t-AML patients ... ...

Abstract	Studies of therapy-related AML (t-AML) are usually performed in selected cohorts and reliable incidence rates are lacking. In this study, we characterized, defined the incidence over time and studied prognostic implications in all t-AML patients diagnosed in Sweden between 1997 and 2015. Data were retrieved from nationwide population-based registries. In total, 6,779 AML patients were included in the study, of whom 686 (10%) had t-AML. The median age for t-AML was 71 years and 392 (57%) patients were females. During the study period, the incidence of t-AML almost doubled with a yearly increase in t-AML of 4.5% (95% confidence interval: 2.8%-6.2%), which contributed significantly to the general increase in AML incidence over the study period. t-AML solidly constituted over 10% of all AML cases during the later period of the study. Primary diagnoses with the largest increase in incidence and decrease in mortality rate during the study period (i.e., breast and prostate cancer) contributed significantly to the increased incidence of t-AML. In multivariable analysis, t-AML was associated with poorer outcome in cytogenetically intermediate- and adverse-risk cases but t-AML had no significant impact on outcome in favorable-risk AML, including core binding leukemias, acute promyelocytic leukemia and AML with mutated NPM1 without FLT3-ITD. We conclude that there is a strong increase in incidence in t-AML over time and that t-AML constitutes a successively larger proportion of the AML cases. Furthermore, we conclude that t-AML confers a poor prognosis in cytogenetically intermediate- and adverse-risk, but not in favorable-risk AML.
MeSH term(s)	Male ; Female ; Humans ; Aged ; Prognosis ; Nuclear Proteins/genetics ; Nucleophosmin ; Incidence ; Mutation ; Leukemia, Myeloid, Acute/diagnosis ; Leukemia, Myeloid, Acute/epidemiology ; Leukemia, Myeloid, Acute/etiology ; fms-Like Tyrosine Kinase 3
Chemical Substances	Nuclear Proteins ; Nucleophosmin (117896-08-9) ; fms-Like Tyrosine Kinase 3 (EC 2.7.10.1)
Language	English
Publishing date	2023-04-01
Publishing country	Italy
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2022.281233
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Article ; Online: Income, education and their impact on treatments and survival in patients with myelodysplastic syndromes.

Larfors, Gunnar / Moreno Berggren, Daniel / Garelius, Hege / Jädersten, Martin / Nilsson, Lars / Rasmussen, Bengt / Ejerblad, Elisabeth

European journal of haematology

2021 Volume 107, Issue 2, Page(s) 219–228

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 ... ...

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.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Disease Management ; Female ; Health Impact Assessment ; Health Knowledge, Attitudes, Practice ; Humans ; Income ; Male ; Middle Aged ; Myelodysplastic Syndromes/diagnosis ; Myelodysplastic Syndromes/epidemiology ; Myelodysplastic Syndromes/mortality ; Myelodysplastic Syndromes/therapy ; Prognosis ; Public Health Surveillance ; Socioeconomic Factors ; Sweden/epidemiology ; Young Adult
Language	English
Publishing date	2021-05-24
Publishing country	England
Document type	Journal Article
ZDB-ID	392482-8
ISSN	1600-0609 ; 0902-4441
ISSN (online)	1600-0609
ISSN	0902-4441
DOI	10.1111/ejh.13641
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Article ; Online: Early transfusion patterns improve the Molecular International Prognostic Scoring System (IPSS-M) prediction in myelodysplastic syndromes.

Creignou, Maria / Bernard, Elsa / Gasparini, Alessandro / Tranberg, Anna / Todisco, Gabriele / Moura, Pedro Luis / Ejerblad, Elisabeth / Nilsson, Lars / Garelius, Hege / Antunovic, Petar / Lorenz, Fryderyk / Rasmussen, Bengt / Walldin, Gunilla / Mortera-Blanco, Teresa / Jansson, Monika / Tobiasson, Magnus / Elena, Chiara / Ferrari, Jacqueline / Gallì, Anna /

Pozzi, Sara / Malcovati, Luca / Edgren, Gustaf / Crowther, Michael J / Jädersten, Martin / Papaemmanuil, Elli / Hellström-Lindberg, Eva

Journal of internal medicine

2024

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 ... ...

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.
Language	English
Publishing date	2024-04-23
Publishing country	England
Document type	Journal Article
ZDB-ID	96274-0
ISSN	1365-2796 ; 0954-6820
ISSN (online)	1365-2796
ISSN	0954-6820
DOI	10.1111/joim.13790
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Article ; Online: PCR with electrospray ionization-mass spectrometry on bronchoalveolar lavage for detection of invasive mold infections in hematological patients.

Krifors, Anders / Özenci, Volkan / Ullberg, Måns / Ackefors, Malin / Jädersten, Martin / Strålin, Kristoffer / Blennow, Ola

PloS one

2019 Volume 14, Issue 2, Page(s) e0212812

Abstract: Invasive mold infections are life-threatening complications in patients with hematological malignancies. Conventional microbiological methods for diagnosing invasive pulmonary mold infections have low sensitivity, and molecular methods are being ... ...

Abstract	Invasive mold infections are life-threatening complications in patients with hematological malignancies. Conventional microbiological methods for diagnosing invasive pulmonary mold infections have low sensitivity, and molecular methods are being developed. Detection of molds using PCR with a narrow spectrum has been reported, but data with broad-spectrum PCR are lacking. In this study, the diagnostic performance and utility of a broad-spectrum PCR (broad-spectrum PCR with subsequent electrospray ionization-mass spectrometry, PCR/ESI-MS) for detection of molds in bronchoalveolar lavage (BAL) in 27 hematological patients with a new pulmonary infiltrate was analyzed. Using the revised EORTC/MSG criteria, PCR/ESI-MS was the only positive microbiological test in patients with proven invasive mold infection (n = 2) and correctly identified all cases of probable invasive pulmonary aspergillosis (n = 5). In patients with a possible invasive mold infection (n = 5), PCR/ESI-MS was positive in three patients. Mucorales was identified with PCR/ESI-MS in four patients that were all culture negative. The PCR/ESI-MS results had a clinical impact on antifungal therapy in 12 (44%) of the patients: modification of treatment in 6 (22%) patients and discontinuation in 6 (22%) patients. This study provides proof of concept that routine use of a broad-spectrum PCR for molds in bronchoalveolar lavage in immunocompromised patients is sensitive, fast, and has an impact on clinical decision-making.
MeSH term(s)	Adult ; Aged ; Bronchoalveolar Lavage Fluid/microbiology ; Female ; Hematologic Neoplasms/microbiology ; Humans ; Male ; Middle Aged ; Mucorales ; Mucormycosis/diagnosis ; Mucormycosis/microbiology ; Polymerase Chain Reaction ; Pulmonary Aspergillosis/diagnosis ; Pulmonary Aspergillosis/microbiology ; Retrospective Studies ; Spectrometry, Mass, Electrospray Ionization
Language	English
Publishing date	2019-02-22
Publishing country	United States
Document type	Clinical Trial ; Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0212812
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Article ; Online: Screening for neurodegeneration in Langerhans cell histiocytosis with neurofilament light in plasma.

Sveijer, Malin / von Bahr Greenwood, Tatiana / Jädersten, Martin / Kvedaraite, Egle / Zetterberg, Henrik / Blennow, Kaj / Lourda, Magda / Gavhed, Désirée / Henter, Jan-Inge

British journal of haematology

2022 Volume 198, Issue 4, Page(s) 721–728

Abstract: Patients with Langerhans cell histiocytosis (LCH) may develop progressive neurodegeneration in the central nervous system (ND-CNS-LCH). Neurofilament light protein (NFL) in cerebrospinal fluid (CSF) is a promising biomarker to detect and monitor ND-CNS- ... ...

Abstract	Patients with Langerhans cell histiocytosis (LCH) may develop progressive neurodegeneration in the central nervous system (ND-CNS-LCH). Neurofilament light protein (NFL) in cerebrospinal fluid (CSF) is a promising biomarker to detect and monitor ND-CNS-LCH. We compared paired samples of NFL in plasma (p-NFL) and CSF in 10 patients (19 samples). Nine samples had abnormal CSF-NFL (defined as ≥380 ng/l) with corresponding p-NFL ≥ 2 ng/l. Ten samples had CSF-NFL < 380 ng/l; eight (80%) with p-NFL < 2 ng/l (p < 0.001; Fisher's exact test). Thus, our results suggest that p-NFL may be used to screen for ND-CNS-LCH. Further studies are encouraged, including the role of p-NFL for monitoring of ND-CNS-LCH.
MeSH term(s)	Biomarkers ; Cognitive Dysfunction ; Histiocytosis, Langerhans-Cell/diagnosis ; Humans ; Intermediate Filaments ; Neurofilament Proteins/cerebrospinal fluid
Chemical Substances	Biomarkers ; Neurofilament Proteins
Language	English
Publishing date	2022-05-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.18247
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