Prognostic Factors in Hodgkin Lymphoma

Cuccaro, Annarosa; Bartolomei, Francesca; Cupelli, Elisa; Galli, Eugenio; Giachelia, Manuela; Hohaus, Stefan

doi:10.4084/mjhid.2014.053

Cited by 48 publications

(38 citation statements)

References 62 publications

(65 reference statements)

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“…Lymphomas are generally divided into Hodgkin's (HL) and non‐Hodgkin's lymphomas (NHL). Due to advances in treatment, HL is highly curable and currently 80%‐90% of patients respond to treatment . NHL include at least 40 distinct types of malignancies that vary in clinical behavior, morphologic appearance, immunologic, and molecular phenotype.…”

Section: Lymphoid Malignanciesmentioning

confidence: 99%

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Cell‐free DNA — Minimally invasive marker of hematological malignancies

Kubaczková

Vrábel

Sedlaříková

et al. 2017

European J of Haematology

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Although tumor cells are the most reliable source of tumor DNA, biopsy of the tumor is an invasive procedure that should be avoided in some cases. The main limitation of any biopsy is sampling of one tumor site, which may not represent all malignant clones due to the heterogeneity of the tumor. These clones respond to treatment differently and thus directly influence survival of the patient. Circulating cell-free DNA (cfDNA) is released from multiple tumor sites, reflects overall heterogeneity of the tumor, and correlates with its progression. Detection of tumor-specific genetic and epigenetic aberrations in cfDNA could have a direct impact on molecular diagnosis, prognosis, follow-up of disease, monitoring of minimal residual disease, and response to treatment. While most cfDNA data are still experimental, they are very promising. This review focuses on cfDNA in hematological malignancies. K E Y W O R D Sacute lymphoblastic leukemia, acute myeloid leukemia, multiple myeloma, myelodysplastic syndromes | INTRODUCTION AND HISTORYIn recent years, significant advances in diagnosis and treatment of cancer have been made. Nevertheless, invasive and painful procedures, such as tissue or bone marrow (BM) biopsy, are gold standard for disease diagnosis and monitoring. At the same time, they should be avoided in some cases-if BM is fibrotic or tumor tissue is not easily accessible.1 As a single tumor site is sampled during BM biopsy, it may not contain all malignant clones. 2,3 As these clones react to treatment differently, they directly influence survival of patients; thus, easily accessible markers that would mirror the entire heterogeneity of the tumor are sought after. Such putative markers are present in peripheral blood (PB), for example, circulating tumor cells (CTC) or circulating nucleic acids. 3,4 Biopsies of PB-the so-called liquid biopsies-are at the center of attention of researchers as well as clinicians and represent a newer and more comprehensive approach to obtain tumor information. Analysis of circulating molecules (microRNA, cell-free DNA, and others) as well as CTC might describe the tumor in more detail.Cell-free DNA (cfDNA) is one of these possibilities.CfDNA is formed by DNA fragments. These fragments are gathered from all tumor sites into circulation; thus, they mirror the complexity and heterogeneity of the entire tumor. 3 CfDNA may serve as an excellent diagnostic marker as it reflects the disease in more detail than existing biomarkers. Moreover, because of easy access, cfDNA sampling is suitable for repeated analyses. 4 As it correlates with disease progression, it could serve as a prognostic marker as well. 5,6The first reference of cfDNA dates back to 1948. In that year, CfDNA may shortly become such a marker. | CHARACTERISTICS OF CFDNAMolecules of cfDNA are extracellular fragments of short doublestranded DNA found in PB and other body fluids, for example, in urine, saliva, breast milk, and synovial fluid. 16,17 Generally, cfDNA is found in very low concentrations in PB of HD (10-100...

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Section: Lymphoid Malignanciesmentioning

confidence: 99%

“…Flow cytometry assessment of MRD in diffuse large B‐cell lymphoma (DLBCL) is possible only in very few cases as CTC are not usually detectable. Therefore, new possibilities are being explored, especially as DLBCL is the most common form accounting for 30%‐40% of newly diagnosed NHL cases . Armand et al.…”

Section: Lymphoid Malignanciesmentioning

confidence: 99%

Cell‐free DNA — Minimally invasive marker of hematological malignancies

Kubaczková

Vrábel

Sedlaříková

et al. 2017

European J of Haematology

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“…Aggressive treatment of advanced stage disease using the BEACOPP regimen has certainly improved disease-free survival, at the cost of infertility and risk of secondary organ damage and neoplasias [3][4][5][6][7]. Classical clinical and laboratory risk factors at diagnosis appear to be of little help for treatment decisions in patients with advanced HL [8,9].…”

Section: Introductionmentioning

confidence: 99%

CD68+ cell count, early evaluation with PET and plasma TARC levels predict response in Hodgkin lymphoma

et al. 2016

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Early response evaluation with [18F]fluordeoxyglucose (FDG) positron emission tomography after 2 cycles of chemotherapy (interim PET) has been indicated as the strongest predictor for outcome in classical Hodgkin lymphoma (HL). We studied the prognostic role of the number of tumor‐infiltrating CD68+ cells and of the plasma levels of TARC (thymus and activation‐regulated chemokine) in the context of interim PET in 102 patients with classical HL treated with Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD). After 2 ABVD cycles, interim PET according to Deauville criteria was negative (score 0–3) in 85 patients and positive (score 4–5) in 15 patients (2 patients technically not evaluable). TARC levels were elevated in 89% of patients at diagnosis, and decreased after 2 cycles in 82% of patients. Persistently elevated TARC levels in 18% of patients were significantly associated with a positive PET result (P = 0.007). Strong predictors for progression‐free survival (PFS) were a negative interim PET (85% vs. 28%, P < 0.0001) and CD68+ cell counts <5% (89% vs. 67%, P = 0.006), while TARC levels at diagnosis and at interim evaluation had no prognostic role. In multivariate analysis, interim PET, CD68+ cell counts and presence of B‐symptoms were independently associated with PFS. We conclude that although TARC levels are a biomarker for early response evaluation, they cannot substitute for interim PET as outcome predictor in HL. The evaluation of CD68 counts and B‐symptoms at diagnosis may help to identify low‐risk patients regardless positive interim PET.

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“…Classical Hodgkin lymphoma (CHL) ranks among the most frequently occurring lymphomas in the western world and is marked by characteristic Hodgkin and Reed‐Sternberg (HRS) cells, frequently multinucleated neoplastic cells derived from germinal center B lymphocytes (Kuppers, ; Kuppers et al, ). While most patients with CHL generally respond well to combination chemo‐ or radiation therapy, approximately 15–20% fail initial treatment or undergo relapse (Cuccaro et al, ). Further, even in patients in whom initial treatment is successful, secondary complications, including gonadal dysfunction, growth retardation, and secondary malignancies may occur (Evens et al, ).…”

Section: Introductionmentioning

confidence: 99%

Recurrent somatic loss of TNFRSF14 in classical Hodgkin lymphoma

Salipante

Adey

Thomas

et al. 2015

Genes Chromosomes & Cancer

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Investigation of the genetic lesions underlying classical Hodgkin lymphoma (CHL) has been challenging due to the rarity of Hodgkin and Reed-Sternberg (HRS) cells, the pathognomonic neoplastic cells of CHL. In an effort to catalog more comprehensively recurrent copy number alterations occurring during oncogenesis, we investigated somatic alterations involved in CHL using whole-genome sequencing-mediated copy number analysis of purified HRS cells. We performed low-coverage sequencing of small numbers of intact HRS cells and paired non-neoplastic B lymphocytes isolated by flow cytometric cell sorting from 19 primary cases, as well as two commonly used HRS-derived cell lines (KM-H2 and L1236). We found that HRS cells contain strikingly fewer copy number abnormalities than CHL cell lines. A subset of cases displayed non-integral chromosomal copy number states, suggesting internal heterogeneity within the HRS cell population. Recurrent somatic copy number alterations involving known factors in CHL pathogenesis were identified (REL, the PD-1 pathway, and TNFAIP3). In eight cases (42%) we observed recurrent copy number loss of chr1:2,352,236-4,574,271, a region containing the candidate tumor suppressor TNFRSF14. Using flow cytometry, we demonstrated reduced TNFRSF14 expression in HRS cells from five of 22 additional cases (23%) and in two of three CHL cell lines. These studies suggest that TNFRSF14 dysregulation may contribute to the pathobiology of CHL in a subset of cases.

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Prognostic Factors in Hodgkin Lymphoma

Cited by 48 publications

References 62 publications

Cell‐free DNA — Minimally invasive marker of hematological malignancies

Cell‐free DNA — Minimally invasive marker of hematological malignancies

CD68+ cell count, early evaluation with PET and plasma TARC levels predict response in Hodgkin lymphoma

Recurrent somatic loss of TNFRSF14 in classical Hodgkin lymphoma

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