Rates and Outcomes of Follicular Lymphoma Transformation in the Immunochemotherapy Era: A Report From the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource

Link, Brian K.; Maurer, Matthew J.; Nowakowski, Grzegorz S.; Ansell, Stephen M.; Macon, William R.; Syrbu, Sergei; Slager, Susan L.; Thompson, Carrie A.; Inwards, David J.; Johnston, Patrick B.; Colgan, Joseph P.; Witzig, Thomas E.; Habermann, Thomas M.; Cerhan, James R.

doi:10.1200/jco.2012.48.3990

Cited by 263 publications

(294 citation statements)

References 40 publications

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“…Details on the cohort have been previously reported. 18 Patients selected for this analysis had newly diagnosed grades 1 to 3a FL, were enrolled in the MER between September 2002 and February 2008, and had an available pretreatment serum sample (Table 1). Patients were excluded if they had prior diagnoses of lymphoma, leukemia, or HIV infection.…”

Section: Study Populationsmentioning

confidence: 99%

Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma

Mir¹,

Maurer²,

Ziesmer³

et al. 2015

Blood

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• Elevated IL-2R, IL-1RA, and CXCL9 are associated with shorter event-free survival in newly diagnosed FL, treated with chemoimmunotherapy.• Increased serum IL-12 and IL-1RA is associated with shorter event-free survival in patients who were observed or treated with rituximab alone.Serum cytokines and chemokines may reflect tumor biology and host response in follicular lymphoma (FL). To determine whether the addition of these biological factors may further refine prognostication, 30 cytokines and chemokines were measured in pretreatment serum specimens from newly diagnosed FL patients (n 5 209) and from 400 matched controls. Cytokine levels were correlated with clinical outcome in patients who were observed or received single agent rituximab, or those who received chemotherapy.Correlations with outcome in chemotherapy treated patients were further examined in a separate cohort of 183 South West Oncology Group (SWOG) patients and all patients were then included in a meta-analysis. Six cytokines were associated with outcome in the Molecular Epidemiology Resource (MER) after adjusting for the FL international prognostic index. In patients who were observed or treated with rituximab alone, increased serum IL-12 and interleukin 1 receptor antagonist (IL-1RA) (P 5 .005 and .02) were associated with a shorter event-free survival. In patients receiving chemotherapy, hepatocyte growth factor, IL-8, IL-1RA, and CXCL9 (P 5 .015, .048, .004, and .0005) predicted a shorter EFS. When the MER chemotherapy treated patients and SWOG patients were combined in a meta-analysis, IL-2R, IL-1RA, and CXCL9 (P 5 .013, .042, and .0012) were associated with a poor EFS. (Blood. 2015;125(6):992-998) Introduction Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma in the United States.1 While classified as an indolent B-cell lymphoma, the clinical course exhibits a spectrum based on the FL international prognostic index (FLIPI) score with a remarkable tendency for patients to relapse.2 The overall survival rate of patients with FL was previous reported as 75% at 5 years, and ranged from 71% at 10 years for patients with a FLIPI score between 0 to 1, and 36% for those with a FLIPI score of .3. Currently, the median survival of all newly diagnosed patients is approximately 9 years. 3Although the overall survival appears to have improved with advances in chemoimmunotherapy, the median event free survival (EFS) remains around 2 years for patients with advanced disease. 4 As a prognostic score, the FLIPI has several limitations. It focuses on clinical factors and does not take into account biological factors such as the tumor microenvironment and the host response. Indeed, some studies have found better prognostication of the very high-risk group with the international prognostic index (IPI) rather than with the FLIPI. 5,6 The FLIPI may potentially be further improved, particularly in the high-risk categories, if biological data are added. Gene expression profiling studies on pretreatment specimens from patients with FL hav...

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Section: Study Populationsmentioning

confidence: 99%

Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma

Mir¹,

Maurer²,

Ziesmer³

et al. 2015

Blood

Self Cite

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show abstract

“…7 FL is a low grade lymphoma with variable clinical course; in some patients, the disease is indolent and slowly progressive over a period of many years, with waxing and waning lymphadenopathy, whereas in others the disease progresses rapidly, often with transformation to aggressive lymphoma and early death. 8 Despite advances in the treatment of FL, most FL patients remain incurable and, at 5 years approximately 11% 9 to 13% of cases, 10 and at 10 years 15% 10 to 28% 11 of cases will transform to an aggressive phenotype, typically diffuse large B-cell lymphoma (DLBCL). Management strategies include watch and wait, immunochemotherapy, and new targeted treatment options.…”

Section: Introductionmentioning

confidence: 99%

Follicular Lymphoma: The Role of the Tumor Microenvironment in Prognosis

Sugimoto

Watanabe

2016

J Clin Exp Hematopathol

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The microenvironment of follicular lymphoma (FL) is composed of tumor-infiltrating CD8 + T cells, follicular regulatory T cells, lymphoma-associated macrophages and mast cells, follicular helper T cells, follicular dendritic cells, and follicular reticular cells, all of which have been reported to have relevance in the prognosis of FL patients. In addition, some of these cells play a role in the histologic transformation of FL. Macrophages contribute to a poor prognosis in FL patients treated in the prerituximab era, but are associated with good prognosis in those treated in the rituximab era. T-cell immunoglobulin and mucin domain protein (TIM) 3 are markers of T-cell exhaustion, and T cells co-expressing programed death 1 (PD1) in peripheral blood and lymph nodes secrete interleukin (IL)-12 in the serum. Serum CXCL9, IL-2 receptor, and IL-1 receptor agonist are associated with shorter survival of FL patients. Agents for manipulation of the microenvironment surrounding FL cells include the immunomodulatory drug lenalidomide, immune check-point inhibitors, and cyclophosphamide prior to rituximab. To battle FL and to improve the outcomes of FL patients, understanding the relationship between neoplastic cells and the various microenvironmental cellular components is crucial for developing therapeutics against the microenvironment.

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“…12 A detailed study by Maeshima et al 13 on transformed FL histopathological parameters influencing survival showed that asynchronous histology has a worse prognosis than those with synchronous presentation. Those with three or more regimens of chemotherapy had a shorter OS attributed to chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

Autologous Stem Cell Transplantation for Transformed Lymphoma: Single-Center Experience

2016

Lymphoma and Chronic Lymphocytic Leukemias

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This is a single-center review of retrospectively collected computerized data and medical records of all the patients who have undergone high dose chemotherapy and ASCT for transformed lymphoma from 1999-2014. The primary endpoint of the study was overall survival (OS) and secondary endpoint was progression free survival (PFS). A total of 27 patients with histological transformation were identified. This included transformation from follicular lymphoma Grade 1-3A and non-follicular indolent lymphoma, synchronous and asynchronous presentation. All transformed to diffuse large B cell lymphoma. 33% were chemotherapy naive prior to transformation. Median follow up was 47 months. For the entire cohort OS at 3 years was 73% and PFS = 82%. The treatment has low risk for nonrelapse mortality providing durable remission.

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Rates and Outcomes of Follicular Lymphoma Transformation in the Immunochemotherapy Era: A Report From the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource

Cited by 263 publications

References 40 publications

Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma

Elevated serum levels of IL-2R, IL-1RA, and CXCL9 are associated with a poor prognosis in follicular lymphoma

Follicular Lymphoma: The Role of the Tumor Microenvironment in Prognosis

Autologous Stem Cell Transplantation for Transformed Lymphoma: Single-Center Experience

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