Anaplastic Large-cell Lymphoma in Children: State of the Art in 2023

Anaplastic large-cell lymphoma is a rare disease and account for approximately 10% to 15% of pediatric non-Hodgkin lymphomas. They are characterized by extended stages, a high frequency of B signs and extra nodal involvement. Multiagent chemotherapy cures ∽60% to 75% of patients and relapse occurs in 35% of cases. For relapsed patients, various treatments ranging from vinblastine monotherapy to therapeutic intensification with hematopoietic stem cell transplantation have been evaluated, but there is currently no consensus on the optimal therapeutic strategy. New therapeutic perspectives are being evaluated for relapses and refractory forms as well as high-risk forms including monoclonal antibodies (Anti CD30), ALK inhibitors, and CART cells.

[1]  A. Kada,et al.  A Multicenter, Open-label, Clinical Trial to Assess the Effectiveness and Safety of Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced-intensity Conditioning in Relapsed/refractory Anaplastic Large-cell Lymphoma in Children. , 2020, Acta medica Okayama.

[2]  Ji-gang Yang,et al.  Anaplastic Large Cell Lymphoma Involving 7 Different Organs in a Pediatric Patient Demonstrated by FDG PET/CT. , 2020, Clinical nuclear medicine.

[3]  A. Agrawal,et al.  Prognostic Value of 18F-FDG PET/CT-Metabolic Parameters at Baseline and Interim Assessment in Pediatric Anaplastic Large Cell Lymphoma. , 2020, Clinical nuclear medicine.

[4]  Jiamei Gu,et al.  18F-FDG PET/CT imaging findings in anaplastic large cell lymphoma, a rare subtype of lymphoma , 2020, Cancer Imaging.

[5]  B. Geoerger,et al.  Efficacy of nivolumab in a patient with systemic refractory ALK+ anaplastic large cell lymphoma , 2018, Pediatric blood & cancer.

[6]  P. Provero,et al.  IRF4 Mediates the Oncogenic Effects of STAT3 in Anaplastic Large Cell Lymphomas , 2018, Cancers.

[7]  S. Swerdlow.  WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues , 2017 .

[8]  R. Orentas,et al.  Tumor Antigen and Receptor Densities Regulate Efficacy of a Chimeric Antigen Receptor Targeting Anaplastic Lymphoma Kinase. , 2017, Molecular therapy : the journal of the American Society of Gene Therapy.

[9]  Hao Liu,et al.  Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes. , 2017, The Journal of clinical investigation.

[10]  D. Grandér,et al.  PD-L1 is commonly expressed and transcriptionally regulated by STAT3 and MYC in ALK-negative anaplastic large-cell lymphoma , 2017, Leukemia.

[11]  M. Wasik,et al.  Nucleophosmin-anaplastic lymphoma kinase: the ultimate oncogene and therapeutic target. , 2017, Blood.

[12]  N. Rizvi,et al.  PD-L1 biomarker testing for non-small cell lung cancer: truth or fiction? , 2016, Journal of Immunotherapy for Cancer.

[13]  H. Abken,et al.  Superior Therapeutic Index in Lymphoma Therapy: CD30(+) CD34(+) Hematopoietic Stem Cells Resist a Chimeric Antigen Receptor T-cell Attack. , 2016, Molecular therapy : the journal of the American Society of Gene Therapy.

[14]  P. Khong,et al.  Pembrolizumab for relapsed anaplastic large cell lymphoma after allogeneic haematopoietic stem cell transplantation: efficacy and safety , 2016, Annals of Hematology.

[15]  R. Advani,et al.  The 2016 revision of the World Health Organization classification of lymphoid neoplasms. , 2016, Blood.

[16]  L. Kenner,et al.  Anaplastic large cell lymphoma in paediatric and young adult patients , 2016, British journal of haematology.

[17]  E. Jaffe,et al.  Morphologic Features of ALK-negative Anaplastic Large Cell Lymphomas With DUSP22 Rearrangements , 2016, The American journal of surgical pathology.

[18]  B. Bain,et al.  ALK‐positive anaplastic large cell lymphoma presenting with hemophagocytic lymphohistiocytosis , 2015, American journal of hematology/oncology.

[19]  S. Perkins,et al.  Revised International Pediatric Non-Hodgkin Lymphoma Staging System. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  A. Rosenwald,et al.  Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma. , 2015, Cancer cell.

[21]  A. Baruchel,et al.  Hematopoietic stem cell transplantation in relapsed ALK+ anaplastic large cell lymphoma in children and adolescents: a study on behalf of the SFCE and SFGM-TC , 2015, Bone Marrow Transplantation.

[22]  K. Kawa,et al.  Haematopoietic stem cell transplantation for relapsed or refractory anaplastic large cell lymphoma: a study of children and adolescents in Japan , 2015, British journal of haematology.

[23]  Lynette M. Smith,et al.  Advanced stage anaplastic large cell lymphoma in children and adolescents: Results of ANHL0131, a randomized phase III trial of APO versus a modified regimen with vinblastine: A report from the children's oncology group , 2014, Pediatric Blood & Cancer.

[24]  D. Ribatti,et al.  ALK-dependent control of hypoxia-inducible factors mediates tumor growth and metastasis. , 2014, Cancer research.

[25]  R. Advani,et al.  Brentuximab vedotin in the front-line treatment of patients with CD30+ peripheral T-cell lymphomas: results of a phase I study. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  B. Levine,et al.  Adoptive immunotherapy for cancer or viruses. , 2014, Annual review of immunology.

[27]  M. Poljak,et al.  Current Views and Perspectives on Classification of Squamous Intraepithelial Lesions of the Head and Neck , 2014, Head and Neck Pathology.

[28]  L. Guerra,et al.  Crizotinib in advanced, chemoresistant anaplastic lymphoma kinase-positive lymphoma patients. , 2014, Journal of the National Cancer Institute.

[29]  G. Delsol,et al.  Clinical analysis and prognostic significance of haemophagocytic lymphohistiocytosis‐associated anaplastic large cell lymphoma in children , 2014, British journal of haematology.

[30]  W. Klapper,et al.  Early assessment of minimal residual disease identifies patients at very high relapse risk in NPM-ALK-positive anaplastic large-cell lymphoma. , 2014, Blood.

[31]  J. Tobias,et al.  Malignant Transformation of CD4+ T Lymphocytes Mediated by Oncogenic Kinase NPM/ALK Recapitulates IL-2–Induced Cell Signaling and Gene Expression Reprogramming , 2013, The Journal of Immunology.

[32]  M. Chiu,et al.  Ten‐year follow‐up of pediatric patients with non‐hodgkin lymphoma treated with allogeneic or autologous stem cell transplantation , 2013, Pediatric blood & cancer.

[33]  A. Uyttebroeck,et al.  Central nervous system involvement in anaplastic large cell lymphoma in childhood: Results from a multicentre European and Japanese study , 2013, Pediatric blood & cancer.

[34]  E. Lowe,et al.  Anaplastic Large Cell Lymphoma in Children and Adolescents , 2013, Pediatric hematology and oncology.

[35]  K. Ballen,et al.  Umbilical cord blood transplantation: the first 25 years and beyond. , 2013, Blood.

[36]  R. Cohn,et al.  Transplant-Related Mortality Following Allogeneic Hematopoeitic Stem Cell Transplantation for Pediatric Acute Lymphoblastic Leukemia: 25-Year Retrospective Review , 2013, Pediatric blood & cancer.

[37]  P. Adam,et al.  Identification of C/EBPβ Target Genes in ALK+ Anaplastic Large Cell Lymphoma (ALCL) by Gene Expression Profiling and Chromatin Immunoprecipitation , 2013, PloS one.

[38]  M. Pillon,et al.  Use of minimal disseminated disease and immunity to NPM-ALK antigen to stratify ALK-positive ALCL patients with different prognosis , 2013, Leukemia.

[39]  N. Santoro,et al.  Results of AIEOP LNH‐97 protocol for the treatment of anaplastic large cell lymphoma of childhood , 2012, Pediatric blood & cancer.

[40]  Jeffrey W. Clark,et al.  Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. , 2012, The Lancet. Oncology.

[41]  R. Advani,et al.  Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  W. Klapper,et al.  Prognostic impact of morphologic and phenotypic features of childhood ALK-positive anaplastic large-cell lymphoma: results of the ALCL99 study. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[43]  W. Klapper,et al.  Relapsed or refractory anaplastic large-cell lymphoma in children and adolescents after Berlin-Frankfurt-Muenster (BFM)-type first-line therapy: a BFM-group study. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[44]  J. Cavaille,et al.  MiR-29a down-regulation in ALK-positive anaplastic large cell lymphomas contributes to apoptosis blockade through MCL-1 overexpression. , 2011, Blood.

[45]  M. Wasik,et al.  Oncogenic kinase NPM/ALK induces expression of HIF1α mRNA , 2011, Oncogene.

[46]  A. Attarbaschi,et al.  Vinblastine in children and adolescents with high-risk anaplastic large-cell lymphoma: results of the randomized ALCL99-vinblastine trial. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[47]  Rajender Kumar,et al.  Unresectable basaloid squamous cell carcinoma of the trachea treated with concurrent chemoradiotherapy: a case report with review of literature. , 2010, Journal of Cancer Research and Therapeutics.

[48]  M. Raffeld,et al.  C/EBPβ expression in ALK-positive anaplastic large cell lymphomas is required for cell proliferation and is induced by the STAT3 signaling pathway , 2010, Haematologica.

[49]  W. Klapper,et al.  Correlation of the autoantibody response to the ALK oncoantigen in pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with tumor dissemination and relapse risk. , 2010, Blood.

[50]  S. Davies,et al.  Hematopoietic stem cell transplantation for refractory or recurrent non-Hodgkin lymphoma in children and adolescents. , 2010, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[51]  Patrick Lutz,et al.  Single-drug vinblastine as salvage treatment for refractory or relapsed anaplastic large-cell lymphoma: a report from the French Society of Pediatric Oncology. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[52]  W. Klapper,et al.  Distribution of NPM1‐ALK and X‐ALK fusion transcripts in paediatric anaplastic large cell lymphoma: a molecular–histological correlation , 2009, British journal of haematology.

[53]  M. Ranalli,et al.  Primary Testicular Presentation of ALK-1–negative Anaplastic Large Cell Lymphoma in a Pediatric Patient , 2009, Journal of pediatric hematology/oncology.

[54]  S. Perkins,et al.  Intensive chemotherapy for systemic anaplastic large cell lymphoma in children and adolescents: Final results of children's cancer group study 5941 , 2009, Pediatric blood & cancer.

[55]  K. Horibe,et al.  Impact of the methotrexate administration dose on the need for intrathecal treatment in children and adolescents with anaplastic large-cell lymphoma: results of a randomized trial of the EICNHL Group. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[56]  Y. Li,et al.  Long-term disease control of refractory anaplastic large cell lymphoma with vinblastine. , 2009, Journal of pediatric hematology/oncology.

[57]  R. Lai,et al.  Proteome-wide identification of novel binding partners to the oncogenic fusion gene protein, NPM-ALK, using tandem affinity purification and mass spectrometry. , 2009, The American journal of pathology.

[58]  M. Wasik,et al.  Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1) , 2008, Proceedings of the National Academy of Sciences.

[59]  M. Wasik,et al.  γc-Signaling Cytokines Induce a Regulatory T Cell Phenotype in Malignant CD4+ T Lymphocytes1 , 2008, The Journal of Immunology.

[60]  L. Staudt,et al.  IRF4 addiction in multiple myeloma , 2008, Nature.

[61]  G. Inghirami,et al.  The anaplastic lymphoma kinase is an effective oncoantigen for lymphoma vaccination , 2008, Nature Medicine.

[62]  G. Delsol,et al.  Prognostic factors in childhood anaplastic large cell lymphoma: results of a large European intergroup study. , 2008, Blood.

[63]  W. Klapper,et al.  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. , 2007, Blood.

[64]  Roberto Piva,et al.  Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and BCL2A1 as critical target genes. , 2006, The Journal of clinical investigation.

[65]  K. Horibe,et al.  Recurrent childhood anaplastic large cell lymphoma: a retrospective analysis of registered cases in Japan , 2006, British journal of haematology.

[66]  M. Pillon,et al.  Anaplastic large cell lymphoma treated with a leukemia‐like therapy , 2005, Cancer.

[67]  N. Santoro,et al.  Prevalence and clinical implications of bone marrow involvement in pediatric anaplastic large cell lymphoma , 2005, Leukemia.

[68]  G. Janka,et al.  Hemophagocytic lymphohistiocytosis , 2005, Hematology.

[69]  D. Levy,et al.  New and Old Functions of STAT3: A Pivitol Target for Individualized Treatment of Cancer , 2005, Cell cycle.

[70]  Nicola Pimpinelli,et al.  WHO-EORTC classification for cutaneous lymphomas. , 2005, Blood.

[71]  D. Levy,et al.  Stat3 is required for ALK-mediated lymphomagenesis and provides a possible therapeutic target , 2005, Nature Medicine.

[72]  N. Tarbell,et al.  Advanced-stage large-cell lymphoma in children and adolescents: results of a randomized trial incorporating intermediate-dose methotrexate and high-dose cytarabine in the maintenance phase of the APO regimen: a Pediatric Oncology Group phase III trial. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[73]  G. Delsol,et al.  Oncogenic protein tyrosine kinases , 2004, Cellular and Molecular Life Sciences CMLS.

[74]  A. Lanfranco,et al.  CTLA-4 and PD-1 Receptors Inhibit T-Cell Activation by Distinct Mechanisms , 2004, Molecular and Cellular Biology.

[75]  K. Pulford,et al.  Anaplastic lymphoma kinase proteins in growth control and cancer , 2004, Journal of cellular physiology.

[76]  T. Curiel,et al.  Blockade of B7-H1 improves myeloid dendritic cell–mediated antitumor immunity , 2003, Nature Medicine.

[77]  H. Shimada,et al.  Anaplastic large cell lymphoma in Japanese children: retrospective analysis of 34 patients diagnosed at the National Research Institute for Child Health and Development , 2003, British journal of haematology.

[78]  P. Marynen,et al.  Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large‐cell lymphoma and inflammatory myofibroblastic tumor , 2002, Genes, chromosomes & cancer.

[79]  C. R. Pinkerton,et al.  Anaplastic large cell lymphoma in childhood: analysis of 72 patients treated on The United Kingdom Children's Cancer Study Group chemotherapy regimens , 2002, British journal of haematology.

[80]  K. Schultz,et al.  A population‐based study of pediatric anaplastic large cell lymphoma , 2002, Cancer.

[81]  D. Levy,et al.  Anaplastic lymphoma kinase (ALK) activates Stat3 and protects hematopoietic cells from cell death , 2002, Oncogene.

[82]  S. Morris,et al.  Translocations involving anaplastic lymphoma kinase (ALK) , 2001, Oncogene.

[83]  M. Tiemann,et al.  Short-pulse B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: a report of the Berlin-Frankfurt-Münster Group Trial NHL-BFM 90. , 2001, Blood.

[84]  R. Willemze,et al.  Lymphomatoid papulosis in children: a study of 10 children registered by the Dutch Cutaneous Lymphoma Working Group , 2001, The British journal of dermatology.

[85]  S. Pileri,et al.  CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. , 2000, Blood.

[86]  M. Ladanyi,et al.  ATIC-ALK: A novel variant ALK gene fusion in anaplastic large cell lymphoma resulting from the recurrent cryptic chromosomal inversion, inv(2)(p23q35). , 2000, The American journal of pathology.

[87]  A. Rosenwald,et al.  TRK-fused gene (TFG) is a new partner of ALK in anaplastic large cell lymphoma producing two structurally different TFG-ALK translocations. , 1999, Blood.

[88]  K. Pulford,et al.  A new fusion gene TPM3-ALK in anaplastic large cell lymphoma created by a (1;2)(q25;p23) translocation. , 1999, Blood.

[89]  S. Morris,et al.  Nucleophosmin-Anaplastic Lymphoma Kinase of Large-Cell Anaplastic Lymphoma Is a Constitutively Active Tyrosine Kinase That Utilizes Phospholipase C-γ To Mediate Its Mitogenicity , 1998, Molecular and Cellular Biology.

[90]  S. Pileri,et al.  ALK-positive lymphoma: a single disease with a broad spectrum of morphology. , 1998, Blood.

[91]  K. Pulford,et al.  Role of the nucleophosmin (NPM) portion of the non-Hodgkin's lymphoma-associated NPM-anaplastic lymphoma kinase fusion protein in oncogenesis , 1997, Molecular and cellular biology.

[92]  D. Wright,et al.  Childhood non-Hodgkin lymphomas in the United Kingdom: findings from the UK Children's Cancer Study Group. , 1997, Journal of clinical pathology.

[93]  H. Satoh,et al.  Characterization of the transforming activity of p80, a hyperphosphorylated protein in a Ki-1 lymphoma cell line with chromosomal translocation t(2;5). , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[94]  A. Verdeguer,et al.  Secondary acute promyelocytic leukemia in a child treated with epipodophyllotoxins. , 1994, American Journal Of Pediatric Hematology/Oncology.

[95]  H Stein,et al.  A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. , 1994, Blood.

[96]  M. Tiemann,et al.  Successful treatment strategy for Ki-1 anaplastic large-cell lymphoma of childhood: a prospective analysis of 62 patients enrolled in three consecutive Berlin-Frankfurt-Munster group studies. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[97]  D N Shapiro,et al.  Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. , 1994, Science.

[98]  J. Whitlock,et al.  A Small‐Cell‐Predominant Variant of Primary Ki‐1 (CD30)+ T‐Cell Lymphoma , 1993, The American journal of surgical pathology.

[99]  D. Arber,et al.  Large-cell anaplastic (Ki-1-positive) lymphoma complicated by disseminated intravascular coagulation. , 1991, Archives of Pathology & Laboratory Medicine.

[100]  S. Pileri,et al.  Peripheral T-cell lymphoma associated with hemophagocytic syndrome. , 1990, Blood.

[101]  M Tubiana,et al.  Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. , 1989, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[102]  K. Lennert,et al.  The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. , 1985, Blood.

[103]  Y. Natkunam,et al.  Programmed death-1 ligands PD-L1 and PD-L2 show distinctive and restricted patterns of expression in lymphoma subtypes. , 2018, Human pathology.

[104]  A. Rosenwald,et al.  Essential role of IRF4 and MYC signaling for survival of anaplastic large cell lymphoma. , 2015, Blood.

[105]  R. Hustinx,et al.  18F-FDG PET in children with lymphomas , 2004, European Journal of Nuclear Medicine and Molecular Imaging.

[106]  G. Delsol,et al.  Relapses of childhood anaplastic large-cell lymphoma: treatment results in a series of 41 children--a report from the French Society of Pediatric Oncology. , 2000, Annals of oncology : official journal of the European Society for Medical Oncology.

[107]  G. Leverger,et al.  Anaplastic Large-Cell Lymphoma in Children : Analysis of 82 Patients Enrolled in Two Consecutive Studies of the French Society of Pediatric Oncology , 1998 .

[108]  S. Murphy.  Classification, staging and end results of treatment of childhood non-Hodgkin's lymphomas: dissimilarities from lymphomas in adults. , 1980, Seminars in oncology.