4.25 Update on the International Standardized Approach for Flow Cytometric Residual Disease Monitoring in CLL

Rawstron, Andrew; Böttcher, Sebastian; Letestu, Rémi; Villamor, Neus; Fazi, Claudia; Kartsios, H.; Tute, Ruth de; Shingles, Jane; Ritgen, Matthias; Moreno, Carolina; Kneba, Michael; Montserrat, Emilio; Cymbalista, Florence; Hallek, M.; Hillmen, Peter

doi:10.1016/j.clml.2011.09.145

Cited by 5 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chronic lymphocytic leukemia (CLL) remains an incurable disease with an extremely variable course (1,2). It is featured by a dynamic imbalance between the proliferation and apoptosis of leukemia cells and by the accumulation of neoplastic B lymphocytes co-expressing CD5 and CD19 antigens (3)(4)(5)(6). However, the underlying mechanism involved in the development of this disease still remains unrevealed.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of IL-9 induced by STAT3 phosphorylation is mediated by miR-155 and miR-21 in chronic lymphocytic leukemia

Chen

et al. 2018

Oncol Rep

View full text Add to dashboard Cite

Interleukin‑9 (IL‑9) can function as both a positive and negative regulator of immune response, however the role of IL‑9 in tumor immunity is poorly understood. Chronic lymphocytic leukemia (CLL) is the most common chronic lympho‑proliferative disorder. Twenty CLL patients from 2010 to 2011 were recruited in the study. Expression and phosphorylation of transcription factor STAT3 and differential microRNAs (miRs) in peripheral blood mononuclear cells (PBMCs) from CLL patient samples were analyzed. In a previous study, we found a high level of IL‑9 in CLL patients. Concomitantly, overexpression of pSTAT3, miR‑155, and miR‑21 were observed in PBMCs from CLL patients in the present study. To elucidate whether there was interaction among IL‑9, STAT3, miR‑155, and miR‑21, MEC‑1 cells were used for further study. Our results revealed that there was no detectable IL‑9 in the culture medium of MEC‑1 cells. However, the IL‑9 protein could be detected using western blotting in MEC‑1 cells. Notably, when recombinant human IL‑9 (rIL‑9) was added to the medium of culturing MEC‑1 cells, the expression levels of pSTAT3 and IL‑9 in MEC‑1 cells were increased in a time‑dependent manner, which could be blocked by STAT3 inhibitor. Both miR‑155 and miR‑21 could increase IL‑9 expression, which could also be suppressed by the inhibitor of STAT3. Our data indicated that the existence of the novel 'extracellular IL‑9/pSTAT3/miR‑155/miR‑21/intracellular IL‑9' positive feedback system in CLL cells, provides a novel insight in the pathogenesis and possible therapeutic strategy of CLL.

show abstract

Section: Introductionmentioning

confidence: 99%

Overexpression of IL-9 induced by STAT3 phosphorylation is mediated by miR-155 and miR-21 in chronic lymphocytic leukemia

Chen

et al. 2018

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…[2][3][4] These trials have shown consistent correlation between posttreatment MRD level and therapeutic outcome, [5][6][7][8][9][10][11][12][13][14][15] with MRD status demonstrating independent prognostic significance in patients treated upfront with chemoimmunotherapy. 9,13,14 However, the independent prognostic relevance and long-term benefit of MRD negativity in other therapeutic settings, such as with chemotherapyfree treatments, remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Minimal residual disease is an independent predictor for 10-year survival in CLL

Kwok

Rawstron

Varghese

et al. 2016

Blood

120

View full text Add to dashboard Cite

Key Points• MRD negativity is a predictor for long-term progressionfree and overall survival independent of the type and line of therapy.• MRD negativity confers the greatest prognostic benefit when achieved in the frontline setting.Minimal residual disease (MRD) negativity, defined as <1 chronic lymphocytic leukemia (CLL) cell detectable per 10 000 leukocytes, has been shown to independently predict for clinical outcome in patients receiving combination chemoimmunotherapy in the frontline setting. However, the long-term prognostic value of MRD status in other therapeutic settings remains unclear. Here, we retrospectively analyzed, with up to 18 years follow-up, all patients at our institution who achieved at least a partial response (PR) with various therapies between 1996 and 2007, and received a bone marrow MRD assessment at the end of treatment according to the international harmonized approach. MRD negativity correlated with both progression-free survival (PFS) and overall survival (OS) independent of the type and line of treatment, as well as known prognostic factors including adverse cytogenetics. The greatest impact of achieving MRD negativity was seen in patients receiving frontline treatment, with 10-year PFS of 65% vs 10% and 10-year OS of 70% vs 30% for MRD-negative vs MRD-positive patients, respectively. Our results demonstrate the long-term benefit of achieving MRD negativity, regardless of the therapeutic setting and treatment modality, and support its use as a prognostic marker for long-term PFS and as a potential therapeutic goal in CLL. (Blood. 2016;128(24):2770-2773

show abstract

“…8 The European Research Initiative on CLL established an international standardized approach for flow cytometric MRD evaluation, currently used at MD Anderson Cancer Center. 9,10 Recently, several retrospective studies using different treatment regimens demonstrated the association between MRD-negative status (by different measures) and improved clinical outcomes. [11][12][13] The German CLL study group CLL8 trial provided prospective evidence of the value of achieving MRD-negative status after treatment with fludarabine and cyclophosphamide or FCR.…”

Section: Introductionmentioning

confidence: 99%

Eradication of bone marrow minimal residual disease may prompt early treatment discontinuation in CLL

Strati

Keating

O’Brien

et al. 2014

Blood

138

120

View full text Add to dashboard Cite

Key Points• MRD eradication is a desirable end point in chronic lymphocytic leukemia.• Early MRD eradication may prompt treatment discontinuation.The high complete remission rate with first-line combined fludarabine, cyclophosphamide, and rituximab (FCR) begs the question of the value of minimal residual disease (MRD)-negative status as a treatment end point. We report on 237 patients with chronic lymphocytic leukemia who received first-line FCR. MRD was prospectively assessed by 4-color flow cytometry in bone marrow after course 3 and at final response assessment. After course 3 and at final response assessment, 17% and 43% of patients were MRD negative in bone marrow, respectively. A mutated immunoglobulin heavy chain variable gene and trisomy 12 were independently associated with MRD-negative status both after 3 courses of FCR and at final response assessment in multivariable analyses (MVAs). MRD-negative status was independently associated with significantly longer progression-free survival (PFS) and overall survival (OS) in MVA (P 5 .03 and .02, respectively). This association was confirmed also on landmark MVA at the time of MRD assessment (P 5 .04 and .05, respectively). MRD-negative patients had comparable PFS and OS, independent of the number of courses received or interim staging. Early MRD eradication may be a desirable goal, prompting consideration of early discontinuation of treatment. This trial was registered at www.clinicaltrials.gov as #NCT00759798. (Blood. 2014;123(24):3727-3732)

show abstract

4.25 Update on the International Standardized Approach for Flow Cytometric Residual Disease Monitoring in CLL

Cited by 5 publications

References 0 publications

Overexpression of IL-9 induced by STAT3 phosphorylation is mediated by miR-155 and miR-21 in chronic lymphocytic leukemia

Overexpression of IL-9 induced by STAT3 phosphorylation is mediated by miR-155 and miR-21 in chronic lymphocytic leukemia

Minimal residual disease is an independent predictor for 10-year survival in CLL

Eradication of bone marrow minimal residual disease may prompt early treatment discontinuation in CLL

Contact Info

Product

Resources

About