Childhood anaplastic large cell lymphoma has a high incidence of <i>ALK</i> gene rearrangement as determined by immunohistochemical staining and fluorescent <i>in situ</i> hybridisation: a genetic and pathological correlation*

Perkins, Sherrie L.; Pickering, Diane L.; Lowe, Eric; Zwick, David L.; Abromowitch, Minnie; Davenport, Ginny; Cairo, Mitchell S.; Sanger, Warren G.

doi:10.1111/j.1365-2141.2005.05808.x

Cited by 74 publications

(53 citation statements)

References 10 publications

(11 reference statements)

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“…In addition to MDD and MRD, clinical risk factors (ie, mediastinal, visceral, or skin involvement), uncommon histologic subtype, and ALK antibody titers #1/750 were associated with a significantly higher risk of relapse in univariate analysis. In multivariate analysis including the covariables MDD, MRD, clinical risk factors, histologic subtype, and ALK-antibody titers, the hazard ratio for EFS was 1.83 for MDD (95% confidence interval [CI], 0.55-6.12, P 5 .3), 6.00 for MRD (95% CI, 2.01-17.92, P 5 .001), 1.1 (95% CI, 0.28-4.33, P 5 .90) for clinical risk factors, 3.66 for uncommon histology (95% CI, 1.54-8.68, P 5 .003), and 3.25 for low ALK-antibody titers (95% CI, 1.38-7.68, P 5 .007).…”

Section: Mrdmentioning

confidence: 99%

Early assessment of minimal residual disease identifies patients at very high relapse risk in NPM-ALK–positive anaplastic large-cell lymphoma

Damm‐Welk

Mussolin

Zimmermann

et al. 2014

Blood

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Key Points• Early MRD positivity in NPM-ALK-positive ALCL correlates with a very high relapse risk and inferior survival.Detection of minimal disseminated disease (MDD) at diagnosis correlates with relapse risk in children with anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL). We investigated whether minimal residual disease (MRD) positivity by qualitative reverse-transcriptase polymerase chain reaction (RT-PCR) for Nucleophosmin (NPM)-ALK during treatment identifies patients at the highest relapse risk. Blood and/or bone marrow of 180 patients with NPM-ALK-positive ALCL treated with Berlin-Frankfurt-Münster-type protocols were screened for NPM-ALK transcripts at diagnosis; 103 were found to be MDD-positive. MRD before the second therapy course could be evaluated in 52 MDD-positive patients. MRD positivity correlated with uncommon histology. The cumulative incidence of relapses (CIR) of 26 MDD-positive/MRD-positive patients (81% 6 8%) was significantly higher than the CIR of 26 MDD-positive/MRDnegative (31% 6 9%) and 77 MDD-negative patients (15% 6 5%) (P < .001). Five-year survival of MDD-negative and MDD-positive/ MRD-negative patients was 91% 6 3% and 92% 6 5%, respectively, compared with 65% 6 9% of MDD-positive/MRD-positive patients (P < .001). Early evaluation of MRD in NPM-ALK-positive ALCL identifies patients with a very high relapse risk and inferior survival. (Blood. 2014;123(3):334-337) IntroductionThe relapse rate of children with anaplastic large-cell lymphoma (ALCL) reaches 25% to 35% with current chemotherapy.1-4 More than 95% of childhood ALCL expresses anaplastic lymphoma kinase (ALK) fusion proteins, 90% of which carry the translocation t(2;5)(p23;q35), resulting in the specific fusion gene NPM-ALK. 5,6NPM-ALK-expressing cells can be detected in bone marrow (BM) or peripheral blood (PB) by RT-PCR in 50% to 60% of patients with NPM-ALK-positive ALCL as a sign of minimal disseminated disease (MDD). 7,8 MDD turned out to be a significant prognostic factor 7-9 in addition to the histologic subtype and clinical risk factors. 10,11 In vivo response to chemotherapy measured by minimal residual disease (MRD) has been established as the strongest prognostic factor for children with acute lymphoblastic leukemia. [12][13][14] In Burkitt leukemia, early detection of MRD could identify patients at the highest risk of relapse as well. 15 We therefore investigated whether detection of MRD by qualitative RT-PCR for NPM-ALK in MDD-positive patients in BM or PB early during treatment allows for identification of patients at the highest risk of relapse in ALCL. Patients and methods EligibilityALCL patients treated according to the protocols Non-Hodgkin Lymphoma-Berlin-Frankfurt-Münster 95, Linfomi Non-Hodgkin 97, or ALCL 99 (Italian and German patients) between August 1998 and December 2008 were potentially eligible. Three patients with completely resected stage I disease were excluded because they received no prephase and only 3 courses of chemotherapy. Eligibility was confirme...

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Section: Mrdmentioning

confidence: 99%

Early assessment of minimal residual disease identifies patients at very high relapse risk in NPM-ALK–positive anaplastic large-cell lymphoma

Damm‐Welk

Mussolin

Zimmermann

et al. 2014

Blood

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“…ALCL exhibits a broad morphological spectrum, including common, lymphohistiocytic, and small cell variants [3]. The t(2;5)(p23;q35) translocation, resulting in the fusion of the nucleophosmin gene (NPM) at 5q35 and the tyrosine kinase gene ALK at 2p23, is identified in more than 90% of pediatric ALCL [4]. Expression of the fusion transcript NPM-ALK can be detected by reverse transcriptase polymerase chain reaction (RT-PCR) and represents a tumor-specific marker that can be exploited to evaluate minimal disseminated disease (MDD) in the bone marrow (BM).…”

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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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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“…[12][13][14][15][16][17] The fusion gene transcript can be readily and sensitively detected using reverse-transcriptase polymerase chain reaction (RT-PCR) technology, 18 allowing not only a more accurate diagnosis of this lymphoma entity but also enabling detection of disease extension at a submicroscopic level.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of circulating tumor cells in bone marrow or peripheral blood as detected by qualitative and quantitative PCR in pediatric NPM-ALK–positive anaplastic large-cell lymphoma

Damm‐Welk

Busch

Burkhardt

et al. 2007

Blood

118

116

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Childhood anaplastic large cell lymphoma has a high incidence of ALK gene rearrangement as determined by immunohistochemical staining and fluorescent in situ hybridisation: a genetic and pathological correlation*

Cited by 74 publications

References 10 publications

Early assessment of minimal residual disease identifies patients at very high relapse risk in NPM-ALK–positive anaplastic large-cell lymphoma

Early assessment of minimal residual disease identifies patients at very high relapse risk in NPM-ALK–positive anaplastic large-cell lymphoma

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

Prognostic significance of circulating tumor cells in bone marrow or peripheral blood as detected by qualitative and quantitative PCR in pediatric NPM-ALK–positive anaplastic large-cell lymphoma

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