Anaplastic Large Cell Lymphoma in Children and Adolescents

  • Eric J. LoweEmail author
  • Laurence Brugieres


Anaplastic large cell lymphoma (ALCL) is the most common mature T-cell neoplasm in children and adolescents and one of the most curable cancers in pediatrics. Dissimilar from ALCL in adults, ALCL in children is nearly universally anaplastic large cell lymphoma kinase (ALK) positive. Multiple clinical trials have employed different chemotherapy strategies resulting in survival rates of 70–90%. 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. The elucidation of the pathogenesis of this unique disease has provided insight into many potential new agents for treatment. In fact, our knowledge of the biology of ALCL has now led to clinical challenges in attempting to study all the potential new agents in a limited number of patients. This chapter will provide an overview of the pathology, clinical features, prognostics factors, and treatment for children and adolescents with ALCL.


Anaplastic large cell lymphoma ALCL CD30 ALK-positive lymphoma Non-Hodgkin lymphoma t(2;5) 


  1. 1.
    Prokoph N, Larose H, Lim MS, Burke GAA, Turner SD. Treatment options for paediatric anaplastic large cell lymphoma (ALCL): current standard and beyond. Cancers (Basel). 2018;10(4)PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Sandlund JT, Downing JR, Crist WM. Non-Hodgkin’s lymphoma in childhood. N Engl J Med. 1996;334(19):1238–48.PubMedGoogle Scholar
  3. 3.
    Seidemann K, Tiemann M, Schrappe M, Yakisan E, Simonitsch I, Janka-Schaub G, 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-Munster Group Trial NHL-BFM 90. Blood. 2001;97(12):3699–706.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Stein H, Mason DY, Gerdes J, O’Connor N, Wainscoat J, Pallesen G, 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. Blood. 1985;66(4):848–58.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Kaneko Y, Frizzera G, Edamura S, Maseki N, Sakurai M, Komada Y, et al. A novel translocation, t(2;5)(p23;q35), in childhood phagocytic large T-cell lymphoma mimicking malignant histiocytosis. Blood. 1989;73(3):806–13.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Le Beau MM, Bitter MA, Larson RA, Doane LA, Ellis ED, Franklin WA, et al. The t(2;5)(p23;q35): a recurring chromosomal abnormality in Ki-1-positive anaplastic large cell lymphoma. Leukemia. 1989;3(12):866–70.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Rimokh R, Magaud JP, Berger F, Samarut J, Coiffier B, Germain D, et al. A translocation involving a specific breakpoint (q35) on chromosome 5 is characteristic of anaplastic large cell lymphoma (‘Ki-1 lymphoma’). Br J Haematol. 1989;71(1):31–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL, et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma. Science. 1994;263(5151):1281–4.CrossRefGoogle Scholar
  9. 9.
    Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri S, Stein H, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC; 2008.Google Scholar
  10. 10.
    Chiarle R, Voena C, Ambrogio C, Piva R, Inghirami G. The anaplastic lymphoma kinase in the pathogenesis of cancer. Nat Rev Cancer. 2008;8(1):11–23.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Kinney MC, Higgins RA, Medina EA. Anaplastic large cell lymphoma: twenty-five years of discovery. Arch Pathol Lab Med. 2011;135(1):19–43.PubMedGoogle Scholar
  12. 12.
    Alexander S, Kraveka JM, Weitzman S, Lowe E, Smith L, Lynch JC, 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. Pediatr Blood Cancer. 2014;61(12):2236–42.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Brugieres L, Deley MC, Pacquement H, Meguerian-Bedoyan Z, Terrier-Lacombe MJ, Robert A, et al. CD30(+) anaplastic large-cell lymphoma in children: analysis of 82 patients enrolled in two consecutive studies of the French Society of Pediatric Oncology. Blood. 1998;92(10):3591–8.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Brugieres L, Le Deley MC, Rosolen A, Williams D, Horibe K, Wrobel G, 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. J Clin Oncol. 2009;27(6):897–903.PubMedCrossRefGoogle Scholar
  15. 15.
    Han JY, Suh JK, Lee SW, Koh KN, Im HJ, Seo JJ. Clinical characteristics and treatment outcomes of children with anaplastic large cell lymphoma: a single center experience. Blood Res. 2014;49(4):246–52.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Laver JH, Kraveka JM, Hutchison RE, Chang M, Kepner J, Schwenn M, 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. J Clin Oncol. 2005;23(3):541–7.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Le Deley MC, Rosolen A, Williams DM, Horibe K, Wrobel G, Attarbaschi A, et al. Vinblastine in children and adolescents with high-risk anaplastic large-cell lymphoma: results of the randomized ALCL99-vinblastine trial. J Clin Oncol. 2010;28(25):3987–93.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Lowe EJ, Sposto R, Perkins SL, Gross TG, Finlay J, Zwick D, et al. Intensive chemotherapy for systemic anaplastic large cell lymphoma in children and adolescents: final results of Children’s Cancer Group Study 5941. Pediatr Blood Cancer. 2009;52(3):335–9.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Pillon M, Gregucci F, Lombardi A, Santoro N, Piglione M, Sala A, et al. Results of AIEOP LNH-97 protocol for the treatment of anaplastic large cell lymphoma of childhood. Pediatr Blood Cancer. 2012;59(5):828–33.PubMedCrossRefGoogle Scholar
  20. 20.
    Rosolen A, Pillon M, Garaventa A, Burnelli R, d’Amore ES, Giuliano M, et al. Anaplastic large cell lymphoma treated with a leukemia-like therapy: report of the Italian Association of Pediatric Hematology and Oncology (AIEOP) LNH-92 protocol. Cancer. 2005;104(10):2133–40.PubMedCrossRefGoogle Scholar
  21. 21.
    Turner SD, Lamant L, Kenner L, Brugieres L. Anaplastic large cell lymphoma in paediatric and young adult patients. Br J Haematol. 2016;173(4):560–72.CrossRefGoogle Scholar
  22. 22.
    Williams DM, Hobson R, Imeson J, Gerrard M, McCarthy K, Pinkerton CR. Anaplastic large cell lymphoma in childhood: analysis of 72 patients treated on The United Kingdom Children’s Cancer Study Group chemotherapy regimens. Br J Haematol. 2002;117(4):812–20.PubMedCrossRefGoogle Scholar
  23. 23.
    Mori T, Kiyokawa N, Shimada H, Miyauchi J, Fujimoto J. Anaplastic large cell lymphoma in Japanese children: retrospective analysis of 34 patients diagnosed at the National Research Institute for Child Health and Development. Br J Haematol. 2003;121(1):94–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Kinney MC, Collins RD, Greer JP, Whitlock JA, Sioutos N, Kadin ME. A small-cell-predominant variant of primary Ki-1 (CD30)+ T-cell lymphoma. Am J Surg Pathol. 1993;17(9):859–68.PubMedCrossRefGoogle Scholar
  25. 25.
    Bonzheim I, Geissinger E, Roth S, Zettl A, Marx A, Rosenwald A, et al. Anaplastic large cell lymphomas lack the expression of T-cell receptor molecules or molecules of proximal T-cell receptor signaling. Blood. 2004;104(10):3358–60.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Benharroch D, Meguerian-Bedoyan Z, Lamant L, Amin C, Brugieres L, Terrier-Lacombe MJ, et al. ALK-positive lymphoma: a single disease with a broad spectrum of morphology. Blood. 1998;91(6):2076–84.PubMedGoogle Scholar
  27. 27.
    Pulford K, Lamant L, Morris SW, Butler LH, Wood KM, Stroud D, et al. Detection of anaplastic lymphoma kinase (ALK) and nucleolar protein nucleophosmin (NPM)-ALK proteins in normal and neoplastic cells with the monoclonal antibody ALK1. Blood. 1997;89(4):1394–404.PubMedGoogle Scholar
  28. 28.
    Perkins SL, Pickering D, Lowe EJ, Zwick D, Abromowitch M, Davenport G, et al. 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. Br J Haematol. 2005;131(5):624–7.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Damm-Welk C, Busch K, Burkhardt B, Schieferstein J, Viehmann S, Oschlies I, 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. Blood. 2007;110(2):670–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Lamant L, McCarthy K, d’Amore E, Klapper W, Nakagawa A, Fraga M, et al. Prognostic impact of morphologic and phenotypic features of childhood ALK-positive anaplastic large-cell lymphoma: results of the ALCL99 study. J Clin Oncol. 2011;29(35):4669–76.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Mussolin L, Damm-Welk C, Pillon M, Zimmermann M, Franceschetto G, Pulford K, et al. Use of minimal disseminated disease and immunity to NPM-ALK antigen to stratify ALK-positive ALCL patients with different prognosis. Leukemia. 2013;27(2):416–22.CrossRefGoogle Scholar
  32. 32.
    Pileri S, Falini B, Delsol G, Stein H, Baglioni P, Poggi S, et al. Lymphohistiocytic T-cell lymphoma (anaplastic large cell lymphoma CD30+/Ki-1 + with a high content of reactive histiocytes). Histopathology. 1990;16(4):383–91.PubMedCrossRefGoogle Scholar
  33. 33.
    Ott G, Bastian BC, Katzenberger T, Decoteau JF, Kalla J, Rosenwald A, et al. A lymphohistiocytic variant of anaplastic large cell lymphoma with demonstration of the t(2;5)(p23;q35) chromosome translocation. Br J Haematol. 1998;100(1):187–90.PubMedCrossRefGoogle Scholar
  34. 34.
    Vassallo J, Lamant L, Brugieres L, Gaillard F, Campo E, Brousset P, et al. ALK-positive anaplastic large cell lymphoma mimicking nodular sclerosis Hodgkin’s lymphoma: report of 10 cases. Am J Surg Pathol. 2006;30(2):223–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Hassler MR, Pulverer W, Lakshminarasimhan R, Redl E, Hacker J, Garland GD, et al. Insights into the pathogenesis of anaplastic large-cell lymphoma through genome-wide DNA methylation profiling. Cell Rep. 2016;17(2):596–608.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Marzec M, Zhang Q, Goradia A, Raghunath PN, Liu X, Paessler M, et al. Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1). Proc Natl Acad Sci U S A. 2008;105(52):20852–7.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Murga-Zamalloa CA, Mendoza-Reinoso V, Sahasrabuddhe AA, Rolland D, Hwang SR, McDonnell SR, et al. NPM-ALK phosphorylates WASp Y102 and contributes to oncogenesis of anaplastic large cell lymphoma. Oncogene. 2017;36(15):2085–94.PubMedCrossRefGoogle Scholar
  38. 38.
    Damm-Welk C, Klapper W, Oschlies I, Gesk S, Rottgers S, Bradtke J, et al. Distribution of NPM1-ALK and X-ALK fusion transcripts in paediatric anaplastic large cell lymphoma: a molecular-histological correlation. Br J Haematol. 2009;146(3):306–9.CrossRefGoogle Scholar
  39. 39.
    Tsuyama N, Sakamoto K, Sakata S, Dobashi A, Takeuchi K. Anaplastic large cell lymphoma: pathology, genetics, and clinical aspects. J Clin Exp Hematop. 2017;57(3):120–42.PubMedCrossRefGoogle Scholar
  40. 40.
    Bandini C, Pupuleku A, Spaccarotella E, Pellegrino E, Wang R, Vitale N, et al. IRF4 mediates the oncogenic effects of STAT3 in anaplastic large cell lymphomas. Cancers (Basel). 2018;10(1)PubMedCentralCrossRefPubMedGoogle Scholar
  41. 41.
    Turner SD, Yeung D, Hadfield K, Cook SJ, Alexander DR. The NPM-ALK tyrosine kinase mimics TCR signalling pathways, inducing NFAT and AP-1 by RAS-dependent mechanisms. Cell Signal. 2007;19(4):740–7.CrossRefGoogle Scholar
  42. 42.
    Webb TR, Slavish J, George RE, Look AT, Xue L, Jiang Q, et al. Anaplastic lymphoma kinase: role in cancer pathogenesis and small-molecule inhibitor development for therapy. Expert Rev Anticancer Ther. 2009;9(3):331–56.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Wu C, Molavi O, Zhang H, Gupta N, Alshareef A, Bone KM, et al. STAT1 is phosphorylated and downregulated by the oncogenic tyrosine kinase NPM-ALK in ALK-positive anaplastic large-cell lymphoma. Blood. 2015;126(3):336–45.PubMedCrossRefGoogle Scholar
  44. 44.
    Ait-Tahar K, Damm-Welk C, Burkhardt B, Zimmermann M, Klapper W, Reiter A, 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. Blood. 2010;115(16):3314–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Pulford K, Falini B, Banham AH, Codrington D, Roberton H, Hatton C, et al. Immune response to the ALK oncogenic tyrosine kinase in patients with anaplastic large-cell lymphoma. Blood. 2000;96(4):1605–7.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Stadler S, Singh VK, Knorr F, Damm-Welk C, Woessmann W. Immune response against ALK in children with ALK-positive anaplastic large cell lymphoma. Cancers (Basel). 2018;10(4)PubMedCentralCrossRefPubMedGoogle Scholar
  47. 47.
    Atsaves V, Tsesmetzis N, Chioureas D, Kis L, Leventaki V, Drakos E, et al. PD-L1 is commonly expressed and transcriptionally regulated by STAT3 and MYC in ALK-negative anaplastic large-cell lymphoma. Leukemia. 2017;31(7):1633–7.PubMedCrossRefGoogle Scholar
  48. 48.
    Panjwani PK, Charu V, DeLisser M, Molina-Kirsch H, Natkunam Y, Zhao S. Programmed death-1 ligands PD-L1 and PD-L2 show distinctive and restricted patterns of expression in lymphoma subtypes. Hum Pathol. 2018;71:91–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Parrilla Castellar ER, Jaffe ES, Said JW, Swerdlow SH, Ketterling RP, Knudson RA, et al. ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. Blood. 2014;124(9):1473–80.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    King RL, Dao LN, McPhail ED, Jaffe ES, Said J, Swerdlow SH, et al. Morphologic features of ALK-negative anaplastic large cell lymphomas with DUSP22 rearrangements. Am J Surg Pathol. 2016;40(1):36–43.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Crescenzo R, Abate F, Lasorsa E, Tabbo F, Gaudiano M, Chiesa N, et al. Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma. Cancer Cell. 2015;27(4):516–32.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Le Deley MC, Reiter A, Williams D, Delsol G, Oschlies I, McCarthy K, et al. Prognostic factors in childhood anaplastic large cell lymphoma: results of a large European intergroup study. Blood. 2008;111(3):1560–6.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Lowe EJ, Gross TG. Anaplastic large cell lymphoma in children and adolescents. Pediatr Hematol Oncol. 2013;30(6):509–19.PubMedCrossRefGoogle Scholar
  54. 54.
    Damm-Welk C, Schieferstein J, Schwalm S, Reiter A, Woessmann W. Flow cytometric detection of circulating tumour cells in nucleophosmin/anaplastic lymphoma kinase-positive anaplastic large cell lymphoma: comparison with quantitative polymerase chain reaction. Br J Haematol. 2007;138(4):459–66.PubMedCrossRefGoogle Scholar
  55. 55.
    Mussolin L, Pillon M, d’Amore ES, Santoro N, Lombardi A, Fagioli F, et al. Prevalence and clinical implications of bone marrow involvement in pediatric anaplastic large cell lymphoma. Leukemia. 2005;19(9):1643–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Bayle C, Charpentier A, Duchayne E, Manel AM, Pages MP, Robert A, et al. Leukaemic presentation of small cell variant anaplastic large cell lymphoma: report of four cases. Br J Haematol. 1999;104(4):680–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Ok CY, Wang SA, Amin HM. Leukemic phase of ALK(+) anaplastic large-cell lymphoma, small-cell variant: clinicopathologic pitfalls of a rare entity. Clin Lymphoma Myeloma Leuk. 2014;14(4):e123–6.PubMedCrossRefGoogle Scholar
  58. 58.
    Onciu M, Behm FG, Raimondi SC, Moore S, Harwood EL, Pui CH, et al. ALK-positive anaplastic large cell lymphoma with leukemic peripheral blood involvement is a clinicopathologic entity with an unfavorable prognosis. Report of three cases and review of the literature. Am J Clin Pathol. 2003;120(4):617–25.PubMedCrossRefGoogle Scholar
  59. 59.
    Zecchini Barrese T, Sagramoso C, Bacci F, Sabattini E. Small cell variant of anaplastic large cell lymphoma with leukemic presentation: a diagnostic challenge. Rev Bras Hematol Hemoter. 2017;39(3):269–73.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Williams D, Mori T, Reiter A, Woessman W, Rosolen A, Wrobel G, et al. Central nervous system involvement in anaplastic large cell lymphoma in childhood: results from a multicentre European and Japanese study. Pediatr Blood Cancer. 2013;60(10):E118–21.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Shah M, Karnik L, Nadal-Melsio E, Reid A, Ahmad R, Bain BJ. ALK-positive anaplastic large cell lymphoma presenting with hemophagocytic lymphohistiocytosis. Am J Hematol. 2015;90(8):746.PubMedCrossRefGoogle Scholar
  62. 62.
    Pasqualini C, Minard-Colin V, Saada V, Lamant L, Delsol G, Patte C, et al. Clinical analysis and prognostic significance of haemophagocytic lymphohistiocytosis-associated anaplastic large cell lymphoma in children. Br J Haematol. 2014;165(1):117–25.PubMedCrossRefGoogle Scholar
  63. 63.
    Murphy SB. Classification, staging and end results of treatment of childhood non-Hodgkin’s lymphomas: dissimilarities from lymphomas in adults. Semin Oncol. 1980;7(3):332–9.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Rosolen A, Perkins SL, Pinkerton CR, Guillerman RP, Sandlund JT, Patte C, et al. Revised international pediatric non-hodgkin lymphoma staging system. J Clin Oncol. 2015;33(18):2112–8.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Pillon M, Arico M, Mussolin L, Carraro E, Conter V, Sala A, et al. Long-term results of the AIEOP LNH-97 protocol for childhood lymphoblastic lymphoma. Pediatr Blood Cancer. 2015;62(8):1388–94.PubMedCrossRefGoogle Scholar
  66. 66.
    Doghri R, HadjKacem LB, Houcine Y, Charfi L, Driss M, Kacem K, et al. Prognostic factors of ALK-negative anaplastic large-cell lymphoma: a single-institution experience. Ann Hematol. 2018;97(4):725–6.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Gaulard P, de Leval L. ALK-negative anaplastic large-cell lymphoma. Blood. 2016;127(2):175–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Savage KJ, Harris NL, Vose JM, Ullrich F, Jaffe ES, Connors JM, et al. ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the international peripheral T-cell lymphoma project. Blood. 2008;111(12):5496–504.PubMedCrossRefGoogle Scholar
  69. 69.
    Damm-Welk C, Mussolin L, Zimmermann M, Pillon M, Klapper W, Oschlies I, et al. Early assessment of minimal residual disease identifies patients at very high relapse risk in NPM-ALK-positive anaplastic large-cell lymphoma. Blood. 2014;123(3):334–7.CrossRefGoogle Scholar
  70. 70.
    Mussolin L, Bonvini P, Ait-Tahar K, Pillon M, Tridello G, Buffardi S, et al. Kinetics of humoral response to ALK and its relationship with minimal residual disease in pediatric ALCL. Leukemia. 2009;23(2):400–2.PubMedCrossRefGoogle Scholar
  71. 71.
    Mussolin L, Pillon M, Zimmermann M, Carraro E, Basso G, Knoerr F, et al. Course of anti-ALK antibody titres during chemotherapy in children with anaplastic large cell lymphoma. Br J Haematol. 2018;182(5):733–5.PubMedCrossRefGoogle Scholar
  72. 72.
    Hapgood G, Savage KJ. The biology and management of systemic anaplastic large cell lymphoma. Blood. 2015;126(1):17–25.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Sibon D, Fournier M, Briere J, Lamant L, Haioun C, Coiffier B, et al. Long-term outcome of adults with systemic anaplastic large-cell lymphoma treated within the Groupe d’Etude des Lymphomes de l’Adulte trials. J Clin Oncol. 2012;30(32):3939–46.PubMedCrossRefGoogle Scholar
  74. 74.
    Brugieres L, Quartier P, Le Deley MC, Pacquement H, Perel Y, Bergeron C, 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. Ann Oncol. 2000;11(1):53–8.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Fukano R, Mori T, Kobayashi R, Mitsui T, Fujita N, Iwasaki F, et al. Haematopoietic stem cell transplantation for relapsed or refractory anaplastic large cell lymphoma: a study of children and adolescents in Japan. Br J Haematol. 2015;168(4):557–63.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Mori T, Takimoto T, Katano N, Kikuchi A, Tabuchi K, Kobayashi R, et al. Recurrent childhood anaplastic large cell lymphoma: a retrospective analysis of registered cases in Japan. Br J Haematol. 2006;132(5):594–7.PubMedCrossRefGoogle Scholar
  77. 77.
    Smith SM, Burns LJ, van Besien K, Lerademacher J, He W, Fenske TS, et al. Hematopoietic cell transplantation for systemic mature T-cell non-Hodgkin lymphoma. J Clin Oncol. 2013;31(25):3100–9.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Strullu M, Thomas C, Le Deley MC, Chevance A, Kanold J, Bertrand Y, 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. Bone Marrow Transplant. 2015;50(6):795–801.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Woessmann W, Peters C, Lenhard M, Burkhardt B, Sykora KW, Dilloo D, et al. Allogeneic haematopoietic stem cell transplantation in relapsed or refractory anaplastic large cell lymphoma of children and adolescents--a Berlin-Frankfurt-Munster group report. Br J Haematol. 2006;133(2):176–82.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Woessmann W, Zimmermann M, Lenhard M, Burkhardt B, Rossig C, Kremens B, 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. J Clin Oncol. 2011;29(22):3065–71.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Brugieres L, Pacquement H, Le Deley MC, Leverger G, Lutz P, Paillard C, 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. J Clin Oncol. 2009;27(30):5056–61.PubMedCrossRefGoogle Scholar
  82. 82.
    Ruf R, Brugieres L, Pillon M, Zimmermann M, Attarbaschi A, Melgrenn K, Williams D, Uyttebroeck A, Wrobel G, Reiter A, Woessman W. Risk-adapted therapy for patients with relapsed or refractory ALCL – final report of the prospective ALCL-relapse trial of the EICNHL. Br J Haematol. 2015;171Google Scholar
  83. 83.
    Chihara D, Fanale MA. Management of anaplastic large cell lymphoma. Hematol Oncol Clin North Am. 2017;31(2):209–22.PubMedCrossRefGoogle Scholar
  84. 84.
    Morel A, Briere J, Lamant L, Loschi M, Haioun C, Delarue R, et al. Long-term outcomes of adults with first-relapsed/refractory systemic anaplastic large-cell lymphoma in the pre-brentuximab vedotin era: a LYSA/SFGM-TC study. Eur J Cancer. 2017;83:146–53.PubMedCrossRefGoogle Scholar
  85. 85.
    Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol. 2012;30(18):2190–6.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, et al. Five-year results of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma. Blood. 2017;130(25):2709–17.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Locatelli FM-KC, Neville K, Llort A, Beishuizen A, Daw S, Pillon M, Aladjidi N, Klingebiel T, Landman-Parker J, Medina-Sanson A, August K, Huebner D, Sachs J, Hoffman K, Kinley J, Song S, Song G, Zhang S, Gore L. A phase 1/2 study of brentuximab vedotin in pediatric patients with relapsed/refractory (R/R) systemic anaplastic large-cell lymphoma (sALCL) or R/R Hodgkin lymphoma (HL). Hematol Oncol. 2017;35(S2):248–9.CrossRefGoogle Scholar
  88. 88.
    Mosse YP, Lim MS, Voss SD, Wilner K, Ruffner K, Laliberte J, et al. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children’s Oncology Group phase 1 consortium study. Lancet Oncol. 2013;14(6):472–80.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Mosse YP, Voss SD, Lim MS, Rolland D, Minard CG, Fox E, et al. Targeting ALK with crizotinib in pediatric anaplastic large cell lymphoma and inflammatory myofibroblastic tumor: a Children’s Oncology Group Study. J Clin Oncol. 2017;35(28):3215–21.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Gambacorti-Passerini C, Messa C, Pogliani EM. Crizotinib in anaplastic large-cell lymphoma. N Engl J Med. 2011;364(8):775–6.PubMedCrossRefGoogle Scholar
  91. 91.
    Costa RB, Costa RLB, Talamantes SM, Kaplan JB, Bhave MA, Rademaker A, et al. Systematic review and meta-analysis of selected toxicities of approved ALK inhibitors in metastatic non-small cell lung cancer. Oncotarget. 2018;9(31):22137–46.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Gambacorti-Passerini C, Mussolin L, Brugieres L. Abrupt relapse of ALK-positive lymphoma after discontinuation of crizotinib. N Engl J Med. 2016;374(1):95–6.PubMedCrossRefGoogle Scholar
  93. 93.
    Geoerger B, Schulte J, Zwaan CM, Casanova M, Fischer M, Moreno L, Trahair T, Jimenez I, Kang HJ, Pappo AS, Schafer E, Weiss BD, Healy ME, Li K, Lin T, Boral A, Pearson AD. Phase I study of ceritinib in pediatric patients (Pts) with malignancies harboring a genetic alteration in ALK (ALK+): safety, pharmacokinetic (PK), and efficacy results. J Clin Oncol. 2015;33(Suppl; abstr 10005)Google Scholar
  94. 94.
    Richly H, Kim TM, Schuler M, Kim DW, Harrison SJ, Shaw AT, et al. Ceritinib in patients with advanced anaplastic lymphoma kinase-rearranged anaplastic large-cell lymphoma. Blood. 2015;126(10):1257–8.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Damm-Welk C, Siddiqi F, Fischer M, Hero B, Narayanan V, Camidge DR, et al. Anti-ALK antibodies in patients with ALK-positive malignancies not expressing NPM-ALK. J Cancer. 2016;7(11):1383–7.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Chan TS, Khong PL, Kwong YL. Pembrolizumab for relapsed anaplastic large cell lymphoma after allogeneic haematopoietic stem cell transplantation: efficacy and safety. Ann Hematol. 2016;95(11):1913–5.PubMedCrossRefGoogle Scholar
  97. 97.
    Hebart H, Lang P, Woessmann W. Nivolumab for refractory anaplastic large cell lymphoma: a case report. Ann Intern Med. 2016;165(8):607–8.PubMedCrossRefGoogle Scholar
  98. 98.
    Rigaud C, Abbou S, Minard-Colin V, Geoerger B, Scoazec JY, Vassal G, et al. Efficacy of nivolumab in a patient with systemic refractory ALK+ anaplastic large cell lymphoma. Pediatr Blood Cancer. 2018;65(4)CrossRefGoogle Scholar
  99. 99.
    Laimer D, Dolznig H, Kollmann K, Vesely PW, Schlederer M, Merkel O, et al. PDGFR blockade is a rational and effective therapy for NPM-ALK-driven lymphomas. Nat Med. 2012;18(11):1699–704.PubMedCrossRefGoogle Scholar
  100. 100.
    Chiarle R, Martinengo C, Mastini C, Ambrogio C, D’Escamard V, Forni G, et al. The anaplastic lymphoma kinase is an effective oncoantigen for lymphoma vaccination. Nat Med. 2008;14(6):676–80.PubMedCrossRefGoogle Scholar
  101. 101.
    Ramos CA, Ballard B, Zhang H, Dakhova O, Gee AP, Mei Z, et al. Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes. J Clin Invest. 2017;127(9):3462–71.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Pediatric Hematology-OncologyChildren’s Hospital of the Kings DaughtersNorfolkUSA
  2. 2.Department of Children and Adolescents OncologyGustave Roussy Cancer CampusVillejuifFrance

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