Augmented post-remission therapy for a minimal residual disease-defined high-risk subgroup of children and young people with clinical standard-risk and intermediate-risk acute lymphoblastic leukaemia (UKALL 2003): a randomised controlled trial

Vora, Ajay; Goulden, Nick; Mitchell, Chris; Hancock, Jeremy; Hough, Rachael; Rowntree, Clare; Moorman, Anthony V.; Wade, Rachel

doi:10.1016/s1470-2045(14)70243-8

Cited by 268 publications

(258 citation statements)

References 22 publications

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“…34 It found that the latter measurement was more informative for predicting relapse in T-ALL, with 21% of patients meeting the high-risk criterion of MRD $0.1% on day 78. 34 BLOOD, 6 APRIL 2017 x VOLUME 129, NUMBER 14 …”

Section: Specific Leukemia Subtypes Remain Prognostic In the Contextmentioning

confidence: 99%

“…Pediatric oncologists treating children and adolescents with ALL have pioneered the use of MRD to monitor response to treatment, and all major pediatric oncology centers and cooperative groups worldwide now systematically use MRD levels to guide treatment decisions (Table 1). [8][9][10][11][12][13][14][15][16][17][18][19][20] Because precise measurements of MRD have important prognostic and therapeutic implications, it is essential to understand their clinical significance in the context of presenting clinical and biologic features, treatment regimen, and time interval at which MRD is measured.…”

Section: Introductionmentioning

confidence: 99%

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Minimal residual disease–guided therapy in childhood acute lymphoblastic leukemia

Campana

Pui

2017

Blood

115

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A 3-year-old boy presented with a leukocyte count of 5.9 3 10 9 /L and was found to have near-haploid B-lineage acute lymphoblastic leukemia (ALL) with a 27, X, 1Y, 113, 118, 121 karyotype. He was enrolled in the St. Jude Children's Research Hospital Total Therapy XV study. After 19 days of remission induction therapy with 1 high dose of methotrexate, 14 days of prednisone, 2 doses of vincristine and daunorubicin, and 6 doses of Escherichia coli-derived asparaginase, flow cytometry examination of his bone marrow revealed the presence of minimal residual disease (MRD) amounting to 3 leukemic cells per 10 000 mononucleated cells (0.03%). Upon completion of the remaining remission induction therapy consisting of 1 dose of cyclophosphamide, 14 days of mercaptopurine, and 8 onceper-day doses of cytarabine, he attained a morphologic remission on day 46, with undetectable (,0.01%) MRD by flow cytometry and polymerase chain reaction. Because of the near-haploid ALL karyotype and negative day 46 MRD, he was assigned to receive intensive chemotherapy for 3 years. MRD remained undetectable throughout treatment. He has remained in continuous complete remission for 11.6 years. Case 2A 9-year-old boy presented with a 3-month history of progressive pallor and upper respiratory tract infection. He had no hepatosplenomegaly or mediastinal mass. An abnormal blood count with hemoglobin 3.4 g/dL, leukocytes 4.2 3 10 9 /L with 15% neutrophils, 52% lymphocytes, 33% blasts, and platelets 123 3 10 9 /L prompted a bone marrow examination which disclosed 96% replacement with leukemic lymphoblasts. By flow cytometry, the blasts expressed CD45, surface CD3, CD2, CD7, T-cell receptor g/d, CD11b, and CD13, with a subset of cells positive for CD56, a cell profile indicative of T-cell ALL. He was enrolled on the Total Therapy XV study and began remission induction therapy with high-dose methotrexate followed by prednisone once per day, vincristine once per week, daunorubicin once per week, and E coli-derived asparaginase 3 times per week. On day19 of treatment, 62.9% of bone marrow mononucleated cells were leukemic lymphoblasts by flow cytometry (31% of all cells were blasts by morphology). Three additional doses of asparaginase were given, and the remaining remission induction therapy consisted of cyclophosphamide, mercaptopurine, and cytarabine. On day 46, he attained morphologic remission (with 3% lymphoblasts), but MRD by flow cytometry was 5.82%. After consolidation treatment with 4 courses of high-dose methotrexate plus mercaptopurine as well as 1 course of re-intensification therapy with dexamethasone, etoposide, high-dose cytarabine, and asparaginase, MRD decreased to 0.18%. He attained MRD-negative status (,0.01%) after a second course of re-intensification treatment and subsequently underwent a matched-related allogeneic hematopoietic stem cell transplantation. He has remained in continuous complete remission for 11.9 years.

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Section: Specific Leukemia Subtypes Remain Prognostic In the Contextmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Minimal residual disease–guided therapy in childhood acute lymphoblastic leukemia

Campana

Pui

2017

Blood

115

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“…[16][17][18] However, approximately 20% of children relapse due to the persistence and continued proliferation of leukaemia cells that are resistant to therapy and many cases who relapse do not survive. 19 Treatment itself is extremely toxic and can be life threatening.…”

Section: -15mentioning

confidence: 99%

Functionalized Triblock Copolymer Vectors for the Treatment of Acute Lymphoblastic Leukemia

et al. 2017

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Accordingly, we describe the synthesis, characterisation and testing of a range of biocompatible triblock copolymer micelles as particle-based delivery vectors for the hydrophobic drug Parthenolide.The drug-loaded particles are produced via an emulsion-to-micelle transition method and the effects of introducing anionic and cationic surface charges on stability, drug sequestration, biocompatibility and efficacy are investigated. Significantly, we demonstrate high levels of efficacy in the organic solvent free systems against human mesenchymal stem cells and primary T-acute lymphoblastic leukaemia patient cells, highlighting the effectiveness of the delivery vectors for the treatment of acute lymphoblastic leukaemia.3

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“…152 . 153 Patients with greater than or equal to MRD of 10 -3 were allocated to receive HCT (n = 99).…”

Section: Mrd Assessment In Childhood Allmentioning

confidence: 99%

Acute Lymphoblastic Leukemia, Version 2.2015

Alvarnas

Brown

Aoun

et al. 2015

J Natl Compr Canc Netw

137

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Treatment of acute lymphoblastic leukemia (ALL) continues to advance, as evidenced by the improved risk stratification of patients and development of newer treatment options. Identification of ALL subtypes based on immunophenotyping and cytogenetic and molecular markers has resulted in the inclusion of Philadelphia-like ALL and early T-cell precursor ALL as subtypes that affect prognosis. Identification of Ikaros mutations has also emerged as a prognostic factor. In addition to improved prognostication, treatment options for patients with ALL have expanded, particularly with regard to relapsed/refractory ALL. Continued development of second-generation tyrosine kinase inhibitors and the emergence of immunotherapy, including blinatumomab and chimeric antigen receptor T-cell therapy, have improved survival. Furthermore, incorporation of minimal residual disease (MRD) monitoring has shown insight into patient outcomes and may lead to treatment modification or alternative treatment strategies in select populations. This excerpt focuses on the sections of the ALL guidelines specific to clinical presentation and diagnosis, treatment of relapsed/refractory ALL, and incorporation of MRD monitoring. To view the most recent complete version of these guidelines, visit NCCN.org. (J Natl Compr Canc Netw 2015;13:1240-1279 NCCN Categories of Evidence and ConsensusCategory 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate. Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate. These guidelines are also available on the Internet. For the latest update, visit NCCN.org.

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Augmented post-remission therapy for a minimal residual disease-defined high-risk subgroup of children and young people with clinical standard-risk and intermediate-risk acute lymphoblastic leukaemia (UKALL 2003): a randomised controlled trial

Cited by 268 publications

References 22 publications

Minimal residual disease–guided therapy in childhood acute lymphoblastic leukemia

Minimal residual disease–guided therapy in childhood acute lymphoblastic leukemia

Functionalized Triblock Copolymer Vectors for the Treatment of Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia, Version 2.2015

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