Improvements in observed and relative survival in follicular grade 1-2 lymphoma during 4 decades: the Stanford University experience

Tan, Daryl; Horning, Sandra J.; Hoppe, Richard T.; Levy, Ronald; Rosenberg, Saul A.; Sigal, Bronislava M.; Warnke, Roger A.; Natkunam, Yasodha; Han, Summer S.; Yuen, Alan R.; Plevritis, Sylvia K.; Advani, Ranjana H.

doi:10.1182/blood-2013-03-491514

Cited by 231 publications

(183 citation statements)

References 30 publications

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“…1 Conventional treatment options for FL patients include multiagent chemotherapy combined with anti-CD20 monoclonal Abs 2,3 or radioimmunotherapy, 4,5 leading to an improvement of median overall survival (OS) of 12-14 years in the last decade. 6 High-dose salvage regimens, including chemotherapy, rituximab and/or TBI, followed by autologous hematopoietic cell transplantation (HCT) have also clearly improved 5-year PFS and OS. [7][8][9] More recently, the type II CD20-Ab obinutuzumab, 10,11 bortezomib, 12 lenalidomide, 13 idelalisib, 14 ibrutinib, 15 bcl-2 inhibitors 16 and Car T cells 17 have potential for further refinement of the clinical outcome in FL patients.…”

Section: Introductionmentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation as curative therapy for non-transformed follicular lymphomas

Heinzelmann

Bethge²,

Beelen

et al. 2016

Bone Marrow Transplant

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Allogeneic hematopoietic cell transplantation (HCT) offers the chance of cure for patients with non-transformed follicular lymphoma (FL), but is associated with the risk of non-relapse mortality (NRM). The aim of this study was to identify subgroups of FL patients who benefit from HCT. The European Society for Blood and Marrow Transplantation (EBMT) Minimum-Essential-A Data of 146 consecutive patients who received HCT for FL between 1998 and 2008 were extracted from the database of the German Registry 'DRST'. Diagnosis of FL was verified by contact with the reference pathologists. Estimated 1-, 2-and 5-year overall survivals (OS) were 67%, 60% and 53%, respectively. Day 100 NRM was 15%. Thirteen out of 33 patients (40%) with treatment-refractory disease (RD) at the time of transplantation survived long term. Univariate statistical analysis suggested limited chronic GvHD, donor age ⩽ 42 years and TBI-based conditioning in treatment refractory patients to correlate with favorable OS. Independent prognostic factors for OS were treatmentsensitive disease and limited chronic GvHD for the whole cohort, and additionally TBI-based conditioning for the treatment refractory subgroup. In contrast, patient age ⩾ 55 years had no impact on outcome. Thus, HCT for FL is associated with acceptable NRM, and offers a substantial chance of cure for patients with RD or advanced age. Donors ⩽ 42 years should be preferred if available.

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Section: Introductionmentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation as curative therapy for non-transformed follicular lymphomas

Heinzelmann

Bethge²,

Beelen

et al. 2016

Bone Marrow Transplant

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“…3 Although 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.…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

mentioning

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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“…Andreas Viardot, 5 Kristie A. Blum, 6 Christopher R. Flowers, 7 Wojciech J. Jurczak, 8 Ian W. Flinn, 9 Brad S. Kahl,10 Peter Martin, 11 Yeonhee Kim, 12 Sanatan Shreay, 12 Matthias Will, 13 Bess Sorensen, 13 Madlaina Breuleux, 13 Pier Luigi Zinzani 14 …”

mentioning

confidence: 99%

Efficacy and safety of idelalisib in patients with relapsed, rituximab- and alkylating agent-refractory follicular lymphoma: a subgroup analysis of a phase 2 study

et al. 2016

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Improvements in observed and relative survival in follicular grade 1-2 lymphoma during 4 decades: the Stanford University experience

Abstract: Key Points This study is a retrospective analysis of long-term outcomes of patients with FL treated at Stanford University for 4 decades. Study results showed significant improvement in OS in patients with FL despite no change in event-free survival after first-line therapy.

Cited by 231 publications

References 30 publications

Allogeneic hematopoietic cell transplantation as curative therapy for non-transformed follicular lymphomas

Allogeneic hematopoietic cell transplantation as curative therapy for non-transformed follicular lymphomas

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

Efficacy and safety of idelalisib in patients with relapsed, rituximab- and alkylating agent-refractory follicular lymphoma: a subgroup analysis of a phase 2 study

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