Outcome determinants for transformed indolent lymphomas treated with or without autologous stem-cell transplantation

Madsen, Charlotte Bernhard; Pedersen, Martin Bjerregård; Vase, Maja Ølholm; Bendix, Knud; Møller, Michael; Johansen, Preben; Jensen, Bjarne Astrup; Jensen, Paw; Munksgaard, Lars; Brown, Peter de Nully; Segel, Erik; d’Amore, Francesco

doi:10.1093/annonc/mdu537

Cited by 43 publications

(41 citation statements)

References 35 publications

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“…Our data illustrate that the outcome of patients with a composite histology at time of transformation is better than the outcome of patients with a morphology that is in keeping with DLBCL or BCLU, in line with a prior study. 54 Double-hit lymphoma usually refers to de novo DLBCL with concurrent MYC and BCL2 (or more rarely BCL6) translocations and has been associated with poor outcome following chemotherapy alone or when combined with rituximab in most studies. [27][28][29]55 The prognostic implication of double-hit status at time of transformation from underlying FL is not as clearly established.…”

Section: Discussionmentioning

confidence: 99%

Cell of origin of transformed follicular lymphoma

Kridel

Mottok

Farinha

et al. 2015

Blood

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Key Points• TFL is most commonly of the germinal center B-cell-like phenotype, but a significant minority of cases is of the ABC phenotype (16%).• The absence of BCL2 translocation in FL at diagnosis is associated with transformation into ABC-like large cell lymphoma.Follicular lymphoma (FL) is an indolent disease but transforms in 2% to 3% of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporal changes of routinely available biomarkers, outcome after transformation, as well as molecular subtypes of TFL. We report that the expression of IRF4 is an independent predictor of early transformation (Hazard ratio, 13.3; P < .001). We also show that composite histology at the time of transformation predicts favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to 110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal-center B-cell-like subtype in the majority of cases (80%) but that a significant proportion of cases is of the activated B-cell-like (ABC) subtype (16%). These latter cases are commonly negative for BCL2 translocation and arise preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our study demonstrates the existence of molecular heterogeneity in TFL as well as its relationship to the antecedent FL. (Blood. 2015;126(18):2118-2127

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Section: Discussionmentioning

confidence: 99%

Cell of origin of transformed follicular lymphoma

Kridel

Mottok

Farinha

et al. 2015

Blood

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“…[5][6][7][8] Maintenance rituximab (MR) is subsequently recommended in responding patients to prolong long-term disease control of their indolent lymphoma.…”

Section: -4mentioning

confidence: 99%

Maintenance rituximab following induction R-CHOP chemotherapy in patients with composite or discordant, indolent and aggressive, B-cell non-Hodgkin lymphomas

et al. 2016

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“…Overall survival in patients with tFL is invariably worse compared with patients without transformation in all the reported series . With respect to the risk factors affecting survival after transformation, a composite histology appeared associated with a significantly better outcome in comparison with pure DLBCL or high‐grade morphology in several series, including a large retrospective survey from British Columbia that failed to demonstrate a prognostic impact of the “double‐hit” status . COO, determined either by gene‐expression profiling or by immunohistochemistry, did not show prognostic relevance …”

Section: Prognosis and Therapeutic Options At Htmentioning

confidence: 87%

“…The benefit of high‐dose chemotherapy followed by ASCT among chemosensitive patients with transformed indolent lymphomas, which was demonstrated in the pre‐rituximab era in a series from the EBMT, has become a controversial matter after the advent of combined immunochemotherapy (Table ). In a population of 172 patients from the Canadian registry, a multivariate analysis demonstrated a highly significant survival benefit for ASCT compared with immunochemotherapy.…”

Section: Prognosis and Therapeutic Options At Htmentioning

confidence: 99%

“…In a population of 172 patients from the Canadian registry, a multivariate analysis demonstrated a highly significant survival benefit for ASCT compared with immunochemotherapy. In a multicenter retrospective analysis on 85 patients with histologically confirmed transformed indolent lymphomas, only patients with a diagnosis of transformed lymphoma after prolonged prior indolent disease had a benefit in progression‐free survival (PFS) after ASCT, whereas those with concomitant presentation with both indolent and aggressive lymphomas had a similar outcome after ASCT or immunochemotherapy . In the prospective NCCN cohort including 118 patients with indolent lymphomas and subsequent biopsy‐confirmed HT treated in the rituximab era without transplant (n = 50), or with either ASCT (n = 50) or allogenic stem cell transplantation (alloSCT, n = 18), the transplant led to prolonged survival .…”

Section: Prognosis and Therapeutic Options At Htmentioning

confidence: 99%

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Novel acquisitions on biology and management of transformed follicular lymphoma

Minoia

Zucca

Conconi

2018

Hematological Oncology

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Follicular lymphoma (FL) generally has an indolent clinical course, but in some patients, a histological transformation (HT) into aggressive entities may take place and often lead to a poorer survival. The rituximab era has seen an improved outcome of FL, including those with HT. The current treatment strategies for transformed FL are based on immunochemotherapy for the cases with HT at the time of diagnosis or as the first event after watchful waiting. Patients transforming after prior treatment of FL usually benefit from autologous stem cell transplant. Unfortunately, early assessment of the transformation risk remains elusive. Recent studies delved the mechanisms of HT, showing that this is a complex process, resulting from a number of epigenetic and genetic lesions occurring in the tumour cell population as well as progressive changes in the tumour microenvironment. This novel knowledge has prompted clinical investigations on a variety of new therapeutic strategies.

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Outcome determinants for transformed indolent lymphomas treated with or without autologous stem-cell transplantation

Abstract: ASCT improved the outcome in sequential, but not composite/discordant TIL. The beneficial impact of ASCT was greater in patients, who were rituximab-naïve at transformation.

Cited by 43 publications

References 35 publications

Cell of origin of transformed follicular lymphoma

Cell of origin of transformed follicular lymphoma

Maintenance rituximab following induction R-CHOP chemotherapy in patients with composite or discordant, indolent and aggressive, B-cell non-Hodgkin lymphomas

Novel acquisitions on biology and management of transformed follicular lymphoma

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