A bioclinical prognostic model using MYC and BCL2 predicts outcome in relapsed/refractory diffuse large B-cell lymphoma

Bosch, Mark; Akhter, Ariz; Chen, Bingshu E.; Mansoor, Adnan; LeBrun, David P.; Good, David; Crump, Michael; Shepherd, Lois E.; Scott, David W.; Stewart, Douglas A.

doi:10.3324/haematol.2017.179309

Cited by 16 publications

(21 citation statements)

References 48 publications

(44 reference statements)

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“…Besides, it would be more accessible in health-providing centers. Some studies had successfully validated protein prognostic model in malignancies, such as bladder cancer, lung adenocarcinoma and diffuse large B-cell lymphoma [22][23][24]. The protein models demonstrated vital role for predicting prognosis, which including bladder cancer, esophageal squamous cell carcinoma and pancreatic ductal adenocarcinoma [25][26][27].…”

Section: Discussionmentioning

confidence: 99%

Construction and Validation of a Protein Prognostic Model for Lung Squamous Cell Carcinoma

Fang¹,

Liu²,

Weng³

et al. 2020

Int. J. Med. Sci.

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Lung squamous cell carcinoma (LUSCC), as the major type of lung cancer, has high morbidity and mortality rates. The prognostic markers for LUSCC are much fewer than lung adenocarcinoma. Besides, protein biomarkers have advantages of economy, accuracy and stability. The aim of this study was to construct a protein prognostic model for LUSCC. The protein expression data of LUSCC were downloaded from The Cancer Protein Atlas (TCPA) database. Clinical data of LUSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 237 proteins were identified from 325 cases of LUSCC patients based on the TCPA and TCGA database. According to Kaplan-Meier survival analysis, univariate and multivariate Cox analysis, a prognostic prediction model was established which was consisted of 6 proteins (CHK1_pS345, CHK2, IRS1, PAXILLIN, BRCA2 and BRAF_pS445). After calculating the risk values of each patient according to the coefficient of each protein in the risk model, the LUSCC patients were divided into high risk group and low risk group. The survival analysis demonstrated that there was significant difference between these two groups (p= 4.877e−05). The area under the curve (AUC) value of the receiver operating characteristic (ROC) curve was 0.699, which suggesting that the prognostic risk model could effectively predict the survival of LUSCC patients. Univariate and multivariate analysis indicated that this prognostic model could be used as independent prognosis factors for LUSCC patients. Proteins co-expression analysis showed that there were 21 proteins co-expressed with the proteins in the risk model. In conclusion, our study constructed a protein prognostic model, which could effectively predict the prognosis of LUSCC patients.

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Section: Discussionmentioning

confidence: 99%

Construction and Validation of a Protein Prognostic Model for Lung Squamous Cell Carcinoma

Fang¹,

Liu²,

Weng³

et al. 2020

Int. J. Med. Sci.

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“…suggested in a retrospective study that for Myc-positive patients with relapsed and refractory DLBCL, the 3-year event-free survival (EFS) rate was only 10%, and the OS rate was 29%. 22 In the rituximab era, Although the difference in the improvement of OS between these two groups was not statistically significant, the transplantation group also revealed an advantage in OS. In the present study, the differences in other clinical characteristics between the transplantation group and non-transplantation group were not statistically significant.…”

Section: Discussionmentioning

confidence: 93%

“…Furthermore, studies have concluded that such patients may have resistance to R‐CHOP chemotherapy, and a higher recurrence rate in the central nervous system . Mark et al suggested in a retrospective study that for Myc‐positive patients with relapsed and refractory DLBCL, the 3‐year event‐free survival (EFS) rate was only 10%, and the OS rate was 29% . In the rituximab era, the significance of early HSCT for high‐risk and aggressive lymphoma after induction chemotherapy remains uncertain.…”

Section: Discussionmentioning

confidence: 99%

Autologous hematopoietic stem cell transplantation as first‐line consolidation therapy can improve the prognosis of diffuse large B‐cell lymphoma with high expression of MYC protein

Gao

et al. 2019

The Kaohsiung J of Med Scie

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Myc‐positive diffuse large B‐cell lymphoma has lower curative efficacy and long‐term survival than its negative counterpart, even when treated with R‐CHOP regimen. The present study aims to determine whether the use of autologous hematopoietic stem cell transplantation as a consolidation therapy can improve the curative efficacy in this type of patients after achieving the best effect of chemotherapy for the first time. The data of 50 patients with Myc‐positive diffuse large B‐cell lymphoma were retrospectively analyzed. Autologous transplantation was performed for 23 patients, while transplantation was not performed for 27 patients. The clinicopathological features and survival conditions were compared. The 1‐year and 3‐year progression‐free survival (PFS) rates were 66.7% ± 0.9% and 57.7% ± 1.0%, respectively, in the non transplantation group, and 100% and 82.1% ± 0.1%, respectively, in the transplantation group (P = .021). The 1‐year overall survival (OS) rate for these two groups was 88.7% ± 0.6% vs 100%, respectively, while the 3‐year OS rates for these two groups was 78.6% ± 0.1% vs 91.3% ± 0.1%, respectively (P = .176). Hematopoietic stem cell transplantation performed after chemotherapy is a risk factor for OS. Autologous hematopoietic stem cell transplantation as a consolidation therapy in the early stage can improve the prognosis of patients with Myc‐positive diffuse large B‐cell lymphoma.

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“…Patients with DEL had significantly worse 3-year event-free survival (0% versus 40%, p = 0.001) and OS rates (20% versus 54%, p = 0.004). 8 Miura and colleagues 9 reported similar inferior outcomes for patients with relapsed/ refractory aggressive B-cell lymphomas based on DEL status. This study evaluated 38 patients following salvage R-IVAD (rituximab, ifosfamide, etoposide, cytarabine and dexamethasone) and found a lower ORR (35% versus 71%, p = 0.048) and CR (35% versus 71%, p = 0.048) as well as a significantly lower 2-year PFS (9% versus 67%, p = 0.001) and OS (35% versus 71%, p = 0.037) when comparing DEL to non-DEL patients.…”

Section: Discussionmentioning

confidence: 94%

Co-expression of MYC and BCL2 predicts poorer outcomes for relapsed/refractory diffuse large B-cell lymphoma with R-ICE and intent to transplant

Allen

Mendez

Rybicki

et al. 2018

Therapeutic Advances in Hematology

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/home/tah 81Introduction Diffuse large B-cell lymphoma (DLBCL) with co-expression of MYC and BCL2 protein by immunohistochemistry (IHC) (i.e. doubleexpresser lymphoma, DEL) and/or rearrangements of MYC and BCL2 or BCL6 genes (i.e. double-hit lymphoma, DHL) is associated with poor outcomes after standard frontline therapy, independent of other clinical risk factors. [1][2][3][4] Less is documented concerning the impact of these genetic events in relapsed/refractory disease. R-ICE (rituximab, ifosfamide, carboplatin and etoposide) is an active regimen for patients with relapsed/refractory DLBCL and can effectively mobilize hematopoietic progenitor cells for subsequent autologous stem cell transplantation (ASCT). 5 R-ICE followed by ASCT is a common salvage approach for medically fit patients with relapsed/refractory DLBCL. In this study, we investigated the prognostic impact of DEL in the salvage setting by analyzing outcomes of patients with relapsed/refractory disease treated with R-ICE prior to planned ASCT. Patients and methodsWe reviewed records of 204 consecutive patients with DLBCL treated with salvage R-ICE and intent for ASCT from 2000 to 2015 at the Taussig Cancer Institute of the Cleveland Clinic. A total of 37 patients were excluded for inadequate clinical data and/or follow up. Data were collected from the electronic medical record with IRB approval. Abstract: Diffuse large B-cell lymphoma (DLBCL) with co-expression of MYC and BCL2 protein by immunohistochemistry (IHC) -that is, double-expresser lymphoma (DEL) -is associated with poor outcomes after standard frontline therapy. Less is known about the prognostic impact of DEL in patients with relapsed/refractory disease treated with salvage therapy and autologous stem cell transplantation (ASCT). We analyzed the outcomes of 167 patients with relapsed/refractory DLBCL treated with R-ICE (rituximab, ifosfamide, carboplatin and etoposide), of whom 111 patients (66%) underwent ASCT. Using predefined cutoffs for positivity by IHC at relapse for MYC and BCL2 of ⩾40% and ⩾50% of positive tumor cells, respectively, 26 patients (16%) were categorized as DEL and the rest as non-DEL. Overall and complete response rates to R-ICE did not differ between DEL and non-DEL. With a median follow up of 20 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates for DEL were inferior compared to non-DEL (for PFS: 6% versus 33%, p = 0.044, for OS: 39% versus 56%, p = 0.03). The negative impact of DEL on PFS and OS remained significant on multivariable analysis. In conclusion, positive DEL status predicts poorer outcomes following salvage therapy.

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A bioclinical prognostic model using MYC and BCL2 predicts outcome in relapsed/refractory diffuse large B-cell lymphoma

Cited by 16 publications

References 48 publications

Construction and Validation of a Protein Prognostic Model for Lung Squamous Cell Carcinoma

Construction and Validation of a Protein Prognostic Model for Lung Squamous Cell Carcinoma

Autologous hematopoietic stem cell transplantation as first‐line consolidation therapy can improve the prognosis of diffuse large B‐cell lymphoma with high expression of MYC protein

Co-expression of MYC and BCL2 predicts poorer outcomes for relapsed/refractory diffuse large B-cell lymphoma with R-ICE and intent to transplant

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