PURPOSE: Natural killer (NK) cells are key effector cells for anti-CD20 monoclonal antibodies (mAb), such as obinutuzumab and rituximab. We assessed whether low pretreatment NK-cell count (NKCC) in peripheral blood or tumor tissue was associated with worse outcome in patients receiving antibody-based therapy. PATIENTS AND METHODS: Baseline peripheral blood NKCC was assessed by flow cytometry (CD3-CD56+ and/or CD16+ cells) in 1,064 of 1,202 patients with follicular lymphoma treated with obinutuzumab or rituximab plus chemotherapy in the phase III GALLIUM trial (NCT01332968) and 1,287 of 1,418 patients with diffuse large B-cell lymphoma (DLBCL) treated with obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (G-CHOP or R-CHOP) in the phase III GOYA trial (NCT01287741). The prognostic value of tumor NK-cell gene expression, as assessed by whole-transcriptome gene expression using TruSeq RNA sequencing, was also analyzed. The association of baseline variables, such as treatment arm, was evaluated using multivariate Cox regression models using a stepwise approach. RESULTS: In this exploratory analysis, low baseline peripheral blood NKCC was associated with shorter progression-free survival (PFS) in both follicular lymphoma [hazard ratio (HR), 1.48; 95% confidence interval (CI), 1.02-2.14; P = 0.04] and DLBCL (HR, 1.36; 95% CI, 1.01-1.83; P = 0.04), and overall survival in follicular lymphoma (HR, 2.20; 95% CI, 1.26-3.86; P = 0.0058). Low tumor NK-cell gene expression was associated with shorter PFS in G-CHOP-treated patients with DLBCL (HR, 1.95; 95% CI, 1.22-3.15; P < 0.01). CONCLUSIONS: These findings indicate that the number of NK cells in peripheral blood may affect the outcome of patients with B-cell non-Hodgkin lymphoma receiving anti-CD20-based immunochemotherapy.
- MeSH
- buňky NK imunologie patologie MeSH
- cyklofosfamid aplikace a dávkování MeSH
- difúzní velkobuněčný B-lymfom krev farmakoterapie imunologie patologie MeSH
- doxorubicin aplikace a dávkování MeSH
- folikulární lymfom krev farmakoterapie imunologie patologie MeSH
- humanizované monoklonální protilátky aplikace a dávkování MeSH
- imunoterapie MeSH
- lidé MeSH
- míra přežití MeSH
- prednison aplikace a dávkování MeSH
- prognóza MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- rituximab aplikace a dávkování MeSH
- senioři MeSH
- vinkristin aplikace a dávkování MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Lymphocytopenia is a poor prognostic marker in initial staging of non- Hodgkin lymphomas (below 1.0×109/l) and Hodgkin lymphoma (below 0.6×109/l) and in relapsed diffuse large B cell lymphoma. Early lymphocyte recovery 30.5×109/l after autologous and allogeneic stem cell transplantation is a significant predictor of tumor control and survival in lymphomas. Natural killer cells are involved in tumor cell killing and are the only subset of lymphocytes associated with disease outcome in initial staging and after autologous stem cell transplantation in lymphomas. The antitumor effect of various NK cell subsets should be defined.
- MeSH
- buňky NK transplantace MeSH
- difúzní velkobuněčný B-lymfom diagnóza krev MeSH
- Hodgkinova nemoc diagnóza krev MeSH
- lidé MeSH
- lymfocyty imunologie patologie MeSH
- lymfom diagnóza klasifikace krev MeSH
- medicína založená na důkazech trendy MeSH
- nádorové biomarkery krev MeSH
- nehodgkinský lymfom diagnóza krev MeSH
- podskupiny lymfocytů imunologie patologie MeSH
- prognóza MeSH
- transplantace hematopoetických kmenových buněk metody využití MeSH
- Check Tag
- lidé MeSH