Comparison of a Standard Regimen (CHOP) with Three Intensive Chemotherapy Regimens for Advanced Non-Hodgkin's Lymphoma

Fisher, Richard I.; Gaynor, Ellen R.; Dahlberg, Steve; Oken, Martin M.; Grogan, Thomas M.; Mize, Evonne M.; Glick, John H.; Coltman, Charles A.; Miller, Thomas P.

doi:10.1056/nejm199304083281404

Cited by 1,965 publications

(940 citation statements)

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“…These patients should be treated with radiation therapy alone when the disease is localized without nodal involvement. 4 For the rare remaining patients, due to the high relapse rate, we think that chemotherapy is advisable, however, the optimal regimen is not yet known 17 but it must be chosen based on its low early and long-term toxicity in light of the long survival of these patients. For cutaneous B cell lymphoma, radiation therapy alone can only be recommended to patients whose disease is not localized to the leg and has no nodal involvement, nor elevated LDH and a good performance status.…”

Section: Discussionmentioning

confidence: 99%

Primary cutaneous large-cell lymphoma: analysis of 49 patients included in the LNH87 prospective trial of polychemotherapy for high-grade lymphomas

et al. 1998

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The objectives of this study were to evaluate the outcome after polychemotherapy for patients with primary cutaneous largecell lymphomas (PCLL) and to validate the recently proposed immunohistologic classification of cutaneous lymphomas. Among 140 patients with positive skin biopsies included in the LNH87 protocol (for treatment of aggressive lymphomas), 49 patients met the criteria of PCLL. Characteristics were: sex ratio M/F, 2.3; age 18 to 83 years (median, 52), peripheral lymph nodes, n = 22; diffuse disease, n = 12; median tumor size, 4.5 cm; elevated lactate dehydrogenase, n = 9; ECOG: 0/1, n = 49. Histology was: follicular center B cell, n = 23; B-lymphoblastic, n = 1; anaplastic large-cell lymphoma, n = 14 (T cell phenotype n = 8); CD30 ؊ T cell lymphoma, n = 11. All patients received polychemotherapy: under 70 years, ACVBP (three to four cycles and consolidation for 6 months) n = 25; mBACOD (eight cycles) n = 16; over 70 years, C(T)VP (six cycles) n = 8. Radiation therapy was not included in the protocol. With a median follow-up of 5 years, 24/49 patients had relapsed, with 20 skin relapses. Event-free (EFS) and overall survival (OS) at 5 years were, respectively, 50 and 77%. Significant adverse prognostic factors were: histology (CD30 ؊ T cell lymphoma) and diffuse cutaneous disease (Ͼ Ͼ Ͼ10% of skin). The presence of nodal involvement was only significant for EFS. When compared to 140 non-cutaneous lymphoma patients included in the same trial and fully matched for the main clinical characteristics, OS was similar. In conclusion, PCLL behaves like other localized B or T cell extranodal lymphomas with the same prognostic factors (LDH, ECOG, age) except for CD30 ؉ PCLL which have a very good prognosis.

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Section: Discussionmentioning

confidence: 99%

Primary cutaneous large-cell lymphoma: analysis of 49 patients included in the LNH87 prospective trial of polychemotherapy for high-grade lymphomas

et al. 1998

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“…The mortality for NHL rose at a similar rate, stabilised in the early 1990s and then started to fall at the end of the 1990s. The survival pattern for NHL had not changed significantly in over two decades up to the late 1990s [1] despite attempts to increase the efficacy of the standard treatment, combination chemotherapy (CHOP), with the addition of other cytotoxic drugs [2]. Two pivotal clinical trials in the late 1990s showed that the addition of the monoclonal antibody targeting the CD20 antigen expressed on almost all malignant B cells, rituximab, to standard chemotherapy regimens improved the survival for patients with indolent NHL, and patients with diffuse large B-cell lymphoma (the two commonest NHL subtypes) [1].…”

Section: Introductionmentioning

confidence: 99%

Improved survival for non-Hodgkin lymphoma patients in New South Wales, Australia

Chen²,

O’Connell

2010

BMC Cancer

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Background We evaluated if the survival benefit of adding rituximab to standard chemotherapy for non-Hodgkin lymphoma (NHL) observed in clinical trials has been experienced by an Australian NHL patient population. Methods NHL cases diagnosed in 1985-2004 in New South Wales (NSW) were followed-up to the end of 2004. Rituximab prescription data were obtained from Medicare Australia. Using a Poisson regression model adjusted for age group, sex, NHL subtype and time period (1990-1994, 1995-1999 and 2000-2004), we estimated excess risk of death after a diagnosis of NHL. To give context to the survival trend, trends in incidence and mortality were also estimated. Results Compared with 1990-1994, after adjusting for age, sex and NHL subtype the relative excess risk of death was significantly lower (p < 0.0001) in 1995-1999 (0.89) and 2000-2004 (0.74). A sharp fall in mortality was observed from 2000 to 2004 (annual percentage change (APC) = -4.7, p = 0.009), while a small but significant rise in incidence was seen from 1990 to 2004 (APC = 0.5, p = 0.01). The number of times rituximab was dispensed in NSW increased rapidly from 1274 in 1999 to 9250 in 2004. Conclusion It is likely that some benefit of adding rituximab to the standard chemotherapy for NHL has been experienced at the population level.

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“…A current frontline therapeutic protocol for NPM‐ALK + T‐cell lymphoma is the CHOP polychemotherapy. Alas, severe adverse reactions, including therapy‐related death, are sometimes encountered during clinical utilization of CHOP (Fisher et al ., 1993; Lim et al ., 2010; Sitzia et al ., 1997; Tulpule et al ., 2006). In a previous study from our laboratory, using a full concentration of CHOP in mice with systemic NPM‐ALK + T‐cell lymphoma resulted in significant toxic effects including therapy‐related death (George et al ., 2014).…”

Section: Discussionmentioning

confidence: 99%

TrkA is a binding partner of NPM‐ALK that promotes the survival of ALK⁺ T‐cell lymphoma

Shi

George

et al. 2017

Molecular Oncology

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Nucleophosmin‐anaplastic lymphoma kinase‐expressing (NPM‐ALK +) T‐cell lymphoma is an aggressive neoplasm that is more commonly seen in children and young adults. The pathogenesis of NPM‐ALK + T‐cell lymphoma is not completely understood. Wild‐type ALK is a receptor tyrosine kinase that is physiologically expressed in neural tissues during early stages of human development, which suggests that ALK may interact with neurotrophic factors. The aberrant expression of NPM‐ALK results from a translocation between the ALK gene on chromosome 2p23 and the NPM gene on chromosome 5q35. The nerve growth factor (NGF) is the first neurotrophic factor attributed to non‐neural functions including cancer cell survival, proliferation, and metastasis. These functions are primarily mediated through the tropomyosin receptor kinase A (TrkA). The expression and role of NGF/TrkA in NPM‐ALK + T‐cell lymphoma are not known. In this study, we tested the hypothesis that TrkA signaling is upregulated and sustains the survival of this lymphoma. Our data illustrate that TrkA and NGF are expressed in five NPM‐ALK + T‐cell lymphoma cell lines and TrkA is expressed in 11 of 13 primary lymphoma tumors from patients. In addition, we found evidence to support that NPM‐ALK and TrkA functionally interact. A selective TrkA inhibitor induced apoptosis and decreased cell viability, proliferation, and colony formation of NPM‐ALK + T‐cell lymphoma cell lines. These effects were associated with downregulation of cell survival regulatory proteins. Similar results were also observed using specific knockdown of TrkA in NPM‐ALK + T‐cell lymphoma cells by siRNA. Importantly, the inhibition of TrkA signaling was associated with antitumor effects in vivo, because tumor xenografts in mice regressed and the mice exhibited improved survival. In conclusion, TrkA plays an important role in the pathogenesis of NPM‐ALK + T‐cell lymphoma, and therefore, targeting TrkA signaling may represent a novel approach to eradicate this aggressive neoplasm.

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Comparison of a Standard Regimen (CHOP) with Three Intensive Chemotherapy Regimens for Advanced Non-Hodgkin's Lymphoma

Abstract: CHOP remains the best available treatment for patients with advanced-stage intermediate-grade or high-grade non-Hodgkin's lymphoma.

Cited by 1,965 publications

References 25 publications

Primary cutaneous large-cell lymphoma: analysis of 49 patients included in the LNH87 prospective trial of polychemotherapy for high-grade lymphomas

Primary cutaneous large-cell lymphoma: analysis of 49 patients included in the LNH87 prospective trial of polychemotherapy for high-grade lymphomas

Improved survival for non-Hodgkin lymphoma patients in New South Wales, Australia

TrkA is a binding partner of NPM‐ALK that promotes the survival of ALK⁺ T‐cell lymphoma

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Comparison of a Standard Regimen (CHOP) with Three Intensive Chemotherapy Regimens for Advanced Non-Hodgkin's Lymphoma

Abstract: CHOP remains the best available treatment for patients with advanced-stage intermediate-grade or high-grade non-Hodgkin's lymphoma.

Cited by 1,965 publications

References 25 publications

Primary cutaneous large-cell lymphoma: analysis of 49 patients included in the LNH87 prospective trial of polychemotherapy for high-grade lymphomas

Primary cutaneous large-cell lymphoma: analysis of 49 patients included in the LNH87 prospective trial of polychemotherapy for high-grade lymphomas

Improved survival for non-Hodgkin lymphoma patients in New South Wales, Australia

TrkA is a binding partner of NPM‐ALK that promotes the survival of ALK+ T‐cell lymphoma

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Product

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TrkA is a binding partner of NPM‐ALK that promotes the survival of ALK⁺ T‐cell lymphoma