Long-Term Follow-Up Analysis of HD9601 Trial Comparing ABVD Versus Stanford V Versus MOPP/EBV/CAD in Patients With Newly Diagnosed Advanced-Stage Hodgkin's Lymphoma: A Study From the Intergruppo Italiano Linfomi

Chisesi, Teodoro; Bellei, Monica; Luminari, Stefano; Montanini, Antonella; Marcheselli, Luigi; Levis, Alessandro; Gobbi, Paolo G.; Vitolo, Umberto; Stelitano, Caterina; Pavone, Vincenzo; Merli, Francesco; Liberati, Marina; Baldini, Luca; Bordonaro, Roberto; Pesce, Emanuela; Federico, Massimo

doi:10.1200/jco.2010.30.9799

Cited by 50 publications

(33 citation statements)

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“…13 Here, we report the results of a prospective, randomized, multicenter trial that compared ABVD and SV in advanced-stage HL. 12 The 5-year FFS was significantly lower for patients treated with SV (54%) compared with ABVD (78%) and MEC (81%).…”

Section: Journal Of Clinical Oncologymentioning

confidence: 99%

Randomized Comparison of the Stanford V Regimen and ABVD in the Treatment of Advanced Hodgkin's Lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244

Hoskin

Lowry

Horwich

et al. 2009

JCO

172

112

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Section: Journal Of Clinical Oncologymentioning

confidence: 99%

Randomized Comparison of the Stanford V Regimen and ABVD in the Treatment of Advanced Hodgkin's Lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244

Hoskin

Lowry

Horwich

et al. 2009

JCO

172

112

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“…2 In contrast, the prognosis of the remaining patients who relapse or fail to make complete remission, and in stage III and IV patients, is relatively poor. [3][4][5][6][7][8][9] In addition, patients who achieve long-term disease-free survival frequently have infertility and secondary malignancies, including breast cancer and cardiac failure, which are related to chemotherapeutic agents and radiation therapies. [10][11][12] Therefore, the development of new therapeutic strategies is necessary to improve clinical outcome and reduce the long-term side effects of current treatments in these patients.…”

Section: Introductionmentioning

confidence: 99%

PU.1 is a potent tumor suppressor in classical Hodgkin lymphoma cells

Yuki

Ueno

Tatetsu

et al. 2013

Blood

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Key Points• PU.1 is a potent tumor suppressor in cHL cells and the induction of PU.1 is a possible therapeutic option for patients with cHL.PU.1 has previously been shown to be down-regulated in classical Hodgkin lymphoma (cHL) cells via promoter methylation. We performed bisulfite sequencing and proved that the promoter region and the ؊17 kb upstream regulatory element of the PU.1 gene were highly methylated. To evaluate whether down-regulation of PU.1 is essential for the growth of cHL cells, we conditionally expressed PU.1 in 2 cHL cell lines, L428 and KM-H2. Overexpression of PU.1 induced complete growth arrest and apoptosis in both cell lines. Furthermore, in a Hodgkin lymphoma tumor xenograft model using L428 and KM-H2 cell lines, overexpression of PU.1 led to tumor regression or stable disease. Lentiviral transduction of PU.1 into primary cHL cells also induced apoptosis. DNA microarray analysis revealed that among genes related to cell cycle and apoptosis, p21 (CDKN1A) was highly up-regulated in L428 cells after PU.1 induction. Stable knockdown of p21 rescued PU.1-induced growth arrest in L428 cells, suggesting that the growth arrest and apoptosis observed are at least partially dependent on p21 up-regulation. These data strongly suggest that PU.1 is a potent tumor suppressor in cHL and that induction of PU.1 with demethylation agents and/or histone deacetylase inhibitors is worth exploring as a possible therapeutic option for patients with cHL. (Blood. 2013;121(6):962-970) IntroductionHodgkin lymphoma is a B-cell malignancy that occurs frequently in the white population, and is relatively rare within Japanese and other Asian populations. 1 To date, the combination of chemotherapy and irradiation has led to a dramatic improvement in both progression-free survival and overall survival of stage I and II patients, which now exceeds 90%. 2 In contrast, the prognosis of the remaining patients who relapse or fail to make complete remission, and in stage III and IV patients, is relatively poor. [3][4][5][6][7][8][9] In addition, patients who achieve long-term disease-free survival frequently have infertility and secondary malignancies, including breast cancer and cardiac failure, which are related to chemotherapeutic agents and radiation therapies. [10][11][12] Therefore, the development of new therapeutic strategies is necessary to improve clinical outcome and reduce the long-term side effects of current treatments in these patients. Nevertheless, our understanding of the mechanisms underlying the pathogenesis of Hodgkin lymphoma, which are necessary for the generation of novel, molecularly targeted agents, remains incomplete. It is known that both alleles of tumor necrosis factor, ␣-induced protein 3 (TNFAIP3)(A20) are deleted in a third of patients with Hodgkin lymphoma of nodular sclerosis histology and in the classic Hodgkin lymphoma (cHL) cell line, Hodgkin lymphoma is subdivided into cHL, which constitutes the majority of patients (95%), and nodular lymphocyte predominant Hodgkin lymphoma. 1 In cHL, lym...

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“…Four studies showed interim FDG-PET-negative patients after two cycles of ABVD to have an excellent PFS ranging between 92% and 95% (19,20,25,29) (Table 3). However, other studies in similar settings and with similar patient spectra reported PFS rates ranging between 81% and 85.5% (28,30,31,33), which can be considered rather poor regarding the a priori PFS (without taking into account the interim FDG-PET results) of approximately 75% (3)(4)(5)(6). Aforementioned findings underline that a negative interim FDG-PET result cannot exclude residual disease, which is inherent to its limited spatial resolution (34).…”

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confidence: 90%

Controversies on the prognostic value of interim FDG‐PET in advanced‐stage Hodgkin lymphoma

Adams

Kwee

2016

European J of Haematology

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Hodgkin lymphoma, even in advanced-stage, is a highly curable malignancy, but treatment is associated with short-term toxicity and long-term side effects. Early predictive markers are required to identify those patients who do not require the full-length standard therapy (and thus qualify for therapy de-escalation) and those patients who will not be cured by standard therapy (and thus qualify for therapy escalation). Multiple trials have assessed the value of 18 F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) after a few cycles of chemotherapy (also known as 'interim FDG-PET') in predicting outcome in advancedstage Hodgkin lymphoma. Furthermore, multiple interim FDG-PET-adapted trials, in which patients with positive interim FDG-PET scans are assigned to escalated therapies, and patients with negative interim FDG-PET scans are assigned to de-escalated therapies, have recently been published or are currently ongoing, with generally heterogeneous results. The present article reports the currently available evidence (and controversies) on the prognostic value of interim FDG-PET in advanced-stage Hodgkin lymphoma in patients with positive and negative interim FDG-PET findings following continuation of standard chemotherapy or escalated/de-escalated therapy. Hodgkin lymphoma is one of the most frequently occurring malignancies in young adults aged 20-40 yr, whereas a second incidence peak is observed in people aged >55 yr (1). Early-stage Hodgkin lymphoma is usually treated with two to three cycles of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) followed by radiation therapy (RT), whereas there is less consensus on the optimal treatment of advanced-stage Hodgkin lymphoma, in which six to eight cycles of ABVD or six to eight cycles of a more intense regimen of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (BEACOPP) are proposed (2). An important question in treating Hodgkin lymphoma is whether intensified chemotherapy should be applied upfront or reserved for patients with resistance to first-line therapy. In advancedstage Hodgkin lymphoma, the administration of six to eight cycles of ABVD has been reported to result in a long-term progression-free survival (PFS) of approximately 75% (3-6), whereas with upfront BEACOPP chemotherapy, the long-term PFS is approximately 85% (7-10). However, upfront BEACOPP chemotherapy is associated with an increased toxicity profile compared to ABVD therapy (7, 10). Furthermore, whether upfront BEACOPP will result in an improved overall survival (OS) compared to ABVD chemotherapy has not been consistently proven, with heterogeneous results among studies (7,8,(10)(11)(12). Therefore, there are strong arguments to reserve intensified treatments as second-line therapy for patients in whom standard firstline ABVD treatment fails, rather than exposing the entire population to an intensified treatment as would happen in case of upfront BEACOPP chemotherapy.To reduce toxicity and maximise patient outcome, id...

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Long-Term Follow-Up Analysis of HD9601 Trial Comparing ABVD Versus Stanford V Versus MOPP/EBV/CAD in Patients With Newly Diagnosed Advanced-Stage Hodgkin's Lymphoma: A Study From the Intergruppo Italiano Linfomi

Abstract: The long-term analysis confirmed ABVD and MEC superiority to StV. The use of RT after StV was established as mandatory. ABVD is still to be considered as the standard treatment with a good balance between efficacy and toxicity.

Cited by 50 publications

References 17 publications

Randomized Comparison of the Stanford V Regimen and ABVD in the Treatment of Advanced Hodgkin's Lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244

Randomized Comparison of the Stanford V Regimen and ABVD in the Treatment of Advanced Hodgkin's Lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244

PU.1 is a potent tumor suppressor in classical Hodgkin lymphoma cells

Controversies on the prognostic value of interim FDG‐PET in advanced‐stage Hodgkin lymphoma

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