Case report: Good response to CMOP regimen containing mitoxantrone hydrochloride liposome (PLM60) as induction chemotherapy in patients with angioimmunoblastic T-cell lymphoma
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PROVIDER: S-EPMC10864495 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:There have been no large studies comparing reduced-intensity/non-myeloablative conditioning (RIC/NMA) to myeloablative conditioning (MAC) regimens in T-cell non-Hodgkin lymphoma (T-NHL) patients undergoing allogeneic transplant (allo-HCT). A total of 803 adults with peripheral T-cell lymphoma, anaplastic large cell lymphoma and angioimmunoblastic T-cell lymphoma (age 18-65 years), undergoing allo-HCT between 2008-2019 and reported to the Center for International Blood and Marrow Transplant Research with either MAC (n = 258) or RIC/NMA regimens (n = 545) were evaluated. There were no significant differences between the two cohorts in terms of patient sex, race and performance scores. Significantly more patients in the RIC/NMA cohort had peripheral blood grafts, haematopoietic cell transplantation-specific comorbidity index (HCT-CI) of ≥3 and chemosensitive disease compared to the MAC cohort. On multivariate analysis, overall survival (OS) was not significantly different in the RIC/NMA cohort compared to the MAC cohort (hazard ratio (HR) = 1.01, 95% confidence interval (CI) = 0.79-1.29; p = 0.95). Similarly, non-relapse mortality (NRM) (HR = 0.85, 95% CI = 0.61-1.19; p = 0.34), risk of progression/relapse (HR = 1.29; 95% CI = 0.98-1.70; p = 0.07) and therapy failure (HR = 1.14; 95% CI = 0.92-1.41, p = 0.23) were not significantly different between the two cohorts. Relative to MAC, RIC/NMA was associated with a significantly lower risk of grade 3-4 acute graft-versus-host disease (HR = 0.67; 95% CI = 0.46-0.99, p = 0.04). Among chemorefractory patients, there was no difference in OS, therapy failure, relapse, or NRM between RIC/NMA and MAC regimens. In conclusion, we found no association between conditioning intensity and outcomes after allo-HCT for T-cell NHL.
| S-EPMC9018546 | biostudies-literature
Project description:BackgroundDaunorubicin, a component of the four-drug induction chemotherapy regimen for de novo pediatric high-risk acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LLy), was unavailable in 2011 due to a national drug shortage. During this time, our institution substituted mitoxantrone 6.25 mg/m(2) for daunorubicin 25 mg/m(2) on induction Days 1, 8, 15, and 22. While mitoxantrone has been shown to be effective for relapsed ALL, it has not been studied in de novo pediatric ALL/LLy.ProcedureWe conducted a retrospective cohort study of newly diagnosed patients with ALL or LLy at our institution 1/2009-4/2013 to compare induction toxicity and response of patients treated with mitoxantrone versus daunorubicin.ResultsEleven patients received mitoxantrone, 121 patients received daunorubicin. Induction toxicities including deaths, intensive care unit admissions, fever, bacteremia, and invasive fungal disease were similar for the two groups. Mean number of days hospitalized during induction was also similar (mitoxantrone 9.7 days vs. daunorubicin 11.2 days, P = 0.60). Minimal residual disease prevalence at the end of induction was not significantly different (mitoxantrone 33.3% vs. daunorubicin 23.0%, P = 0.44). The only significant difference between the groups was that a higher proportion of patients who received mitoxantrone had consolidation delayed due to myelosuppression (mitoxantrone 30.0% vs. daunorubicin 6.0%, P = 0.03).ConclusionInduction toxicity and response for new ALL/LLy patients treated with mitoxantrone in place of daunorubicin were similar to the toxicity and response seen with conventional daunorubicin. Mitoxantrone is a reasonable replacement for daunorubicin in times of drug shortage.
| S-EPMC4317248 | biostudies-literature
Project description:BackgroundIn immunocompetent patients with primary central nervous system lymphoma (PCNSL), combined modality therapy (CMT) using high-dose methotrexate and radiotherapy (WBRT) has improved response rates compared with chemotherapy alone. The trade-off is delayed and potentially devastating treatment-related neurotoxicity (NT).MethodsA cost-effectiveness analysis using a Markov model compared CMT with chemotherapy alone in age-stratified patients with PCNSL. Baseline probabilities were derived from a systematic literature review. Direct and lost productivity costs were collected from a Canadian perspective and presented in Can$ in 2011. Outcomes were life expectancy, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio.ResultsThe quality-adjusted life expectancy was 1.55 QALYs for CMT and 1.53 QALYs for chemotherapy alone. In younger patients (aged <60 years), CMT yielded 2.44 QALYs, compared with 1.89 QALYs for chemotherapy alone, yielding an expected benefit with CMT of 0.55 QALYs or 6.6 quality-adjusted months. The CMT strategy dominated in younger patients, as it was Can$11 951 less expensive than chemotherapy alone. The chemotherapy-alone strategy dominated in older patients, as it was Can$11 244 less expensive than CMT, and there was no difference in QALYs between the strategies. The model was robust in sensitivity analyses of key variables tested through the plausible ranges obtained from costing sources and published literature.ConclusionThe preferred induction strategy for younger patients with PCNSL appears to be CMT, which minimized cost while maximizing life expectancy and QALYs. This analysis confirms that the preferred strategy for older patients is chemotherapy alone.
| S-EPMC4165417 | biostudies-literature
Project description:FMS-like tyrosine kinase 3 (FLT3) is the most frequently mutated gene in acute myeloid leukemia (AML), and is associated with a poor prognosis and high relapse rate. Gilteritinib, as a second-generation FLT3 inhibitor, is an important target drug in the treatment of FLT3-ITD AML patients, but it still faces the problems of drug resistance and reduced potency. In this study, we found that mitoxantrone-liposome can sensensitized gilteritinib and enhanced the therapeutic effect in vivo and in vitro. RNA-sequencing revealed that the combination treatment resulted in specific changes in gene expression, reduced drug resistance and the mechanism. Primary AML cells harvested from patients with FLT3-ITD AML showed a significant response to combination treatment in vitro. Our data suggest represents a novel and promising therapeutic strategy for FLT3-ITD AML patients and relapsed/refractory(R/R) AML.
2025-03-19 | GSE276384 | GEO
Project description:PurposeThis trial aimed to evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection (Lipo-MIT) in advanced breast cancer (ABC).MethodsIn this randomized, open-label, active-controlled, single-center, phase II clinical trial, eligible patients were randomized in a ratio of 1:1 to receive Lipo-MIT or mitoxantrone hydrochloride injection (MIT) intravenously. The primary endpoint was objective response rate (ORR). The secondary endpoints were disease control rate (DCR), progression-free survival (PFS), and safety outcomes.ResultsSixty patients were randomized to receive Lipo-MIT or MIT. The ORR was 13.3% (95% confidence interval (CI): 3.8-30.7%) for Lipo-MIT and 6.7% (95% CI: 0.8-22.1%) for MIT. The DCR was 50% (95% CI: 31.3-68.7%) with Lipo-MIT vs. 30% (95% CI: 14.7-49.4%) with MIT. The median PFS was 1.92 months (95% CI: 1.75-3.61) for Lipo-MIT and 1.85 months (95% CI: 1.75-2.02) for MIT. The most common toxicity was myelosuppression. Lipo-MIT resulted in an incidence of 86.7% of leukopenia and 80.0% of neutropenia, which was marginally superior to MIT (96.7% and 96.7%, respectively). Lipo-MIT showed a lower incidence of cardiovascular events (13.3% vs. 20.0%) and increased cardiac troponin T (3.3% vs. 36.7%); but higher incidence of anemia (76.7% vs. 46.7%), skin hyperpigmentation (66.7% vs. 3.3%), and fever (23.3% vs. 10.0%) than MIT. Conclusions The clinical benefit parameters of Lipo-MIT and MIT were comparable. Lipo-MIT provided a different toxicity profile, which might be associated with the altered distribution of the drug. Additional study is needed to elucidate the potential benefit of Lipo-MIT in ABC.Clinical trial registrationThis study is registered with ClinicalTrials.gov (No. NCT02596373) on Nov 4, 2015.
| S-EPMC8993786 | biostudies-literature
Project description:Patients with angioimmunoblastic T-cell lymphoma (AITL), one of the most common types of peripheral T-cell lymphoma (PTCL), typically present with advanced disease, systemic symptoms, and immune deregulation. Treatment can be challenging owing to frequent relapses after initial and subsequent therapy. The front-line treatment approach currently mirrors the approach used for other nodal PTCLs with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy and consideration for autologous stem-cell transplant (SCT). In the relapsed and refractory settings, allogeneic SCT offers the chance for long-term remission. Choice of treatment of relapsed or refractory disease depends on whether an allogeneic SCT is planned. Agents with preferential activity in relapsed or refractory AITL include epigenetic modifiers such as histone deacetylase inhibitors and hypomethylating agents. Other targeted agents show promise in AITL, including brentuximab vedotin and phosphoinositide-3-kinase inhibitors. Ongoing studies are evaluating new potential targets for AITL, with particular focus on identifying markers of response and resistance. Additional studies are assessing incorporation of novel agents into the front-line treatment of AITL. These studies will lead to more individualized treatment approaches and, ultimately, improved outcomes for patients with AITL.
| S-EPMC7850668 | biostudies-literature
Project description:It has been nearly half a century since angioimmunoblastic T-cell lymphoma (AITL) was characterized in the early 1970's. Our understanding of the disease has dramatically changed due to multiple discoveries and insights. One of the key features of AITL is aberrant immune activity. Although AITL is now understood to be a neoplastic disease, pathologists appreciated that it was an inflammatory condition. The more we understand AITL at cellular and genetic levels, the more we view it as both a neoplastic and an inflammatory disease. Here, we review recent progress in our understanding of AITL, focusing on as yet unsolved questions.
| S-EPMC7376827 | biostudies-literature
Project description:Mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) occur in most grade 2 and 3 gliomas, secondary glioblastomas, and a subset of acute myelogenous leukemias but have not been detected in other tumor types. The mutations occur at specific arginine residues and result in the acquisition of a novel enzymatic activity that converts 2-oxoglutarate to D-2-hydroxyglutarate. This study reports IDH1 and IDH2 genotyping results from a set of lymphomas, which included a large set of peripheral T-cell lymphomas. IDH2 mutations were identified in approximately 20% of angioimmunoblastic T-cell lymphomas (AITLs), but not in other peripheral T-cell lymphoma entities. These results were confirmed in an independent set of AITL patients, where the IDH2 mutation rate was approximately 45%. This is the second common genetic lesion identified in AITL after TET2 and extends the number of neoplastic diseases where IDH1 and IDH2 mutations may play a role.
| S-EPMC3293643 | biostudies-literature
Project description:Angioimmunoblastic T cell lymphoma (AITL) originates from follicular helper T-cells and is characterised by a polymorphic infiltrate with the neoplastic T-cells forming small clusters around the follicle and high endothelial venules. Despite the recent advances in its phenotypic characterisation, the genetics and molecular mechanisms underlying AITL are not fully understood. In the present study, we performed whole exome sequencing in 9 cases of AITL from Taiwan (n = 6) and U.K. (n = 3). We confirmed frequent mutations in TET2 (9/9), DNMT3A (3/9), IDH2 (3/9), RHOA (3/9) and PLCG1 (2/9) as recently reported by others. More importantly, we identified mutations in TNFRSF21 (1/9), CCND3 (1/9) and SAMSN1 (1/9), which are not yet seen or strongly implicated in the pathogenesis of AITL. Among the pathogenic mutations identified in AITL, mutations in DNA methylation regulators TET2 and DNMT3A occur early in hematopoietic stem cells as shown by previous studies, and these genetic events enhance the self-renewal of hematopoietic stem cells, but are unlikely to have any major impact on T-cell differentiation. Mutations in RHOA, PLCG1 and TNFRSF21 (DR6), which encode proteins critical for T-cell biology, most likely promote T-cell differentiation and malignant transformation, consequently generating the malignant phenotype. Our findings extend the molecular insights into the multistage development of AITL.
| S-EPMC5392284 | biostudies-literature
Project description:Somatic G17V RHOA mutations were found in 50-70% of angioimmunoblastic T-cell lymphoma (AITL). The mutant RHOA lacks GTP binding capacity, suggesting defects in the classical RHOA signaling. Here, we discovered the novel function of the G17V RHOA: VAV1 was identified as a G17V RHOA-specific binding partner via high-throughput screening. We found that binding of G17V RHOA to VAV1 augmented its adaptor function through phosphorylation of 174Tyr, resulting in acceleration of T-cell receptor (TCR) signaling. Enrichment of cytokine and chemokine-related pathways was also evident by the expression of G17V RHOA. We further identified VAV1 mutations and a new translocation, VAV1-STAP2, in seven of the 85 RHOA mutation-negative samples (8.2%), whereas none of the 41 RHOA mutation-positive samples exhibited VAV1 mutations. Augmentation of 174Tyr phosphorylation was also demonstrated in VAV1-STAP2. Dasatinib, a multikinase inhibitor, efficiently blocked the accelerated VAV1 phosphorylation and the associating TCR signaling by both G17V RHOA and VAV1-STAP2 expression. Phospho-VAV1 staining was demonstrated in the clinical specimens harboring G17V RHOA and VAV1 mutations at a higher frequency than those without. Our findings indicate that the G17V RHOA-VAV1 axis may provide a new therapeutic target in AITL.
| S-EPMC5843900 | biostudies-literature