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

Pillon, Marta; Gregucci, Fabiana; Lombardi, Alessandra; Santoro, Nicola; Piglione, Matilde; Sala, Alessandra; dʼAmore, Emanuele S.G.; Santis, R. De; Casale, Fiorina; Zecca, Marco; Mussolin, Lara; Rosolen, Angelo

doi:10.1002/pbc.24125

Cited by 38 publications

(29 citation statements)

References 35 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While some studies have stratified treatment on stage, stage has never been a strong prognostic feature. In a few studies (POG 9315, CCG 5941, AIEOP LNH-92, AIEOP LNH-97), only bone marrow involvement in a single study demonstrated prognostic value with the remainder of the studies finding no prognostic feature [6,[8][9][10]. In contrast, the "European Intergroup Study for ALCL" combined data on 235 patients from the BFM, UKCCSG, and SFOP studies [31].…”

Section: Clinicalmentioning

confidence: 96%

See 1 more Smart Citation

Anaplastic Large Cell Lymphoma in Children and Adolescents

Lowe

Gross

2013

Pediatric Hematology and Oncology

View full text Add to dashboard Cite

Anaplastic Large Cell Lymphoma (ALCL) is the most common mature T-cell neoplasm in children and adolescents. ALCLs comprise approximately 15% of all non-Hodgkin lymphomas (NHL) in children and adolescents and commonly present with advanced systemic disease. Dissimilar from ALCL in adults, ALCL in children is nearly universally anaplastic large cell lymphoma kinase (ALK) positive. Despite the relative rarity of the disease, a great deal of insight into the pathogenesis of ALCL has been learned by researching the essential oncogenic role of ALK. Many different treatment strategies have been utilized with similar event free survival (EFS) rates of 65-75%. This review will provide an overview of the pathology, clinical features, prognostics factors, and treatment for children and adolescents with ALK positive ALCL.

show abstract

Section: Clinicalmentioning

confidence: 96%

“…Pediatric ALCL is usually characterized by advanced disease at presentation with a high incidence of extra-nodal involvement. Current treatment strategies using multiagent chemotherapy achieve ∼70% event free survival (EFS) [2,[4][5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Anaplastic Large Cell Lymphoma in Children and Adolescents

Lowe

Gross

2013

Pediatric Hematology and Oncology

View full text Add to dashboard Cite

show abstract

“…[7][8][9] Patients were stratified according to stage (St. Jude staging system) and the involvement of risk organs. 1,16,17 Staging procedures included BM aspiration cytologic and spinal tap. BM involvement was defined by cytologically detectable ALCL cells, irrespective of numbers.…”

Section: Patientsmentioning

confidence: 99%

“…All patients received six 5-day chemotherapy courses over a period of 4 to 6 months. 1,16,17 Twenty-seven patients received vinblastine maintenance therapy in the trial ALCL99 (11 with MRD available). The clinical characteristics of the patients are shown in supplemental Table 1, available on the Blood Web site.…”

Section: Patientsmentioning

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

Self Cite

View full text Add to dashboard Cite

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...

show abstract

“…Pediatric ALCL is characterized clinically by the frequent presence of B-symptoms and the involvement of extranodal sites, such as the lung, bone, skin and soft tissue and, less commonly, the bone marrow (BM) and CNS [3][4][5][6]. The therapies for pediatric ALCL vary considerably in different study groups, including the short-term B-NHL-like strategy and prolonged leukemia-like protocols [7][8][9][10][11]. The Berlin-Frankfurt-Munster 90 (BFM-90) study adopted a short-term therapeutic strategy.…”

Section: Introductionmentioning

confidence: 99%

Treatment Outcome of Chinese Children with Anaplastic Large Cell Lymphoma by Using a Modified B-NHL-BFM-90 Protocol

Sun¹,

Zhen²,

Lin³

et al. 2014

Pediatric Hematology and Oncology

View full text Add to dashboard Cite

Pediatric anaplastic large cell lymphoma (ALCL) has rarely been reported in Chinese pediatric patients. This study evaluated the clinical characteristics and treatment outcome of Chinese pediatric patients with ALCL. Between October 2002 and October 2012, 39 untreated pediatric patients with ALCL were enrolled at a single institution. The patients were stratified into three groups (R1, R2, and R3) based on the stage of the disease, clinical risk factors, and chemotherapeutic response, and received different intensive chemotherapy regimens based on a modified B-NHL-BFM-90 protocol. Of the 39 patients, 22 were boys, and 17 were girls, with a median age at diagnosis of 10 years (range 2-16 years), 91.2% were anaplastic lymphoma kinase (ALK)-positive. The patient groups R1, R2, and R3 accounted for 12.8%, 30.4%, and 56.4% of the total, respectively. 87.2% of patients were stage III/IV. At a median follow-up period of 52 months (range 15-136 months), seven patients relapsed and three patients died of their disease. The 5-year event-free survival for all patients was 81.4% ± 6.4%, with 100%, 83.3% ± 10% and 75.3% ± 9.8% for groups R1, R2, and R3, respectively. The overall survival for all patients was 92.2% ± 4.3%. Our study demonstrates that a risk-stratified treatment with a modified B-NHL-BFM-90 protocol is efficacious for Chinese children with ALCL.

show abstract

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

Cited by 38 publications

References 35 publications

Anaplastic Large Cell Lymphoma in Children and Adolescents

Anaplastic Large Cell Lymphoma in Children and Adolescents

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

Treatment Outcome of Chinese Children with Anaplastic Large Cell Lymphoma by Using a Modified B-NHL-BFM-90 Protocol

Contact Info

Product

Resources

About