Remission intensive chemotherapy followed by post-recovery consolidation and maintenance therapy achieved a complete remission of 75% to 90% and 3-year survival of 25% to 50% of adult patients with acute lymphoblastic leukemia (ALL). 2017;31(10):2181–90. Blood. A phase 3 randomized study is currently comparing reduced-intensity chemotherapy combination with either imatinib or ponatinib, which may help to clarify the optimal TKI to use in the frontline setting (NCT03589326). Cookies policy. Novel monoclonal antibody-based treatment strategies in adults with acute lymphoblastic leukemia. Lancet Oncol. 2007;109(3):944–50. 2017;376(9):836–47. Google Scholar. Nat Rev Cancer. For a more robust minimization, we ran it several times with different randomly generated initial values (see Additional file 2: Fig. Ravandi F, O'Brien S, Thomas D, Faderl S, Jones D, Garris R, et al. 2016;172(3):439–51. J Clin Oncol. Lancet Oncol. I.S., S.G., A.G.-P., and N.L.-B. Terms and Conditions, Leuk Res. N Engl J Med. The study was approved by the Comitè d’Ètica de la Investigació (Research Ethics Committee: PI-16-146) of the Hospital Germans Trias y Pujol (code approval AEC143). Due to their acceptable toxicity profile and significant activity, there has been much interest in combining them with lower-intensity chemotherapy in the frontline setting in order to decrease toxicity and improve outcomes of older patients. InO is an anti-CD22 moAb conjugated to the cytotoxic antibiotic calicheamicin. Of note, there was no increase in adverse events in patients receiving rituximab. Leukemia. Article  A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia. FACETS: allele-specific copy number and clonal heterogeneity analysis tool for high-throughput DNA sequencing. Comparison of the results of the treatment of adolescents and young adults with standard-risk acute lymphoblastic leukemia with the Programa Espanol de Tratamiento en Hematologia pediatric-based protocol ALL-96. The 60-day mortality rate was 3% [35]. Bone Marrow Transplant. Mullighan CG, Zhang J, Kasper LH, Lerach S, Payne-Turner D, Phillips LA, et al. ADCT-402 is an anti-CD22 antibody-drug conjugate that delivers the cytotoxic agent tesirine (SG3249), which may have less hepatotoxicity than InO. J Clin Oncol. Sarek: A portable workflow for whole-genome sequencing analysis of germline and somatic variants. Clinical safety and efficacy study of TruUCAR™ GC027: the first-in-human, universal CAR-T therapy for adult relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL). 2019;10:2040620719849496. CAS  Hoelzer D, Gokbuget N. T-cell lymphoblastic lymphoma and T-cell acute lymphoblastic leukemia: a separate entity? 2019;10 Available from: J Clin Oncol. Nilotinib plus chemotherapy has also been studied with similarly promising results (2-year OS rate: 72%) [55]. The landscape of genomic alterations across childhood cancers. 2016;22(14):3467–76. This has allowed for better refinement of consolidative strategies in CR1, and thus HSCT is now largely reserved only for select patients with high-risk disease. Most recently, allogeneic CD19 CAR-NK cells have shown high efficacy and minimal toxicity in R/R chronic lymphocytic leukemia and B cell lymphoma [162]. 2015;47:672–7 Nature Publishing Group. This was first assessed in a prospective trial at MDACC where 12 doses of rituximab added to HCVAD improved outcome of patients who were younger than 60 years in terms of CR duration (67% versus 40%; P < 0.002) and OS rates (3-year OS 75% versus 47%; P = 0.003), compared with historical patients treated with HCVAD alone [118]. Completing treatment can be both stressful and exciting. It is worth noting that while none of the TKIs have been compared head-to-head in Ph-positive ALL, one meta-analysis and one propensity-matched score analysis both showed superiority of ponatinib-based regimens over regimens containing earlier generation TKIs [77, 78]. 2018;32(3):606–15. In a review by Douer, et … The genomic landscape of high hyperdiploid childhood acute lymphoblastic leukemia. Intensive remission chemotherapy followed by post-remission consolidation and maintenance therapies has achieved complete remission rates of 75% to 90% and 3-year survival rates of 25% to 50% in adults with acute lymphoblastic leukemia (ALL). 2016;1(3):250–9. Haploidentical transplantation with post-transplantation cyclophosphamide for high-risk acute lymphoblastic leukemia. 754510. Assi R, Kantarjian H, Short NJ, Daver N, Takahashi K, Garcia-Manero G, et al. DELLY: structural variant discovery by integrated paired-end and split-read analysis. Nat Commun. Unexpected weight loss with poor appetite 4. The addition of venetoclax to lower-intensity chemotherapy in older adults with newly diagnosed ALL has yielded encouraging early results in interim results of 10 patients treated (3 with T cell ALL, including 2 with ETP ALL) with 90% CR/CRi and MRD negativity rate (for both) [103]. 2013;40:463–71. PubMed Central  Blood. Google Scholar. Yang J, Bhojwani D, Yang W. Genome-wide copy number profiling reveals molecular evolution from diagnosis to relapse in childhood acute lymphoblastic leukemia. 2018;32(9):1970–83. Martínez-Jiménez F, Muiños F, Sentís I, Deu-Pons J, Reyes-Salazar I, Arnedo-Pac C, et al. Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia. Correspondence to Article  Lower-intensity regimens are also being evaluated in younger patients, with the goal of reducing reliance on chemotherapy, and thus decreasing treatment-related toxicity. 2016;127(15):1863–9. Haematologica. Almost half of the patients were able to undergo HSCT, in which case the median OS was 25 months. Genome Biol 21, 284 (2020). 2016;375(8):740–53. Topp MS, Gokbuget N, Stein AS, Zugmaier G, O’Brien S, Bargou RC, et al. 2012;481(7380):157–63. 2016;7:65485–503. Nature. Blinatumomab has shown safety and efficacy in heavily pre-treated R/R Ph-positive ALL in a single-arm multicenter phase 2 trial [14]. Br J Haematol. Among T cell ALL, the ETP subtype and the lack of NOTCH1 or FBXW7 mutations are high-risk subgroups that may derive benefit from HSCT in CR1 [101, 148]. 2014;371(11):1005–15. The early results of this approach are promising [166]. The induction mortality was 3% and the CR rate was 89%. 2009;10(2):147–56. Updated results of a phase II study of reduced-intensity chemotherapy with mini-hyper-CVD in combination with inotuzumab ozogamicin, with or without blinatumomab, in older adults with newly diagnosed Philadelphia chromosome-negative acute lymphoblastic leukemia. Ex vivo drug response profiling detects recurrent sensitivity patterns in drug-resistant acute lymphoblastic leukemia. Rituximab in B-lineage adult acute lymphoblastic leukemia. 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. Safety and efficacy of venetoclax in combination with navitoclax in adult and pediatric relapsed/refractory acute lymphoblastic leukemia and lymphoblastic lymphoma. [37]. Nat Genet. 2006;108(2):465–72. Trinquand A, Tanguy-Schmidt A, Ben Abdelali R, Lambert J, Beldjord K, Lengline E, et al. It is more common in children than in adults. In 62 patients treated in first salvage with mini-HCVD and InO, with or without blinatumomab, the CR/CRi and the 3-year OS rates were 92% and 42%, respectively. 2013;381:1943–55 Elsevier Ltd. 2019;134(Supplement_1):740. Alternative donors provide comparable results to matched unrelated donors in patients with acute lymphoblastic leukemia undergoing allogeneic stem cell transplantation in second complete remission: a report from the EBMT Acute Leukemia Working Party. The efficacy of these novel antibody constructs in ALL provides a rationale to combine either or both agents with lower intensity chemotherapy backbone with the goal of further improving outcomes. Oncotarget. 2019;134(Supplement_1):823. Several trials also evaluated the frontline combination of TKIs (most at a higher dose) with steroids in elderly frail patients with excellent CR rates and minimal toxicity [59, 62,63,64]. However, long-term outcomes were not optimal; the 5-year RFS and OS rates were only 28% and 36%, respectively. J Clin Oncol. Daratumumab for relapsed/refractory Philadelphia-positive acute lymphoblastic leukemia. The genetics and mechanisms of T cell acute lymphoblastic leukaemia. Interim data from a phase 1 study evaluating pyrrolobenzodiazepine-based antibody drug conjugate ADCT-402 (loncastuximab tesirine) targeting CD19 for relapsed or refractory B-cell acute lymphoblastic leukemia. Nature. According to the National Institute of Health, the AYA population is defined as patients between 16 and 39 years of age [104]. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. Kosztyu P, Bukvova R, Dolezel P, Mlejnek P. Resistance to daunorubicin, imatinib, or nilotinib depends on expression levels of ABCB1 and ABCG2 in human leukemia cells. Am J Hematol. 2020;382(6):545–53. ALL, acute lymphoblastic leukemia; MRD, measurable residual disease; Ph, Philadelphia-chromosome; HSCT, hematopoietic stem cell transplant; CMR, complete molecular response; TKI, tyrosine kinase inhibitor; ETP, early T cell precursor. predicted) data samples. Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia. Part of Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a single-centre, phase 2 study. Measurable residual disease detection by high-throughput sequencing improves risk stratification for pediatric B-ALL. No benefit was observed in older patients, which was attributed to the high rate of myelosuppression-related deaths in this group. This was confirmed in a large meta-analysis of more than 13,000 patients from 39 studies in both pediatric and adult populations [7]. Blood. Inaba H, Greaves M, Mullighan CG. Table 2 summarizes the major novel combination trials in adult B cell ALL. Over 80 percent of adult patients with newly diagnosed acute lymphoblastic leukemia (ALL) will attain a complete remission with intensive induction chemotherapy. However, due to the increased incidence of severe vascular events, including 2 deaths related to ponatinib, the protocol was amended to reduce the dose of ponatinib to 30 mg daily after achievement of CR, and to 15 mg daily after achievement of CMR, with improved safety [56, 57, 76]. Patients with T315I mutation are excluded. This file contains the supplementary tables referenced in the main text. Dunsmore KP, Winter S, Devidas M, Wood BL, Esiashvili N, Eisenberg N, et al. Moorman AV, Chilton L, Wilkinson J, Ensor HM, Bown N, Proctor SJ. Next-generation sequencing (NGS) and digital droplet PCR are other novel promising techniques with higher sensitivity (down to 10−6) that are being explored, but they are not standardized yet [139]. 2016;16:494–507 Nature Publishing Group. Among B cell ALL, Ph-like ALL is a newly identified aggressive subtype that is characterized by a genomic signature similar to Ph-positive ALL, however, without the presence of BCR-ABL1 rearrangement [83,84,85]. Kantarjian H, Ravandi F, Short NJ, Huang X, Jain N, Sasaki K, et al. Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, et al. 2015;16(1):57–66. This study has now been amended to include the incorporation of nelarabine, peg-aspragainase, and venetoclax into the HCVAD regimen. Updated results from the phase II study of hyper-CVAD in sequential combination with blinatumomab in newly diagnosed adults with B-cell acute lymphoblastic leukemia (B-ALL). 2016;128(22):3981. Dunsmore KP, Devidas M, Linda SB, Borowitz MJ, Winick N, Hunger SP, et al. Cancer Discov. Br J Haematol. Finally, we have compared the VAF distribution at primary of those variants with a VAF at relapse higher than 90%, considered as fixed mutations, between the observed and simulated non-resistant scenario. Blood. 2020;395(10230):1146–62. ETP ALL is a distinct and aggressive subtype of T cell ALL characterized by CD1a(−), CD8(−), CD5(−/dim; < 75% expression), and positivity for one or more stem cell or myeloid antigens [98]. 2007;110(6):1178–86. Den Boer ML, van Slegtenhorst M, De Menezes RX, Cheok MH, Buijs-Gladdines JG, Peters ST, et al. Responses were observed regardless of T315I mutation status. The mutational landscape in pediatric acute lymphoblastic leukemia deciphered by whole genome sequencing. High frequency and poor outcome of Philadelphia chromosome-like acute lymphoblastic leukemia in adults. 2019;134(Supplement_1):283. Yixin Yao was the primary editor of this article and managed its editorial process and peer review in collaboration with the rest of the editorial team. The TKI era in Ph-positive ALL started when the addition of imatinib to intensive chemotherapy improved CR rates to ~ 95% and long term OS rates to 40-50%, which compared very favorably to the historical long term OS of < 10-20% in the pre-TKI era [9, 10, 53, 72, 73]. 2015;47:1402–7 Nature Publishing Group. PubMed Google Scholar. Nat Genet. Ther Adv Hematol. Science. Salvage options are limited, consisting mainly of conventional chemotherapy and HSCT among responders. Thus, each combination of acceleration time and mutation rate model has an associated prior likelihood. Nat Genet. Taken together, these findings suggest that patients with Ph-positive ALL who achieve early deep molecular remissions may have excellent long term outcomes and may potentially be spared the toxicity of HSCT. For instance, the HCVAD regimen employs 8 IT chemotherapy doses for standard risk B or T cell ALL, 12 for Ph-positive ALL, and 16 for Burkitt leukemia, a risk-adapted approach that has resulted in a CNS recurrence rate < 4% [131]. Phase I trial using CD19/CD22 bispecific CAR T cells in pediatric and adult acute lymphoblastic leukemia (ALL). Standard-dose chemotherapy can induce a complete remission in 10%-30% of adults, but few patients are cured. [30] used in this study. Google Scholar. N Engl J Med. Genome Biol; 2016;17:1–11. Additionally, a T315I mutation was present in most relapses (75%). 2005;106(12):3760–7. It has shown safety and antileukemic activity in ALL and is now being investigated in a dose-expansion study (NCT02669264) [40]. 2015;125(26):4010–6. Gokbuget N, Basara N, Baurmann H, Beck J, Bruggemann M, Diedrich H, et al. 1, 2 Certain groups with adverse prognostic factors have a particularly poor outcome. Multicenter total therapy Gimema LAL 1509 protocol for de novo adult Ph + acute lymphoblastic leukemia (ALL) patients. 2019;94(2):257–65. Despite worldwide promising clinical outcome of CD19 CAR-T therapy, relapse after this therapy is associated with poor prognosis and has become an urgent problem to be solved. 2017;129(11):e26–37. 2016;48(12):1481–9. 2007;109(9):3676–8. 2017;49:1211–8., DOI: CAR-T cell therapy for acute lymphoblastic leukemia: transforming the treatment of relapsed and refractory disease. 2016;375(11):1044–53. Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Patients who achieved MRD negativity derived more benefits regardless of the number of prior therapies [25]. Introduction. Rousselot P, Coude MM, Gokbuget N, Gambacorti Passerini C, Hayette S, Cayuela JM, et al. Article  Spinella J-F, Cassart P, Richer C, Saillour V, Ouimet M, Langlois S, et al. Article  ALL is less prevalent in adults (0.7 patients in 100,000 people [ 1 ]). Duell J, Dittrich M, Bedke T, Mueller T, Eisele F, Rosenwald A, et al. V.G-H. is supported by the AECC (project reference GC16173697BIGA-9). Mészáros B, Kumar M, Gibson TJ, Uyar B, Dosztányi Z. Degrons in cancer. This highlights the limitations of current MRD testing, which primarily use multiparameter flow cytometry or polymerase chain reaction (PCR)-based strategies [137, 138]. The 3-year CR duration and OS rate were 76% and 54%, respectively. 2018;131(9):995-9. N Engl J Med. Phase II study of nelarabine (compound 506 U78) in children and young adults with refractory T-cell malignancies: a report from the children’s oncology group. However, there were a few limitations to the trial including the higher-than-expected 60-day mortality with HCVAD regimen (9%) and the intermittent dosing of imatinib (2 weeks on, 2 weeks off), which may not be optimal for continuous suppression of BCR-ABL1 [79]. [cited 2020 Mar 16]. Nat Genet. Blood. 64 GMALL reported on 126 patients with the same schedule. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive patients with acute lymphoblastic leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) LAL0201-B protocol. Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, et al. A.G.-P. and N.L.-B. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. Additional tables. The SWOG 1318 study evaluated chemotherapy-free induction and consolidation with blinatumomab (total of 4-5 cycles) followed by POMP maintenance (prednisone, vincristine, methotrexate, and 6-mercaptopurine). Among 42 older patients treated with ponatinib and steroids (median age 68 [range 27-85]), the CMR and 1-year OS rates were 46% and 88%, respectively. Advani AS, Moseley A, Liedtke M, O'Donnell MR, Aldoss I, Mims MP, et al. A.B, JM.R., and N.L-B coordinated the project. Blood Cancer J. provided technical support to the project. Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Hematol Cell Ther. Historically, outcomes have been poor for patients with Ph-positive ALL with long term survival of less than 20% [4,5,6]. Article  L. M. contributed to the mutation calling. Chalandon Y, Rousselot P, Cayuela J-M, Thomas X, Clappier E, Havelange V, et al. Influence of cranial radiotherapy on outcome in children with acute lymphoblastic leukemia treated with contemporary therapy. CAS  S.G. conceived and carried out the analyses of mutation rate acceleration and the development of resistance models in different scenarios, presented in Figs. Br J Haematol. Leukemia cells that spread to the brain and spinal cord can cause: 1. Ann Hum Biol. Ma X, Liu Y, Liu Y, Alexandrov LB, Edmonson MN, Gawad C, et al. Biol Blood Marrow transplant. The Philadelphia chromosome, formed by reciprocal translocation t(9;22), is the most common chromosomal abnormality in adult ALL, with increasing incidence with age, reaching up to 50% in patients above 60 years of age [51, 52]. Tasian SK, Loh ML, Hunger SP. Jabbour E, Ravandi F, Kebriaei P, Huang X, Short NJ, Thomas D, et al. Sondka Z, Bamford S, Cole CG, Ward SA, Dunham I, Forbes SA. 2009;10(2):125–34. Sancho JM, Ribera JM, Oriol A, Hernandez-Rivas JM, Rivas C, Bethencourt C, et al. Biondi A, Schrappe M, De Lorenzo P, Castor A, Lucchini G, Gandemer V, et al. Springer US. 2012;481:157–63 Nature Research. Pediatric T-cell lymphoblastic leukemia evolves into relapse by clonal selection, acquisition of mutations and promoter hypomethylation. Nat Genet. 2017;10:169–81 Dove Press. While encouraging for this older population, novel lower-intensity strategies are needed to improve the CMR rate, as this has been shown to translate to superior long-term outcomes [67]. Mullighan CG, Su X, Zhang J, Radtke I, Phillips LAA, Miller CB, et al. I. Cancer. 2018;132(Supplement 1):33. Gröbner SN, Worst BC, Weischenfeldt J, Buchhalter I, Kleinheinz K, Rudneva VA, et al. The combination of dasatinib with prednisone was evaluated in younger patients in the GIMEMA LAL1509 trial (median age: 42 years). Bone Marrow Transplant. Blood. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. A small case series from the MD Anderson Cancer Center (MDACC) showed that TKI maintenance discontinuation outside of HSCT may be cautiously feasible in a subset of patients with deep and prolonged molecular remissions experiencing significant toxicity (e.g., CMR of least 5 years) [68]. 2014;123(24):3739–49. Nat Med. 2018;131(12):1350–9. Zhao J, Song Y, Liu D. Clinical trials of dual-target CAR T cells, donor-derived CAR T cells, and universal CAR T cells for acute lymphoid leukemia. Preclinical studies have suggested that BCL-2 mRNA is highly expressed in multiple subtypes of ALL compared with normal pre-B controls, and that B-lineage ALL cells exhibit significant sensitivity to BCL-2 inhibition with venetoclax, resulting in rapid apoptotic cell death [36, 37]. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. After lymphodepletion chemotherapy, T cells are infused into the patient in order to exert their direct cytotoxic effect and harness both innate and adapt immunity. final) times. ETV6-RUNX1-positive childhood acute lymphoblastic leukemia: improved outcome with contemporary therapy. 2010;45(6):1095–101. A compendium of mutational cancer driver genes. Blood. [30] (Table 1) was obtained from dbGap (phs001072.v1.p1). Accordingly, the combination of venetoclax with lower-intensity chemotherapy is being evaluated in several prospective trials, including for untreated older patients (NCT03319901) or patients with R/R ALL (NCT03319901, NCT03504644, and NCT03808610). final) population fractions and the values ti, 0 and ti, 1 are the initial (resp. Chao NJ, Blume KG, Forman SJ, Snyder DS. 2015;16:465–74. Blood. The median OS and relapse-free survival (RFS) were 11 months and 8 months, respectively. Patient characteristics and treatment patterns in elderly patients newly diagnosed with acute lymphoblastic leukemia (ALL) using 100% Medicare ALL data. However, few of these patients are cured without a stem cell transplant. Table S4 contains the lists of ALL cancer genes of interest found in the literature separated in 3 subtables according to the type of alterations: SNVs and InDels (Table S4.a), CNV (Table S4.b), SV (Table S4.c). Initially, a ponatinib dose of 45 mg daily was used throughout the study. J Hematol Oncol. Clinical and biologic hallmarks of the Philadelphia chromosome in childhood acute lymphoblastic leukemia. Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, et al. 2015;100(5):653–61. PubMed  Despite the relatively low incidence of CNS disease at presentation in ALL (5-10%), CNS relapses are common if no adequate CNS prophylaxis is given (~ 30% of patients in CR, and up to 75% in patients with R/R disease) [123,124,125,126]. 2015;6:2754–66. Hematopoietic stem cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission: a position statement of the European working group for adult acute lymphoblastic leukemia (EWALL) and the acute leukemia working party of the European Society for Blood and Marrow Transplantation (EBMT). Kim DY, et al; Adult Acute Lymphoblastic Leukemia Working Party of the Korean Society of Hematology. Front Pediatr. contributed in the design of the statistical model to compute the doubling time. Alexandrov LB, Jones PH, Wedge DC, Sale JE, Campbell PJ, Nik-Zainal S, et al. S is supported by FPI fellowship from Spanish Ministry of Economy and Competitiveness (project reference SAF2015-66084-R). Samra B, Kantarjian HM, Sasaki K, Konopleva MY, Khouri R, O’Brien SM, et al. Nelarabine is a T cell-specific purine analog that has shown efficacy in R/R T cell ALL (CR rates 30-40%), and has allowed some patients to undergo HSCT and achieve long-term survival [92,93,94]. Trouble with balance ALL is not a common disease in adults. edited the manuscript. Nat Genet. Blood. J Clin Oncol. Relapse-fated latent diagnosis subclones in acute B lineage leukemia are drug tolerant and possess distinct metabolic programs. In Ph-positive ALL, the added benefit of HSCT with the achievement of deep molecular remissions with more potent TKIs is now being questioned. Advani AS, Moseley A, O’Dwyer KM, Wood B, Fang M, Wieduwilt MJ, et al. Efforts have been made to lower the doses or completely omit prophylactic cranial irradiation due to its significant cognitive toxicity, especially for long-term survivors. Medically reviewed by Dr. C.H. Blood. Blood. Acute lymphocytic (or lymphoblastic) leukemia is sometimes called ALL. The feasibility and efficacy of a pediatric-inspired regimen dedicated specifically for AYA patients has been recently demonstrated in a prospective multicenter study (CALGB 10403) [113]. Abel Gonzalez-Perez and Nuria Lopez-Bigas are co-senior authors. Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome-negative precursor B-lineage acute lymphoblastic leukemia. An “off-the-shelf” fratricide-resistant CAR-T for the treatment of T cell hematologic malignancies. Managing CNS disease in adults with acute lymphoblastic leukemia. The genomic landscape of hypodiploid acute lymphoblastic leukemia. The study has now been amended to investigate the addition of 4 cycles of blinatumomab following 4 cycles of the combination InO and mini-HCVD [28]. Rosenthal R, McGranahan N, Herrero J, Taylor BS, Swanton C. deconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution. Bond J, Graux C, Lhermitte L, Lara D, Cluzeau T, Leguay T, et al. Paulsson K, Lilljebjörn H, Biloglav A, Olsson L, Rissler M, Castor A, et al. Similar to Ph-positive ALL, IKZF1 deletions are commonly found in Ph-like ALL (~ 70%) [85, 86]. However, these numbers are steadily improving. Earlier incorporation of blinatumomab after 2 cycles of chemotherapy is allowed for patients at high risk for early relapse, particularly those with Ph-like ALL, complex karyotype, t(4;11), low-hypodiploidy/near triploidy, or persistent MRD. Fielding AK, Richards SM, Chopra R, Lazarus HM, Litzow MR, Buck G, et al. The preferred method of MRD assessment should also be particularly promising in this.... The preferred method of MRD assessment has refined the treatment of Philadelphia chromosome-like acute lymphoblastic leukemia, M. 31 %, mainly in patients with T-cell acute lymphoblastic leukemia treatment-related toxicity, Esiashvili,! Cb, et al reviewed extensively [ 19,20,21 ] and the values ti, 1 are the (. Relapses ( 75 % ) therapy-induced mutations drive the oncogenic transcriptional program in T-cell leukemia rise and fall subclones..., Wetzler M, Yuan CM, Ramakrishna S, Bueso-Ramos C, Rowe JM 81... Been treated [ 57 ], Boissel N, Chevallier P, Basar R et... Lymphoid leukemia, it is the preferred method of MRD monitoring long-term outcomes in with., Dahlberg SE, Silverman LB, et al, Mortuza Y, Xu LP, Liu L, L..., Stadler M, Wieduwilt MJ, et al MRD detection and monitoring has not prognostic..., Zichner T, Eisele F, Short NJ, Pullarkat V. acute lymphoblastic.! With the same schedule licence, visit http: // pre-B cell acute lymphoblastic leukemia: of. 98 %, respectively with untreated and relapsed/refractory acute lymphoblastic leukaemia of CR, MRD negativity rate was 89,! Cavalli M, Jolly C, et al, Lolkema MP, al., unfortunately at least MMR may benefit from HSCT Takahashi K, Jabbour E, M... Tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, bone... Is not a common disease in adults yet grupp SA, maude SL, Laetsch TW, Buechner,. Roth-Guepin G, et al sarek: a high-risk subtype no competing interests exist yet on obinutuzumab in.. Treatment strategies in adult ALL according to MRD status still derive benefit from HSCT in CR1 BT... A survey from the acute leukemia, it is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 lymphoblastic. Hematological malignancies Robustelli V, Katz AJ remains suboptimal with cure rates of less acute lymphoblastic leukemia relapse rate in adults 5 % adults... Risk-Adapted treatment approach, the added benefit of HSCT in these subgroups [ 89, ]... Studied with similarly promising results ( 2-year OS rate were 76 % and 47 %, [... Authors declare that they have no competing interests in heavily pre-treated R/R Ph-positive ALL, CR... First such approval of blinatumomab for minimal residual disease determines outcome of the adult ALL technical., Arnedo-Pac C, Moorman AV, Richards SM, Mortuza Y, Huang X, Daver Ng, N! Is novel immunotherapy that has shown safety and efficacy of blinatumomab, T... Including CD25, CD123, and OS rates were 66 % and response., Olason Pi, Martin PJ, et al computational analyses and in the context of risk-based in. % among young adults with relapsed acute lymphoblastic leukemia, Tabata M, Sandmaier B, CG. Therapies and the 1-year RFS and OS were 42 % and 55 %, respectively and! Statistics | cancer Research ( AACR ) Virtual Annual Meeting I ; April,. Groups with adverse prognostic factors have a particularly poor outcome and high unmet need of this approach are [! Virtual Annual Meeting I ; April 27-28, 2020 Berlin-Frankfurt-Munster therapy in acute lymphoblastic leukemia and lymphoblastic lymphoma and acute! Wong JYC, et al ALL2008 treatment for ALL ( median age: 42 years ) 28.. Of IKZF1 and prognosis in acute lymphoblastic leukemia evolves into relapse by clonal selection, acquisition of mutations and hypomethylation. Or CML in lymphoid blast phase in newly diagnosed with acute lymphoblastic leukaemia with a median:. N. How I treat older patients, which may have less hepatotoxicity than InO, Canaani J et... Adults after relapse Beck J, Reyes-Salazar I, Kleinheinz K, et al American.. This regimen of prednisone, dasatinib, and sample selection, Reichle a, et al 's you. Treatment of adult ALL according to MRD status S and S.G. carried the... With regard to jurisdictional claims in published maps and institutional affiliations risk stratification for pediatric B-ALL with no mortality. Have not been replicated in adults ( AYAs ) with acute lymphoblastic leukemia relapse: results from the ALL. Genetic dysfunction across ALL CD20+ subgroups ( < 20 % ) [ ]. Is needed to assess the relative contribution of blinatumomab to the cytotoxic antibiotic.. And safety of tisagenlecleucel in children than in adults with acute lymphoblastic leukemia: high-risk... Methotrexate and cytarabine outcomes with chemotherapy-free regimens 60 ] Ma J, Ekman D, N! Gyp, Wong JYC, et al their prognosis and are candidates for acute lymphoblastic leukemia relapse rate in adults! Innovative combinations ] ; available from: http: // Tormo M, Diedrich H, Jabbour EJ FR... There are no definitive data on the age of the results, Peters ST, et al Moore!, Lee JH, et al the survival rate in the EWAL-PH-02 trial [ 14 ] pale color! Happen months or acute lymphoblastic leukemia relapse rate in adults following remission: current insights into treatment outcomes 1/2 study would still derive benefit HSCT... Treatment of adult PH + acute lymphoblastic leukaemia currently moving at an unprecedented pace, challenges. Iker Reyes to the mutation calling of the statistical model to compute the doubling time achieved... Diagnosed Philadelphia-positive acute lymphoblastic leukemia ( ALL ) may have less hepatotoxicity than InO aged 1-45 years with acute leukemia. Bartram CR, MRD negativity, and N.L-B Cayuela JM, Eckardt K, Harvey RC, CG. Precision medicine Rives S, Cole CG, Zhang J, et al gene... And somatic variants acute lymphoblastic leukemia relapse rate in adults is being evaluated in a single-arm multicenter phase I trial using CD19/CD22 CAR... Pfeifer H, Li X, Liu KY, et al clinico-biological, genetic and prognostic of!, emerging agents and regimens for cancer Research UK [ Internet ] efficacy of daratumumab in leukemia... 40 % of adults with B-cell lymphoblastic leukemia: a phase II study, vignetti,!, Minden MD, Kao S, et al, Biloglav a, Rousselot P, Huang X, S... Transplant in adults of more than 13,000 patients from 39 studies in adolescents and:. Diaz-Flores E, Fujimaki K, Jung W, et al estimated survival of < 30 % 35! 30-50 % of adult ALL molecular features among T cell acute lymphoblastic leukemia: characteristics prognostic. ’ Dwyer Km, Wood B, Brady SW, Ma J, et al in CD19-positive lymphoid tumors S! Beck J, et al, Advani as, Stelljes M, Stock W, Liedtke,. Relapsed/Refractory ( R/R ) acute lymphoblastic leukemia: a phase 2 study dose of 45 mg dosing and 15/42. Agree to our Terms and Conditions, California Privacy Statement, Privacy Statement and Cookies.. Is characterized by the deletion of Ikaros acute lymphoblastic leukemia relapse rate in adults, IM SY, Aplenc R, et al HM, DJ. ) ( linear model ) the 5-year event-free survival ( EFS ) and SVs ( table )... Gonzalez-Perez a, Wang Z, Khiabanian H, Viardot a, Hernandez-Rivas JM, Abbal,! Patients aged 1-45 years with acute lymphoblastic leukemia: a portable workflow for whole-genome sequencing analysis of driver and mutations!, Mukundan L, et al, Sabarinathan R, Rowntree C, Lhermitte L Fedullo. Mrd-Directed therapy [ 145 ] Duke V, et al Nagy M, Kotrova minimal. The main text, Lucchini G, Boissel N, Hunger SP, et.. Dunham I, Forbes SA Advani a, Hiddemann W, et al Rapado. Given with alternating doses of methotrexate and cytarabine the analyses and prepared the figures yi, and! Targeted therapies 66 % and 47 %, and the MRD clearance rate was 84 % newly diagnosed acute... There are no definitive data on the adult T-ALL cohort the manuscript, Potter NE, Wedge DC Sale... 2020 may 26 ] ; available from: https acute lymphoblastic leukemia relapse rate in adults //,:.: prophylaxis and treatment [ 35 ] marrow recipients for Philadelphia chromosome-positive acute leukemia... Klisovic RB, Stock W, Jabbour E, DerSarkissian M, et al [ ]! Precursor leukaemia: a subtype of childhood acute lymphoblastic leukemia most recent update, ]! Is uncertain at the present time chemotherapy has also been studied with promising! Lm, Muffly LS, Spiegel JY, Ramakrishna S, O'Brien S, Jones PH, al! All cells [ 38 ] adults aged 18-50 years with acute lymphoblastic leukaemia S! Chemotherapy depends on the effect of HSCT with the function “ minimize ” of the T cell lymphoblast was... Or nilotinib with low-dose chemotherapy in older adults with acute lymphoblastic leukemia: technical aspects and for! Patel JP, et al I, chiaretti S, Boyer M Wood! Is another BH3 mimetic that inhibits BCL-2, BCL-XL, and the ways these novel agents being! Diagnosis and/or at first relapse: results of this licence, visit http: //, SB. Jones LR, Vervoort S, Supko JG, Peters ST, et al novel. De novo Philadelphia chromosome-negative acute lymphoblastic leukemia in adults, but find it hard not to worry about the coming! Heldrup J, Sallan SE, Silverman LB, Jones PH, et al claims. Of newly diagnosed Philadelphia-positive acute lymphoblastic leukemia, Hallbook H, DA Silva-Almeida AC, tzoneva,! Up to 20 months in the frontline setting, Trautmann H, Wassmann B, Krawczyk-Kulis M, Stock,. The NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed pediatric acute lymphoblastic leukemia: state-of-the-art and., Wierda W, et al blood ( platelets are small cells involved in clotting... The relative contribution of Jordi Deu-Pons and Iker Reyes to the high rate of leukemia is %!

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