Vinblastine in Children and Adolescents With High-Risk Anaplastic Large-Cell Lymphoma: Results of the Randomized ALCL99-Vinblastine Trial

Deley, Marie-Cécile Le; Rosolen, Angelo; Williams, Denise; Horibe, Keizo; Wróbel, Grażyna; Attarbaschi, Andishe; Zsíros, József; Uyttebroeck, Anne; Márky, Ildikó; Lamant, Laurence; Woessmann, Wilhelm; Pillon, Marta; Hobson, Rachel; Mauguen, Audrey; Reiter, Alfred; Brugières, Laurence

doi:10.1200/jco.2010.28.5999

Cited by 171 publications

(163 citation statements)

References 28 publications

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“…The AIEOP LNH-97 protocol used higher doses of chemotherapy compared to the ALCL99 protocol, but achieved comparable outcome (5-year EFS 68% vs. 2-year EFS 71%). This confirms the results of the randomized use of two different doses and schedules of high-dose MTX and of the addition of vinblastine, evaluated prospectively in the ALCL-99 trial, which failed to demonstrate any significant difference in terms of efficacy [19,20]. These observations raise the question of whether dose intensity, or dose of specific agents, such as MTX, may play a role in ALCL therapy or whether other characteristics in the treatment strategy, such as continuous lowdose chemotherapy, might be most important for the overall outcome.…”

Section: Discussionsupporting

confidence: 77%

“…This study also showed that intrathecal prophylaxis is not necessary to prevent disease recurrence to the CNS. Adding vinblastine to the same therapy backbone significantly delayed the occurrence of relapse but did not reduce the risk of failure [20]. The event-free survival (EFS) rate ranges from 60% to 75% for most of the studies and recurrence is observed in up to 35% of patients [7][8][9][10][11][12][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

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Results of AIEOP LNH‐97 protocol for the treatment of anaplastic large cell lymphoma of childhood

Pillon

Gregucci

Lombardi

et al. 2012

Pediatric Blood & Cancer

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BackgroundAnaplastic large cell lymphoma (ALCL) represents approximately 15% of all pediatric non‐Hodgkin lymphomas (NHL). It has distinct clinical features, including frequent involvement of extranodal sites and rare localization to the central nervous system (CNS). Despite varying treatment approaches the outcome of patients with ALCL has not significantly improved during the last two decades.ProcedureFrom October 1997 to beginning of 2000, newly diagnosed ALCL patients were enrolled into AIEOP LNH‐97 protocol for ALCL. Thereafter and until 2007, only CNS positive patients were included. AIEOP LNH‐97 was based on the BFM‐95 schema for ALCL and included six high‐dose chemotherapy courses. CNS prophylaxis was obtained with one intrathecal injection of chemotherapy in each course, whereas treatment of CNS involvement included three intrathecal injections without irradiation.ResultsThirty‐two patients were eligible for the study. Lymph‐node disease was the most frequent localization (69% of the cases), followed by mediastinal (25%), CNS (22%), bone marrow (16%), and skin (13%) involvement. Probabilities of overall survival (OS) and of event‐free survival (EFS) at 5 years for the whole population were 87% (SE 6%) and 68% (SE 8%), respectively.ConclusionsThis study confirmed that short pulse chemotherapy is an efficacious treatment option for first line therapy of pediatric ALCL, and that dose intensity may have some relevance for outcome, but not in all of the patients. Refinement and optimization of therapy strategies for ALCL may originate from a combination of clinical and biological prospective studies, as those in the pipeline of current international collaboration. Pediatr Blood Cancer 2012; 59: 828–833. © 2012 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Results of AIEOP LNH‐97 protocol for the treatment of anaplastic large cell lymphoma of childhood

Pillon

Gregucci

Lombardi

et al. 2012

Pediatric Blood & Cancer

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“…In a pediatric series, vinblastine was shown to be a very active drug as a single agent in patients with relapsed anaplastic large-cell lymphoma [49]. However, when vinblastine was added to an intensive, leukemia-like chemotherapy regimen, it did not reduce the frequency of relapse [50].…”

Section: Risk-adapted Therapy Of Specific Subtypesmentioning

confidence: 99%

The aggressive peripheral T‐cell lymphomas: 2015

Armitage

2015

American J Hematol

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Background: T‐cell lymphomas make up approximately 10%–15% of lymphoid malignancies. The frequency of these lymphomas varies geographically, with the highest incidence in parts of Asia.Diagnosis: The diagnosis of aggressive peripheral T‐cell lymphoma (PTCL) is usually made using the World Health Organization classification. The ability of hematopathologists to reproducibly diagnosis aggressive PTCL is lower than that for aggressive B‐cell lymphomas, with a range of 72%–97% for the aggressive PTCLs.Risk Stratification: Patients with aggressive PTCL are staged using the Ann Arbor Classification. Although somewhat controversial, positron emission tomography scans seem to be useful as they are in aggressive B‐cell lymphomas. The most commonly used prognostic index is the International Prognostic Index. The specific subtype of aggressive PTCL is an important risk factor, with the best survival seen in anaplastic large‐cell lymphoma—particularly young patients with the anaplastic lymphoma kinase positive subtype.Risk‐Adapted Therapy: Anaplastic large‐cell lymphoma is the only subgroup to have a good response to a CHOP‐like regimen. Angioimmunoblastic T‐cell lymphoma has a prolonged disease‐free survival in only ∼20% of patients, but younger patients who have an autotransplant in remission seem to do better. PTCL‐not otherwise specified is not one disease. Anthracycline‐containing regimens have disappointing results, and a new approach is needed. Natural killer/T‐cell lymphoma localized to the nose and nasal sinuses seems to be best treated with radiotherapy‐containing regimens. Enteropathy‐associated PTCL and hepatosplenic PTCL are rare disorders with a generally poor response to therapy, although selected patients with enteropathy‐associated PTCL seem to benefit from intensive therapy. Am. J. Hematol. 90:666–673, 2015. © 2015 Wiley Periodicals, Inc.

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“…6,7 Clinical risk factors have been defined and used for therapy stratification. 8,9 Minimal disseminated disease, as detected by polymerase chain reaction analysis for NPM-ALK in blood or bone marrow, serum antibody titers against ALK and the morphological subtype are strong predictors of clinical outcome. [10][11][12][13][14] The main morphological subtypes are: (i) the common type, which is composed of large tumor cells with pleomorphic nuclei; (ii) the small cell variant with ALK proteinexpressing tumor cells that do not differ in size from reactive T-cells; (iii) the lymphohistiocytic variant with abundant histiocytes admixed with the lymphoma cells which are as small as in the small cell variant; and (iv) other rare subtypes.…”

Section: Introductionmentioning

confidence: 99%

Expression of CD8 is associated with non-common type morphology and outcome in pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma

et al. 2013

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Anaplastic lymphoma kinase-positive anaplastic large T-cell lymphoma is characterized by morphological variability. Morphological variants (non-common subtype) are associated with a poor outcome. They display abundant reactive bystander cells admixed with the lymphoma cells. So far, the difficulty in distinguishing lymphoma cells from bystander cells by visual inspection has prevented detailed and reliable immunophenotypic analysis using conventional immunohistochemistry. To overcome these limitations, we analyzed 124 cases of pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma treated within clinical trials using immunofluorescence multi-staining and digital image analysis combining antibodies against anaplastic lymphoma kinase to specifically identify lymphoma cells with antibodies against CD30, CD3, CD5, CD8, Ki67 and phosphorylated STAT3. Non-common type anaplastic lymphoma kinase-positive anaplastic large cell lymphomas express CD8 more frequently than common type anaplastic lymphoma kinase-positive anaplastic large cell lymphomas (35.4% and 5.6%, respectively; P=0.0002). CD8 expression was associated with a poorer outcome. Importantly, in a multivariate analysis including clinical risk factors, histological subtype and CD8 expression, CD8-positivity proved to be an independent prognostic predictor of worse outcome (hazard ratio for survival 3.38, P=0.042).

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Vinblastine in Children and Adolescents With High-Risk Anaplastic Large-Cell Lymphoma: Results of the Randomized ALCL99-Vinblastine Trial

Abstract: Adding vinblastine during induction and as maintenance for a total treatment duration of 1 year significantly delayed the occurrence of relapses but did not reduce the risk of failure.

Cited by 171 publications

References 28 publications

Results of AIEOP LNH‐97 protocol for the treatment of anaplastic large cell lymphoma of childhood

Results of AIEOP LNH‐97 protocol for the treatment of anaplastic large cell lymphoma of childhood

The aggressive peripheral T‐cell lymphomas: 2015

Expression of CD8 is associated with non-common type morphology and outcome in pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma

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