Chronic lymphocytic leukemia in Iceland from 2003 to 2013: Incidence, presentation and diagnosis

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.B-eitilfrumna. Einstofna B-eitilfrumudreyri (monoclonal B-cell lymphocytosis, MBL) er talið forstig sjúkdómsins. Sjúkdómurinn er ólæknandi en hæggengur og greinist oft fyrir tilviljun við skoðun blóðhags. Langvinnt eitilfrumuhvítblæði hefur ekki verið rannsakað á Íslandi hvað varðar nýgengi, greiningu, sjúkdómseinkenni eða hækkanir á eitilfrumutalningu í blóði fyrir greiningu. Efniviður og aðferðir: Um er að ræða afturskyggna, lýsandi rannsókn sem nær til sjúklinga sem greindust á árunum 2003-2013. Fengin voru gögn yfir sjúklinga frá Krabbameinsskrá, blóðmeinafræðideild Landspítala og Læknasetrinu í Mjódd og var skráning tilfella rakin. Sjúkraskrár voru skoðaðar með tilliti til einkenna, greininga og meðferðar. Upplýsingar um lifun fengust úr Þjóðskrá og um dánarorsakir frá landlækni. Niðurstöður: Fjöldi sjúklinga sem greindist með langvinnt eitilfrumuhvítblæði á rannsóknartímabilinu var 161 (109 karlar, 52 konur). Nýgengi mældist 4,55/100.000 en aldursstaðlað nýgengi 3,00/100.000. Meðalaldur við greiningu var 70,9 ár (35-96 ár). Krabbameinsskrá skorti upplýsingar um 28 sjúklinga (17,4%), en upphafleg greining var í 47,2% tilfella eingöngu gerð með flæðisjá. Sjúkdómseinkenni voru til staðar við greiningu hjá 67 af 151 sjúklingi (44,4%). Rúmur þriðjungur hópsins fékk lyfjameð- ferð og var meðaltími að meðferð 1,3 ár. Fimm ára lifun var um 70% en miðgildi lifunar 9,4 ár. Hækkun eitilfrumutalningar (4,0x109 /L) í blóði (0,1- 13,4 árum) fyrir greiningu fannst hjá 85 af 99 sjúklingum (85,9%). Ályktun: Nýgengi langvinns eitilfrumuhvítblæðis á Íslandi er svipað því sem þekkist á Vesturlöndum. Bæta þarf lögbundna skráningu tilfella í Krabbameinsskrá, sérstaklega þegar greining byggir á frumuflæðisjárrannsókn eingöngu. Eitilfrumuhækkun var til staðar hjá stórum hluta sjúklinga fyrir greiningu.Introduction: Chronic lymphocytic leukemia (CLL) is characterized by the proliferation of monoclonal B-lymphocytes. MBL (monoclonal B-cell lymphocytosis) is considered a precursor state of the disease. Although CLL is incurable it is an indolent disorder and often detected incidentally on routine blood counts. Until now little information has been available on CLL in Iceland, including the incidence, diagnosis, symptoms or MBL precursor state. Material and methods: This is a retrospective, descriptive study including CLL patients diagnosed in Iceland over the years 2003-2013. Registries of patients with a CLL diagnosis were obtained from the Icelandic Cancer Registry, Landspitali National University Hospital and the Medical Center in Mjódd. Medical records were reviewed for information on symptoms, diagnosis and treatment. Survival data and causes of death were obtained from national registries. Results: The number of patients diagnosed with CLL over the study period was 161 (109 males, 52 females). The calculated incidence was 4.55/100,000, and the age-standardized incidence was 3.00/100,000. Mean age at diagnosis was 70.9 years (range 35-96 years). The Icelandic Cancer Registry lacked information on 28 patients (17.4%). The initial diagnosis of CLL was obtained exclusively with flow cytometry in 47.2% of cases. Symptoms were present at diagnosis in 67 of 151 patients (44.4%). One third of the group received chemotherapy and the average time to treatment was 1.3 years. Five-year survival was 70% and median survival was 9.4 years. Elevated lymphocyte counts (≥4,0x109 /L) in peripheral blood prior (0.1 to 13.4 years) to diagnosis of CLL was identified in 85 of 99 CLL patients (85.9%). Conclusion: The incidence of CLL in Iceland is similar to other Western countries. The registration of CLL cases in the Icelandic Cancer Registry must be improved, especially in cases where diagnosis is based solely on flow cytometry. Elevated lymphocyte counts were present in a large proportion of cases prior to the diagnosis of CLL

Defining new reference intervals for serum free light chains in individuals with chronic kidney disease : Results of the iStopMM study

Publisher Copyright: © 2022. The Author(s). © 2022. The Author(s).Serum free light chain (FLC) concentration is greatly affected by kidney function. Using a large prospective population-based cohort, we aimed to establish a reference interval for FLCs in persons with chronic kidney disease (CKD). A total of 75422 participants of the iStopMM study were screened with serum FLC, serum protein electrophoresis and immunofixation. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine. Central 99% reference intervals were determined, and 95% confidence intervals calculated. Included were 6461 (12%) participants with measured FLCs, eGFR < 60 mL/min/1.73 m2, not receiving renal replacement therapy, and without evidence of monoclonality. Using current reference intervals, 60% and 21% had kappa and lambda FLC values outside the normal range. The FLC ratio was outside standard reference interval (0.26-1.65) in 9% of participants and outside current kidney reference interval (0.37-3.10) in 0.7%. New reference intervals for FLC and FLC ratio were established. New reference intervals for the FLC ratio were 0.46-2.62, 0.48-3.38, and 0.54-3.30 for eGFR 45-59, 30-44, and < 30 mL/min/1.73 m2 groups, respectively. The crude prevalence of LC-MGUS in CKD patients was 0.5%. We conclude that current reference intervals for FLC and FLC ratio are inaccurate in CKD patients and propose new eGFR based reference intervals to be implemented.Peer reviewe

Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadMonoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.Black Swan Research Initiative by the International Myeloma Foundation Icelandic Centre for Research European Research Council (ERC) University of Iceland Landspitali University Hospita

Case of the month: Autoimmune hemolytic anemia [case reports]

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenTæplega áttræð áður hraust kona leitaði á heilsugæslustöð vegna nokkurra vikna sögu um vaxandi slappleika, lystarleysi og mæði. Við skoðun reyndist hún áberandi föl og kvartaði um mæði. Að öðru leyti var skoðun ómarkverð. Gert var skyndipróf á blóðrauða sem mældist 44 g/L. Hún var því send á Landspítala til frekari uppvinnslu. Við komu á bráðamóttöku kvartaði hún um mæði en skoðun leiddi ekkert nýtt í ljós. Hún tók engin lyf og ekki sást merki um blóð í hægðum (neikvætt Hemoccult ®). Nákvæmari mælingar á blóðhag sýndu verulegt blóðleysi með blóðrauðagildi 45 g/L, MCV 120fL (vikmörk 80-97fL) og RDW 26,5% (vikmörk 10,6-13,2%). Fengið var blóðstrok sem sýnt er á mynd 1. Hver er líklegasta greiningin og meðferð

Case of the month: Autoimmune hemolytic anemia [case reports]

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenTæplega áttræð áður hraust kona leitaði á heilsugæslustöð vegna nokkurra vikna sögu um vaxandi slappleika, lystarleysi og mæði. Við skoðun reyndist hún áberandi föl og kvartaði um mæði. Að öðru leyti var skoðun ómarkverð. Gert var skyndipróf á blóðrauða sem mældist 44 g/L. Hún var því send á Landspítala til frekari uppvinnslu. Við komu á bráðamóttöku kvartaði hún um mæði en skoðun leiddi ekkert nýtt í ljós. Hún tók engin lyf og ekki sást merki um blóð í hægðum (neikvætt Hemoccult ®). Nákvæmari mælingar á blóðhag sýndu verulegt blóðleysi með blóðrauðagildi 45 g/L, MCV 120fL (vikmörk 80-97fL) og RDW 26,5% (vikmörk 10,6-13,2%). Fengið var blóðstrok sem sýnt er á mynd 1. Hver er líklegasta greiningin og meðferð

Chronic lymphocytic leukemia in Iceland from 2003 to 2013: Incidence, presentation and diagnosis

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.B-eitilfrumna. Einstofna B-eitilfrumudreyri (monoclonal B-cell lymphocytosis, MBL) er talið forstig sjúkdómsins. Sjúkdómurinn er ólæknandi en hæggengur og greinist oft fyrir tilviljun við skoðun blóðhags. Langvinnt eitilfrumuhvítblæði hefur ekki verið rannsakað á Íslandi hvað varðar nýgengi, greiningu, sjúkdómseinkenni eða hækkanir á eitilfrumutalningu í blóði fyrir greiningu. Efniviður og aðferðir: Um er að ræða afturskyggna, lýsandi rannsókn sem nær til sjúklinga sem greindust á árunum 2003-2013. Fengin voru gögn yfir sjúklinga frá Krabbameinsskrá, blóðmeinafræðideild Landspítala og Læknasetrinu í Mjódd og var skráning tilfella rakin. Sjúkraskrár voru skoðaðar með tilliti til einkenna, greininga og meðferðar. Upplýsingar um lifun fengust úr Þjóðskrá og um dánarorsakir frá landlækni. Niðurstöður: Fjöldi sjúklinga sem greindist með langvinnt eitilfrumuhvítblæði á rannsóknartímabilinu var 161 (109 karlar, 52 konur). Nýgengi mældist 4,55/100.000 en aldursstaðlað nýgengi 3,00/100.000. Meðalaldur við greiningu var 70,9 ár (35-96 ár). Krabbameinsskrá skorti upplýsingar um 28 sjúklinga (17,4%), en upphafleg greining var í 47,2% tilfella eingöngu gerð með flæðisjá. Sjúkdómseinkenni voru til staðar við greiningu hjá 67 af 151 sjúklingi (44,4%). Rúmur þriðjungur hópsins fékk lyfjameð- ferð og var meðaltími að meðferð 1,3 ár. Fimm ára lifun var um 70% en miðgildi lifunar 9,4 ár. Hækkun eitilfrumutalningar (4,0x109 /L) í blóði (0,1- 13,4 árum) fyrir greiningu fannst hjá 85 af 99 sjúklingum (85,9%). Ályktun: Nýgengi langvinns eitilfrumuhvítblæðis á Íslandi er svipað því sem þekkist á Vesturlöndum. Bæta þarf lögbundna skráningu tilfella í Krabbameinsskrá, sérstaklega þegar greining byggir á frumuflæðisjárrannsókn eingöngu. Eitilfrumuhækkun var til staðar hjá stórum hluta sjúklinga fyrir greiningu.Introduction: Chronic lymphocytic leukemia (CLL) is characterized by the proliferation of monoclonal B-lymphocytes. MBL (monoclonal B-cell lymphocytosis) is considered a precursor state of the disease. Although CLL is incurable it is an indolent disorder and often detected incidentally on routine blood counts. Until now little information has been available on CLL in Iceland, including the incidence, diagnosis, symptoms or MBL precursor state. Material and methods: This is a retrospective, descriptive study including CLL patients diagnosed in Iceland over the years 2003-2013. Registries of patients with a CLL diagnosis were obtained from the Icelandic Cancer Registry, Landspitali National University Hospital and the Medical Center in Mjódd. Medical records were reviewed for information on symptoms, diagnosis and treatment. Survival data and causes of death were obtained from national registries. Results: The number of patients diagnosed with CLL over the study period was 161 (109 males, 52 females). The calculated incidence was 4.55/100,000, and the age-standardized incidence was 3.00/100,000. Mean age at diagnosis was 70.9 years (range 35-96 years). The Icelandic Cancer Registry lacked information on 28 patients (17.4%). The initial diagnosis of CLL was obtained exclusively with flow cytometry in 47.2% of cases. Symptoms were present at diagnosis in 67 of 151 patients (44.4%). One third of the group received chemotherapy and the average time to treatment was 1.3 years. Five-year survival was 70% and median survival was 9.4 years. Elevated lymphocyte counts (≥4,0x109 /L) in peripheral blood prior (0.1 to 13.4 years) to diagnosis of CLL was identified in 85 of 99 CLL patients (85.9%). Conclusion: The incidence of CLL in Iceland is similar to other Western countries. The registration of CLL cases in the Icelandic Cancer Registry must be improved, especially in cases where diagnosis is based solely on flow cytometry. Elevated lymphocyte counts were present in a large proportion of cases prior to the diagnosis of CLL

Iceland screens, treats, or prevents multiple myeloma (iStopMM) : a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies

Funding Information: P.K. is an employee of The Binding Site. BGMD has done consultancy for Amgen, Janssen, Celgene, Takeda. S.H. is the director of The Binding Site. O.L. has received research funding from: National Institutes of Health (NIH), National Cancer Institute (NCI), U.S. Food and Drug Administration (FDA), Multiple Myeloma Research Foundation (MMRF), International Myeloma Foundation (IMF), Leukemia and Lymphoma Society (LLS), Perelman Family Foundation, Rising Tide Foundation, Amgen, Celgene, Janssen, Takeda, Glenmark, Seattle Genetics, Karyopharm; Honoraria/ad boards: Adaptive, Amgen, Binding Site, BMS, Celgene, Cellectis, Glenmark, Janssen, Juno, Pfizer; and serves on Independent Data Monitoring Committees (IDMCs) for clinical trials lead by Takeda, Merck, Janssen, Theradex. S.Y.K. has received research funding from International Myeloma Foundation, European Research Council, Icelandic Center for Research (Rannís), Amgen, Celgene. The remaining authors declare no competing interests. Funding Information: The iStopMM study is funded by the Black Swan Research Initiative by the International Myeloma Foundation and the Icelandic Centre for Research (grant agreement No 173857). Furthermore, this project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 716677). Screening tests are performed by The Binding Site Ltd. Birmingham, UK. Additional funding is provided by the University of Iceland, Landspítali University Hospital, and the Icelandic Cancer Society. Crosslinking of study data to national registries is performed by the Icelandic Directorate of Health and the Icelandic Cancer Society. The study is made possible by the hundreds of nurses, laboratory technicians, and physicians around Iceland who collect blood samples from participants for screening or during follow-up and provide clinical care that is not part of the study. Icelandic and International myeloma patient organizations including Perluvinir, the Icelandic myeloma patient organization, and the International Myeloma Foundation have provided the project with important perspectives and networks. The information technology department and clinical laboratory staff at LUH made the complex sampling processes required for the study possible. The staff at Loftfar, Aton, Miðlun and Hvíta Húsið played an integral part in the development of recruiting strategies and media campaigns. Decode genetics have generously provided the study team with important insights and access to their state-of-the-art facilities. Presidents Vigdís Finnbogadóttir and Guðni Th Jóhannesson are thanked for their public support of the study. The iStopMM team including Sigurlína H Steinarsdóttir, Hera Hallbera Björnsdóttir, Tinna Hallsdóttir, Ingibjörg Björnsdóttir, and Eva Brynjarsdóttir are particularly acknowledged for their hard and dedicated work. Special thanks go to the residents of Akranes, Iceland who participated in the pilot and proof-of-concept of the study’s recruitment. Most importantly, acknowledgments go to the thousands of Icelanders who have generously provided their informed consent for the study, answered questionnaires, provided blood samples, and undergone diagnostic testing and follow-up. Publisher Copyright: © 2021, The Author(s).Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.Peer reviewe

Correction : Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies (Blood Cancer Journal, (2021), 11, 5, (94), 10.1038/s41408-021-00480-w)

Publisher Copyright: © The Author(s) 2023.In this article the author name Malin Hultcrantz was incorrectly written as Malin Hulcrantz. The original article has been corrected