therapy that may increase their chance of cure. : Adolescents with acute lymphoblastic leukaemia: outcome on UK national paediatric (ALL97) and adult (UKALLXII/E2993) trials. : Improving the identification of high risk precursor B acute lymphoblastic leukemia patients with earlier quantification of minimal residual disease. The 6-year EFS rate was 46.1%, and the OS rate was 58.2%; these rates were not statistically different from the rates observed in the predecessor Interfant-99 protocol. : Monthly pulses of vincristine and prednisone prevent bone marrow and testicular relapse in low-risk childhood acute lymphoblastic leukemia: a report of the CCG-161 study by the Childrens Cancer Study Group. Leukemia 28 (2): 302-10, 2014. Children with ALL are typically classified by risk group to make sure that the correct types and doses of drugs are given. : Higher Reported Lung Dose Received During Total Body Irradiation for Allogeneic Hematopoietic Stem Cell Transplantation in Children With Acute Lymphoblastic Leukemia Is Associated With Inferior Survival: A Report from the Children's Oncology Group. Hallböök H, Gustafsson G, Smedmyr B, et al. : Unrelated donor vs HLA-haploidentical α/β T-cell- and B-cell-depleted HSCT in children with acute leukemia. Nebral K, Denk D, Attarbaschi A, et al. : Difference in outcome of adolescents with acute lymphoblastic leukemia (ALL) enrolled in pediatric (AIEOP) and adult (GIMEMA) protocols. All therapeutic regimens for childhood ALL include intrathecal chemotherapy. Wood BL, Winter SS, Dunsmore KP, et al. Sutton R, Lonergan M, Tapp H, et al. ERG deletion connotes an excellent prognosis, with OS rates exceeding 90%; even when the IZKF1 deletion is present, prognosis remains highly favorable. dexamethasone). Multiple clinical trials investigating new agents, new combinations of agents, and immunotherapeutic approaches are available. BMC Cancer 18 (1): 755, 2018. The 3-year EFS rate was 59%, and the median OS was not reached. [34], The median WBC count at diagnosis is much higher for T-ALL (>50,000/µL) than for B-ALL (<10,000/µL), and there is no consistent effect of WBC count at diagnosis on prognosis for T-ALL.[34-41]. Enshaei A, Schwab CJ, Konn ZJ, et al. Gilchrist GS, Tubergen DG, Sather HN, et al. TBI resulted in higher cure rates than chemotherapy-only : Outcome of children with hypodiploid ALL treated with risk-directed therapy based on MRD levels. : Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia. Biol Blood Marrow Transplant 18 (8): 1204-10, 2012. Uderzo C, Conter V, Dini G, et al. Two retrospective analyses investigated the role of HSCT in first CR for patients with hypodiploid ALL. The COG reported that risk group classification at the time of initial diagnosis was prognostically significant after relapse; patients who met National Cancer Institute (NCI) standard-risk criteria at initial diagnosis fared better after relapse than did NCI high-risk patients. TBI for all but the youngest children (age <3 or 4 years) remains standard of care in most centers in North America and Europe. Shago M, Abla O, Hitzler J, et al. [104] Point mutations in kinase genes, aside from those in JAK1 and JAK2, are uncommon in Ph-like ALL cases.[8]. J Pediatr Psychol 26 (1): 1-9, 2001 Jan-Feb. Copeland DR, Moore BD, Francis DJ, et al. Pulses of vincristine and corticosteroid are often added to the The BFM risk groups include the following:[120]. present with mature B-cell leukemia (surface Ig expression, generally with French-American-British criteria L3 mercaptopurine without serious toxicity, but they do require more frequent dose Pharmacogenomics J 4 (1): 66-72, 2004. Standard-risk patients on both arms will continue to receive imatinib until the completion of all planned chemotherapy (2 years of treatment). : International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia. [4] While it is more frequent in older and higher-risk patients, the Ph-like subtype has also been identified in NCI standard-risk patients. J Clin Oncol 31 (9): 1202-10, 2013. : Clinical characteristics and outcome of children with biphenotypic acute leukemia. We’ve invested more than $4.9 billion in cancer research since 1946, all to find more – and better – treatments, uncover factors that may cause cancer, and improve cancer patients’ quality of life. Patients with this phenotype respond well to therapy used for B-ALL. Rubnitz JE, Hijiya N, Zhou Y, et al. Initial studies focused on the ETV6-RUNX1 translocation and used reverse transcriptase (RT)–polymerase chain reaction (PCR) to identify RNA transcripts indicating the presence of the gene fusion. Pui CH, Pei D, Sandlund JT, et al. Intrathecal chemotherapy typically consists of one of the following:[5], Unlike intrathecal cytarabine, intrathecal methotrexate has a significant systemic effect, which may contribute to prevention of marrow relapse.[6]. Vrooman LM, Blonquist TM, Supko JG, et al. : Intensified chemotherapy without SCT in infant ALL: results from COG P9407 (Cohort 3). : Trisomy of leukemic cell chromosomes 4 and 10 identifies children with B-progenitor cell acute lymphoblastic leukemia with a very low risk of treatment failure: a Pediatric Oncology Group study. [28-30], Multiple retrospective studies have established that adolescents aged 16 to 21 years have a better outcome when treated on pediatric versus adult protocols. A meta-analysis of randomized trials compared thiopurines and found the following: Thioguanine did not improve the overall EFS, although particular subgroups may benefit from its use. More than 95% of children with ALL enter remission after 1 month of induction treatment. Participants who received testicular radiation therapy achieved a 5-year EFS rate of 73% versus 61% for those who did not receive radiation (. [, An analysis of data from the Center for International Blood and Marrow Transplant Research (CIBMTR) on 27 Down syndrome patients with ALL who underwent hematopoietic stem cell transplantation (HSCT) between 2000 and 2009 substantiated this finding. standard maintenance backbone, although the benefit of these pulses within the context of contemporary multiagent chemotherapy regimens remains controversial. Genome Res 27 (2): 185-195, 2017. Blood 126 (8): 964-71, 2015. Evidence (use of pegaspargase versus native E. coli L-asparaginase): Patients with an allergic reaction to pegaspargase are typically switched to Erwinia L-asparaginase. Lancet Oncol 16 (4): 465-74, 2015. Understanding of the genomics of B-ALL at relapse is less advanced than the understanding of ALL genomics at diagnosis. Hrusak O, de Haas V, Stancikova J, et al. : Assessment of dexrazoxane as a cardioprotectant in doxorubicin-treated children with high-risk acute lymphoblastic leukaemia: long-term follow-up of a prospective, randomised, multicentre trial. : Bortezomib reinduction chemotherapy in high-risk ALL in first relapse: a report from the Children's Oncology Group. Genomic alterations in CRLF2, a cytokine receptor gene located on the pseudoautosomal regions of the sex chromosomes, have been identified in 5% to 10% of cases of B-ALL; they represent approximately 50% of cases of Ph-like ALL. USP7 germline and somatic mutations are generally mutually exclusive and are most commonly observed in T-ALL patients with TAL1 alterations. : Declining childhood and adolescent cancer mortality. Lilljebjörn H, Ågerstam H, Orsmark-Pietras C, et al. J Clin Oncol 31 (19): 2460-8, 2013. editorially independent of NCI. This was more common in the past, but recent studies have found that many children even with high-risk ALL may not need radiation therapy if they are given more intensive chemo. Schrappe M, Bleckmann K, Zimmermann M, et al. : Prognostic value of genetic alterations in children with first bone marrow relapse of childhood B-cell precursor acute lymphoblastic leukemia. with prednisone and one dose of intrathecal methotrexate (a good prednisone DFCI: The DFCI ALL Consortium protocols include 30 weeks of pegaspargase therapy beginning at week 7 of therapy, given in conjunction with maintenance regimen (vincristine/dexamethasone pulses, weekly low-dose methotrexate, daily mercaptopurine). : Prognostic value of rare IKZF1 deletion in childhood B-cell precursor acute lymphoblastic leukemia: an international collaborative study. A study from St. Jude Children's Research Hospital (SJCRH) suggests that a good outcome can be achieved with aggressive conventional chemotherapy without radiation. : Substitution of oral and intravenous thioguanine for mercaptopurine in a treatment regimen for children with standard risk acute lymphoblastic leukemia: a collaborative Children's Oncology Group/National Cancer Institute pilot trial (CCG-1942). : Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Biopsy of the other testicle is performed at the time of relapse to determine if additional local control (surgical removal or radiation) is to be performed. : CD4/CD8 T-Cell Selection Affects Chimeric Antigen Receptor (CAR) T-Cell Potency and Toxicity: Updated Results From a Phase I Anti-CD22 CAR T-Cell Trial. 40%; it is approximately 85% for boys with late testicular relapse.[168]. : IgH-V(D)J NGS-MRD measurement pre- and early post-allotransplant defines very low- and very high-risk ALL patients. Blood Adv 3 (21): 3393-3405, 2019. : Identification of novel NOTCH1 mutations: increasing our knowledge of the NOTCH signaling pathway. : CD22 CAR T-cell therapy in refractory or relapsed B acute lymphoblastic leukemia. Blood 101 (10): 3809-17, 2003. NCI standard (low) risk: Includes children aged 1 year to <10 years with WBC <50,000/µL at the time of diagnosis. The children were younger than 16 years of age and had a diagnosis of ALL de novo . [74] In addition to the TCF3-HLF fusion, the genomic landscape of this ALL subtype was characterized by deletions in genes involved in B-cell development (PAX5, BTG1, and VPREB1) and by mutations in RAS pathway genes (NRAS, KRAS, and PTPN11). : Mercaptopurine Ingestion Habits, Red Cell Thioguanine Nucleotide Levels, and Relapse Risk in Children With Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group Study AALL03N1. : Transitional pre-B-cell acute lymphoblastic leukemia of childhood is associated with favorable prognostic clinical features and an excellent outcome: a Pediatric Oncology Group study. Mature B-cell ALL is now termed Burkitt leukemia and requires different treatment than has been given for B-ALL (precursor B-cell ALL). Biol Blood Marrow Transplant 15 (1 Suppl): 62-71, 2008. persistent circulating leukemia cells at 7 to 10 days after the initiation of J Clin Oncol 31 (27): 3397-402, 2013. The half-life of Erwinia L-asparaginase (0.65 days) is much shorter than that of native E. coli (1.2 days) or pegaspargase (5.7 days). This study demonstrated that long-term salvage of patients failing CD19-targeted CAR T cells can occur with CD22-targeted CAR T cells plus HSCT. Treatment involves a combination of medicines. Therefore, all children with acute lymphoblastic leukemia (ALL) should receive systemic combination Leukemia 23 (6): 1073-9, 2009. Br J Haematol 147 (3): 371-8, 2009. Crombet O, Lastrapes K, Zieske A, et al. Postinduction Treatment for Specific ALL Subgroups. [27], Near triploidy (68–80 chromosomes) and near tetraploidy (>80 chromosomes) are much less common and appear to be biologically distinct from high hyperdiploidy. Chromosomal translocations may be seen with high hyperdiploidy, and in those cases, patients are more appropriately risk-classified on the basis of the prognostic significance of the translocation. 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