Prognostic factors in childhood anaplastic large cell lymphoma: results of a large European intergroup study

Deley, Marie-Cécile Le; Reiter, Alfred; Williams, Denise; Delsol, Georges; Oschlies, Ilske; McCarthy, Keith; Zimmermann, Martin; Brugières, Laurence

doi:10.1182/blood-2007-07-100958

Cited by 158 publications

(127 citation statements)

References 28 publications

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“…The negative prognostic impact of high LDH levels was previously suggested by the French study LMB-89 [7,13]. Our findings would support that observation but, possibly due to the relatively small cohort of patients, none of the common prognostic parameters analyzed showed an impact on prognosis, including CNS involvement.…”

Section: Discussionsupporting

confidence: 90%

“…MDD at diagnosis is frequently detected in pediatric ALCL and can identify patients at risk of relapse [5]. The most common clinical features of ALCL in the pediatric population include systemic symptoms, especially high fever, generalized lymph-adenopathy and involvement of extranodal sites such as skin, bone, soft tissue, lung, and liver [6][7][8][9][10][11][12][13]. The central nervous system (CNS) is rarely involved [14].…”

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: 90%

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 children, 18-25% of systemic ALCLs develop skin manifestations during the course of the disease and this is a poor prognostic factor. [4][5][6][7][8][9] Systemic ALK-negative (ALK -) ALCL is included in the updated WHO classification as a separate preliminary entity.…”

Section: Introductionmentioning

confidence: 99%

ALK-positive anaplastic large cell lymphoma limited to the skin: clinical, histopathological and molecular analysis of 6 pediatric cases. A report from the ALCL99 study

et al. 2012

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Anaplastic large cell lymphomas are peripheral T-cell lymphomas that are characterized by a proliferation of large anaplastic blasts expressing CD30. In children, systemic anaplastic large cell lymphomas often present at advanced clinical stage and harbor translocations involving the anaplastic lymphoma kinase (ALK) gene leading to the expression of chimeric anaplastic lymphoma kinase (ALK)-fusion proteins. Primary cutaneous anaplastic large cell lymphoma is regarded as an ALK-negative variant confined to the skin and is part of the spectrum of primary cutaneous CD30-positive T-cell lymphoproliferative disorders. Thirty-three of 487 pediatric patients registered within the Anaplastic Large Cell Lymphoma-99 trial (1999 to 2006) presented with a skin limited CD30-positive lymphoproliferative disorder. In 23 of the 33 patients, material for international histopathological review was available, and the cases were studied for histopathological, immunophenotypical and clinical features as well as for breaks within the ALK gene. Five of 23 cases and one additional case (identified after closure of the trial) expressed ALKprotein. Complete staging excluded any other organ involvement in all children. Expression of ALK proteins was demonstrated by immunohistochemistry in all cases and the presence of breaks of the ALK gene was genetically confirmed in 5 evaluable cases. The histopathological and clinical picture of these skin-restricted ALK-positive lymphomas was indistinguishable from that of cutaneous anaplastic large cell lymphoma. Five children presented with a single skin lesion that was completely resected in 4 and incompletely resected in one. Three of these patients received no further therapy, 2 additional local radiotherapy, and one chemotherapy. All children remain in complete remission with a median follow up of seven years (range 1-8 years). We present 6 pediatric cases of ALK-positive primary cutaneous anaplastic large cell lymphomas. After thorough exclusion of systemic involvement, therapy confined to local measures seems to be sufficient to induce cure. ©2013 Ferrata Storti Foundation. This is an open

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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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Prognostic factors in childhood anaplastic large cell lymphoma: results of a large European intergroup study

Cited by 158 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

ALK-positive anaplastic large cell lymphoma limited to the skin: clinical, histopathological and molecular analysis of 6 pediatric cases. A report from the ALCL99 study

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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