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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00008535naa a2200697 4500
001oai:DiVA.org:uu-463425
003SwePub
008220110s2021 | |||||||||||000 ||eng|
009oai:DiVA.org:liu-182031
009oai:prod.swepub.kib.ki.se:148418470
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4634252 URI
0247 a https://doi.org/10.1016/j.jtct.2021.08.0282 DOI
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-1820312 URI
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1484184702 URI
040 a (SwePub)uud (SwePub)liud (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Wedge, Eileenu Copenhagen Univ Hosp, Dept Hematol, Juliane Maries Vej 6, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Biotech Res & Innovat Ctr, Copenhagen, Denmark.;Univ Copenhagen, Danish Stem Cell Ctr Danstem, Copenhagen, Denmark.4 aut
2451 0a Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelomonocytic Leukemia :b Clinical and Molecular Genetic Prognostic Factors in a Nordic Population
264 1b Elsevier,c 2021
338 a print2 rdacarrier
500 a Funding Agencies|Rigshopitalets Research Foundation; University of Copenhagen; Greater Copenhagen Health Science Partners (Clinical Academic Group in Translational Hematology); Danish Cancer Society (Danish Research Center for Precision Medicine in Blood Cancer) [223-A13071-18-S68]; Novo Nordisk Foundation (Novo Nordisk Foundation Center for Stem Cell Biology, DanStem) [NNF17CC0027852]; Swedish Cancer SocietySwedish Cancer Society [19 0200 Pj]; Stockholm County CouncilStockholm County Council [20190150]; Region Stockholm
520 a Chronic myelomonocytic leukemia (CMML) is an aggressive disease in which survival after allogeneic hematopoietic stem cell transplantation (HCT) remains relatively poor. An assessment of prognostic factors is an important part of treatment decision making and has the potential to be greatly improved by the inclusion of molecular genetics. However, there is a significant knowledge gap in the interpretation of mutational patterns. This study aimed to describe outcomes of allogeneic HCT in patients with CMML in relation to clinical and molecular genetic risk factors. This retrospective study included 64 patients with CMML who underwent allogeneic HCT between 2008 and 2018, with a median follow-up of 5.4 years. Next-generation sequencing using targeted myeloid panels was carried out on saved material from 51 patients from the time of transplantation. Kaplan-Meier and Cox regression were used for analysis of overall survival (OS), and cumulative incidence with competing risks and Fine and Gray models were used for analysis of relapse and nonrelapse mortality (NRM). Mutations were detected in 48 patients (94%), indicating high levels of minimal residual disease (MRD) positivity at transplantation, even among those in complete remission (CR) (n = 14), 86% of whom had detectable mutations. The most frequently mutated genes were ASXL1 (37%), TET2 (37%), RUNX1 (33%), SRSF2 (26%), and NRAS (20%). Risk stratification using the CMML-specific Prognostic Scoring System molecular score (CPSS-Mol) resulted in 45% of patients moving to a higher risk-group compared with risk stratification using the CPSS. High leucocyte count (>= 13 x 10(9)/L), transfusion requirement, and previous intensive chemotherapy were associated with higher incidence of relapse. Being in CR was not linked to better outcomes. Neither ASXL1 nor RUNX1 mutation was associated with a difference in OS, relapse, or NRM, despite being high risk in the nontransplantation setting. TET2 mutations were associated with a significantly higher 3-year OS (73% versus 40%; P =.039). Achieving MRD-negative CR was rare in this CMML cohort, which may explain why we did not observe better outcomes for those in CR. This merits further investigation. Our analyses suggest that the negative impact of ASXL1 and RUNX1 mutations can be overcome by allogeneic HCT; however, risk stratification is complex in CMML and requires larger cohorts and multivariate models, presenting an ongoing challenge in this rare disease.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Hematologi0 (SwePub)302022 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Hematology0 (SwePub)302022 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
653 a Chronic myelomonocytic leukemia
653 a Hematopoietic stem cell transplantation
653 a Risk factors
653 a High-throughput nucleotide sequencing
653 a Mutations
7001 a Hansen, Jakob Werneru Copenhagen Univ Hosp, Dept Hematol, Juliane Maries Vej 6, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Biotech Res & Innovat Ctr, Copenhagen, Denmark.;Univ Copenhagen, Danish Stem Cell Ctr Danstem, Copenhagen, Denmark.4 aut
7001 a Dybedal, Ingunnu Oslo Univ Hosp, Dept Hematol, Oslo, Norway.4 aut
7001 a Creignou, Mariau Karolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.4 aut
7001 a Ejerblad, Elisabethu Karolinska Institutet,Uppsala universitet,Hematologi,Uppsala Univ Hosp, Sweden4 aut0 (Swepub:uu)eleje020
7001 a Lorenz, Fryderyku Univ Hosp Umeå, Dept Med, Umeå, Sweden.4 aut
7001 a Werlenius, Olleu Sahlgrens Univ Hosp, Sect Hematol & Coagulat, Gothenburg, Sweden.4 aut
7001 a Ungerstedt, Johannau Karolinska Institutet4 aut
7001 a Holm, Mette Skovu Aarhus Univ Hosp, Dept Hematol, Aarhus, Denmark.4 aut
7001 a Nilsson, Larsu Skane Univ Hosp, Dept Med, Lund, Sweden.4 aut
7001 a Kittang, Astrid Olsnesu Haukeland Hosp, Dept Med, Sect Hematol, Bergen, Norway.4 aut
7001 a Antunovic, Petaru Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Hematologiska kliniken US,Linköping Univ Hosp, Dept Hematol, Linköping, Sweden.4 aut0 (Swepub:liu)petan27
7001 a Rohon, Peteru Univ Hosp Olomouc, Dept Hematooncol, Olomouc, Czech Republic.4 aut
7001 a Andersen, Mette Klarskovu Karolinska Institutet4 aut
7001 a Papaemmanuil, Elliu Mem Sloan Kettering Canc Ctr, Computat Oncol Serv, 1275 York Ave, New York, NY 10021 USA.;Mem Sloan Kettering Canc Ctr, Ctr Hematol Malignancies, 1275 York Ave, New York, NY 10021 USA.4 aut
7001 a Bernard, Elsau Mem Sloan Kettering Canc Ctr, Computat Oncol Serv, 1275 York Ave, New York, NY 10021 USA.;Mem Sloan Kettering Canc Ctr, Ctr Hematol Malignancies, 1275 York Ave, New York, NY 10021 USA.4 aut
7001 a Jädersten, Martinu Karolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.4 aut
7001 a Hellström-Lindberg, Evau Karolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.4 aut
7001 a Gronbaek, Kirstenu Copenhagen Univ Hosp, Dept Hematol, Juliane Maries Vej 6, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Biotech Res & Innovat Ctr, Copenhagen, Denmark.;Univ Copenhagen, Danish Stem Cell Ctr Danstem, Copenhagen, Denmark.4 aut
7001 a Ljungman, Peru Karolinska Institutet4 aut
7001 a Friis, Lone Smidstrupu Copenhagen Univ Hosp, Dept Hematol, Juliane Maries Vej 6, DK-2100 Copenhagen, Denmark.4 aut
7102 a Copenhagen Univ Hosp, Dept Hematol, Juliane Maries Vej 6, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Biotech Res & Innovat Ctr, Copenhagen, Denmark.;Univ Copenhagen, Danish Stem Cell Ctr Danstem, Copenhagen, Denmark.b Oslo Univ Hosp, Dept Hematol, Oslo, Norway.4 org
7730 t Transplantation and Cellular Therapyd : Elsevierg 27:12, s. 991.e1-991.e9q 27:12<991.e1-991.e9x 2666-6375x 2666-6367
8564 u https://doi.org/10.1016/j.jtct.2021.08.028
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-463425
8564 8u https://doi.org/10.1016/j.jtct.2021.08.028
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-182031
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:148418470

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