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Minimal residual disease undetectable by next-generation sequencing predicts improved outcome in CLL after chemoimmunotherapy.
Thompson, Philip A; Srivastava, Jaya; Peterson, Christine; Strati, Paolo; Jorgensen, Jeffrey L; Hether, Tyler; Keating, Michael J; O'Brien, Susan M; Ferrajoli, Alessandra; Burger, Jan A; Estrov, Zeev; Jain, Nitin; Wierda, William G.
Afiliação
  • Thompson PA; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Srivastava J; Adaptive Biotechnologies Corporation, Seattle, WA.
  • Peterson C; Department of Biostatistics and.
  • Strati P; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Jorgensen JL; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX; and.
  • Hether T; Adaptive Biotechnologies Corporation, Seattle, WA.
  • Keating MJ; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • O'Brien SM; The Chao Comprehensive Cancer Center, University of California, Irvine, CA.
  • Ferrajoli A; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Burger JA; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Estrov Z; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Jain N; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Wierda WG; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Blood ; 134(22): 1951-1959, 2019 11 28.
Article em En | MEDLINE | ID: mdl-31537528
Patients with chronic lymphocytic leukemia (CLL) who achieve blood or bone marrow (BM) undetectable minimal residual disease (U-MRD) status after first-line fludarabine, cyclophosphamide, and rituximab (FCR) have prolonged progression-free survival (PFS), when assessed by an assay with sensitivity 10-4 (MRD4). Despite reaching U-MRD4, many patients, especially those with unmutated IGHV, subsequently relapse, suggesting residual disease <10-4 threshold and the need for more sensitive MRD evaluation. MRD evaluation by next-generation sequencing (NGS) has a sensitivity of 10-6 (MRD6). To better assess the depth of remission following first-line FCR treatment, we used NGS (Adaptive Biotechnologies Corporation) to assess MRD in 62 patients, all of whom had BM U-MRD by multicolor flow cytometry (sensitivity 10-4) at end-of-FCR treatment. Samples from these patients included 57 BM samples, 29 peripheral blood mononuclear cell (PBMC) samples, and 32 plasma samples. Only 27.4% of the 62 patients had U-MRD by NGS. Rate of U-MRD by NGS was lowest in BM (25%), compared with PBMC (55%) or plasma (75%). No patient with U-MRD by NGS in BM or PBMC was MRD+ in plasma. Patients with mutated IGHV were more likely to have U-MRD by NGS at the end of treatment (EOT; 41% vs 13%, P = .02) than those with unmutated IGHV. Median follow-up was 81.6 months. Patients with U-MRD at EOT had superior PFS vs MRD+ patients, regardless of sample type assessed (BM, P = .02, median not reached [NR] vs 67 months; PBMC, P = .02, median NR vs 74 months). More sensitive MRD6 testing increases prognostic discrimination over MRD4 testing.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Leucemia Linfocítica Crônica de Células B / Protocolos de Quimioterapia Combinada Antineoplásica / Sequenciamento de Nucleotídeos em Larga Escala / Citometria de Fluxo / Imunoterapia Tipo de estudo: Clinical_trials / Observational_studies / Prognostic_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Leucemia Linfocítica Crônica de Células B / Protocolos de Quimioterapia Combinada Antineoplásica / Sequenciamento de Nucleotídeos em Larga Escala / Citometria de Fluxo / Imunoterapia Tipo de estudo: Clinical_trials / Observational_studies / Prognostic_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article