Abstract
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, affecting approximately 2800 children and adolescents in the United States each year (Siegel et al. Cancer J Clin 73(1), 17–48, 2023). Survival has improved from less than 10% a half century ago to nearly 90% today. From the first introduction of single-agent chemotherapy in the 1940s, combination chemotherapy and intensification of post-induction therapy have largely been responsible for advances in the treatment of ALL, as has therapy directed at the central nervous system (CNS). Over time, the stratification of patients by their risk of relapse, such that therapy intensity is tailored to this risk, has been a major contributor to both improvements in survival rates and reductions in toxicity from therapy. Clinical features, leukemia biology, and early response to therapy have emerged as important components of risk stratification. The biology of ALL, key prognostic factors, and treatment approaches will be discussed, with an emphasis on new developments in the treatment of pediatric ALL.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aricò M, Valsecchi MG, Camitta B, Schrappe M, Chessells J, Baruchel A, et al. Outcome of treatment in children with philadelphia chromosome–positive acute lymphoblastic leukemia. N Engl J Med. 2000;342(14):998–1006. https://doi.org/10.1056/NEJM200004063421402.
Aricò M, Schrappe M, Hunger SP, Carroll WL, Conter V, Galimberti S, et al. Clinical outcome of children with newly diagnosed philadelphia chromosome–positive acute lymphoblastic leukemia treated between 1995 and 2005. J Clin Oncol. 2010;28(31):4755–61. http://jco.ascopubs.org/content/28/31/4755.abstract
Attarbaschi A, Möricke A, Harrison CJ, Mann G, Baruchel A, De Moerloose B, et al. Outcomes of childhood noninfant acute lymphoblastic leukemia with 11q23/KMT2A rearrangements in a modern therapy era: a retrospective international study. J Clin Oncol. 2022:Jco2201297. https://doi.org/10.1200/jco.22.01297.
Aur RJA, Simone J, Hustu HO, Walters T, Borella L, Pratt C, et al. Central nervous system therapy and combination chemotherapy of childhood lymphocytic leukemia. Blood. 1971;37(3):272–81. http://www.bloodjournal.org/content/37/3/272.abstract
Bargou R, Leo E, Zugmaier G, Klinger M, Goebeler M, Knop S, et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody (clinical trial, Phase I Multicenter Study Research Support, Non-U.S. Gov't). Science. 2008;321(5891):974–7. https://doi.org/10.1126/science.1158545.
Benjamin R, Graham C, Yallop D, Jozwik A, Mirci-Danicar OC, Lucchini G, et al. Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: results of two phase 1 studies. Lancet. 2020;396(10266):1885–94. https://doi.org/10.1016/s0140-6736(20)32334-5.
Berg SL, Blaney SM, Devidas M, Lampkin TA, Murgo A, Bernstein M, et al. Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children’s Oncology Group. J Clin Oncol. 2005;23(15):3376–82. https://doi.org/10.1200/jco.2005.03.426.
Bernt KM, Hunger SP. Current concepts in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia. Front Oncol. 2014;4:54. https://doi.org/10.3389/fonc.2014.00054.
Biondi A, Valsecchi MG, Seriu T, D'Aniello E, Willemse MJ, Fasching K, et al. Molecular detection of minimal residual disease is a strong predictive factor of relapse in childhood B-lineage acute lymphoblastic leukemia with medium risk features. A case control study of the International BFM study group. Leukemia. 2000;14(11):1939–43. http://www.ncbi.nlm.nih.gov/pubmed/11069029
Biondi A, Schrappe M, De Lorenzo P, Castor A, Lucchini G, Gandemer V, et al. Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study. Lancet Oncol. 2012;13(9):936–45. https://doi.org/10.1016/S1470-2045(12)70377-7.
Borowitz MJ, Devidas M, Hunger SP, Bowman WP, Carroll AJ, Carroll WL, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study. Blood. 2008;111(12):5477–85. https://doi.org/10.1182/blood-2008-01-132837.
Borowitz MJ, Wood BL, Devidas M, Loh ML, Raetz EA, Salzer WL, et al. Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children’s Oncology Group study AALL0232. Blood. 2015;126(8):964–71. https://doi.org/10.1182/blood-2015-03-633685.
Brentjens RJ, Davila ML, Riviere I, Park J, Wang X, Cowell LG, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia (Clinical Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't). Sci Transl Med. 2013;5(177):177ra38. https://doi.org/10.1126/scitranslmed.3005930.
Brown PA, Ji L, Xu X, Devidas M, Hogan LE, Borowitz MJ, et al. Effect of postreinduction therapy consolidation with blinatumomab vs chemotherapy on disease-free survival in children, adolescents, and young adults with first relapse of B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325(9):833–42. https://doi.org/10.1001/jama.2021.0669.
Campos-Sanchez E, Toboso-Navasa A, Romero-Camarero I, Barajas-Diego M, Sánchez-García I, Cobaleda C. Acute lymphoblastic leukemia and developmental biology. Cell Cycle. 2011;10(20):3473–86. https://doi.org/10.4161/cc.10.20.17779.
Clarke S, O'Reilly J, Romeo G, Cooney J. NUP214-ABL1 positive T-cell acute lymphoblastic leukemia patient shows an initial favorable response to imatinib therapy post relapse. Leuk Res. 2011;35(7):e131–3. https://doi.org/10.1016/j.leukres.2011.03.025.
Conter V, Valsecchi MG, Silvestri D, Campbell M, Dibar E, Magyarosy E, et al. Pulses of vincristine and dexamethasone in addition to intensive chemotherapy for children with intermediate-risk acute lymphoblastic leukaemia: a multicentre randomised trial. Lancet. 2007;369(9556):123–31. https://doi.org/10.1016/s0140-6736(07)60073-7.
Conter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer-Grümayer R, Möricke A, et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood. 2010;115(16):3206–14. https://doi.org/10.1182/blood-2009-10-248146.
Conter V, Valsecchi MG, Parasole R, Putti MC, Locatelli F, Barisone E, et al. Childhood high-risk acute lymphoblastic leukemia in first remission: results after chemotherapy or transplant from the AIEOP ALL 2000 study. Blood. 2014;123(10):1470–8. https://doi.org/10.1182/blood-2013-10-532598. http://www.bloodjournal.org/content/123/10/1470.abstract
Coustan-Smith E, Sancho J, Hancock ML, Boyett JM, Behm FG, Raimondi SC, et al. Clinical importance of minimal residual disease in childhood acute lymphoblastic leukemia. Blood. 2000;96(8):2691–6. http://www.bloodjournal.org/content/96/8/2691.abstract
Coustan-Smith E, Mullighan CG, Onciu M, Behm FG, Raimondi SC, Pei D, et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol. 2009;10(2):147–56. https://doi.org/10.1016/S1470-2045(08)70314-0.
Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med. 2014;6(224):224ra25. https://doi.org/10.1126/scitranslmed.3008226.
Deenik W, Beverloo HB, Wattel MM, van Esser JWJ, Valk PJM, Cornelissen JJ. Rapid complete cytogenetic remission after upfront dasatinib monotherapy in a patient with a NUP214-ABL1-positive T-cell acute lymphoblastic leukemia. Leukemia. 2009;23(3):627–9. https://doi.org/10.1038/leu.2008.318.
Den Boer ML, van Slegtenhorst M, De Menezes RX, Cheok MH, Buijs-Gladdines JG, Peters ST, et al. A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study. Lancet Oncol. 2009;10(2):125–34. https://doi.org/10.1016/s1470-2045(08)70339-5.
den Boer ML, Cario G, Moorman AV, Boer JM, de Groot-Kruseman HA, Fiocco M, et al. Outcomes of paediatric patients with B-cell acute lymphocytic leukaemia with ABL-class fusion in the pre-tyrosine-kinase inhibitor era: a multicentre, retrospective, cohort study. Lancet Haematol. 2021;8(1):e55–66. https://doi.org/10.1016/s2352-3026(20)30353-7.
Diaz-Flores E, Comeaux EQ, Kim KL, Melnik E, Beckman K, Davis KL, et al. Bcl-2 is a therapeutic target for hypodiploid B-lineage acute lymphoblastic leukemia. Cancer Res. 2019;79(9):2339–51. https://doi.org/10.1158/0008-5472.Can-18-0236.
Dreyer ZE, Hilden JM, Jones TL, Devidas M, Winick NJ, Willman CL, et al. Intensified chemotherapy without SCT in infant ALL: results from COG P9407 (Cohort 3). Pediatr Blood Cancer. 2015;62(3):419–26. https://doi.org/10.1002/pbc.25322.
Duffner PK, Armstrong FD, Chen L, Helton KJ, Brecher ML, Bell B, et al. Neurocognitive and neuroradiologic central nervous system late effects in children treated on Pediatric Oncology Group (POG) P9605 (Standard Risk) and P9201 (Lesser Risk) acute lymphoblastic leukemia protocols (ACCL0131): a methotrexate consequence? A report from the Children’s Oncology Group. J Pediatr Hematol Oncol. 2014;36(1):8–15. https://doi.org/10.1097/mph.0000000000000000.
Dunsmore KP, Devidas M, Linda SB, Borowitz MJ, Winick N, Hunger SP, et al. Pilot study of nelarabine in combination with intensive chemotherapy in high-risk T-cell acute lymphoblastic leukemia: a report From the Children's Oncology Group. J Clin Oncol. 2012;30(22):2753–9. https://doi.org/10.1200/jco.2011.40.8724.
Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, 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(28):3282–93. https://doi.org/10.1200/jco.20.00256.
Eapen M, Raetz E, Zhang MJ, Muehlenbein C, Devidas M, Abshire T, et al. Outcomes after HLA-matched sibling transplantation or chemotherapy in children with B-precursor acute lymphoblastic leukemia in a second remission: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research. Blood. 2006;107(12):4961–7. https://doi.org/10.1182/blood-2005-12-4942.
Farber S, Diamond LK, Mercer RD, Sylvester RF, Wolff JA. Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid (aminopterin). N Engl J Med. 1948;238(23):787–93. https://doi.org/10.1056/NEJM194806032382301.
Forestier E, Heyman M, Andersen MK, Autio K, Blennow E, Borgström G, et al. Outcome of ETV6/RUNX1-positive childhood acute lymphoblastic leukaemia in the NOPHO-ALL-1992 protocol: frequent late relapses but good overall survival. Br J Haematol. 2008;140(6):665–72. https://doi.org/10.1111/j.1365-2141.2008.06980.x.
Freiwan A, Zoine JT, Crawford JC, Vaidya A, Schattgen SA, Myers JA, et al. Engineering naturally occurring CD7− T cells for the immunotherapy of hematological malignancies. Blood. 2022;140(25):2684–96. https://doi.org/10.1182/blood.2021015020.
Gardner RA, Finney O, Annesley C, Brakke H, Summers C, Leger K, et al. Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood. 2017;129(25):3322–31. https://doi.org/10.1182/blood-2017-02-769208.
Gaynon PS, Desai AA, Bostrom BC, Hutchinson RJ, Lange BJ, Nachman JB, et al. Early response to therapy and outcome in childhood acute lymphoblastic leukemia: a review. Cancer. 1997;80(9):1717–26. http://www.ncbi.nlm.nih.gov/pubmed/9351539
George P, Hernandez K, Hustu O, Borella L, Holton C, Pinkel D. A study of “total therapy” of acute lymphocyticleukemia in children. J Pediatr. 1968;72(3):399–408. https://doi.org/10.1016/S0022-3476(68)80217-3.
Gossai N, Devidas M, Chen Z, Wood BL, Zweidler-McKay PA, Rabin KR, et al. Central nervous system status is prognostic in T-cell acute lymphoblastic leukemia: a Children's Oncology Group Report. Blood. 2023;141(15):1802–11. https://doi.org/10.1182/blood.2022018653.
Grant SJ, Grimshaw AA, Silberstein J, Murdaugh D, Wildes TM, Rosko AE, et al. Clinical presentation, risk factors, and outcomes of immune effector cell-associated neurotoxicity syndrome following chimeric antigen receptor T cell therapy: a systematic review. Transplant Cell Ther. 2022;28(6):294–302. https://doi.org/10.1016/j.jtct.2022.03.006.
Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, et al. Chimeric antigen receptor–modified T cells for acute lymphoid leukemia. N Engl J Med. 2013;368(16):1509–18. https://doi.org/10.1056/NEJMoa1215134.
Guest E, Kairalla J, Devidas M, Hibbitts E, Carroll AJ, Heerema NA, et al. A pilot study of azacitidine as epigenetic priming for chemotherapy in infants less than 1 year of age with KMT2A-rearranged Acute Lymphoblastic Leukemia (ALL); Results from the Children's Oncology Group (COG) Trial AALL15P1. Blood. 2022;140(Suppl. 1):3256–7. https://doi.org/10.1182/blood-2022-167765.
Gupta S, Teachey DT, Chen Z, Rabin KR, Dunsmore KP, Larsen EC, et al. Sex-based disparities in outcome in pediatric acute lymphoblastic leukemia: a Children's Oncology Group report. Cancer. 2022;128(9):1863–70. https://doi.org/10.1002/cncr.34150.
Gupta S, Dai Y, Chen Z, Winestone LE, Teachey DT, Bona K, et al. Racial and ethnic disparities in childhood and young adult acute lymphocytic leukaemia: secondary analyses of eight Children's Oncology Group cohort trials. Lancet Haematol. 2023;10(2):e129–41. https://doi.org/10.1016/s2352-3026(22)00371-4.
Harewood L, Robinson H, Harris R, Al-Obaidi MJ, Jalali GR, Martineau M, et al. Amplification of AML1 on a duplicated chromosome 21 in acute lymphoblastic leukemia: a study of 20 cases. Leukemia. 2003;17(3):547–53. https://doi.org/10.1038/sj.leu.2402849.
Harrison CJ, Moorman AV, Broadfield ZJ, Cheung KL, Harris RL, Reza Jalali G, et al. Three distinct subgroups of hypodiploidy in acute lymphoblastic leukaemia. Br J Haematol. 2004;125(5):552–9. https://doi.org/10.1111/j.1365-2141.2004.04948.x.
Harrison CJ, Haas O, Harbott J, Biondi A, Stanulla M, Trka J, et al. Detection of prognostically relevant genetic abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: recommendations from the Biology and Diagnosis Committee of the International Berlin-Frankfurt-Munster study group. Br J Haematol. 2010;151(2):132–42. https://doi.org/10.1111/j.1365-2141.2010.08314.x.
Harrison CJ, Moorman AV, Schwab C, Carroll AJ, Raetz EA, Devidas M, et al. An international study of intrachromosomal amplification of chromosome 21 (iAMP21): cytogenetic characterization and outcome. Leukemia. 2014;28(5):1015–21. https://doi.org/10.1038/leu.2013.317.
Harvey RC, Mullighan CG, Chen IM, Wharton W, Mikhail FM, Carroll AJ, et al. Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia. Blood. 2010a;115(26):5312–21. https://doi.org/10.1182/blood-2009-09-245944.
Harvey RC, Mullighan CG, Wang X, Dobbin KK, Davidson GS, Bedrick EJ, et al. Identification of novel cluster groups in pediatric high-risk B-precursor acute lymphoblastic leukemia with gene expression profiling: correlation with genome-wide DNA copy number alterations, clinical characteristics, and outcome. Blood. 2010b;116(23):4874–84. https://doi.org/10.1182/blood-2009-08-239681. http://www.bloodjournal.org/content/116/23/4874.abstract
Heerema NA, Nachman JB, Sather HN, Sensel MG, Lee MK, Hutchinson R, et al. Hypodiploidy with less than 45 chromosomes confers adverse risk in childhood acute lymphoblastic leukemia: a report from the children's cancer group. Blood. 1999;94(12):4036–45. http://www.ncbi.nlm.nih.gov/pubmed/10590047
Heerema NA, Carroll AJ, Devidas M, Loh ML, Borowitz MJ, Gastier-Foster JM, et al. Intrachromosomal amplification of chromosome 21 is associated with inferior outcomes in children with acute lymphoblastic leukemia treated in contemporary standard-risk Children's Oncology Group Studies: a report from the Children's Oncology Group. J Clin Oncol. 2013;31(27):3397–402. https://doi.org/10.1200/jco.2013.49.1308.
Hijiya N, Gaynon P, Barry E, Silverman L, Thomson B, Chu R, et al. A multi-center phase I study of clofarabine, etoposide and cyclophosphamide in combination in pediatric patients with refractory or relapsed acute leukemia. Leukemia. 2009;23(12):2259–64. https://doi.org/10.1038/leu.2009.185.
Hijiya N, Thomson B, Isakoff MS, Silverman LB, Steinherz PG, Borowitz MJ, et al. Phase 2 trial of clofarabine in combination with etoposide and cyclophosphamide in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. Blood. 2011;118(23):6043–9. https://doi.org/10.1182/blood-2011-08-374710.
Hijiya N, Barry E, Arceci RJ. Clofarabine in pediatric acute leukemia: current findings and issues. Pediatr Blood Cancer. 2012;59(3):417–22. https://doi.org/10.1002/pbc.24112.
Holmfeldt L, Wei L, Diaz-Flores E, Walsh M, Zhang J, Ding L, et al. The genomic landscape of hypodiploid acute lymphoblastic leukemia. Nat Genet. 2013;45(3):242–52. https://doi.org/10.1038/ng.2532.
Horton TM, Gannavarapu A, Blaney SM, D'Argenio DZ, Plon SE, Berg SL. Bortezomib interactions with chemotherapy agents in acute leukemia in vitro. Cancer Chemother Pharmacol. 2006;58(1):13–23. https://doi.org/10.1007/s00280-005-0135-z.
Horton TM, Pati D, Plon SE, Thompson PA, Bomgaars LR, Adamson PC, et al. A Phase 1 study of the proteasome inhibitor bortezomib in pediatric patients with refractory leukemia: a Children's Oncology Group Study. Clin Cancer Res. 2007;13(5):1516–22. https://doi.org/10.1158/1078-0432.ccr-06-2173.
Hunger SP. Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis. Blood. 1996;87(4):1211–24. http://www.bloodjournal.org/content/87/4/1211.abstract
Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. 2015a;373(16):1541–52. https://doi.org/10.1056/NEJMra1400972.
Hunger SP, Mullighan CG. Redefining ALL classification: toward detecting high-risk ALL and implementing precision medicine. Blood. 2015b;125(26):3977–87. https://doi.org/10.1182/blood-2015-02-58004310.1182/blood-2015-02-580043. http://www.bloodjournal.org/content/125/26/3977.abstract
Hunger SP, Galili N, Carroll AJ, Crist WM, Link MP, Cleary ML. The t(1;19)(q23;p13) results in consistent fusion of E2A and PBX1 coding sequences in acute lymphoblastic leukemias. Blood. 1991;77(4):687–93. http://www.bloodjournal.org/content/77/4/687.abstract
Hunger SP, Ohyashiki K, Toyama K, Cleary ML. Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties following fusion to E2A in t(17;19) acute lymphoblastic leukemia. Genes Dev. 1992;6(9):1608–20. https://doi.org/10.1101/gad.6.9.1608.
Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the Children's Oncology Group. J Clin Oncol. 2012;30(14):1663–9. https://doi.org/10.1200/jco.2011.37.8018.
Issa GC, Ravandi F, DiNardo CD, Jabbour E, Kantarjian HM, Andreeff M. Therapeutic implications of menin inhibition in acute leukemias. Leukemia. 2021;35(9):2482–95. https://doi.org/10.1038/s41375-021-01309-y.
Jeha S, Gaynon PS, Razzouk BI, Franklin J, Kadota R, Shen V, et al. Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. J Clin Oncol. 2006;24(12):1917–23. https://doi.org/10.1200/jco.2005.03.8554.
Jerchel IS, Hoogkamer AQ, Ariës IM, Steeghs EMP, Boer JM, Besselink NJM, et al. RAS pathway mutations as a predictive biomarker for treatment adaptation in pediatric B-cell precursor acute lymphoblastic leukemia. Leukemia. 2018;32(4):931–40. https://doi.org/10.1038/leu.2017.303.
Kadauke S, Myers RM, Li Y, Aplenc R, Baniewicz D, Barrett DM, et al. Risk-adapted preemptive tocilizumab to prevent severe cytokine release syndrome after CTL019 for pediatric B-cell acute lymphoblastic leukemia: a prospective clinical trial. J Clin Oncol. 2021;39(8):920–30. https://doi.org/10.1200/jco.20.02477.
Kantarjian H, Thomas D, Jorgensen J, Jabbour E, Kebriaei P, Rytting M, et al. Inotuzumab ozogamicin, an anti-CD22–calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. Lancet Oncol. 2012;13(4):403–11. https://doi.org/10.1016/S1470-2045(11)70386-2.
Kantarjian H, Thomas D, Jorgensen J, Kebriaei P, Jabbour E, Rytting M, et al. Results of inotuzumab ozogamicin, a CD22 monoclonal antibody, in refractory and relapsed acute lymphocytic leukemia. Cancer. 2013;119(15):2728–36. https://doi.org/10.1002/cncr.28136.
Kantarjian H, Stein A, Gökbuget N, Fielding AK, Schuh AC, Ribera JM, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376(9):836–47. https://doi.org/10.1056/NEJMoa1609783.
Krivtsov AV, Armstrong SA. MLL translocations, histone modifications and leukaemia stem-cell development. Nat Rev Cancer. 2007;7(11):823–33. https://doi.org/10.1038/nrc2253.
Krull KR, Brinkman TM, Li C, Armstrong GT, Ness KK, Srivastava DK, et al. Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukemia: a report from the St Jude Lifetime Cohort Study. J Clin Oncol. 2013;31(35):4407–15. https://doi.org/10.1200/jco.2012.48.2315.
Kurtzberg J, Ernst TJ, Keating MJ, Gandhi V, Hodge JP, Kisor DF, et al. Phase I study of 506U78 administered on a consecutive 5-day schedule in children and adults with refractory hematologic malignancies. J Clin Oncol. 2005;23(15):3396–403. https://doi.org/10.1200/jco.2005.03.199.
Laetsch TW, Maude SL, Rives S, Hiramatsu H, Bittencourt H, Bader P, et al. Three-year update of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia in the ELIANA trial. J Clin Oncol. 2022:Jco2200642. https://doi.org/10.1200/jco.22.00642.
Larsen EC, Devidas M, Chen S, Salzer WL, Raetz EA, Loh ML, et al. Dexamethasone and high-dose methotrexate improve outcome for children and young adults with high-risk B-acute lymphoblastic leukemia: a report from Children's Oncology Group Study AALL0232. J Clin Oncol. 2016;34(20):2380–8. https://doi.org/10.1200/jco.2015.62.4544.
Lauten M, Möricke A, Beier R, Zimmermann M, Stanulla M, Meissner B, et al. Prediction of outcome by early bone marrow response in childhood acute lymphoblastic leukemia treated in the ALL-BFM 95 trial: differential effects in precursor B-cell and T-cell leukemia. Haematologica. 2012;97(7):1048–56. https://doi.org/10.3324/haematol.2011.047613.
LeBien TW. Fates of human B-cell precursors. Blood. 2000;96(1):9–23. http://www.bloodjournal.org/content/96/1/9.abstract
Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2014; https://doi.org/10.1016/S0140-6736(14)61403-3.
Linabery AM, Ross JA. Trends in childhood cancer incidence in the U.S. (1992–2004). Cancer. 2008;112(2):416–32. https://doi.org/10.1002/cncr.23169.
Liu Y, Easton J, Shao Y, Maciaszek J, Wang Z, Wilkinson MR, et al. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat Genet. 2017;49(8):1211–8. https://doi.org/10.1038/ng.3909.
Locatelli F, Testi AM, Bernardo ME, Rizzari C, Bertaina A, Merli P, et al. Clofarabine, cyclophosphamide and etoposide as single-course re-induction therapy for children with refractory/multiple relapsed acute lymphoblastic leukaemia. Br J Haematol. 2009;147(3):371–8. https://doi.org/10.1111/j.1365-2141.2009.07882.x.
Loh ML, Zhang J, Harvey RC, Roberts K, Payne-Turner D, Kang H, et al. Tyrosine kinome sequencing of pediatric acute lymphoblastic leukemia: a report from the Children's Oncology Group TARGET Project. Blood. 2013;121(3):485–8. https://doi.org/10.1182/blood-2012-04-422691. http://www.bloodjournal.org/content/121/3/485.abstract
Ma X, Edmonson M, Yergeau D, Muzny DM, Hampton OA, Rusch M, et al. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia (Article). Nat Commun. 2015;6 https://doi.org/10.1038/ncomms7604.
Maloney KW, Devidas M, Wang C, Mattano LA, Friedmann AM, Buckley P, et al. Outcome in children with standard-risk B-cell acute lymphoblastic leukemia: results of Children's Oncology Group Trial AALL0331. J Clin Oncol. 2020;38(6):602–12. https://doi.org/10.1200/jco.19.01086.
Maude SL, Barrett D, Teachey DT, Grupp SA. Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer J. 2014a;20(2):119–22. https://doi.org/10.1097/PPO.0000000000000035.
Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014b;371(16):1507–17. https://doi.org/10.1056/NEJMoa1407222.
Maude SL, Dolai S, Delgado-Martin C, Vincent T, Robbins A, Selvanathan A, et al. Efficacy of JAK/STAT pathway inhibition in murine xenograft models of early T-cell precursor (ETP) acute lymphoblastic leukemia. Blood. 2015;125(11):1759–67. https://doi.org/10.1182/blood-2014-06-580480.
Maude SL, Teachey DT, Rheingold SR, Shaw PA, Aplenc R, Barrett DM, et al. Sustained remissions with CD19-specific chimeric antigen receptor (CAR)-modified T cells in children with relapsed/refractory ALL. J Clin Oncol. 2016;34(Suppl. 15):3011. https://doi.org/10.1200/JCO.2016.34.15_suppl.3011.
McNeer JL, O'Brien MM, Rheingold SR, Devidas M, Chen Z, Bhojwani D, et al. A Phase 3 randomized trial of inotuzumab ozogamicin for newly diagnosed high-risk B-ALL: safety phase results from Children's Oncology Group Protocol AALL1732. Blood. 2021;138(Suppl. 1):3398. https://doi.org/10.1182/blood-2021-149478.
Messinger YH, Gaynon PS, Sposto R, van der Giessen J, Eckroth E, Malvar J, et al. Bortezomib with chemotherapy is highly active in advanced B-precursor acute lymphoblastic leukemia: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study. Blood. 2012;120(2):285–90. https://doi.org/10.1182/blood-2012-04-418640.
Miller DR, Leikin S, Albo V, Sather H, Karon M, Hammond D. Prognostic factors and therapy in acute lymphoblastic leukemia of childhood: CCG-141: a report from childrens cancer study group. Cancer. 1983;51(6):1041–9. https://doi.org/10.1002/1097-0142(19830315)51:6<1041::AID-CNCR2820510612>3.0.CO;2-G.
Minson KA, Prasad P, Vear S, Borinstein S, Ho R, Domm J, et al. t(17;19) in Children with acute lymphocytic leukemia: a report of 3 cases and a review of the literature. Case Rep Hematol. 2013;2013:563291. https://doi.org/10.1155/2013/563291.
Moorman AV, Ensor HM, Richards SM, Chilton L, Schwab C, Kinsey SE, et al. Prognostic effect of chromosomal abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: results from the UK Medical Research Council ALL97/99 randomised trial. Lancet Oncol. 2010;11(5):429–38. https://doi.org/10.1016/S1470-2045(10)70066-8.
Moorman AV, Robinson H, Schwab C, Richards SM, Hancock J, Mitchell CD, et al. Risk-directed treatment intensification significantly reduces the risk of relapse among children and adolescents with acute lymphoblastic leukemia and intrachromosomal amplification of chromosome 21: a comparison of the MRC ALL97/99 and UKALL2003 trials. J Clin Oncol. 2013;31(27):3389–96. https://doi.org/10.1200/jco.2013.48.9377.
Möricke A, Zimmermann M, Reiter A, Henze G, Schrauder A, Gadner H, et al. Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000. Leukemia. 2010;24(2):265–84. https://doi.org/10.1038/leu.2009.257.
Mullighan CG, Collins-Underwood JR, Phillips LA, Loudin MG, Liu W, Zhang J, et al. Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia. Nat Genet. 2009a;41(11):1243–6. https://doi.org/10.1038/ng.469.
Mullighan CG, Su X, Zhang J, Radtke I, Phillips LA, Miller CB, et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med. 2009b;360(5):470–80. https://doi.org/10.1056/NEJMoa0808253.
Mullighan CG, Zhang J, Harvey RC, Collins-Underwood JR, Schulman BA, Phillips LA, et al. JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 2009c;106(23):9414–8. https://doi.org/10.1073/pnas.0811761106.
Myers RM, Li Y, Barz Leahy A, Barrett DM, Teachey DT, Callahan C, et al. Humanized CD19-targeted Chimeric Antigen Receptor (CAR) T Cells in CAR-naive and CAR-exposed children and young adults with relapsed or refractory acute lymphoblastic leukemia. J Clin Oncol. 2021;39(27):3044–55. https://doi.org/10.1200/jco.20.03458.
Nachman JB, Heerema NA, Sather H, Camitta B, Forestier E, Harrison CJ, et al. Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia. Blood. 2007;110(4):1112–5. https://doi.org/10.1182/blood-2006-07-038299.
Nagorsen D, Kufer P, Baeuerle PA, Bargou R. Blinatumomab: a historical perspective. Pharmacol Ther. 2012;136(3):334–42. https://doi.org/10.1016/j.pharmthera.2012.07.013.
Nelken B, Cave H, Leverger G, Galambrun C, Plat G, Schmitt C, et al. A Phase I study of clofarabine with multiagent chemotherapy in childhood high risk relapse of acute lymphoblastic leukemia (VANDEVOL Study of the French SFCE Acute Leukemia Committee). Pediatr Blood Cancer. 2016;63(2):270–5. https://doi.org/10.1002/pbc.25751.
O'Brien MM, Ji L, Shah NN, Rheingold SR, Bhojwani D, Yuan CM, et al. Phase II trial of inotuzumab ozogamicin in children and adolescents with relapsed or refractory B-cell acute lymphoblastic leukemia: Children's Oncology Group Protocol AALL1621. J Clin Oncol. 2022;40(9):956–67. https://doi.org/10.1200/jco.21.01693.
Pan J, Tan Y, Wang G, Deng B, Ling Z, Song W, et al. Donor-derived CD7 chimeric antigen receptor T cells for T-cell acute lymphoblastic leukemia: first-in-human. Phase I Trial J Clin Oncol. 2021;39(30):3340–51. https://doi.org/10.1200/jco.21.00389.
Patrick K, Vora A. Update on biology and treatment of T-cell acute lymphoblastic leukaemia. Curr Opin Pediatr. 2015;27(1):44–9. https://doi.org/10.1097/mop.0000000000000171.
Paulsson K, Johansson B. High hyperdiploid childhood acute lymphoblastic leukemia. Genes Chromosomes Cancer. 2009;48(8):637–60. https://doi.org/10.1002/gcc.20671.
Paulsson K, Forestier E, Andersen MK, Autio K, Barbany G, Borgström G, et al. High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols. Haematologica. 2013;98(9):1424–32. https://doi.org/10.3324/haematol.2013.085852.
Paulsson K, Lilljebjorn H, Biloglav A, Olsson L, Rissler M, Castor A, et al. The genomic landscape of high hyperdiploid childhood acute lymphoblastic leukemia (Letter). Nat Genet. 2015;47(6):672–6. https://doi.org/10.1038/ng.3301. http://www.nature.com/ng/journal/v47/n6/abs/ng.3301.html#supplementary-information
Peters C, Schrappe M, von Stackelberg A, Schrauder A, Bader P, Ebell W, et al. Stem-cell transplantation in children with acute lymphoblastic leukemia: a prospective international multicenter trial comparing sibling donors with matched unrelated donors—the ALL-SCT-BFM-2003 Trial. J Clin Oncol. 2015;33(11):1265–74. http://jco.ascopubs.org/content/33/11/1265.abstract
Pieters R, Schrappe M, De Lorenzo P, Hann I, De Rossi G, Felice M, et al. A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial. Lancet. 2007;370(9583):240–50. https://doi.org/10.1016/S0140-6736(07)61126-X.
Pieters R, De Lorenzo P, Ancliffe P, Aversa LA, Brethon B, Biondi A, et al. Outcome of infants younger than 1 year with acute lymphoblastic leukemia treated with the Interfant-06 protocol: results from an international phase III randomized study. J Clin Oncol. 2019;37(25):2246–56. https://doi.org/10.1200/jco.19.00261.
Pui CH, Williams DL, Raimondi SC, Rivera GK, Look AT, Dodge RK, et al. Hypodiploidy is associated with a poor prognosis in childhood acute lymphoblastic leukemia. Blood. 1987;70(1):247–53. http://www.ncbi.nlm.nih.gov/pubmed/3474042
Pui CH, Carroll AJ, Raimondi SC, Land VJ, Crist WM, Shuster JJ, et al. Clinical presentation, karyotypic characterization, and treatment outcome of childhood acute lymphoblastic leukemia with a near-haploid or hypodiploid less than 45 line. Blood. 1990;75(5):1170–7. http://www.ncbi.nlm.nih.gov/pubmed/2306521
Pui C-H, Campana D, Pei D, Bowman WP, Sandlund JT, Kaste SC, et al. Treating childhood acute lymphoblastic leukemia without cranial irradiation. N Engl J Med. 2009;360(26):2730–41. https://doi.org/10.1056/NEJMoa0900386.
Pui CH, Pei D, Sandlund JT, Ribeiro RC, Rubnitz JE, Raimondi SC, et al. Long-term results of St Jude Total Therapy Studies 11, 12, 13A, 13B, and 14 for childhood acute lymphoblastic leukemia. Leukemia. 2010;24(2):371–82. https://doi.org/10.1038/leu.2009.252.
Pui C-H, Yang JJ, Hunger SP, Pieters R, Schrappe M, Biondi A, et al. Childhood acute lymphoblastic leukemia: progress through collaboration. J Clin Oncol. 2015;33(27):2938–48. https://doi.org/10.1200/jco.2014.59.1636.
Pullarkat VA, Lacayo NJ, Jabbour E, Rubnitz JE, Bajel A, Laetsch TW, et al. Venetoclax and navitoclax in combination with chemotherapy in patients with relapsed or refractory acute lymphoblastic leukemia and lymphoblastic lymphoma. Cancer Discov. 2021;11(6):1440–53. https://doi.org/10.1158/2159-8290.Cd-20-1465.
Pulsipher MA, Langholz B, Wall DA, Schultz KR, Bunin N, Carroll WL, et al. The addition of sirolimus to tacrolimus/methotrexate GVHD prophylaxis in children with ALL: a phase 3 Children’s Oncology Group/Pediatric Blood and Marrow Transplant Consortium trial. Blood. 2014;123(13):2017–25. https://doi.org/10.1182/blood-2013-10-534297. http://www.bloodjournal.org/content/123/13/2017.abstract
Raetz EA, Bhatla T. Where do we stand in the treatment of relapsed acute lymphoblastic leukemia? ASH Educ Progr Book. 2012;2012(1):129–36. https://doi.org/10.1182/asheducation-2012.1.129.
Raimondi SC, Zhou Y, Mathew S, Shurtleff SA, Sandlund JT, Rivera GK, et al. Reassessment of the prognostic significance of hypodiploidy in pediatric patients with acute lymphoblastic leukemia. Cancer. 2003;98(12):2715–22. https://doi.org/10.1002/cncr.11841.
Rivera-Reyes A, Hayer KE, Bassing CH. Genomic alterations of non-coding regions underlie human cancer: lessons from T-ALL. Trends Mol Med. 2016;22(12):1035–46. https://doi.org/10.1016/j.molmed.2016.10.004.
Roberts KG, Morin RD, Zhang J, Hirst M, Zhao Y, Su X, et al. Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia. Cancer Cell. 2012;22(2):153–66. https://doi.org/10.1016/j.ccr.2012.06.005.
Roberts KG, Li Y, Payne-Turner D, Harvey RC, Yang Y-L, Pei D, et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med. 2014;371(11):1005–15. https://doi.org/10.1056/NEJMoa1403088.
Russell LJ, Capasso M, Vater I, Akasaka T, Bernard OA, Calasanz MJ, et al. Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. Blood. 2009;114(13):2688–98. https://doi.org/10.1182/blood-2009-03-208397.
Salzer WL, Burke MJ, Devidas M, Chen S, Gore L, Larsen EC, et al. Toxicity associated with intensive postinduction therapy incorporating clofarabine in the very high-risk stratum of patients with newly diagnosed high-risk B-lymphoblastic leukemia: A report from the Children's Oncology Group study AALL1131. Cancer. 2018;124(6):1150–9. https://doi.org/10.1002/cncr.31099.
Schafer E, Irizarry R, Negi S, McIntyre E, Small D, Figueroa ME, et al. Promoter hypermethylation in MLL-r infant acute lymphoblastic leukemia: biology and therapeutic targeting. Blood. 2010;115(23):4798–809. https://doi.org/10.1182/blood-2009-09-243634.
Schrappe M, Reiter A, Zimmermann M, Harbott J, Ludwig WD, Henze G, et al. Long-term results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981 to 1995. Berlin-Frankfurt-Munster Leukemia. 2000;14(12):2205–22. http://www.ncbi.nlm.nih.gov/pubmed/11187912
Schrappe M, Valsecchi MG, Bartram CR, Schrauder A, Panzer-Grümayer R, Möricke A, et al. Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. Blood. 2011;118(8):2077–84. https://doi.org/10.1182/blood-2011-03-338707.
Schultz KR, Pullen DJ, Sather HN, Shuster JJ, Devidas M, Borowitz MJ, et al. Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG). Blood. 2007;109(3):926–35. https://doi.org/10.1182/blood-2006-01-024729.
Schultz KR, Bowman WP, Aledo A, Slayton WB, Sather H, Devidas M, et al. Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a children's oncology group study. J Clin Oncol. 2009;27(31):5175–81. https://doi.org/10.1200/JCO.2008.21.2514.
Schultz KR, Carroll A, Heerema NA, Bowman WP, Aledo A, Slayton WB, et al. Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children's Oncology Group study AALL0031. Leukemia. 2014;28(7):1467–71. https://doi.org/10.1038/leu.2014.30.
Sheth VS, Gauthier J. Taming the beast: CRS and ICANS after CAR T-cell therapy for ALL. Bone Marrow Transplant. 2021;56(3):552–66. https://doi.org/10.1038/s41409-020-01134-4.
Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48. https://doi.org/10.3322/caac.21763.
Silverman LB, Stevenson KE, O'Brien JE, Asselin BL, Barr RD, Clavell L, et al. Long-term results of Dana-Farber Cancer Institute ALL Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1985–2000). Leukemia. 2010;24(2):320–34. https://doi.org/10.1038/leu.2009.253.
Smith M, Arthur D, Camitta B, Carroll AJ, Crist W, Gaynon P, et al. Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. J Clin Oncol. 1996;14(1):18–24. http://jco.ascopubs.org/content/14/1/18.abstract
Soulier J, Trakhtenbrot L, Najfeld V, Lipton JM, Mathew S, Avet-Loiseau H, et al. Amplification of band q22 of chromosome 21, including AML1, in older children with acute lymphoblastic leukemia: an emerging molecular cytogenetic subgroup. Leukemia. 2003;17(8):1679–82. https://doi.org/10.1038/sj.leu.2403000.
Stary J, Zimmermann M, Campbell M, Castillo L, Dibar E, Donska S, et al. Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental Trial ALL IC-BFM 2002. J Clin Oncol. 2014;32(3):174–84. https://doi.org/10.1200/jco.2013.48.6522.
Stumpel DJPM, Schotte D, Lange-Turenhout EAM, Schneider P, Seslija L, de Menezes RX, et al. Hypermethylation of specific microRNA genes in MLL-rearranged infant acute lymphoblastic leukemia: major matters at a micro scale. Leukemia. 2011;25(3):429–39. http://www.nature.com/leu/journal/v25/n3/suppinfo/leu2010282s1.html
Summers RJ, Jain J, Vasileiadi E, Smith B, Chimenti ML, Yeung TY, et al. Therapeutic targeting of MERTK and BCL-2 in T-cell and early T-precursor acute lymphoblastic leukemia. Cancers (Basel). 2022;14(24) https://doi.org/10.3390/cancers14246142.
Sutcliffe MJ, Shuster JJ, Sather HN, Camitta BM, Pullen J, Schultz KR, et al. High concordance from independent studies by the Children's Cancer Group (CCG) and Pediatric Oncology Group (POG) associating favorable prognosis with combined trisomies 4, 10, and 17 in children with NCI Standard-Risk B-precursor Acute Lymphoblastic Leukemia: a Children's Oncology Group (COG) initiative. Leukemia. 2005;19(5) http://www.nature.com/leu/journal/v19/n5/suppinfo/2403673s1.html
Tasian SK, Doral MY, Borowitz MJ, Wood BL, Chen IM, Harvey RC, et al. Aberrant STAT5 and PI3K/mTOR pathway signaling occurs in human CRLF2-rearranged B-precursor acute lymphoblastic leukemia. Blood. 2012;120(4):833–42. https://doi.org/10.1182/blood-2011-12-389932.
Tasian SK, Assad A, Hunter DS, Du Y, Loh ML. A Phase 2 study of ruxolitinib with chemotherapy in children with Philadelphia Chromosome-like Acute Lymphoblastic Leukemia (INCB18424-269/AALL1521): dose-finding results from the Part 1 Safety Phase. Blood. 2018;132(Suppl. 1):555. https://doi.org/10.1182/blood-2018-99-110221.
Teachey DT, Hunger SP. Predicting relapse risk in childhood acute lymphoblastic leukaemia. Br J Haematol. 2013;162(5):606–20. https://doi.org/10.1111/bjh.12442.
Teachey DT, Pui CH. Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia. Lancet Oncol. 2019;20(3):e142–54. https://doi.org/10.1016/s1470-2045(19)30031-2.
Teachey DT, Rheingold SR, Maude SL, Zugmaier G, Barrett DM, Seif AE, et al. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood. 2013;121(26):5154–7. https://doi.org/10.1182/blood-2013-02-485623.
Teachey DT, Devidas M, Wood BL, Chen Z, Hayashi RJ, Hermiston ML, et al. Children's Oncology Group Trial AALL1231: a Phase III clinical trial testing bortezomib in newly diagnosed T-cell acute lymphoblastic leukemia and lymphoma. J Clin Oncol. 2022;40(19):2106–18. https://doi.org/10.1200/jco.21.02678.
Teicher BA, Ara G, Herbst R, Palombella VJ, Adams J. The proteasome inhibitor PS-341 in cancer therapy. Clin Cancer Res. 1999;5(9):2638–45. http://www.ncbi.nlm.nih.gov/pubmed/10499643
Topp MS, Gökbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015;16(1):57–66. https://doi.org/10.1016/S1470-2045(14)71170-2.
Uderzo C, Valsecchi MG, Bacigalupo A, Meloni G, Messina C, Polchi P, et al. Treatment of childhood acute lymphoblastic leukemia in second remission with allogeneic bone marrow transplantation and chemotherapy: ten-year experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association. J Clin Oncol. 1995;13(2):352–8. http://www.ncbi.nlm.nih.gov/pubmed/7844596
Van der Velden VHJ, Corral L, Valsecchi MG, Jansen MWJC, De Lorenzo P, Cazzaniga G, et al. Prognostic significance of minimal residual disease in infants with acute lymphoblastic leukemia treated within the Interfant-99 protocol. Leukemia. 2009;23(6):1073–9. https://doi.org/10.1038/leu.2009.17.
Veerman AJ, Kamps WA, van den Berg H, van den Berg E, Bökkerink JPM, Bruin MCA, et al. 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(10):957–66. https://doi.org/10.1016/S1470-2045(09)70228-1.
von Stackelberg A, Locatelli F, Zugmaier G, Handgretinger R, Trippett TM, Rizzari C, et al. Phase I/Phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. J Clin Oncol. 2016;34(36):4381–9. https://doi.org/10.1200/jco.2016.67.3301.
Vora A, Andreano A, Pui C-H, Hunger SP, Schrappe M, Moericke A, et al. Influence of cranial radiotherapy on outcome in children with acute lymphoblastic leukemia treated with contemporary therapy. J Clin Oncol. 2016; https://doi.org/10.1200/jco.2015.64.2850.
Wehrli M, Gallagher K, Chen YB, Leick MB, McAfee SL, El-Jawahri AR, et al. Single-center experience using anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (ICANS). J Immunother Cancer. 2022;10(1) https://doi.org/10.1136/jitc-2021-003847.
Weston BW, Hayden MA, Roberts KG, Bowyer S, Hsu J, Fedoriw G, et al. Tyrosine kinase inhibitor therapy induces remission in a patient with refractory EBF1-PDGFRB-positive acute lymphoblastic leukemia. J Clin Oncol. 2013;31(25):e413–6. https://doi.org/10.1200/JCO.2012.47.6770.
Wiemels JL, Cazzaniga G, Daniotti M, Eden OB, Addison GM, Masera G, et al. Prenatal origin of acute lymphoblastic leukaemia in children. Lancet. 1999;354(9189):1499–503. http://www.ncbi.nlm.nih.gov/pubmed/10551495
Wilejto M, Giuseppe GD, Hitzler J, Gupta S, Abla O. Treatment of young children with CNS-positive acute lymphoblastic leukemia without cranial radiotherapy. Pediatr Blood Cancer. 2015;62(11):1881–5. https://doi.org/10.1002/pbc.25620.
Winter SS, Dunsmore KP, Devidas M, Eisenberg N, Asselin BL, Wood BL, et al. Safe integration of nelarabine into intensive chemotherapy in newly diagnosed T-cell acute lymphoblastic leukemia: Children's Oncology Group Study AALL0434. Pediatr Blood Cancer. 2015;62(7):1176–83. https://doi.org/10.1002/pbc.25470.
Wolf E, Hofmeister R, Kufer P, Schlereth B, Baeuerle PA. BiTEs: bispecific antibody constructs with unique anti-tumor activity (Review). Drug Discov Today. 2005;10(18):1237–44. https://doi.org/10.1016/S1359-6446(05)03554-3.
Yoda A, Yoda Y, Chiaretti S, Bar-Natan M, Mani K, Rodig SJ, et al. Functional screening identifies CRLF2 in precursor B-cell acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 2010;107(1):252–7. https://doi.org/10.1073/pnas.0911726107.
Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature. 2012;481(7380):157–63. https://doi.org/10.1038/nature10725.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Ethics declarations
David T. Teachey serves on advisory boards for Jazz, Sobi, and BEAM Therapeutics. He receives research funding from BEAM Therapeutics, NeoImmune Tech, Jazz, and Servier. He has patents pending on CAR-T.
Rights and permissions
Copyright information
© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Newman, H., Teachey, D.T. (2023). New Developments in the Treatment of Pediatric Acute Lymphoblastic Leukemia. In: Beckwith, S. (eds) Update in Pediatrics. Springer, Cham. https://doi.org/10.1007/978-3-031-41542-5_24
Download citation
DOI: https://doi.org/10.1007/978-3-031-41542-5_24
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-41541-8
Online ISBN: 978-3-031-41542-5
eBook Packages: MedicineMedicine (R0)