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Xiaohui Zhang - One of the best experts on this subject based on the ideXlab platform.
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both the subtypes of kit mutation and minimal residual disease are associated with prognosis in core binding factor acute myeloid leukemia a retrospective clinical cohort study in single center
Annals of Hematology, 2021Co-Authors: Wenbing Duan, Yu Wang, Qian Jiang, Xiaohong Liu, Xiaosu Zhao, Jinsong Jia, Jing Wang, Lizhong Gong, Ting Zhao, Xiaohui ZhangAbstract:Core binding factor acute myeloid leukemia (CBF-AML), including cases with KIT mutation, is currently defined as a low-risk AML. However, some patients have poor response to treatment, and the prognostic significance of KIT mutation is still controversial. This study aimed to explore the prognostic significance of different KIT mutation subtypes and minimal residual disease (MRD) in CBF-AML. We retrospectively evaluated continuous patients diagnosed with CBF-AML in our center between January 2014 and April 2019. Of the 215 patients, 147 (68.4%) and 68 (31.6%) patients were RUNX1-RUNX1T1- and CBFB-MYH11 positive, respectively. KIT mutations were found in 71 (33.0%) patients; of them, 38 (53.5%) had D816/D820 mutations. After excluding 10 patients who died or were lost to follow-up within a half year, 42.0% (n = 86) of the remaining 205 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). An MRD > 0.1% at the end of two cycles of Consolidation predicted relapse (P 0.1% at the end of two cycles of Consolidation were independent adverse factors affecting relapse-free survival (RFS) and overall survival (OS). Allo-HSCT could improve RFS (74.4% vs. 34.6%, P 0.1% at the end of two cycles of Consolidation Chemotherapy predicted poor survivals, and allo-HSCT can improve the survival of properly identified patients.
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minimal residual disease and graft vs host disease guided multiple Consolidation Chemotherapy and donor lymphocyte infusion prevent second acute leukemia relapse after allotransplant
Journal of Hematology & Oncology, 2016Co-Authors: Chenhua Yan, Yu Wang, Yuhong Chen, Wei Han, Fengrong Wang, Yuqian Sun, Yao Chen, Xiaohui ZhangAbstract:Persons with acute leukemia relapsing after allotransplant and who respond to anti-leukemia interventions are at high risk of a second relapse. We studied the impact of minimal residual disease (MRD)- and graft-vs.-host disease (GvHD)-guided multiple Consolidation Chemotherapy and donor lymphocyte infusions (DLIs) to prevent second relapse in patients with acute leukemia relapsing post-transplant and who achieved complete remission after induction Chemotherapy and DLI. Forty-seven subjects with acute leukemia relapsing after an allotransplant and who achieved complete remission after post-relapse induction Chemotherapy and DLI were eligible. The use of Consolidation Chemotherapy and DLI was guided by the results of MRD testing and whether or not DLI caused acute and/or chronic GvHD. Outcomes were compared with those of 34 similar historical controls who did not receive Consolidation Chemotherapy and DLIs after induction Chemotherapy and DLI. One-year cumulative incidence of relapse (CIR; 22 % 95 % confidence interval (10, 35 %) vs. 56 % (39, 73 %); P < 0.0001), leukemia-free survival (LFS; 71 % (57, 84 %) vs. 35 % (19, 51 %); P < 0.0001), and survival (78 % (66, 90 %) vs. 44 % (27, 61 %); P < 0.0001) was significantly better in subjects than controls. In multivariate analyses, no chronic GvHD after therapy (hazard ratio (HR) = 3.56 (1.09, 11.58); P = 0.035) and a positive MRD test after therapy (HR = 21.04 (4.44, 94.87); P < 0.0001) were associated with an increased CIR. These data suggest MRD- and GvHD-guided multiple Consolidation Chemotherapy and DLIs reduce CIR and increase LFS and survival compared with controls in persons relapsing after allotransplant for acute leukemia. ChiCTR-ONC-12002912 . Donor lymphocyte infusion for the treatment of leukemia relapse following allogeneic hematopoeitic stem cell transplant.
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minimal residual disease and graft vs host disease guided multiple Consolidation Chemotherapy and donor lymphocyte infusion prevent second acute leukemia relapse after allotransplant
Journal of Hematology & Oncology, 2016Co-Authors: Chenhua Yan, Yu Wang, Yuhong Chen, Wei Han, Fengrong Wang, Yuqian Sun, Yao Chen, Jingzhi Wang, Huan Chen, Xiaohui ZhangAbstract:Background Persons with acute leukemia relapsing after allotransplant and who respond to anti-leukemia interventions are at high risk of a second relapse. We studied the impact of minimal residual disease (MRD)- and graft-vs.-host disease (GvHD)-guided multiple Consolidation Chemotherapy and donor lymphocyte infusions (DLIs) to prevent second relapse in patients with acute leukemia relapsing post-transplant and who achieved complete remission after induction Chemotherapy and DLI.
Eunice S Wang - One of the best experts on this subject based on the ideXlab platform.
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crenolanib versus midostaurin combined with induction and Consolidation Chemotherapy in newly diagnosed flt3 mutated aml
Journal of Clinical Oncology, 2019Co-Authors: Richard Stone, Kendra L. Sweet, Aaron David Goldberg, Amir T. Fathi, Eunice S Wang, Boo MessahelAbstract:TPS7068Background: Despite the approval of multi-targeted protein kinase inhibitor midostaurin for use in combination with Chemotherapy which improves 5-year survival in newly diagnosed (NDx) acute...
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bortezomib added to daunorubicin and cytarabine during induction therapy and to intermediate dose cytarabine for Consolidation in patients with previously untreated acute myeloid leukemia age 60 to 75 years calgb alliance study 10502
Journal of Clinical Oncology, 2013Co-Authors: Eyal C. Attar, Martha Wadleigh, Philip C Amrein, Bayard L Powell, Daniel J Deangelo, Jeffrey L Johnson, Peter M Voorhees, Gerard Lozanski, Jonathan E Kolitz, Eunice S WangAbstract:Purpose The purpose of this study was to determine remission induction frequency when bortezomib was combined with daunorubicin and cytarabine in previously untreated older adults with acute myeloid leukemia (AML) and safety of bortezomib in combination with Consolidation Chemotherapy consisting of intermediate-dose cytarabine (Int-DAC). Patients and Methods Ninety-five adults (age 60 to 75 years; median, 67 years) with previously untreated AML (including therapy-related and previous myelodysplastic syndrome) received bortezomib 1.3 mg/m2 intravenously (IV) on days 1, 4, 8, and 11 with daunorubicin 60 mg/m2 on days 1 through 3 and cytarabine 100 mg/m2 by continuous IV infusion on days 1 through 7. Patients who achieved complete remission (CR) received up to two courses of Consolidation Chemotherapy with cytarabine 2 gm/m2 on days 1 through 5 with bortezomib. Three cohorts with escalating dose levels of bortezomib were tested (0.7, 1.0, and 1.3 mg/m2). Dose-limiting toxicities were assessed during the firs...
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a phase ii study of bortezomib added to standard daunorubicin and cytarabine during induction therapy and to intermediate dose cytarabine int dac for Consolidation in patients with previously untreated acute myeloid leukemia aml age 60 75 years calgb study 10502
Journal of Clinical Oncology, 2012Co-Authors: Eyal C. Attar, Martha Wadleigh, Philip C Amrein, Bayard L Powell, Daniel J Deangelo, Jeffrey L Johnson, Peter M Voorhees, Gerard Lozanski, Jonathan E Kolitz, Eunice S WangAbstract:6526 Background: We conducted a clinical trial to determine the complete remission (CR) rate in older AML patients treated with bortezomib (Bz) plus daunorubicin and cytarabine induction therapy and the maximal tolerated dose (MTD) of Bz when added to Int-DAC Consolidation therapy. Methods: Ninety-five adults (60-75 yrs old; median, 67) with previously untreated AML (including therapy-related and prior MDS) received Bz 1.3 mg/m2 IV on days 1, 4, 8 and 11 with daunorubicin 60 mg/m2 on days 1-3 and cytarabine 100 mg/m2 by continuous IV infusion on days 1-7. Patients who achieved a CR received 2 courses of Consolidation Chemotherapy with cytarabine 2 gm/m2 over 3 hours on days 1-5 (Int-DAC) with Bz administered on days 1, 4, 8 and 11. Three cohorts with escalating dose levels of Bz were tested (0.7, 1.0, and 1.3 mg/m2). Dose limiting toxicities were assessed during the first cycle of Consolidation. Predictors of response, including CD74 expression, were assessed. Results: The CR frequency was 65% (62/95). An...
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phase ii study of bortezomib added to standard daunorubicin and cytarabine induction and dose escalation of bortezomib with intermediate dose cytarabine Consolidation therapy for patients with previously untreated acute myeloid leukemia age 60 75 years cancer and leukemia group b calgb study 10502
Blood, 2010Co-Authors: Eyal C. Attar, Martha Wadleigh, Philip C Amrein, Bayard L Powell, Daniel J Deangelo, Peter M Voorhees, Eunice S Wang, Jonathan E Kolitz, Kathleen Donohue, William BlumAbstract:Abstract Abstract 331 We previously demonstrated that bortezomib can be safely added to induction Chemotherapy in patients with AML. We conducted a clinical trial in order to determine (a) the complete remission (CR) frequency in older patients treated with bortezomib plus daunorubicin and cytarabine induction Chemotherapy and (b) the maximal tolerated dose (MTD) of bortezomib added to intermediate-dose cytarabine Consolidation Chemotherapy. Adults ages 60–75 with previously untreated, including therapy-related, AML received bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 with daunorubicin 60 mg/m2/day on days 1–3 and cytarabine100 mg/m2/day by continuous IV infusion on days 1–7. A bone marrow biopsy was conducted on day 18. For patients with residual disease, reinduction, consisting of identical doses of daunorubicin on days 1 and 2, cytarabine days 1–5, and bortezomib days 1 and 4, was administered. The phase II induction portion of this trial was designed to discriminate between true CR rates of no more than 45% versus at least 65%. If at least 25 CRs (at least 56%) were observed among the 45 evaluable patients, the regimen was to be considered worthy of further testing. A two-stage design was employed, which yielded greater than 90% power to detect a true response rate of at least 65%. There was at least a 0.91 probability of a negative result if the true response rate was no more than 45%, with at least 0.69 probability of early negative stopping. Patients who achieved a CR or partial remission received Consolidation Chemotherapy consisting of cytarabine 2 gm/m2/day over 3 hours on days 1–5 (Int-DAC). Bortezomib was administered on days 1, 4, 8 and 11. Three cohorts of escalating dose levels of bortezomib were tested (0.7, 1.0, and 1.3 mg/m2). Patients could receive up to two courses of Consolidation. Dose limiting toxicities (DLTs) were assessed during the first cycle of Consolidation and were defined as grade 3 or 4 neurotoxicity, prolonged grade 4 myelosuppression, or any ≥ grade 3 toxicity that did not resolve to at least grade 2 by day 42. A total of 98 patients were enrolled. Of the first 45 patients, 30 (67%) patients achieved CR, thereby excluding a true CR incidence of In Consolidation, there were no DLTs within the first two 3-person cohorts treated with bortezomib 0.7 and 1.0 mg/m2. One of the first 3 patients treated with Int-DAC and bortezomib at 1.3 mg/m2 sustained a DLT consisting of grade 3 sensory neuropathy. There were no DLTs in the second cohort of 3 patients treated with bortezomib at 1.3 mg/m2 and Int-DAC. Thus, an additional 11 patients were treated with 1.3 mg/m2 in Consolidation. Grade 3 and 4 non-hematologic and non-infectious toxicities observed in at least 10% of patients consisted of rash (14%), diarrhea (13%), and pain (13%). Among the first 45 patients treated with induction and the 23 patients assessed for DLT in Consolidation, overall grade 3 and 4 neurotoxicities were sensory neuropathy (13%), motor neuropathy (7%), confusion (2%), mood alteration (2%), cranial neuropathy (2%), somnolence (2%), and syncope (2%). There were no grade 3 or 4 pulmonary toxicities observed and no deaths during Consolidation within the patient cohorts assessed for DLT. In conclusion, the addition of bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 to standard “3+7” daunorubicin and cytarabine induction Chemotherapy for AML is tolerable and results in a remission rate at least as high as would be expected with “3+7” alone in older patients. The maximum tested dose of bortezomib given for Consolidation Chemotherapy was 1.3 mg/m2 which proved to be tolerable in combination with Int-DAC. All patients have now completed treatment, and final response and toxicity data are being analyzed. CR data within clinically important subsets will be presented. The duration of relapse-free survival among patients in CR will influence planning a possible phase III trial. Disclosures: Off Label Use: Botezomib in AML. Blum: Millennium: Research Funding.
Daniel J Deangelo - One of the best experts on this subject based on the ideXlab platform.
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the use of prophylactic anticoagulation during induction and Consolidation Chemotherapy in adults with acute lymphoblastic leukemia
Journal of Thrombosis and Thrombolysis, 2018Co-Authors: Daniel J Deangelo, Donna Neuberg, Rachael F Grace, Kristen E Stevenson, Stephen E Sallan, Yasser Abou Mourad, Julie Bergeron, Matthew D SeftelAbstract:Treatment for acute lymphoblastic leukemia (ALL) in adults confers a high risk of venous thromboembolic (VTE) complications. We describe the implementation and results of prophylactic anticoagulation guidelines in adults (18-50 years) treated on a Dana-Farber Cancer Institute ALL pediatric inspired consortium protocol from 2007 to 2013. A high rate of asparaginase related toxicity events, including thrombosis, resulted in a protocol amendment adding guidelines for prophylactic anticoagulation and a modified asparaginase dose and schedule. After excluding patients with Philadelphia positive ALL, a cohort of 36 patients were treated after the protocol amendment with prophylactic anticoagulation and compared to 49 patients who received no prophylactic anticoagulation. Bleeding complications were not significantly different in those treated with prophylactic anticoagulation compared with those enrolled prior to the amendment (p = 0.26). No patients on prophylactic anticoagulation had grade ≥ 3 bleeding. Prior to the amendment, the 2 year cumulative incidence of VTE post-induction was 41% compared to 28% while on prophylactic anticoagulation (p = 0.32). The 2 year cumulative incidence pulmonary embolus pre-amendment was 16% compared with 8% post-amendment (p = 0.34). Prophylactic anticoagulation can be safely administered to adults with ALL without increasing the number or severity of bleeding events and, in addition to modifications in the asparaginase regimen, resulted in a reduction in the cumulative incidence of VTE.
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bortezomib added to daunorubicin and cytarabine during induction therapy and to intermediate dose cytarabine for Consolidation in patients with previously untreated acute myeloid leukemia age 60 to 75 years calgb alliance study 10502
Journal of Clinical Oncology, 2013Co-Authors: Eyal C. Attar, Martha Wadleigh, Philip C Amrein, Bayard L Powell, Daniel J Deangelo, Jeffrey L Johnson, Peter M Voorhees, Gerard Lozanski, Jonathan E Kolitz, Eunice S WangAbstract:Purpose The purpose of this study was to determine remission induction frequency when bortezomib was combined with daunorubicin and cytarabine in previously untreated older adults with acute myeloid leukemia (AML) and safety of bortezomib in combination with Consolidation Chemotherapy consisting of intermediate-dose cytarabine (Int-DAC). Patients and Methods Ninety-five adults (age 60 to 75 years; median, 67 years) with previously untreated AML (including therapy-related and previous myelodysplastic syndrome) received bortezomib 1.3 mg/m2 intravenously (IV) on days 1, 4, 8, and 11 with daunorubicin 60 mg/m2 on days 1 through 3 and cytarabine 100 mg/m2 by continuous IV infusion on days 1 through 7. Patients who achieved complete remission (CR) received up to two courses of Consolidation Chemotherapy with cytarabine 2 gm/m2 on days 1 through 5 with bortezomib. Three cohorts with escalating dose levels of bortezomib were tested (0.7, 1.0, and 1.3 mg/m2). Dose-limiting toxicities were assessed during the firs...
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a phase ii study of bortezomib added to standard daunorubicin and cytarabine during induction therapy and to intermediate dose cytarabine int dac for Consolidation in patients with previously untreated acute myeloid leukemia aml age 60 75 years calgb study 10502
Journal of Clinical Oncology, 2012Co-Authors: Eyal C. Attar, Martha Wadleigh, Philip C Amrein, Bayard L Powell, Daniel J Deangelo, Jeffrey L Johnson, Peter M Voorhees, Gerard Lozanski, Jonathan E Kolitz, Eunice S WangAbstract:6526 Background: We conducted a clinical trial to determine the complete remission (CR) rate in older AML patients treated with bortezomib (Bz) plus daunorubicin and cytarabine induction therapy and the maximal tolerated dose (MTD) of Bz when added to Int-DAC Consolidation therapy. Methods: Ninety-five adults (60-75 yrs old; median, 67) with previously untreated AML (including therapy-related and prior MDS) received Bz 1.3 mg/m2 IV on days 1, 4, 8 and 11 with daunorubicin 60 mg/m2 on days 1-3 and cytarabine 100 mg/m2 by continuous IV infusion on days 1-7. Patients who achieved a CR received 2 courses of Consolidation Chemotherapy with cytarabine 2 gm/m2 over 3 hours on days 1-5 (Int-DAC) with Bz administered on days 1, 4, 8 and 11. Three cohorts with escalating dose levels of Bz were tested (0.7, 1.0, and 1.3 mg/m2). Dose limiting toxicities were assessed during the first cycle of Consolidation. Predictors of response, including CD74 expression, were assessed. Results: The CR frequency was 65% (62/95). An...
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comparison of autologous stem cell transplantation versus Consolidation Chemotherapy for patients with cytogenetically normal acute myeloid leukemia cn aml and flt3itd
American Journal of Hematology, 2011Co-Authors: Harshabad Singh, Martha Wadleigh, Philip C Amrein, Daniel J Deangelo, Lillian Werner, Salma Asali, Karen K Ballen, Ilene Galinsky, Brian M Wolpin, Joseph PidalaAbstract:Acute myeloid leukemia (AML) is a relatively resistant myeloid neoplasm commonly occurring in older patients (median age at diagnosis is 67 years).(1) AML outcomes are heterogeneous, with cure rates ranging from essentially zero in subsets of older patients to 80% in younger patients with favorable disease features.(2) Among various risk factors, karyotype is an important independent risk factor and is used to divide AML into good, intermediate and poor prognostic groups.(3, 4) The normal karyotype group is considered to be at intermediate risk and constitutes approximately 40% of patients with AML. However, even these patients have a heterogeneous outcome, with OS rates ranging from 24% to 42%. This group may be further stratified according to the presence or absence of mutations or expression levels of various molecular markers. (5, 6) FLT3ITD represents a segmental duplication within the juxtamembrane domain of FLT3 receptor and is found in 30–40% of CN-AML patients.(8) FLT3ITD is associated with monocytoid differentiation (FAB M5), higher white blood cell counts, increased serum lactate dehydrogenase, and higher peripheral and bone marrow blasts compared to wild-type FLT3 (wt FLT3) CN-AML patients.(9, 10) Patients with this mutation have similar complete remission (CR) rates but significantly increased relapse rates and a reduced OS as compared to patients with wt FLT3.(9–11) It has been further identified that the allelic ratio of mutant:wt transcripts impacts prognosis.(8, 10, 12–14) The length of the duplicated fragment and its specific location within FLT3 may also affect prognosis.(13, 15–17) Overall, CN-AML patients with a FLT3ITD mutation have an inferior prognosis compared to those with a wtFLT3. There is considerable debate over the best postremission treatment for FLT3ITD CN-AML patients.(18, 19) Another mutation, FLT3TKD, is a point mutation in the tyrosine kinase domain of the receptor and is found in approximately 10% of all CN-AML patients.(8) Similar to patients with FLT3ITD mutations, patients with FLT3TKD also have an elevated white blood cell count at presentation. However, the prognostic significance of TKD mutations is unclear.(9–11, 22–24) We analyzed patients with CN-AML and mutated FLT3 to determine the relationship between different postremission therapies and outcome. Our study includes all consecutively treated patients at our institutions who consented for determination of their FLT3 mutation status at diagnosis on a research study. The choice of post-remission therapy was not randomized but instead reflects the availability of open protocols and physician and patient preference. There were a total of 37 patients who were below the age of 60 years at diagnosis and had a normal karyotype with a FLT3ITD. Treatment histories of these patients are described in supplemental material (Fig S1). Patients who were positive for both the ITD and TKD mutation were included in the ITD group (n=7) because these individuals have similar outcomes as those with an isolated ITD mutation.(23, 27) The remission frequency for this patient population was 81.1% (30/37). There were 19 newly diagnosed AML patients with an isolated TKD mutation who were under the age of 60 and had a normal karyotype. Their treatment histories are shown in Supplemental Figure 2 (Fig S2). The CR frequency for this group was 89.5% (17/19). Excluded from our research question were 4/37 patients with FLT3ITD and 1/19 with FLT3TKD who received allogeneic SCT in CR1. However, we included patients who received an allogeneic SCT after first relapse (ITD: n=5; TKD: n=3). Time dependent covariate analysis indicated that receiving an allogeneic SCT after relapse did not significantly improve OS (p=0.62 for the ITD group and 0.83 for the entire cohort of patients; there were too few patients in the TKD group for this analysis to be conducted). Patient characteristics such as age at diagnosis, time to CR1, WBC at diagnosis and gender are in presented in Table 1. These features were balanced between those who were assigned to autologous SCT or Consolidation Chemotherapy in both ITD and TKD patient groups. Also, there was no significant difference in the distribution of allelic ratio and ITD length within the two treatment groups for ITD patients (p=.22 and .2, respectively). We then studied the relationship between baseline characteristics and clinical outcome and we found that among the characteristics listed in Table 1, only female gender was associated with a better DFS in patients with an isolated TKD mutation (p=.03). Table 1 Patient characteristics for ITD and TKD positive patients who initiated autologous SCT or Consolidation Chemotherapy. P value corresponds to comparisons within each type of mutation and not across FLT3 mutation types. We also found that an allelic ratio of >.2 was associated with a worse DFS and OS in ITD mutation positive patients who had initiated postremission autologous SCT or Chemotherapy (n=21) (p=0.01 and 0.04). A value of 0.2 was determined as the optimal cut point by recursive partitioning analysis. The median length of the ITD in patients who initiated postremission autologous SCT or Chemotherapy was 33bps (n=21) (Range=17–210). For patients with more than one mutation (n=5), the length of the most dominant mutation was chosen for analysis. In our study, the ITD length was not associated with DFS or OS. No other variable was noted to influence DFS or OS. We next analyzed the survival of patients with an isolated TKD mutation according to type of postremission therapy. For the 7 patients who initiated autologous SCT compared to the 9 patients who initiated Consolidation Chemotherapy, there was no significant difference in DFS or OS (p=0.97 and 0.082, respectively). Similarly, there was no significant difference in DFS or OS for patients who received a stem cell infusion or at least 3 cycles of Consolidation Chemotherapy (n=6 and 8, respectively; p=0.78 and 0.25, respectively). On the other hand, patients with an ITD mutation who initiated autologous SCT (n=10) had an improved DFS compared to those who initiated Consolidation Chemotherapy (n=11) (p=0.05) (Figure IA), however there was no difference in OS (p=.27) (Figure IB). Since some patients in each cohort (n=2 for autologous SCT and n=2 for Consolidation Chemotherapy) did not complete the initiated postremission therapy, defined as having received infusion of stem cells or at least 3 cycles of Chemotherapy, respectively, we then compared the survival in patients who had completed their postremission therapy as defined above. Again, we found that autologous SCT (n=8) was significantly associated with an improved DFS compared to Consolidation Chemotherapy (n=9) (p=.03) while no significant difference in OS was observed (p=.19). Figure 1 A. DFS in months of patients with FLT3R ITD according to type of postremission therapy initiated Lastly we compared the survival outcomes of patients with ITD versus TKD who achieved CR and progressed to postremission therapy, excluding those who underwent allogeneic SCT in CR1. Patients with an isolated TKD mutation (n=16) had a significantly longer DFS and OS compared to patients with ITD (n=21) (p=.031 and .014). In summary, we analyzed the outcome of AML patients under 60 years with normal cytogenetics and FLT3 mutations according to the type of postremission therapy they initiated or received. Younger adults with ITD who initiated or received autologous SCT had an improved DFS compared to Consolidation Chemotherapy. OS, however, was not different for the two treatment modalities. For patients with isolated TKD, there was no difference in DFS or OS of patients who received autologous SCT versus Consolidation Chemotherapy. There is considerable debate about the optimal postremission therapy for CN-AML patients with a FLT3ITD mutation. Current options vary among allogeneic SCT, autologous SCT, and/or Chemotherapy along with use of novel FLT3R inhibitors. In general, comparisons of autologous SCT and Chemotherapy have not shown a clear difference in outcome when all AML patients are included. The potential benefit of autologous SCT in AML subgroups has not been extensively studied. Yoshimoto et al., in a retrospective analysis, demonstrated a similar DFS and OS for patients with a wtFLT3 versus a FLT3ITD who underwent an autologous SCT in CR1.(28) Bornhauser et al. also noted a decrease in probability of relapse and an improvement in OS for patients with FLT3ITD who received an autologous SCT in CR1 compared to those receiving Chemotherapy alone.(19) In contrast, Schlenk et al. found no difference in relapse free survival and OS between normal cytogenetic patients receiving autologous SCT or conventional Consolidation Chemotherapy in both FLT3ITD and wt FLT3 patient groups.(18) Our data raise the question as to whether autologous SCT may be considered over Consolidation Chemotherapy for patients with ITD who are not undergoing allogeneic SCT or therapy with a FLT3 inhibitor.
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comparison of high dose Chemotherapy with autologous stem cell rescue asct versus Consolidation Chemotherapy for patients 60 with cytogenetically normal aml cn aml and flt3 itd
Blood, 2010Co-Authors: Harshabad Singh, Martha Wadleigh, Philip C Amrein, Daniel J Deangelo, Donna Neuberg, Lillian Werner, Karen K Ballen, Ilene Galinsky, Edward A Fox, Richard StoneAbstract:Abstract 3555 Introduction: Cytogenetic status represents a major prognostic factor for individuals with AML. However, approximately 50% of individuals have CN-AML and, within this cohort, genetic features have important prognostic and therapeutic implications. Mutations in the FLT3 receptor are found in 30–40% of patients with CN-AML. While the FLT3-internal tandem duplication (ITD) is associated with a poor DFS and OS when compared to CN-AML patients with a wtFLT3R, the prognostic significance of the FLT3-tyrosine kinase domain (TKD) mutation is less clear. There is considerable debate over the best postremission treatment for CN-AML patients who have a FLT3ITD. Our primary objective was to determine the relationship between different postremission therapies and outcome in CN-AML patients with FLT3 mutations. Methods: We retrospectively reviewed the outcomes of newly diagnosed AML patients at the Massachusetts General Hospital and Dana-Farber Cancer Institute/Brigham and Women Hospital between 2002–2008 who were younger than 60 years of age, had a normal karyotype, and had a FLT3ITD and/or TKD mutation at diagnosis. The method of Kaplan and Meier was used to estimate DFS and OS; groups were compared using the log-rank test. A p-value less than .05 was interpreted as statistically significant. Results: At diagnosis, there were 37 patients with an ITD mutation (7 also had a TKD mutation) and 19 patients with an isolated TKD mutation at diagnosis. Patients who received an allogeneic SCT were not included in the analysis. ITD positive patients with an allelic ratio (AR) of mutant to wt FLT3 >.2 had a significantly worse DFS and OS than those with an AR ITD positive patients who underwent an autologous SCT in CR1 had an improved DFS (Figure 1) but similar OS compared to those who received a minimum of three cycles of Consolidation Chemotherapy (n=8 and 9, respectively) (p=.026 for DFS and .19 for OS). In contrast, for individuals with an isolated TKD mutation, DFS and OS were similar for those who received an autologous SCT (n=6) or Consolidation Chemotherapy (n=8) (p=.78 for DFS and .25 for OS, respectively). Among patients who initiated postremission therapy, we observed that individuals with an isolated TKD (n=16 for auto SCT or Chemotherapy) had an improved DFS and OS compared to ITD patients (n=11) treated with Chemotherapy. However, the DFS and OS of TKD patients (n=16 for auto SCT or Chemotherapy) versus ITD patients (n=10) who initiated auto SCT was similar (p=.44 for DFS and .09 for OS) (Figure 2A and B, respectively). Conclusion: Our findings suggest that patients with isolated TKD have a similar prognosis regardless of the type of postremission therapy utilized, and that their prognosis is superior to that of patients with ITD. For patients with ITD, autologous SCT in CR1 is associated with improved DFS compared to Consolidation Chemotherapy alone and is similar to that of patients with TKD. Our data raise the question as to whether autologous SCT should be preferred over Consolidation Chemotherapy for patients with ITD who are not undergoing allogeneic SCT in CR1 or therapy with a FLT3 inhibitor. Disclosures: DeAngelo: Deminimus: Consultancy. Stone: Novartis: Consultancy.
Yu Wang - One of the best experts on this subject based on the ideXlab platform.
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both the subtypes of kit mutation and minimal residual disease are associated with prognosis in core binding factor acute myeloid leukemia a retrospective clinical cohort study in single center
Annals of Hematology, 2021Co-Authors: Wenbing Duan, Yu Wang, Qian Jiang, Xiaohong Liu, Xiaosu Zhao, Jinsong Jia, Jing Wang, Lizhong Gong, Ting Zhao, Xiaohui ZhangAbstract:Core binding factor acute myeloid leukemia (CBF-AML), including cases with KIT mutation, is currently defined as a low-risk AML. However, some patients have poor response to treatment, and the prognostic significance of KIT mutation is still controversial. This study aimed to explore the prognostic significance of different KIT mutation subtypes and minimal residual disease (MRD) in CBF-AML. We retrospectively evaluated continuous patients diagnosed with CBF-AML in our center between January 2014 and April 2019. Of the 215 patients, 147 (68.4%) and 68 (31.6%) patients were RUNX1-RUNX1T1- and CBFB-MYH11 positive, respectively. KIT mutations were found in 71 (33.0%) patients; of them, 38 (53.5%) had D816/D820 mutations. After excluding 10 patients who died or were lost to follow-up within a half year, 42.0% (n = 86) of the remaining 205 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). An MRD > 0.1% at the end of two cycles of Consolidation predicted relapse (P 0.1% at the end of two cycles of Consolidation were independent adverse factors affecting relapse-free survival (RFS) and overall survival (OS). Allo-HSCT could improve RFS (74.4% vs. 34.6%, P 0.1% at the end of two cycles of Consolidation Chemotherapy predicted poor survivals, and allo-HSCT can improve the survival of properly identified patients.
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minimal residual disease and graft vs host disease guided multiple Consolidation Chemotherapy and donor lymphocyte infusion prevent second acute leukemia relapse after allotransplant
Journal of Hematology & Oncology, 2016Co-Authors: Chenhua Yan, Yu Wang, Yuhong Chen, Wei Han, Fengrong Wang, Yuqian Sun, Yao Chen, Xiaohui ZhangAbstract:Persons with acute leukemia relapsing after allotransplant and who respond to anti-leukemia interventions are at high risk of a second relapse. We studied the impact of minimal residual disease (MRD)- and graft-vs.-host disease (GvHD)-guided multiple Consolidation Chemotherapy and donor lymphocyte infusions (DLIs) to prevent second relapse in patients with acute leukemia relapsing post-transplant and who achieved complete remission after induction Chemotherapy and DLI. Forty-seven subjects with acute leukemia relapsing after an allotransplant and who achieved complete remission after post-relapse induction Chemotherapy and DLI were eligible. The use of Consolidation Chemotherapy and DLI was guided by the results of MRD testing and whether or not DLI caused acute and/or chronic GvHD. Outcomes were compared with those of 34 similar historical controls who did not receive Consolidation Chemotherapy and DLIs after induction Chemotherapy and DLI. One-year cumulative incidence of relapse (CIR; 22 % 95 % confidence interval (10, 35 %) vs. 56 % (39, 73 %); P < 0.0001), leukemia-free survival (LFS; 71 % (57, 84 %) vs. 35 % (19, 51 %); P < 0.0001), and survival (78 % (66, 90 %) vs. 44 % (27, 61 %); P < 0.0001) was significantly better in subjects than controls. In multivariate analyses, no chronic GvHD after therapy (hazard ratio (HR) = 3.56 (1.09, 11.58); P = 0.035) and a positive MRD test after therapy (HR = 21.04 (4.44, 94.87); P < 0.0001) were associated with an increased CIR. These data suggest MRD- and GvHD-guided multiple Consolidation Chemotherapy and DLIs reduce CIR and increase LFS and survival compared with controls in persons relapsing after allotransplant for acute leukemia. ChiCTR-ONC-12002912 . Donor lymphocyte infusion for the treatment of leukemia relapse following allogeneic hematopoeitic stem cell transplant.
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minimal residual disease and graft vs host disease guided multiple Consolidation Chemotherapy and donor lymphocyte infusion prevent second acute leukemia relapse after allotransplant
Journal of Hematology & Oncology, 2016Co-Authors: Chenhua Yan, Yu Wang, Yuhong Chen, Wei Han, Fengrong Wang, Yuqian Sun, Yao Chen, Jingzhi Wang, Huan Chen, Xiaohui ZhangAbstract:Background Persons with acute leukemia relapsing after allotransplant and who respond to anti-leukemia interventions are at high risk of a second relapse. We studied the impact of minimal residual disease (MRD)- and graft-vs.-host disease (GvHD)-guided multiple Consolidation Chemotherapy and donor lymphocyte infusions (DLIs) to prevent second relapse in patients with acute leukemia relapsing post-transplant and who achieved complete remission after induction Chemotherapy and DLI.
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minimal residual disease and graft vs host disease guided multiple Consolidation Chemotherapy and donor lymphocyte infusion prevent second acute leukemia relapse after allotransplant
Journal of Hematology & Oncology, 2016Co-Authors: Chenhua Yan, Yu Wang, Yuhong Chen, Wei Han, Fengrong Wang, Yuqian Sun, Yao Chen, Xiaohui ZhangAbstract:Persons with acute leukemia relapsing after allotransplant and who respond to anti-leukemia interventions are at high risk of a second relapse. We studied the impact of minimal residual disease (MRD)- and graft-vs.-host disease (GvHD)-guided multiple Consolidation Chemotherapy and donor lymphocyte infusions (DLIs) to prevent second relapse in patients with acute leukemia relapsing post-transplant and who achieved complete remission after induction Chemotherapy and DLI. Forty-seven subjects with acute leukemia relapsing after an allotransplant and who achieved complete remission after post-relapse induction Chemotherapy and DLI were eligible. The use of Consolidation Chemotherapy and DLI was guided by the results of MRD testing and whether or not DLI caused acute and/or chronic GvHD. Outcomes were compared with those of 34 similar historical controls who did not receive Consolidation Chemotherapy and DLIs after induction Chemotherapy and DLI. One-year cumulative incidence of relapse (CIR; 22 % 95 % confidence interval (10, 35 %) vs. 56 % (39, 73 %); P < 0.0001), leukemia-free survival (LFS; 71 % (57, 84 %) vs. 35 % (19, 51 %); P < 0.0001), and survival (78 % (66, 90 %) vs. 44 % (27, 61 %); P < 0.0001) was significantly better in subjects than controls. In multivariate analyses, no chronic GvHD after therapy (hazard ratio (HR) = 3.56 (1.09, 11.58); P = 0.035) and a positive MRD test after therapy (HR = 21.04 (4.44, 94.87); P < 0.0001) were associated with an increased CIR. These data suggest MRD- and GvHD-guided multiple Consolidation Chemotherapy and DLIs reduce CIR and increase LFS and survival compared with controls in persons relapsing after allotransplant for acute leukemia. ChiCTR-ONC-12002912 . Donor lymphocyte infusion for the treatment of leukemia relapse following allogeneic hematopoeitic stem cell transplant.
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minimal residual disease and graft vs host disease guided multiple Consolidation Chemotherapy and donor lymphocyte infusion prevent second acute leukemia relapse after allotransplant
Journal of Hematology & Oncology, 2016Co-Authors: Chenhua Yan, Yu Wang, Yuhong Chen, Wei Han, Fengrong Wang, Yuqian Sun, Yao Chen, Jingzhi Wang, Huan Chen, Xiaohui ZhangAbstract:Background Persons with acute leukemia relapsing after allotransplant and who respond to anti-leukemia interventions are at high risk of a second relapse. We studied the impact of minimal residual disease (MRD)- and graft-vs.-host disease (GvHD)-guided multiple Consolidation Chemotherapy and donor lymphocyte infusions (DLIs) to prevent second relapse in patients with acute leukemia relapsing post-transplant and who achieved complete remission after induction Chemotherapy and DLI.