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Allogeneic Hematopo...
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Wedge, EileenCopenhagen 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.
(author)
Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelomonocytic Leukemia : Clinical and Molecular Genetic Prognostic Factors in a Nordic Population
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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Elsevier,2021
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-463425
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-463425URI
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https://doi.org/10.1016/j.jtct.2021.08.028DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-182031URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:148418470URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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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
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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.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Hansen, Jakob WernerCopenhagen 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.
(author)
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Dybedal, IngunnOslo Univ Hosp, Dept Hematol, Oslo, Norway.
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Creignou, MariaKarolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.
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Ejerblad, ElisabethKarolinska Institutet,Uppsala universitet,Hematologi,Uppsala Univ Hosp, Sweden(Swepub:uu)eleje020
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Lorenz, FryderykUniv Hosp Umeå, Dept Med, Umeå, Sweden.
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Werlenius, OlleSahlgrens Univ Hosp, Sect Hematol & Coagulat, Gothenburg, Sweden.
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Ungerstedt, JohannaKarolinska Institutet
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Holm, Mette SkovAarhus Univ Hosp, Dept Hematol, Aarhus, Denmark.
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Nilsson, LarsSkane Univ Hosp, Dept Med, Lund, Sweden.
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Kittang, Astrid OlsnesHaukeland Hosp, Dept Med, Sect Hematol, Bergen, Norway.
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Antunovic, PetarLinköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Hematologiska kliniken US,Linköping Univ Hosp, Dept Hematol, Linköping, Sweden.(Swepub:liu)petan27
(author)
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Rohon, PeterUniv Hosp Olomouc, Dept Hematooncol, Olomouc, Czech Republic.
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Andersen, Mette KlarskovKarolinska Institutet
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Papaemmanuil, ElliMem 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.
(author)
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Bernard, ElsaMem 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.
(author)
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Jädersten, MartinKarolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.
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Hellström-Lindberg, EvaKarolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.
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Gronbaek, KirstenCopenhagen 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.
(author)
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Ljungman, PerKarolinska Institutet
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Friis, Lone SmidstrupCopenhagen Univ Hosp, Dept Hematol, Juliane Maries Vej 6, DK-2100 Copenhagen, Denmark.
(author)
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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.Oslo Univ Hosp, Dept Hematol, Oslo, Norway.
(creator_code:org_t)
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In:Transplantation and Cellular Therapy: Elsevier27:12, s. 991.e1-991.e92666-63752666-6367
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Wedge, Eileen
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Hansen, Jakob We ...
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Dybedal, Ingunn
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Creignou, Maria
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Ejerblad, Elisab ...
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Lorenz, Fryderyk
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Werlenius, Olle
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Ungerstedt, Joha ...
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Holm, Mette Skov
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Antunovic, Petar
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Rohon, Peter
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Andersen, Mette ...
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Papaemmanuil, El ...
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Bernard, Elsa
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Hellström-Lindbe ...
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