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). The rate of complete remission was 31% (95% CI, 17, 48%), the median DFS and OS were 20 weeks with a 1-year OS of 28%.77 However, there is still more that needs to be done to achieve a better response and overall survival in patients with relapsed/refractory B- and T-cell ALL. Jabbour E, O'Brien S, Konopleva M, Kantarjian H. New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia, Acute lymphoblastic leukemia with treatmentnaive Fanconi anemia, Bloom's syndrome. Updated results from phase II study of combination of hyper-CVAD (HCVAD) with ponatinib in frontline therapy of patients (pts) with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL)[abstract]. 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. Volumes | Blood Cancer Journal - Nature In a pre-B-ALL xenograft model, overall survival was improved with obinutuzumab compared to ritixumab.108 In clinical trials, obinutuzumab has been added to chlorambucil for treatment of adults with CLL and shown to prolong progression-free survival and improve complete response rate when compared to rituximab and chlorambucil.109 Taken together, these results suggest a role for obinutuzumab in CD20+ pre-B-ALL. Tavernier E, Boiron JM, Huguet F, Bradstock K, Vey N, Kovacsovics T et al. Research articles Bannerji R, Brown JR, Advani RH, Arnason J, O'Brien SM, Allan JN et al. 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. Thank you for visiting nature.com. Archive of "Blood Cancer Journal". - PMC - National Center for Nation-wide randomized comparative study of doxorubicin, vincristine and prednisolone combination therapy with and without L-asparaginase for adult acute lymphoblastic leukemia. National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894. Obinutuzumab was engineered to have enhanced affinity for the FcRIIIa receptor on effector cells and thus enhanced antibody-dependent cell-mediated cytotoxicity (ADCC).107 This compromises the ability of obinutuzumab to activate complement and predictably, CDC was inferior to that of rituximab and ofatumumab in vitro. Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemiaresults of the prospective multicenter LALA-94 trial. Cumulative doses were equivalent among the two treatment strategies. Blood Cancer Journal 4 Year Journal's Impact IF 2021-2022 | Trend A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. However, obinutuzumab induced direct cell death and ADCC more rapidly and effectively. Epratuzumab, a humanized monoclonal antibody targeting CD22: characterization of. Most of the clinical manifestations of ALL reflect the accumulation of malignant, poorly differentiated lymphoid cells within the bone marrow, peripheral blood, and, extramedullary sites. HCVAD has demonstrated similar efficacy to the ECOG trial with a 92% complete response rate and 32% 5-year disease-free survival.44 Several studies have suggested a benefit to using dexamethasone as opposed to prednisone due to the ability of dexamethasone to achieve higher concentrations in the CNS. Final results of a single institution experience with a pediatric-based regimen, the augmented Berlin-Frankfurt-Munster, in adolescents and young adults with acute lymphoblastic leukemia, and comparison to the hyper-CVAD regimen. Use of vincristine and prednisone alone. In some studies, CD25 expression has been as high as 30% of pre-B-ALL lymphoblasts, including 100% expression among the Ph-positive subset.124. Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia. However, toxicity was greatly improved by weekly dosing, with a significant reduction in fever, hepatotoxicity and veno-occlusive disease.89 A second phase 2 study of 35 patients with CD22+ ALL in second salvage or later showed similar complete response rate (66%) and median overall survival (7.4 months).90 Based on these results, Kantarjian et al.91 compared weekly dosing of InO to standard chemotherapy for relapsed/refractory ALL. Blood Cancer Journal. official website and that any information you provide is encrypted B-ALL with recurrent genetic abnormalities is further delineated based on the specific chromosomal rearrangement present (Table 1).20 In 2016, two new provisional entities were added to the list of recurrent genetic abnormalities and the hypodiploid was redefined as either low hypodiploid or hypodiploid with TP53 mutations.21 In adults, B-cell ALL accounts for ~75% of cases while T-cell ALL comprises the remaining cases. Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia. Younes A, Kim S, Romaguera J, Copeland A, Farial Sdc, Kwak LW et al. [PMC free article] [Google Scholar] Scavino HF, George JN, Sears DA. The most common rearrangements in Ph-like ALL involve the transmembrane receptor CRLF2, which signals through downstream JAK kinases. Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C et al. 's Oncology Group (COG) study (AALL07P1) [Abstract]. Acceptance of manuscripts is based on View full aims & scope Blood First Edition Another novel anti-CD20 monoclonal antibody, obinutuzumab, has shown promise in preclinical trials for CD20-positive B-ALL. Multi-Center US Intergroup Study of Intensive Chemotherapy Plus Dasatinib Followed By Allogeneic Stem Cell Transplant in Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Younger Than 60. Vall d'Hebron University Hospital. While 8590% of patients go into remission after induction therapy, there are subsets that are refractory to induction therapy. ); 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. Leukemia Research is an international journal which brings comprehensive and current information to all health care professionals involved in basic and applied clinical research in hematological malignancies. Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas. Accurate assessment of prognosis is central to the management of ALL. Zammarchi F, Williams DG, Adams L, Havenith K, Chivers S, D'Hooge F et al. Journal of Hematology & Oncology | Case report - BioMed Central Faderl et al.66 treated 90 patients (median age 34) with relapsed or refractory disease with HCVAD in which the dosing of vincristine, dexamethasone and asparaginase where intensified as follows: vincristine 2mg i.v. Shah NN, Stevenson MS, Yuan CM, Richards K, Delbrook C, Kreitman RJ et al. Blood for culturing was taken from the central venous catheter (CVC) before initiation of i.v. Free Books, Magazines & Care Journals for Cancer Patients 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). Visit the Nature Research journals metrics page for a description of these metrics. 104days to first decision for reviewed manuscripts only (Median), Usage:799,993 Article page views (in 2021)1,336,195 Downloads (in 2022)4,741 Altmetric mentions (2021), *2021Journal Citation ReportsScience Edition(Clarivate Analytics, 2022). Herrera L, Bostrom B, Gore L, Sandler E, Lew G, Schlegel PG et al. On the basis of what is known about prognostic factors in adult ALL, the National Comprehensive Cancer Network (NCCN) has developed recommendations to approach risk stratification.16 The National Cancer Institutes defines adolescent and young adults (AYA) to be those aged 1539 years. Accessibility In a pilot study at the Childrens Hospital of Philadelphia, Grupp et al.151 treated 53 children with relapsed/refractory ALL with lymphocyte depleting chemotherapy followed by CD19-directed CAR-Ts. SCImago Institutions Rankings SCImago Media Rankings SCImago Iber SCImago Research Centers Ranking SCImago Graphica Cortes J, Thomas D, Koller C, Giles F, Estey E, Faderl S et al. CD19 amplifies B lymphocyte signal transduction by regulating Src-family protein tyrosine kinase activation, CD19-dependent Activation of Akt Kinase in B-lymphocytes. Leukemia Research | Journal | ScienceDirect.com by Elsevier Select an AACR Journal - American Association for Cancer Research Mark Tyson, II, M.D., a Mayo Clinic urologic surgeon, explains: Blood in the urine may be the first sign of bladder cancer. The antibody was administered as a single-agent followed by the antibody in combination with standard re-induction chemotherapy. Raetz EA, Cairo MS, Borowitz MJ, Blaney SM, Krailo MD, Leil TA et al. Recent advances in pediatric hematology and oncology have improved overall survival and life expectancy in children with cancer and blood disease. Recent studies have suggested that the AYA population, defined as aged 1539, may benefit from treatment on pediatric-inspired protocols. In a multivariate analysis of 326 adolescent and adult patients with high-risk Ph-negative ALL treated in The Programa Espanol de Tratamientos en Hematologia (PETHEMA ALL-AR-03), Ribera et al.35 showed that poor MRD clearance, defined as levels >1 103 after induction and levels >5 104 after early consolidation by flow cytometry, was the only significant prognostic factor for disease-free and overall survival. 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.