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
This study analyzed the prognostic significance of soluble interleukin-2 receptor α (sIL-2Rα) levels in 100 prospectively enrolled patients with previously untreated follicular lymphoma. It showed that sIL-2Rα level ≥ 115 pmol/L at the time of treatment initiation correlated with a high Follicular Lymphoma International Prognostic Index-2 (FLIPI-2), bulky disease, advanced clinical stage, number of involved lymph nodes, bone marrow involvement and elevated β2-microglobulin (B2M) level. When testing all patients, sIL-2Rα ≥ 115 pmol/L was associated with significantly shorter progression-free (PFS; p < 0.03, hazard ratio [HR] 2.04) but not overall (OS; p = 0.06, HR 2.36) survival rates. Subanalysis of patients receiving cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) ± rituximab showed higher predictive power for both PFS (HR 2.75, 95% confidence interval [CI] 1.24-6.11, p = 0.01) and OS (HR 3.33, 95% CI 1.15-9.63, p = 0.02). In the whole population (n = 100), only B2M proved a significant univariate predictor (p = 0.007, HR = 2.8) of PFS. When testing patients treated with CHOP ± rituximab, sIL-2Rα was found to be the best univariate predictor for PFS among all FLIPI-2 factors (HR = 2.68, p = 0.015). Serum IL-2Rα levels may help to refine risk assessment in the modern immunotherapy era complementary to FLIPI-2 factors.
- MeSH
- cyklofosfamid aplikace a dávkování MeSH
- dospělí MeSH
- doxorubicin aplikace a dávkování MeSH
- folikulární lymfom krev diagnóza farmakoterapie mortalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- prednison aplikace a dávkování MeSH
- prognóza MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- receptory interleukinu-2 krev MeSH
- rituximab aplikace a dávkování MeSH
- senioři MeSH
- staging nádorů MeSH
- vinkristin aplikace a dávkování MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Follicular lymphoma (FL) is highly associated with the molecular rearrangement BCL2/IGH. Although BCL2/IGH has been studied many times in follicular lymphoma, its real clinical value remains controversial. In this study, we performed quantitative testing by real-time polymerase chain reaction in 56 FL patients with median follow-up of 44 months (range, 9-102 months); chemotherapy was administered in 52 of 56 cases. Pretreatment numbers of BCL2/IGH varied in wide ranges, with a median of 2947 (range, 0-1,261,013) copies/10(6) cellular equivalent in peripheral blood (PB) and 4650 copies/10(6) cellular equivalent (range, 1-1,056,813) in bone marrow (BM), the difference between PB and BM was significant (p = 0.006). Pretreatment of BCL2/IGH quantities were correlated to clinical parameters (e.g., age, stage, sex, lactate dehydrogenase, B symptoms, grade, bulky disease, chemotherapy regimen) and to progression free-survival. Advanced clinical stage (III and IV) and microscopic BM involvement were significantly associated with higher numbers of BCL2/IGH in PB (p < 0.05) and in BM (p = 0.05), regardless all or newly diagnosed patients were evaluated. High pretreatment burden of BCL2/IGH was associated with significantly shorter progression-free survival; p = 0.003 and p = 0.047 for PB and BM, respectively. In conclusion, pretreatment quantity of BCL2/IGH in PB or BM seems to mirror the extent of disease and can provide an auxiliary prognostic parameter in FL. Our results also support evidence of the negative prognostic value of microscopic BM involvement in FL.
- MeSH
- dospělí MeSH
- folikulární lymfom krev farmakoterapie genetika mortalita MeSH
- fúzní onkogenní proteiny MeSH
- kostní dřeň metabolismus patologie MeSH
- kvantitativní polymerázová řetězová reakce metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- následné studie MeSH
- přežití po terapii bez příznaků nemoci MeSH
- protoonkogenní proteiny c-bcl-2 MeSH
- retrospektivní studie MeSH
- RNA nádorová krev genetika MeSH
- senioři MeSH
- těžké řetězce imunoglobulinů MeSH
- translokace genetická MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
Serum thymidine kinase 1 (TK1) is a sensitive marker of tumor cell proliferation. TK1 has been reported as a reliable prognostic factor in solid tumors and chronic lymphocytic leukemia, but has not yet been tested in large populations of patients with non-Hodgkin lymphoma. In this study, the prognostic significance of TK1 levels was assessed in 170 prospectively enrolled patients with previously untreated follicular lymphoma (FL). The TK1 level at the time of treatment initiation was shown to correlate with the clinical stage, Follicular Lymphoma International Prognostic Index (FLIPI) score, β(2)-microglobulin level, lactate dehydrogenase level and B symptoms. No correlation was found with FL grade or Ki-67 proliferation index. Cox regression analysis identified high TK1 levels (≥ 15I U/L) as a prognostic factor for overall survival (hazard ratio 2.91, p = 0.019) and progression-free survival (hazard ratio 1.94, p = 0.022) independent of FLIPI score variables. Thus, TK1 levels may help to refine risk assessment in the modern immunotherapy era.
- MeSH
- autologní transplantace MeSH
- beta-2-mikroglobulin krev MeSH
- dospělí MeSH
- folikulární lymfom krev patologie terapie MeSH
- hodnocení výsledků zdravotní péče statistika a číselné údaje MeSH
- kombinovaná terapie MeSH
- L-laktátdehydrogenasa krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- multivariační analýza MeSH
- prediktivní hodnota testů MeSH
- přežití po terapii bez příznaků nemoci MeSH
- prognóza MeSH
- proporcionální rizikové modely MeSH
- prospektivní studie MeSH
- protokoly antitumorózní kombinované chemoterapie MeSH
- regresní analýza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- thymidinkináza krev MeSH
- transplantace kmenových buněk metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- finanční podpora výzkumu jako téma MeSH
- folikulární lymfom genetika krev patologie MeSH
- geny bcl-2 genetika MeSH
- kostní dřeň chemie MeSH
- lidé MeSH
- nehodgkinský lymfom MeSH
- přežití MeSH
- prognóza MeSH
- progrese nemoci MeSH
- statistika jako téma MeSH
- translokace genetická genetika MeSH
- Check Tag
- lidé MeSH
