Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelomonocytic Leukemia: Clinical and Molecular Genetic Prognostic Factors in a Nordic Population

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Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelomonocytic Leukemia : Clinical and Molecular Genetic Prognostic Factors in a Nordic Population

Wedge, Eileen (författare): 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.

Hansen, Jakob Werner (författare): 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.

Dybedal, Ingunn (författare): Oslo Univ Hosp, Dept Hematol, Oslo, Norway.

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Creignou, Maria (författare): Karolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.

Ejerblad, Elisabeth (författare): Karolinska Institutet,Uppsala universitet,Hematologi,Uppsala Univ Hosp, Sweden

Lorenz, Fryderyk (författare): Univ Hosp Umeå, Dept Med, Umeå, Sweden.

Werlenius, Olle (författare): Sahlgrens Univ Hosp, Sect Hematol & Coagulat, Gothenburg, Sweden.

Ungerstedt, Johanna (författare): Karolinska Institutet

Holm, Mette Skov (författare): Aarhus Univ Hosp, Dept Hematol, Aarhus, Denmark.

Nilsson, Lars (författare): Skane Univ Hosp, Dept Med, Lund, Sweden.

Kittang, Astrid Olsnes (författare): Haukeland Hosp, Dept Med, Sect Hematol, Bergen, Norway.

Antunovic, Petar (författare): Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Hematologiska kliniken US,Linköping Univ Hosp, Dept Hematol, Linköping, Sweden.

Rohon, Peter (författare): Univ Hosp Olomouc, Dept Hematooncol, Olomouc, Czech Republic.

Andersen, Mette Klarskov (författare): Karolinska Institutet

Papaemmanuil, Elli (författare): 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.

Bernard, Elsa (författare): 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.

Jädersten, Martin (författare): Karolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.

Hellström-Lindberg, Eva (författare): Karolinska Inst, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden.

Gronbaek, Kirsten (författare): 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.

Ljungman, Per (författare): Karolinska Institutet

Friis, Lone Smidstrup (författare): Copenhagen Univ Hosp, Dept Hematol, Juliane Maries Vej 6, DK-2100 Copenhagen, Denmark.

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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)

Elsevier, 2021
2021
Engelska.
Ingår i: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 27:12, s. 991.e1-991.e9

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Tidskriftsartikel (refereegranskat)

Abstract Ämnesord

Stäng

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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Chronic myelomonocytic leukemia
Hematopoietic stem cell transplantation
Risk factors
High-throughput nucleotide sequencing
Mutations

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Hematologi

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