A phase 2 study of bortezomib in combination with ifosfamide/vinorelbine in paediatric patients and young adults with refractory/recurrent Hodgkin lymphoma: a Children's Oncology Group study

Horton, Terzah M.; Drachtman, Richard A.; Chen, Lu; Cole, Peter D.; McCarten, Kathleen; Voss, Stephan D.; Guillerman, R. Paul; Buxton, Allen; Howard, Scott C.; Hogan, Shirley; Sheehan, Andrea M.; López‐Terrada, Dolores; Mrazek, Matthew D.; Agrawal, Neeraj; Wu, Meng; Líu, Hao; Alarcón, Pedro A. de; Trippet, Tanya M.; Schwartz, Cindy L.

doi:10.1111/bjh.13388

Cited by 26 publications

(16 citation statements)

References 8 publications

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“… 27 This may explain why bortezomib was not effective in inhibiting IL-6 secretion in L428 cells and failed as treatment for some HL patients. 42 , 43 Although, the idea of using bortezomib as an NF- κ B inhibitor in the clinic has failed so far, nevertheless, better alternative NF- κ B inhibitors have the potential to be successful in treating HL.…”

Section: Discussionmentioning

confidence: 99%

Reed-Sternberg cells in Hodgkin’s lymphoma present features of cellular senescence

et al. 2016

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Hodgkin's Lymphoma (HL) is one of the most prevailing malignancies in young adults. Reed–Sternberg (RS) cells in HL have distinctive large cell morphology, are characteristic of the disease and their presence is essential for diagnosis. Enlarged cells are one of the hallmarks of senescence, but whether RS cells are senescent has not been previously investigated. Here we show that RS cells have characteristics of senescent cells; RS cells in HL biopsies specifically express the senescence markers and cell cycle inhibitors p21Cip1 and p16INK4a and are negative for the proliferation marker Ki-67, suggesting that these cells have ceased to proliferate. Moreover, the RS-like cells in HL lines, stained specifically for senescence-associated β-galactosidase (SA-β-gal). Oxidative stress promoted senescence in these cells as demonstrated by their staining for p21Cip1, p16INK4a, p53 and γH2AX. Senescent cells produce copious amounts of inflammatory cytokines termed ‘senescence-associated secretory phenotype' (SASP), primarily regulated by Nuclear Factor κB (NF-κB). Indeed, we show that NF-κB activity and NF-κB-dependent cytokines production (e.g., IL-6, TNF-α, GM-CSF) were elevated in RS-like cells. Furthermore, NF-κB inhibitors, JSH-23 and curcumin reduced IL-6 secretion from RS-like cells. Thus, defining RS cells as senescent offers new insights on the origin of the proinflammatory microenvironment in HL.

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Section: Discussionmentioning

confidence: 99%

Reed-Sternberg cells in Hodgkin’s lymphoma present features of cellular senescence

et al. 2016

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“…At 3 months post induction, an FDG‐PET scan (Figure B) showed progression of disease. Re‐induction was commenced according to the AHOD‐0521 protocol consisting of ifosfamide with mesna, vinorelbine, and bortezomib (Table ).…”

Section: Case Reportmentioning

confidence: 99%

Histiocytic sarcoma in a child—successful management and long‐term survival with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Sandler

Franklin

Hayes‐Jordan

2018

Pediatric Blood & Cancer

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Histiocytic sarcoma is an extremely rare tumor in children. It may occur sporadically or in association with other hematological malignancies. It arises most commonly in the lymph nodes but may occur anywhere in the body and clinical presentation is usually with advanced disease. Following tissue diagnosis and staging, management is with chemotherapy though there are no standard regimes. Surgery has been used successfully for local control. This is the first description of the use of peritonectomy and hyperthermic intraperitoneal chemotherapy to treat histiocytic sarcoma. The 4-year-old patient has been disease free for 6 years.

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“…A COG trial aimed to determine if bortezomib (B) increased the efficacy of ifosfamide and vinorelbine (IV) in pediatric HL. 39 This study enrolled 26 relapsed HL patients (,30 years) treated with 2 to 4 cycles of IVB. The primary endpoint was anatomic CR after2 cycles.…”

Section: Novel Agents Investigated In Pediatric Trialsmentioning

confidence: 99%

Hodgkin lymphoma in children and adolescents: improving the therapeutic index

Kelly

2015

Blood

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Hodgkin lymphoma (HL) is a highly curable form of childhood cancer, with estimated 5 year survival rates exceeding 98%. However, the establishment of a “standard of care” approach to its management is complicated by the recognition that long-term overall survival declines in part from delayed effects of therapy and that there continue to be subgroups of patients at risk for relapse for which prognostic criteria cannot adequately define. This challenge has resulted in the development of various strategies aimed at identifying the optimal balance between maintaining overall survival and avoidance of long-term morbidity of therapy, often representing strategies quite different from those used for adults with HL. More precise risk stratification and methods for assessing the chemosensitivity of HL through imaging studies and biomarkers are in evolution. Recent advances in the understanding of the biology of HL have led to the introduction of targeted therapies in both the frontline and relapsed settings. However, significant barriers exist in the development of new combination therapies, necessitating collaborative studies across pediatric HL research consortia and in conjunction with adult groups for the adolescent and young adult (AYA) population with HL.

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A phase 2 study of bortezomib in combination with ifosfamide/vinorelbine in paediatric patients and young adults with refractory/recurrent Hodgkin lymphoma: a Children's Oncology Group study

Cited by 26 publications

References 8 publications

Reed-Sternberg cells in Hodgkin’s lymphoma present features of cellular senescence

Reed-Sternberg cells in Hodgkin’s lymphoma present features of cellular senescence

Histiocytic sarcoma in a child—successful management and long‐term survival with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Hodgkin lymphoma in children and adolescents: improving the therapeutic index

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