Skip to main content

Advertisement

Springer Nature Link
Log in

Lymphoblastic Lymphoma: a Concise Review

  • Lymphomas (T Hilal, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Lymphoblastic lymphoma (LBL) is a rare, highly aggressive non-Hodgkin lymphoma variant virtually indistinguishable from acute lymphoblastic leukemia (ALL). We review the advancements in diagnostics, staging, treatment, and response assessment.

Recent Findings

T-LBL displays a mediastinal mass with pleuro-pericardic effusions as key distinctive features and is far more frequent than B-LBL. LBL is exquisitely sensitive to ALL-type chemotherapy, achieving cure rates in the order of 70% in adults and even more in children. Positron-emission tomography, genetic risk classifications, and minimal disseminated/residual disease assays are increasingly used to detect occult sites of involvement and predict treatment outcome. Stem cell transplantation is effective and should be considered for very high-risk subsets and/or at salvage.

Summary

Although curable in the majority of patients, about 25–30% of adults with LBL patients experience resistance or relapse following first-line therapy. It is essential to identify these cases early on and to explore new modalities of precision medicine with targeted agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405. https://doi.org/10.1182/blood-2016-03-643544.

    Article  CAS  PubMed  Google Scholar 

  2. Dores GM, Devesa SS, Curtis RE, Linet MS, Morton LM. Acute leukemia incidence and patient survival among children and adults in the United States, 2001–2007. Blood. 2012;119:34–43. https://doi.org/10.1182/blood-2011-04-347872.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sant M, Allemani C, Tereanu C, De Angelis R, Capocaccia R, Visser O, Marcos-Gragera R, Maynadié M, Simonetti A, Lutz J-M, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood. 2010;116:3724–34. https://doi.org/10.1182/blood-2010-05-282632.

    Article  CAS  PubMed  Google Scholar 

  4. Ducassou S, Ferlay C, Bergeron C, Girard S, Laureys G, Pacquement H, Plantaz D, Lutz P, Vannier J-P, Uyttebroeck A, et al. Clinical presentation, evolution, and prognosis of precursor B-cell lymphoblastic lymphoma in trials LMT96, EORTC 58881, and EORTC 58951: paediatric PBLL: evaluation of three trials. Br J Haematol. 2011;152:441–51. https://doi.org/10.1111/j.1365-2141.2010.08541.x.

    Article  CAS  PubMed  Google Scholar 

  5. Preston DL, Kusumi S, Tomonaga M, Izumi S, Ron E, Kuramoto A, Kamada N, Dohy H, Matsuo T, Matsui T [corrected to Matsuo T. Cancer incidence in atomic bomb survivors. Part III. Leukemia, lymphoma and multiple myeloma, 1950-1987. Radiat Res. 1994; 137, S68-97

  6. Anderson LM, Diwan BA, Fear NT, Roman E. Critical windows of exposure for children’s health: cancer in human epidemiological studies and neoplasms in experimental animal models. Environ Health Perspect. 2000;108:22.

    Google Scholar 

  7. Lightfoot TJ, Roman E. Causes of childhood leukaemia and lymphoma. Toxicol Appl Pharmacol. 2004;199:104–17. https://doi.org/10.1016/j.taap.2003.12.032.

    Article  CAS  PubMed  Google Scholar 

  8. Murphy EL, Hanchard B, Figueroa JP, Gibbs WN, Lofters WS, Campbell M, Goedert JJ, Blattner WA. Modelling the risk of adult T-cell leukemia/lymphoma in persons infected with human T-lymphotropic virus type I. Int J Cancer. 1989;43:250–3. https://doi.org/10.1002/ijc.2910430214.

    Article  CAS  PubMed  Google Scholar 

  9. Proietti FA, Carneiro-Proietti ABF, Catalan-Soares BC, Murphy EL. Global epidemiology of HTLV-I infection and associated diseases. Oncogene. 2005;24:6058–68. https://doi.org/10.1038/sj.onc.1208968.

    Article  CAS  PubMed  Google Scholar 

  10. Pisani P, Parkin DM, Muñoz N, Ferlay J. Cancer and infection: estimates of the attributable fraction in 1990. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol. 1997;6:387–400.

    CAS  Google Scholar 

  11. Hasle H, Clemmensen IH, Mikkelsen M. Risks of leukaemia and solid tumours in individuals with Down’s syndrome. Lancet. 2000;355:165–9. https://doi.org/10.1016/S0140-6736(99)05264-2.

    Article  CAS  PubMed  Google Scholar 

  12. Papaemmanuil E, Hosking FJ, Vijayakrishnan J, Price A, Olver B, Sheridan E, Kinsey SE, Lightfoot T, Roman E, Irving JAE, et al. Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia. Nat Genet. 2009;41:1006–10. https://doi.org/10.1038/ng.430.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Treviño LR, Yang W, French D, Hunger SP, Carroll WL, Devidas M, Willman C, Neale G, Downing J, Raimondi SC, et al. Germline genomic variants associated with childhood acute lymphoblastic leukemia. Nat Genet. 2009;41:1001–5. https://doi.org/10.1038/ng.432.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sherborne AL, Hosking FJ, Prasad RB, Kumar R, Koehler R, Vijayakrishnan J, Papaemmanuil E, Bartram CR, Stanulla M, Schrappe M, et al. Variation in CDKN2A at 9p21.3 influences childhood acute lymphoblastic leukemia risk. Nat Genet. 2010;42:492–4. https://doi.org/10.1038/ng.585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Vlaanderen J, Lan Q, Kromhout H, Rothman N, Vermeulen R. Occupational benzene exposure and the risk of chronic myeloid leukemia: a meta-analysis of cohort studies incorporating study quality dimensions. Am J Ind Med. 2012;55:779–85. https://doi.org/10.1002/ajim.22087.

    Article  CAS  PubMed  Google Scholar 

  16. Mostafalou S, Abdollahi M. Pesticides: an update of human exposure and toxicity. Arch Toxicol. 2017;91:549–99. https://doi.org/10.1007/s00204-016-1849-x.

    Article  CAS  PubMed  Google Scholar 

  17. Wang H, Mura Y, Nomura S, Sekine M, Sokejima S, Saka H, Kagamimori S. A meta-analysis of epidemiological studies on the relationship between occupational electromagnetic field exposure and the risk of adult leukemia. 4. Environ Health Prev Med. 2000;5:43–6. https://doi.org/10.1007/BF02935915.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ekström Smedby K, Vajdic CM, Falster M, Engels EA, Martínez-Maza O, Turner J, Hjalgrim H, Vineis P, Seniori Costantini A, Bracci PM, et al. Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. Blood. 2008;111:4029–38. https://doi.org/10.1182/blood-2007-10-119974.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Engels EA, Cerhan JR, Linet MS, Cozen W, Colt JS, Davis S, Gridley G, Severson RK, Hartge P. Immune-related conditions and immune-modulating medications as risk factors for non-Hodgkin’s lymphoma: a case-control study. Am J Epidemiol. 2005;162:1153–61. https://doi.org/10.1093/aje/kwi341.

    Article  PubMed  Google Scholar 

  20. McNeer JL, Bleyer A. Acute lymphoblastic leukemia and lymphoblastic lymphoma in adolescents and young adults. Pediatr Blood Cancer. 2018;65:e26989. https://doi.org/10.1002/pbc.26989.

    Article  PubMed  Google Scholar 

  21. Aldhafiri FK, McColl JH, Reilly JJ. Prevalence of being underweight and overweight and obesity at diagnosis in UK patients with childhood acute lymphoblastic leukaemia 1985–2002. J Hum Nutr Diet. 2014;27:76–9. https://doi.org/10.1111/jhn.12112.

    Article  CAS  PubMed  Google Scholar 

  22. Butturini AM, Dorey FJ, Lange BJ, Henry DW, Gaynon PS, Fu C, Franklin J, Siegel SE, Seibel NL, Rogers PC, et al. Obesity and outcome in pediatric acute lymphoblastic leukemia. J Clin Oncol. 2007;25:2063–9. https://doi.org/10.1200/JCO.2006.07.7792.

    Article  PubMed  Google Scholar 

  23. Reiter A. Intensive ALL-type therapy without local radiotherapy provides a 90% event-free survival for children with T-cell lymphoblastic lymphoma: a BFM Group report. Blood. 2000;95:416–21. https://doi.org/10.1182/blood.V95.2.416.

    Article  CAS  PubMed  Google Scholar 

  24. Burkhardt B, Zimmermann M, Oschlies I, Niggli F, Mann G, Parwaresch R, Riehm H, Schrappe M, Reiter A. for the BFM Group the impact of age and gender on biology, clinical features and treatment outcome of non-Hodgkin lymphoma in childhood and adolescence. Br J Haematol. 2005;131:39–49. https://doi.org/10.1111/j.1365-2141.2005.05735.x.

    Article  PubMed  Google Scholar 

  25. •• Cortelazzo S, Ferreri A, Hoelzer D, Ponzoni M. Lymphoblastic lymphoma. Crit Rev Oncol Hematol. 2017;113:304–17. https://doi.org/10.1016/j.critrevonc.2017.03.020. Most recent, exhaustive review article on LBL.

    Article  PubMed  Google Scholar 

  26. Oschlies I, Burkhardt B, Chassagne-Clement C, d’Amore ES, Hansson U, Hebeda K, Mc Carthy K, Kodet R, Maldyk J, Müllauer L, et al. Diagnosis and immunophenotype of 188 pediatric lymphoblastic lymphomas treated within a randomized prospective trial: experiences and preliminary recommendations from the European childhood lymphoma pathology panel. Am J Surg Pathol. 2011;35:836–44. https://doi.org/10.1097/PAS.0b013e318213e90e.

    Article  PubMed  Google Scholar 

  27. Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, van’t Veer MB. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia. 1995;9:1783–6.

    CAS  PubMed  Google Scholar 

  28. Patel JL, Smith LM, Anderson J, Abromowitch M, Campana D, Jacobsen J, Lones MA, Gross TG, Cairo MS, Perkins SL. The immunophenotype of T-lymphoblastic lymphoma in children and adolescents: a Children’s Oncology Group report. Br J Haematol. 2012;159:454–61. https://doi.org/10.1111/bjh.12042.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Coustan-Smith E, Mullighan CG, Onciu M, Behm FG, Raimondi SC, Pei D, Cheng C, Su X, Rubnitz JE, Basso G, et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol. 2009;10:147–56. https://doi.org/10.1016/S1470-2045(08)70314-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Morita K, Jain N, Kantarjian H, Takahashi K, Fang H, Konopleva M, El Hussein S, Wang F, Short NJ, Maiti A, et al. Outcome of T-cell acute lymphoblastic leukemia/lymphoma: focus on near-ETP phenotype and differential impact of nelarabine. Am J Hematol. 2021;96:589–98. https://doi.org/10.1002/ajh.26144.

    Article  CAS  PubMed  Google Scholar 

  31. Kroeze E, Loeffen JLC, Poort VM, Meijerink JPP. T-cell lymphoblastic lymphoma and leukemia: different diseases from a common premalignant progenitor? Blood Adv. 2020;4:3466–73. https://doi.org/10.1182/bloodadvances.2020001822.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lepretre S, Touzart A, Vermeulin T, Picquenot J-M, Tanguy-Schmidt A, Salles G, Lamy T, Béné M-C, Raffoux E, Huguet F, et al. Pediatric-like acute lymphoblastic leukemia therapy in adults with lymphoblastic lymphoma: the GRAALL-LYSA LL03 study. J Clin Oncol. 2016;34:572–80. https://doi.org/10.1200/JCO.2015.61.5385.

    Article  CAS  PubMed  Google Scholar 

  33. • El-Fattah MA. Prognostic factors and outcomes of adult lymphoblastic lymphoma in the United States. Clin Lymphoma Myeloma Leuk. 2017;17:498-505.e6. https://doi.org/10.1016/j.clml.2017.05.016. Recent outcome data analysis from USA on LBL.

    Article  PubMed  Google Scholar 

  34. Lee WJ, Moon HR, Won CH, Chang SE, Choi JH, Moon KC, Lee MW. Precursor B- or T-lymphoblastic lymphoma presenting with cutaneous involvement: a series of 13 cases including 7 cases of cutaneous T-lymphoblastic lymphoma. J Am Acad Dermatol. 2014;70:318–25. https://doi.org/10.1016/j.jaad.2013.10.020.

    Article  PubMed  Google Scholar 

  35. Cortelazzo S, Intermesoli T, Oldani E, Ciceri F, Rossi G, Pogliani EM, Mattei D, Romani C, Cortelezzi A, Borlenghi E, Corti C, Peruta B, Spinelli O, Rambaldi A, Bassan R. Results of a lymphoblastic leukemia-like chemotherapy program with risk-adapted mediastinal irradiation and stem cell transplantation for adult patients with lymphoblastic lymphoma. Ann Hematol. 2012;91:73–82. https://doi.org/10.1007/s00277-011-1252-x.

    Article  CAS  PubMed  Google Scholar 

  36. Gökbuget N, Beck J, Brandt K, Brüggemann M, Burmeister T, Diedrich H, Faul C, Huettmann A, Kondakci M, Kraemer DM, et al. Significant improvement of outcome in adolescents and young adults (AYAs) aged 15-35 years with acute lymphoblastic leukemia with a pediatric derived adult ALL protocol; results of 1529 AYAs in 2 consecutive trials of the German Multicenter Study Group Dor Adult ALL (GMALL). Blood. 2013;22:839 (Abstract).

    Article  Google Scholar 

  37. Thomas DA, O’Brien S, Cortes J, Giles FJ, Faderl S, Verstovsek S, Ferrajoli A, Koller C, Beran M, Pierce S, et al. Outcome with the hyper-CVAD regimens in lymphoblastic lymphoma. Blood. 2004;104:1624–30. https://doi.org/10.1182/blood-2003-12-4428.

    Article  CAS  PubMed  Google Scholar 

  38. Gouill SL, Lepretre S, Briere J, Morel P, Bouabdallah R, Raffoux E, Sebban C, Lepage E, Brice P. Adult lymphoblastic lymphoma: a retrospective analysis of 92 patients under 61 years included in the LNH87/93 trials. Leukemia. 2003;17:2220–4. https://doi.org/10.1038/sj.leu.2403095.

    Article  CAS  PubMed  Google Scholar 

  39. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, et al. Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. J Clin Oncol. 1999;17:1244–1244. https://doi.org/10.1200/JCO.1999.17.4.1244.

    Article  CAS  PubMed  Google Scholar 

  40. Mussolin L, Buldini B, Lovisa F, Carraro E, Disarò S, Nigro LL, d’Amore ESG, Pillon M, Basso G. Detection and role of minimal disseminated disease in children with lymphoblastic lymphoma: the AIEOP experience: MDD in lymphoblastic lymphoma. Pediatr Blood Cancer. 2015;62:1906–13. https://doi.org/10.1002/pbc.25607.

    Article  PubMed  Google Scholar 

  41. Coustan-Smith E, Sandlund JT, Perkins SL, Chen H, Chang M, Abromowitch M, Campana D. Minimal disseminated disease in childhood T-cell lymphoblastic lymphoma: a report from the Children’s Oncology Group. J Clin Oncol. 2009;27:3533–9. https://doi.org/10.1200/JCO.2008.21.1318.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Coleman CN, Picozzi VJ, Cox RS, McWhirter K, Weiss LM, Cohen JR, Yu KP, Rosenberg SA. Treatment of lymphoblastic lymphoma in adults. J Clin Oncol Off J Am Soc Clin Oncol. 1986;4:1628–37. https://doi.org/10.1200/JCO.1986.4.11.1628.

    Article  CAS  Google Scholar 

  43. Bonn BR, Krieger D, Burkhardt B. Cell cycle regulatory molecular profiles of pediatric T-cell lymphoblastic leukemia and lymphoma. Leuk Lymphoma. 2012;53:557–68. https://doi.org/10.3109/10428194.2011.616614.

    Article  CAS  PubMed  Google Scholar 

  44. Sandlund JT, Pui CH, Zhou Y, Onciu M, Campana D, Hudson MM, Inaba H, Metzger ML, Bhojwani D, Ribeiro RC. Results of treatment of advanced-stage lymphoblastic lymphoma at St Jude Children’s Research Hospital from 1962 to 2002. Ann Oncol. 2013;24:2425–9. https://doi.org/10.1093/annonc/mdt221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hoelzer D, Zwolinski J, Walewski J. Outcome of adult patients with T-lymphoblastic lymphoma treated according to protocols for acute lymphoblastic leukemia. Blood. 2002;99:4379–85. https://doi.org/10.1182/blood-2002-01-0110.

    Article  CAS  PubMed  Google Scholar 

  46. Gökbuget N, Wolf A, Stelljes M, Huettmann A, Buss EC, Viardot A, Brandt K, de Wit M, Frickhofen N, Kebenko M, et al. Favorable outcome in a large cohort of prospectively treated adult patients with T-lymphoblastic lymphoma (T-LBL) despite slowly evolving complete remission assessed by conventional radiography. Blood. 2014;124:370 (abstract).

    Article  Google Scholar 

  47. Dabaja BS, Ha CS, Thomas DA, Wilder RB, Gopal R, Cortes J, Bueso-Ramos C, Hess MA, Cox JD, Kantarjian HM. The role of local radiation therapy for mediastinal disease in adults with T-cell lymphoblastic lymphoma. Cancer. 2002;94:2738–44. https://doi.org/10.1002/cncr.10552.

    Article  PubMed  Google Scholar 

  48. Jabbour E, Thomas D, Cortes J, Kantarjian HM, O’Brien S. Central nervous system prophylaxis in adults with acute lymphoblastic leukemia: current and emerging therapies. Cancer. 2010;116:2290–300. https://doi.org/10.1002/cncr.25008.

    Article  CAS  PubMed  Google Scholar 

  49. Oeffinger KC, Kawashima T, Friedman DL, Kadan-Lottick NS, Robison LL. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med. 2006;355:1572–82. https://doi.org/10.1056/NEJMsa060185.

    Article  CAS  PubMed  Google Scholar 

  50. Pui C-H, Rai SN, Ribeiro RC, Evans WE. Extended follow-up of long-term survivors of childhood acute lymphoblastic leukemia. N Engl J Med. 2003;349:640–9. https://doi.org/10.1056/NEJMoa035091.

    Article  PubMed  Google Scholar 

  51. Hijiya N, Hudson MM, Lensing S, Zacher M, Onciu M, Behm FG, Razzouk BI, Ribeiro RC, Rubnitz JE, Sandlund JT, et al. Cumulative incidence of secondary neoplasms as a first event after childhood acute lymphoblastic leukemia. JAMA. 2007;297:1207–15. https://doi.org/10.1001/jama.297.11.1207.

    Article  CAS  PubMed  Google Scholar 

  52. Geenen MM, Cardous-Ubbink MC, Kremer LCM, van den Bos C, van der Pal HJH, Heinen RC, Jaspers MWM, Koning CCE, Oldenburger F, Langeveld NE, et al. Medical assessment of adverse health outcomes in long-term survivors of childhood cancer. JAMA. 2007;297:2705–15. https://doi.org/10.1001/jama.297.24.2705.

    Article  CAS  PubMed  Google Scholar 

  53. Waber DP, Turek J, Catania L, Stevenson K, Robaey P, Romero I, Adams H, Alyman C, Jandet-Brunet C, Neuberg DS, et al. Neuropsychological outcomes from a randomized trial of triple intrathecal chemotherapy compared with 18 Gy cranial radiation as CNS treatment in acute lymphoblastic leukemia: findings from Dana-Farber Cancer Institute ALL Consortium Protocol 95–01. J Clin Oncol. 2007;25:4914–21. https://doi.org/10.1200/JCO.2007.10.8464.

    Article  CAS  PubMed  Google Scholar 

  54. Richards S, Pui C-H, Gayon P. on behalf of the Childhood Acute Lymphoblastic Leukemia Collaborative Group (CALLCG) systematic review and meta-analysis of randomized trials of central nervous system directed therapy for childhood acute lymphoblastic leukemia: CNS-directed therapy in childhood ALL. Pediatr Blood Cancer. 2013;60:185–95. https://doi.org/10.1002/pbc.24228.

    Article  PubMed  Google Scholar 

  55. Larson RA. Managing CNS disease in adults with acute lymphoblastic leukemia. Leuk Lymphoma. 2018;59:3–13. https://doi.org/10.1080/10428194.2017.1326597.

    Article  CAS  PubMed  Google Scholar 

  56. Burkhardt B, Woessmann W, Zimmermann M, Kontny U, Vormoor J, Doerffel W, Mann G, Henze G, Niggli F, Ludwig W-D, et al. Impact of cranial radiotherapy on central nervous system prophylaxis in children and adolescents with central nervous system–negative stage III or IV lymphoblastic lymphoma. J Clin Oncol. 2006;24:491–9. https://doi.org/10.1200/JCO.2005.02.2707.

    Article  PubMed  Google Scholar 

  57. Moghrabi A, Levy DE, Asselin B, Barr R, Clavell L, Hurwitz C, Samson Y, Schorin M, Dalton VK, Lipshultz SE, et al. Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 95–01 for children with acute lymphoblastic leukemia. Blood. 2007;109:896–904. https://doi.org/10.1182/blood-2006-06-027714.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Veerman AJ, Kamps WA. Dexamethasone-based therapy for childhood acute lymphoblastic leukaemia: results of the prospective Dutch Childhood Oncology Group (DCOG) Protocol ALL-9 (1997–2004). Lancet Oncol. 2009;10:957–66. https://doi.org/10.1016/S1470-2045(09)70228-1.

    Article  CAS  PubMed  Google Scholar 

  59. Pui C-H, Bowman WP, Ribeiro RC, Onciu M, Jeha S, Simmons V, Boyett JM, Downing JR, Relling MV. Treating childhood acute lymphoblastic leukemia without cranial irradiation. N Engl J Med. 2009;360:2730–41. https://doi.org/10.1056/NEJMoa0900386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Portell CA, Sweetenham JW. Adult lymphoblastic lymphoma. Cancer J. 2012;18:432–8. https://doi.org/10.1097/PPO.0b013e31826b1232.

    Article  CAS  PubMed  Google Scholar 

  61. Burkhardt B, Hermiston ML. Lymphoblastic lymphoma in children and adolescents: review of current challenges and future opportunities. Br J Haematol. 2019;185:1158–70. https://doi.org/10.1111/bjh.15793.

    Article  PubMed  Google Scholar 

  62. Michaux K, Bergeron C, Gandemer V, Mechinaud F, Uyttebroeck A, Bertrand Y. for the SFCE and the EORTC children leukemia group relapsed or refractory lymphoblastic lymphoma in children: results and analysis of 23 patients in the EORTC 58951 and the LMT96 protocols: relapsed or refractory lymphoblastic lymphoma in children. Pediatr Blood Cancer. 2016;63:1214–21. https://doi.org/10.1002/pbc.25990.

    Article  PubMed  Google Scholar 

  63. Mitsui T, Fujita N, Koga Y, Fukano R, Osumi T, Hama A, Koh K, Kakuda H, Inoue M, Fukuda T, et al. The effect of graft-versus-host disease on outcomes after allogeneic stem cell transplantation for refractory lymphoblastic lymphoma in children and young adults. Pediatr Blood Cancer. 2020;67: e28129. https://doi.org/10.1002/pbc.28129.

    Article  PubMed  Google Scholar 

  64. Aljurf M, Zaidi SZA. Chemotherapy and hematopoietic stem cell transplantation for adult T-cell lymphoblastic lymphoma: current status and controversies. Biol Blood Marrow Transplant. 2005;11:739–54. https://doi.org/10.1016/j.bbmt.2005.07.001.

    Article  CAS  PubMed  Google Scholar 

  65. Makita S, Fuji S, Takano K, Tanaka T, Inoue Y, Ito R, Ito A, Hayashi Y, Tajima K, Okinaka K, et al. Clinical outcomes after allogeneic stem cell transplantation for adult lymphoblastic lymphoma. J Clin Exp Hematop. 2016;56:28–33. https://doi.org/10.3960/jslrt.56.28.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Brammer JE, Khouri I, Marin D, Ledesma C, Rondon G, Ciurea SO, Nieto Y, Champlin RE, Hosing C, Kebriaei P. Stem cell transplantation outcomes in lymphoblastic lymphoma. Leuk Lymphoma. 2017;58:366–71. https://doi.org/10.1080/10428194.2016.1193860.

    Article  CAS  PubMed  Google Scholar 

  67. Li C, Yang D, Chen J, Wang P, Zhang Y, Wu D. Outcome of allogeneic stem cell transplantation in T cell lymphoblastic lymphoma. Blood. 2017;130(Suppl 1):5535 (abstract).

    Google Scholar 

  68. Guan L, Li X, Wei H, Gu Z, Zhao S, Zhu C, Yang N, Wang F, Luo L, Gao Z, et al. T cell-replete haploidentical peripheral blood hematopoietic cell transplantation for treatment of T-lymphoblastic lymphoma. Ann Transplant. 2018;23:427–33. https://doi.org/10.12659/AOT.909122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Hu M, Wang H, Wang L, Yang M, Lou Y, Jin J. Outcome of adult T-lymphoblastic lymphoma depends on ALL-type chemotherapy, prognostic factors, and performance of allogeneic hematopoietic stem cell transplantation. Medicine (Baltimore). 2018;97:e11374. https://doi.org/10.1097/MD.0000000000011374.

    Article  CAS  Google Scholar 

  70. Yang L, Tan Y, Shi J, Zhao Y, Zhu Y, Hu Y, Pan W, Ye Y, He J, Zheng W, et al. Allogeneic hematopoietic stem cell transplantation should be in preference to conventional chemotherapy as post-remission treatment for adults with lymphoblastic lymphoma. Bone Marrow Transplant. 2018;53:1340–4. https://doi.org/10.1038/s41409-018-0184-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Morita-Fujita M, Arai Y, Yoshioka S, Ishikawa T, Kanda J, Kondo T, Akasaka T, Ueda Y, Imada K, Kyoto Stem Cell Transplantation Group (KSCTG), et al. Indication and benefit of upfront hematopoietic stem cell transplantation for T-cell lymphoblastic lymphoma in the era of ALL-type induction therapies. Sci Rep. 2020;10:21418. https://doi.org/10.1038/s41598-020-78334-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Steiner N, Brunelli L, Hetzenauer G, Lindner B, Göbel G, Rudzki J, Peschel I, Nevinny-Stickel M, Nussbaumer W, Mayer W, et al. Early autologous and allogeneic peripheral blood stem cell transplantation for adult patients with acute B and T cell precursor neoplasms: a 12-year single center experience. Ann Hematol. 2021;100:809–16. https://doi.org/10.1007/s00277-020-04391-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Salhotra A, Nikolaenko L, Chen L, Tsai N-C, Smith DL, Nademanee AP, Popplewell LL, Herrera AF, Mei M, Aldoss I, et al. Outcomes of patients with T-lymphoblastic lymphoma undergoing allogeneic stem cell transplantation: retrospective results from a single center. Blood. 2019;134:5729–5729. https://doi.org/10.1182/blood-2019-131437.

    Article  Google Scholar 

  74. • Candoni A, Lazzarotto D, Ferrara F, Curti A, Lussana F, Papayannidis C, Del Principe MI, Bonifacio M, Mosna F, Delia M, et al. Nelarabine as salvage therapy and bridge to allogeneic stem cell transplant in 118 adult patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma. A CAMPUS ALL study. Am J Hematol. 2020;95:1466–72. https://doi.org/10.1002/ajh.25957. Large retrospective study on nelarabine bridging to HCT in relapsed/refractory T-lymphoblastic neoplasms.

    Article  CAS  PubMed  Google Scholar 

  75. Tian X-P, Huang W-J, Huang H-Q, Liu Y-H, Wang L, Zhang X, Lin T-Y, Rao H-L, Li M, Liu F, et al. Prognostic and predictive value of a microRNA signature in adults with T-cell lymphoblastic lymphoma. Leukemia. 2019;33:2454–65. https://doi.org/10.1038/s41375-019-0466-0.

    Article  CAS  PubMed  Google Scholar 

  76. Tian X-P, Su N, Wang L, Huang W-J, Liu Y-H, Zhang X, Huang H-Q, Lin T-Y, Ma S-Y, Rao H-L, et al. A CpG methylation classifier to predict relapse in adults with T-cell lymphoblastic lymphoma. Clin Cancer Res. 2020;26:3760–70. https://doi.org/10.1158/1078-0432.CCR-19-4207.

    Article  CAS  PubMed  Google Scholar 

  77. • Young KH. Hematopoietic stem cell transplantation for adults with T-cell lymphoblastic lymphoma: can we successfully step into the era of precision medicine? Leukemia. 2020;34:1213–4. https://doi.org/10.1038/s41375-019-0608-4. Considerations on risk factors suggesting a therapeutic role of HCT in LBL.

    Article  PubMed  Google Scholar 

  78. Kantarjian H, Stein A, Gökbuget N, Fielding AK, Schuh AC, Ribera J-M, Wei A, Dombret H, Foà R, Bassan R, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376:836–47. https://doi.org/10.1056/NEJMoa1609783.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kantarjian HM, DeAngelo DJ, Stelljes M, Liedtke M, Stock W, Gökbuget N, O’Brien SM, Jabbour E, Wang T, Liang White J, et al. Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: final report and long-term survival follow-up from the randomized, phase 3 INO-VATE study. Cancer. 2019;125:2474–87. https://doi.org/10.1002/cncr.32116.

    Article  CAS  PubMed  Google Scholar 

  80. Park JH, Rivière I, Gonen M, Wang X, Sénéchal B, Curran KJ, Sauter C, Wang Y, Santomasso B, Mead E, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018;378:449–59. https://doi.org/10.1056/NEJMoa1709919.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Gökbuget N, Basara N, Baurmann H, Beck J, Brüggemann M, Diedrich H, Güldenzoph B, Hartung G, Horst H-A, Hüttmann A, et al. High single-drug activity of nelarabine in relapsed T-lymphoblastic leukemia/lymphoma offers curative option with subsequent stem cell transplantation. Blood. 2011;118:3504–11. https://doi.org/10.1182/blood-2011-01-329441.

    Article  CAS  PubMed  Google Scholar 

  82. DeAngelo DJ, Yu D, Johnson JL, Coutre SE, Stone RM, Stopeck AT, Gockerman JP, Mitchell BS, Appelbaum FR, Larson RA. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. Blood. 2007;109:5136–42. https://doi.org/10.1182/blood-2006-11-056754.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Luskin MR, Ganetsky A, Landsburg DJ, Loren AW, Porter DL, Nasta SD, Svoboda J, Luger SM, Frey NV. Nelarabine, cyclosphosphamide and etoposide for adults with relapsed T-cell acute lymphoblastic leukaemia and lymphoma. Br J Haematol. 2016;174:332–4. https://doi.org/10.1111/bjh.13771.

    Article  PubMed  Google Scholar 

  84. •• Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, et al. Children’s Oncology Group AALL0434: a phase III randomized clinical trial testing nelarabine in newly diagnosed T-cell acute lymphoblastic leukemia. J Clin Oncol. 2020;38:3282–93. https://doi.org/10.1200/JCO.20.00256. Most relevant trial for the upfront use of nelarabine in T-ALL/LBL.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. •• Bond J, Graux C, Lhermitte L, Lara D, Cluzeau T, Leguay T, Cieslak A, Trinquand A, Pastoret C, Belhocine M, et al. Early response–based therapy stratification improves survival in adult early thymic precursor acute lymphoblastic leukemia: a group for research on adult acute lymphoblastic leukemia study. J Clin Oncol. 2017;35:2683–91. https://doi.org/10.1200/JCO.2016.71.8585. Relevant, recent clinical trial in a large series of adult LBL patients.

    Article  CAS  PubMed  Google Scholar 

  86. O’Dwyer KM. The challenge to further improvements in survival of patients with T-ALL: current treatments and new insights from disease pathogenesis. Semin Hematol. 2020;57:149–56. https://doi.org/10.1053/j.seminhematol.2020.11.004.

    Article  PubMed  Google Scholar 

  87. Ofran Y, Ringelstein-Harlev S, Slouzkey I, Zuckerman T, Yehudai-Ofir D, Henig I, Beyar-Katz O, Hayun M, Frisch A. Daratumumab for eradication of minimal residual disease in high-risk advanced relapse of T-cell/CD19/CD22-negative acute lymphoblastic leukemia. Leukemia. 2020;34:293–5. https://doi.org/10.1038/s41375-019-0548-z.

    Article  PubMed  Google Scholar 

  88. Vogiatzi F, Winterberg D, Lenk L, Buchmann S, Cario G, Schrappe M, Peipp M, Richter-Pechanska P, Kulozik AE, Lentes J, et al. Daratumumab eradicates minimal residual disease in a preclinical model of pediatric T-cell acute lymphoblastic leukemia. Blood. 2019;134:713–6. https://doi.org/10.1182/blood.2019000904.

    Article  CAS  PubMed  Google Scholar 

  89. Cerrano M, Castella B, Lia G, Olivi M, Faraci DG, Butera S, Martella F, Scaldaferri M, Cattel F, Boccadoro M, et al. Immunomodulatory and clinical effects of daratumumab in T‐cell acute lymphoblastic leukaemia. Br J Haematol. 2020;191,e28–e32, https://doi.org/10.1111/bjh.16960

  90. Hixon JA, Andrews C, Kashi L, Kohnhorst CL, Senkevitch E, Czarra K, Barata JT, Li W, Schneider JP, Walsh STR, et al. New anti-IL-7Rα monoclonal antibodies show efficacy against T cell acute lymphoblastic leukemia in pre-clinical models. Leukemia. 2020;34:35–49. https://doi.org/10.1038/s41375-019-0531-8.

    Article  CAS  PubMed  Google Scholar 

  91. Cooper ML, Choi J, Staser K, Ritchey JK, Devenport JM, Eckardt K, Rettig MP, Wang B, Eissenberg LG, Ghobadi A, et al. An “off-the-shelf” fratricide-resistant CAR-T for the treatment of T cell hematologic malignancies. Leukemia. 2018;32:1970–83. https://doi.org/10.1038/s41375-018-0065-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Wang X, Li S, Gao L, Yuan Z, Wu K, Liu L, Luo L, Liu Y, Zhang C, Liu J, et al. Abstract CT052: clinical safety and efficacy study of TruUCARTM GC027: the first-in-human, universal CAR-T therapy for adult relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL). Cancer Res. 2020;80:16 (abstract).

    Google Scholar 

  93. •• Bassan R, Bourquin J-P, DeAngelo DJ, Chiaretti S. New approaches to the management of adult acute lymphoblastic leukemia. J Clin Oncol. 2018;36:3504–19. https://doi.org/10.1200/JCO.2017.77.3648. Updated and comprehensive review on new therapeutic possibilities for lymphoblastic disorders.

    Article  CAS  Google Scholar 

  94. Chiaretti S, Messina M, Foà R. BCR/ABL1-like acute lymphoblastic leukemia: how to diagnose and treat?: Open questions in BCR/ABL1-like ALL. Cancer. 2019;125:194–204. https://doi.org/10.1002/cncr.31848.

    Article  CAS  PubMed  Google Scholar 

  95. Tanasi I, Ba I, Sirvent N, Braun T, Cuccuini W, Ballerini P, Duployez N, Tanguy-Schmidt A, Tamburini J, Maury S, et al. Efficacy of tyrosine kinase inhibitors in Ph-like acute lymphoblastic leukemia harboring ABL-class rearrangements. Blood. 2019;134:1351–5. https://doi.org/10.1182/blood.2019001244.

    Article  PubMed  Google Scholar 

  96. Moorman AV, Schwab C, Winterman E, Hancock J, Castleton A, Cummins M, Gibson B, Goulden N, Kearns P, James B, et al. Adjuvant tyrosine kinase inhibitor therapy improves outcome for children and adolescents with acute lymphoblastic leukaemia who have an ABL-class fusion. Br J Haematol. 2020;191:844–51. https://doi.org/10.1111/bjh.17093.

    Article  CAS  PubMed  Google Scholar 

  97. Jabbour EJ, Pullarkat VA, Lacayo NJ, Bajel A, Rubnitz JE, Leonard J, Mullighan CG, Khaw SL, Colace SI, Opferman JT, et al. Venetoclax and navitoclax in relapsed or refractory acute lymphoblastic leukemia and lymphoblastic lymphoma. HemaSphere. 2020;4(S1):9 (abstract).

    Google Scholar 

  98. • Frismantas V, Dobay MP, Rinaldi A, Tchinda J, Dunn SH, Kunz J, Richter-Pechanska P, Marovca B, Pail O, Jenni S, et al. Ex vivo drug response profiling detects recurrent sensitivity patterns in drug-resistant acute lymphoblastic leukemia. Blood. 2017;129:e26–37. https://doi.org/10.1182/blood-2016-09-738070. Clinical work focusing on drug sensitivity screening in relapsed/refractory ALL.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. • Snijder B, Vladimer GI, Krall N, Miura K, Schmolke A-S, Kornauth C, Lopez de la Fuente O, Choi H-S, van der Kouwe E, Gültekin S, et al. Image-based ex-vivo drug screening for patients with aggressive haematological malignancies: interim results from a single-arm, open-label, pilot study. Lancet Haematol. 2017;4:e595–606. https://doi.org/10.1016/S2352-3026(17)30208-9. Clinical trial guided by drug sensitivity screening in relapsed/refractory ALL/LBL.

    Article  PubMed  PubMed Central  Google Scholar 

  100. • La Starza R, Cambò B, Pierini A, Bornhauser B, Montanaro A, Bourquin J-P, Mecucci C, Roti G. Venetoclax and bortezomib in relapsed/refractory early T-cell precursor acute lymphoblastic leukemia. JCO Precis Oncol. 2019;3:PO.19.00172, https://doi.org/10.1200/PO.19.00172. Successful example of drug sensitivity screening for the treatment of highly resistant T-lymphoblastic malignancy.

Download references

Author information

Authors and Affiliations

  1. Hematology and Bone Marrow Transplant Unit, Azienda Socio Sanitaria Territoriale (ASST), Ospedale Papa Giovanni XXIII, 24127, Bergamo, Italy

    Tamara Intermesoli & Alessandra Weber

  2. Hematology Unit, Azienda Ulss3 Serenissima, Ospedale dell’Angelo, Venezia-Mestre, 30174, Venice, Italy

    Matteo Leoncin, Luca Frison, Cristina Skert & Renato Bassan

Authors
  1. Tamara Intermesoli
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Alessandra Weber
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Matteo Leoncin
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Luca Frison
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Cristina Skert
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Renato Bassan
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Renato Bassan.

Ethics declarations

Conflict of Interest

Tamara Intermesoli declares that she has no conflict of interest.

Alessandra Weber declares that she has no conflict of interest.

Matteo Leoncin declares that he has no conflict of interest.

Luca Frison declares that he has no conflict of interest.

Cristina Skert declares that she has no conflict of interest.

Renato Bassan has received compensation from Amgen for service on advisory boards, and has received travel support from Amgen.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Lymphomas

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Intermesoli, T., Weber, A., Leoncin, M. et al. Lymphoblastic Lymphoma: a Concise Review. Curr Oncol Rep 24, 1–12 (2022). https://doi.org/10.1007/s11912-021-01168-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11912-021-01168-x

Keywords