In addition, a majority of patients that do achieve CR go on to relapse. Eigenfactor score*:0.01211 Chiarini F, Fala F, Tazzari PL, Ricci F, Astolfi A, Pession A et al. The journal is printed on paper that meets the requirements of ANSI/NISO Z39.48-1992 (Permanence of Paper). Web Policies FOIA HHS Vulnerability Disclosure. He is also in the editorial board of several other journals including Journal of Clinical Oncology, Blood, Cancer, Leukemia Research, Acta Haematologica, and Leukemia and Lymphoma. Recruitment is ongoing for a phase 3 trial of standard chemotherapy with or without bortezomib in children and young adults (age 230) with newly diagnosed T-cell ALL or T-cell lymphoblastic lymphoma ({"type":"clinical-trial","attrs":{"text":"NCT02112916","term_id":"NCT02112916"}}NCT02112916). Bassan R, Spinelli O, Oldani E, Intermesoli T, Tosi M, Peruta B et al. The addition of rituximab, a first-generation anti-CD20 monoclonal antibody, has improved outcomes in these patients, but resistance to rituximab represents a limitation to its use. Alvarnas JC, Brown PA, Aoun P, Ballen KK, Barta SK, Borate U et al. Lower incidence of meningeal leukemia when prednisone is replaced by dexamethasone in the treatment of acute lymphocytic leukemia, Treatment of acute lymphoblastic leukemia in adults. Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ et al. Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: results of a phase I study. Mullighan CG, Collins-Underwood JR, Phillips LA, Loudin ML, Liu W, Zhang J et al. EpratuzumabSN-38: A New AntibodyDrug Conjugate for the Therapy of Hematologic Malignancies. Acute lymphoblastic leukemia (ALL) is a malignant transformation and proliferation of lymphoid progenitor cells in the bone marrow, blood and extramedullary sites. The Journal will consider for publication original research, reviews, guidelines and letters that are considered to be of high impact in the field. The PACE trial60 demonstrated the ability of ponatinib to generate a cytogenetic response in 47% of Ph-positve ALL patients after dasatinib failure. JCR Rank*:HEMATOLOGY 12/78; ONCOLOGY 34/245 The 5-year OS rates based on these risk categories were 55, 34 and 5%, respectively.23, Although clinical factors play an important role in guiding therapy, cytogenetic changes have a significant role in risk determination. Given the high replicative potential of these T cells, this methods also offers the advantage of a profound antitumor response.150 However, the effects of direct mRNA insertion are transient and antitumor activity rarely persists beyond 7 days. In the meantime, to ensure continued support, we are displaying the site without styles Jabbour E, OBrien S, Thomas D, Sasaki K, Garcia-Manero G, Ravandi F et al. It consists of four cycles of hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternated with four cycles of high dose cytarabine and methotrexate.44 CNS prophylaxis with 4-16 doses of intrathecal chemotherapy depending on predetermined risk of CNS disease. ); those with EPOR and JAK2 rearrangements were sensitive to JAK kinase inhibitors (for example, ruxolitinib); and those with ETV6-NTRK3 fusion were sensitive to ALK inhibitors crizotinib. ISSN 2044-5385 (online). From molecules to medicine, from proteomics to prevention, the journals of the AACR cover the entire spectrum of cancer research. In subgroup analysis of 70 patients receiving second salvage therapy with a single agent (most commonly vinorelbine (6), clofarabine (5), nelarabine (4) and topotecan (4)), only 3 achieved a complete response.67, 68 Vincristine sulfate liposomes injection (VSLI) was developed to overcome the dosing and pharmacokinetic limitations of nonliposomal vincristine (VCR). While criteria differ between studies, in general high-risk disease is defined as Ph-positive ALL, elevated WBC count, CNS disease, high-risk gene rearrangements, or hypodiploidy. Gokbuget N, Kneba M, Raff T, Trautmann H, Bartram CR, Arnold R et al. The most common adverse events of InO treatment included thrombocytopenia and neutropenia. PBDs are a class of natural antibiotics derived from actinomycetes bacteria that inhibit cell division by binding in the minor groove of DNA and cross-linking strands of DNA. An official website of the United States government. Please select the journal that is most appropriate for your manuscript and follow the instructions to access the correct submission system. Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W et al. Eligible patients with high-risk disease and a matched donor, then underwent Allo-SCT. A Phase I study of Milademetan (DS3032b) in combination with low dose cytarabine with or without venetoclax in acute myeloid leukemia . Blood Cancer Discovery Research Impact Score* 4 OFFICIAL WEBSITE Ranking & Metrics Research Impact Score*: 4 Research Ranking (Medicine) 1039 Number of Best scientists*: 81 Documents by best scientists*: 45 Journal Information ISSN: 2643-3230 Publisher: Editors-in-Chief: Riccardo Dalla-Favera , Kenneth C. Anderson Theoretic risks of this method include malignant transformation of the engineered T cells if the CAR construct is inserted in such a way that it deregulates the expression of an oncogene.148 Another method of gene delivery involves direct transfer of an mRNA construct through electroporation.149 As no DNA is inserted into the genome of the T-cell, this eliminates the risk of malignant transformation. Bielorai B, Fisher T, Waldman D, Lerenthal Y, Nissenkorn A, Tohami T et al. Thank you for visiting nature.com. DeAngelo DJ, Yu D, Johnson JL, Coutre SE, Stone RM, Stopeck AT et al. Involvement of extramedullary sites commonly occurs and can cause lymphadenopathy, splenomegaly or hepatomegaly in 20% of patients.16, 17 CNS involvement at time of diagnosis occurs in 58% of patients and present most commonly as cranial nerve deficits or meningismus.3 T-cell ALL also may present with a mediastinal mass. Research articles DNA methylation-based subtype prediction for pediatric acute lymphoblastic leukemia. Patients over the age of 60 have particularly poor outcomes, with only 1015% long-term survival.22 Age is at least in part a surrogate for other prognosticators as the elderly tend to have disease with intrinsic unfavorable biology (for example, Philadelphia chromosome positive, hypodiploidy and complex karyotype), more medical comorbidities and inability to tolerate standard chemotherapy regimens but helps guide therapy nonetheless. Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM et al. Early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) in adolescents and adults: a high-risk subtype. A Phase I Study of a Combination of anti-CD19 and anti-CD22 Immunotoxins (Combotox) in Adult Patients with Refractory B-Lineage Acute Lymphoblastic Leukaemia. These results warrant further evaluation of denintuzumab mafodotin for relapsed/refractory ALL. CD22 is a B-lineage differentiation antigen expressed in B-cell ALL in 50100% of adults and 90% of children.78, 79, 80 Upon binding of an antibody, CD22 is rapidly internalized, thus making it an attractive target for delivering immunotoxin to leukemic cells.81, Epratuzumab is an unconjugated monoclonal antibody targeting CD22 that has been studied in pediatric and adult relapsed/refractory ALL. Recently, it has become standard practice to evaluate patients for minimal residual disease (MRD) using molecular techniques such as flow cytometry and PCR.28 Several studies have shown the importance of MRD in assigning risk.29, 30, 31, 32, 33, 34 Bruggemann et al.29 re-stratified standard-risk patients to low risk, intermediate risk and high risk with relapse rates of 0%, 47% and 94%, respectively, based on the persistence of elevated MRD, defined as >104. The Journal also features annotations, reviews, short reports, images in haematology and Letters to the Editor. With 80,000 Participants, the Largest Study of Its Kind Is the First to A novel, native-format bispecific antibody triggering T-cell killing of B-cells is robustly active in mouse tumor models and cynomolgus monkeys. Blood Cancer Journal (Blood Cancer J.) Nearly all of the patients developed cytokine release syndrome (CRS). A maximum tolerated dose (MTD) of 160mg/m2 administered once every three weeks was established. Gas stoves emit benzene, linked to cancer, a new Stanford study shows - NPR Long-term outcome after hyper-CVAD and imatinib (IM) for de novo or minimally treated Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL)[abstract]. However, with the development of TKIs, survival has improved and thus the Ph-status of all patients must be obtained prior to starting therapy. Frontline therapy is the same for B-cell ALL and T-cell ALL. Open access publication ensures that your work is easily discovered, accessed, and shared. 1New York University School of Medicine, New York, USA, 2Department of Hematology, New York University Perlmutter Cancer Center, New York, USA. In an analysis of 262 AYA patients aged 1621 on pediatric protocol CCG 1961, Nachman et al.63 reported a 5-year EFS of 68%. Awasthi A, Ayello J, Van de Ven C, Elmacken M, Sabulski A, Barth MJ et al. REGN1979 prevented the establishment of lymphoma xenografts and led to complete tumor regression in murine models.110 In addition, in a primate model, REGN1979 led to a complete and durable depletion of B-cells. The proposed mechanism of action of blinatumomab is that it engages T cells to activate a B-cell specific inflammatory and cytolytic response.70 Blinatumomab was first studied in patients with MRD positive ALL. Raff T, Gkbuget N, Lschen S, Reutzel R, Ritgen M, Irmer S et al. nature.com Blood Cancer Journal - Academic Accelerator Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial. Moreover, inhibition of proliferation was synergistic when NVP-BEZ235 was combined with cytotoxic agents.144 On the basis of this promising preclinical data, several clinical trials are underway to evaluate the use of mTOR and PI3K inhibitors in combination with multi-agent chemotherapy in the frontline and relapsed/refractory setting ({"type":"clinical-trial","attrs":{"text":"NCT01756118","term_id":"NCT01756118"}}NCT01756118, {"type":"clinical-trial","attrs":{"text":"NCT02484430","term_id":"NCT02484430"}}NCT02484430, {"type":"clinical-trial","attrs":{"text":"NCT01523977","term_id":"NCT01523977"}}NCT01523977, {"type":"clinical-trial","attrs":{"text":"NCT01403415","term_id":"NCT01403415"}}NCT01403415, {"type":"clinical-trial","attrs":{"text":"NCT01614197","term_id":"NCT01614197"}}NCT01614197 and {"type":"clinical-trial","attrs":{"text":"NCT01184885","term_id":"NCT01184885"}}NCT01184885). Hinman LM, Hamann PR, Wallace R, Menendez AT, Durr FE, Upeslacis J. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. Lee et al.154 reported a 66.7%% CR rate in a National Cancer Institute (NCI) intent-to-treat analysis of 20 children and young adults with ALL, with a median CAR-T persistence of 68 days. Frontiers in Hematology | Blood Cancer The British Journal of Haematology publishes original research papers in clinical, laboratory and experimental haematology. Pullarkat V, Slovak ML, Kopecky KJ, Forman SJ, Appelbaum FR. All submissions undergo an initial editorial review by the journal editors. Pre-Clinical Development of Adct-402, a Novel Pyrrolobenzodiazepine (PBD)-Based Antibody Drug Conjugate (ADC) Targeting CD19-Expressing B-Cell Malignancies. It is a humanized monoclonal antibody conjugated to a pyrrolobenzodiazepine (PBD). Submissions are judged on how well the manuscript and described research fit the editorial scope of the journal and its expectations of scientific excellence, importance, and impact on the wider cancer research community. A New Way to Fight Cancer - Scientific American Blog Network Dongen JJMv, v.d. FOIA Hurwitz CA, Silverman LB, Schorin MA, Clavell LA, Dalton VK, Glick KM et al. Total Cites. High incidence of Epstein Barr virus infection in childhood acute lymphocytic leukemia: a preliminary study. To obtain Ravandi F, O'Brien SM, Cortes JE, Thomas DM, Garris R, Faderl S et al. Guide to Authors | Blood Cancer Journal - Nature Twelve patients were bridged to Allo-SCT, with five long-term survivors.69 This study led to the accelerated approval of VSLI for salvage therapy in 2012. A second anti-CD19 conjugated monoclonal antibody, denintuzumab mafodotin, is currently in development. Aberrant STAT5 and PI3K/mTOR pathway signaling occurs in human CRLF2-rearranged B-precursor acute lymphoblastic leukemia. Subsequent analysis of MRC UKALL XII/ECOG E2993, identified cytogenetic subgroups of Ph-negative disease with inferior outcomes. Rearrangement of CRLF2 in B-progenitor and down syndrome associated acute lymphoblastic leukemia. Despite a reduction in CNS relapse and improved event-free survival, dexamethasone has increased risk of adverse events compared to prednisone. Leukemia Research | Journal | ScienceDirect.com by Elsevier Faderl S, Thomas DA, O'Brien S, Ravandi F, Garcia-Manero G, Borthakur G et al. Options of salvage therapy for relapsed/refractory (r/r) Ph-negative disease include augmented cytotoxic chemotherapy, reformulated single-agent chemotherapy and novel monoclonal antibodies. Milani L, Lundmark A, Kiialainen A, Nordlund J, Flaegstad T, Forestier E et al. Advani A, Coiffier B, Czuczman MS, Dreyling M, Foran J, Gine E et al. SA. In adults, 75% of cases develop from precursors of the B-cell lineage, with the remainder of cases consisting of malignant T-cell precursors. Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia. Within the United States, the incidence of ALL is estimated at 1.6 per 100000 population.1 In 2016 alone, an estimated 6590 new cases were diagnosed, with over 1400 deaths due to ALL (American Cancer Society). When compared to treatment with rituximab, treatment with REGN1979 led to significantly more profound depletion of B-cells.110 The safety of REGN1979 was established in a phase 1 trial of 25 patients with NHL and CLL. Research articles | Blood Cancer Journal - Nature To obtain CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia, Genetic modification of lymphocytes by retrovirus-based vectors. Links to Cancer Journals | OncologyPRO - ESMO Maude SL, Teachey DT, Porter DL, Grupp SA. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab. The mammalian target of rapamycin inhibitor RAD001 (everolimus) synergizes with chemotherapeutic agents, ionizing radiation and proteasome inhibitors in pre-B acute lymphocytic leukemia, Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy. Treatment of Philadelphia chromosomepositive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. ISSN 2044-5385 (online). CR was observed in 36 and 88% of whom were MRD negative, and with a median follow-up of 9 months, the median OS was 7.1 months.75 Future investigation is planned for the frontline use of blinatumomab for Ph-positive ALL in conjunction with TKIs.76 The toxicity profile of blinatumomab is acceptable. She was able to undergo Allo-SCT after CR was achieved with re-induction therapy and remained in CR 8 months after transplant.137 In a MD Anderson phase I trial of decitabine for relapsed/refractory ALL, decitabine was shown to have efficacy when used in combination with Hyper-CVAD for re-induction therapy.138 In addition, decitabine monotherapy is well tolerated and thus offers a potential treatment option for relapsed disease in patients that cannot tolerate multi-agent chemotherapy.
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