Efficacy of combination of venetoclax with azacitidine or chemotherapy in refractory/relapse acute leukemias of ambiguous lineage, not otherwise specified.
Ontology highlight
ABSTRACT:
SUBMITTER: Liu K
PROVIDER: S-EPMC8447663 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Acute leukemia of ambiguous lineage (ALAL) is a rare type of leukemia and represents an unmet clinical need. In fact, due to heterogeneity, substantial rarity and absence of clinical trials, there are no therapeutic guidelines available. We investigated the genetic basis of 10 cases of ALAL diagnosed at our centre from 2008 and 2020, through a targeted myeloid and lymphoid sequencing approach. We show that this rare group of acute leukemias is enriched in myeloid-gene mutations. In particular we found that RUNX1 mutations, which have been found double mutated in 40% of patients and tend to involve both alleles, are associated with an undifferentiated phenotype and with lineage ambiguity. Furthermore, because this feature is typical of acute myeloid leukemia with minimal differentiation, we believe that our data strengthen the idea that acute leukemia with ambiguous lineage, especially those with an undifferentiated phenotype, might be genetically more closer to acute myeloid leukemia rather than acute lymphoblastic leukemia. These data enrich the knowledge on the genetic basis of ALAL and could have clinical implications as an acute myeloid leukemia (AML) - oriented chemotherapeutic approach might be more appropriate.
| S-EPMC8444989 | biostudies-literature
Project description:Classifying leukemias of ambiguous lineage as either acute myeloid leukemia or acute lymphoid leukemia using microRNA expression profiling
2013-05-07 | E-MTAB-1459 | biostudies-arrayexpress
Project description:Patients with Myelodysplastic Syndromes (MDS) and secondary Acute Myeloid Leukemia (sAML) have a very poor prognosis after failure of hypomethylating agents (HMA). Stem cell transplantation is the only effective salvage therapy, for which only a limited number of patients are eligible due to age and comorbidity. Combination therapy of venetoclax and azacitidine (5-AZA) seems to be a promising approach in myeloid malignancies, but data from patients with HMA failure are lacking. Furthermore, a considerable concern of combination regimens in elderly AML and MDS patients is the toxicity on the remaining healthy hematopoiesis. Here, we report in vitro data showing the impact of venetoclax and 5-AZA, alone or in combination, in a larger cohort of MDS/sAML patients (n = 21), even after HMA failure (n = 13). We especially focused on the effects on healthy hematopoiesis and the impact on colony forming capacity as a parameter for long-term effects. To the best of our knowledge, we show for the first time that venetoclax in combination with capped dose of 5-AZA targets cell malignancies, while sparing healthy hematopoiesis.
| S-EPMC6469098 | biostudies-literature
Project description:BackgroundRelapsed or refractory acute myeloid leukemia (R/R AML) has a dismal prognosis. The aim of this study was to investigate the activity and tolerability of venetoclax combined with azacitidine plus homoharringtonine (VAH) regimen for R/R AML.MethodsThis phase 2 trial was done at ten hospitals in China. Eligible patients were R/R AML (aged 18-65 years) with an Eastern Cooperative Oncology Group performance status of 0-2. Patients received venetoclax (100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-14) and azacitidine (75 mg/m2 on days 1-7) and homoharringtonine (1 mg/m2 on days 1-7). The primary endpoint was composite complete remission rate [CRc, complete response (CR) plus complete response with incomplete blood count recovery (CRi)] after 2 cycles of treatment. The secondary endpoints include safety and survival.ResultsBetween May 27, 2020, and June 16, 2021, we enrolled 96 patients with R/R AML, including 37 primary refractory AML and 59 relapsed AML (16 relapsed after chemotherapy and 43 after allo-HSCT). The CRc rate was 70.8% (95% CI 60.8-79.2). In the patients with CRc, measurable residual disease (MRD)-negative was attained in 58.8% of CRc patients. Accordingly, overall response rate (ORR, CRc plus partial remission (PR)) was 78.1% (95% CI 68.6-85.4). At a median follow-up of 14.7 months (95% CI 6.6-22.8) for all patients, median overall survival (OS) was 22.1 months (95% CI 12.7-Not estimated), and event-free survival (EFS) was 14.3 months (95% CI 7.0-Not estimated). The 1-year OS was 61.5% (95% CI 51.0-70.4), and EFS was 51.0% (95% CI 40.7-60.5). The most common grade 3-4 adverse events were febrile neutropenia (37.4%), sepsis (11.4%), and pneumonia (21.9%).ConclusionsVAH is a promising and well-tolerated regimen in R/R AML, with high CRc and encouraging survival. Further randomized studies are needed to be explored. Trial registration clinicaltrials.gov identifier: NCT04424147.
| S-EPMC10149010 | biostudies-literature
Project description:Blastic plasmacytoid dendritic cell neoplasm is a rare and aggressive hematological malignancy associated with poor prognosis and limited treatment options. No guideline-directed therapy existed until the approval of tagraxofusp in 2018 by the Food and Drug Administration. Multiple clinical trials are undergoing as treatment options continue to evolve. We report a case refractory to tagraxofusp and pivekimab sunirine with subsequent remission achieved on venetoclax and azacitidine therapy.
| S-EPMC9886378 | biostudies-literature
Project description:BackgroundThe phase 3 VIALE-A trial (NCT02993523) reported that venetoclax-azacitidine significantly prolonged overall survival compared with placebo-azacitidine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy. Herein, efficacy and safety of venetoclax-azacitidine are analyzed in the Japanese subgroup of VIALE-A patients.MethodsEligible Japanese patients were randomized 2:1 to venetoclax-azacitidine (N = 24) or placebo-azacitidine (N = 13). Primary endpoints for Japan were overall survival and complete response (CR) + CR with incomplete hematologic recovery (CRi). Venetoclax (target dose 400 mg) was given orally once daily. Azacitidine (75 mg/m2) was administered subcutaneously or intravenously on Days 1-7 of each 28-day cycle.ResultsMedian follow-up was 16.3 months (range, 1.0-20.3). Median overall survival was not reached with venetoclax-azacitidine (hazard ratio 0.409 and 95% confidence interval: 0.151, 1.109); overall survival estimate was higher with venetoclax-azacitidine than placebo-azacitidine at 12 (67 and 46%) and 18 months (57 and 31%), respectively. CR and CRi rates were 67% with venetoclax-azacitidine and 15% with placebo-azacitidine. Most common any-grade adverse events were febrile neutropenia (79 and 39%), thrombocytopenia (54 and 77%), constipation (54 and 54%) and decreased appetite (54 and 38%) in the venetoclax-azacitidine and placebo-azacitidine arms, respectively. Only 1 patient in the venetoclax-azacitidine arm, and no patients in the placebo-azacitidine arm, had grade 4 febrile neutropenia that led to treatment discontinuation.ConclusionsThis Japanese subgroup analysis of VIALE-A demonstrates comparable safety and efficacy outcomes compared with the global study and supports venetoclax-azacitidine as first-line standard-of-care for Japanese treatment-naive patients with acute myeloid leukemia who are ineligible for intensive chemotherapy.
| S-EPMC9242001 | biostudies-literature
Project description:Venetoclax (ven) plus azacitidine (aza) is the standard of care for patients with newly diagnosed acute myeloid leukemia (AML) who are not candidates for intensive chemotherapy (IC). Some patients who are IC candidates instead receive ven/aza. We retrospectively analyzed patients with newly diagnosed AML who received ven/aza (n = 143) or IC (n = 149) to compare outcomes, seek variables that could predict response to 1 therapy or the other, and ascertain whether treatment recommendations could be refined. The response rates were 76.9% for ven/aza and 70.5% for IC. The median overall survival (OS) was 884 days for IC compared with 483 days for ven/aza (P = .0020). A propensity-matched cohort was used to compare outcomes in the setting of equivalent baseline variables, and when matched for age, biological risk, and transplantation, the median OS was 705 days for IC compared with not reached for ven/aza (P = .0667). Variables that favored response to ven/aza over IC included older age, secondary AML, and RUNX1 mutations. AML M5 favored response to IC over ven/aza. In the propensity-matched cohort analyzing OS, older age, adverse risk, and RUNX1 mutations favored ven/aza over IC, whereas intermediate risk favored IC over ven/aza. In conclusion, patients receiving IC have improved OS compared with those receiving ven/aza. However, in a propensity-matched cohort of patients with equivalent baseline factors, there was a trend toward favorable OS for ven/aza. Specific variables, such as RUNX1 mutations, reported here for the first time, can be identified that favor ven/aza or IC, helping to guide treatment decisions for patients who may be eligible candidates for either therapy.
| S-EPMC8714726 | biostudies-literature
Project description:Chronic neutrophilic leukemia (CNL), atypical chronic myeloid leukemia (aCML), and myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U) are a group of rare and heterogeneous myeloid disorders. There is strong morphologic resemblance among these distinct diagnostic entities as well as a lack of specific molecular markers and limited understanding of disease pathogenesis, which has made diagnosis challenging in certain cases. The treatment has remained empirical, resulting in dismal outcomes. We, therefore, performed whole-exome and RNA sequencing of these rare hematologic malignancies and present the most complete survey of the genomic landscape of these diseases to date. We observed a diversity of combinatorial mutational patterns that generally do not cluster within any one diagnosis. Gene expression analysis reveals enrichment, but not cosegregation, of clinical and genetic disease features with transcriptional clusters. In conclusion, these groups of diseases represent a continuum of related diseases rather than discrete diagnostic entities.
| S-EPMC6742922 | biostudies-literature
Project description:AbstractAlthough induction chemotherapy (IC) is the standard of care in medically fit patients with newly diagnosed acute myeloid leukemia (AML), limited retrospective data indicate that patients at adverse-risk may benefit from azacytidine and venetoclax (aza-ven). Our goal was to perform a Markov decision analysis to determine whether IC or aza-ven is the optimal induction regimen in this population. Using the TreeAge software, Markov models were created for adverse-risk and intermediate-risk cohorts. A systematic review of the literature informed the transition probabilities and utilities included in the analyses. Our primary outcome was quality-adjusted life years (QALYs) gained over 5 years after diagnosis. Overall, patients at adverse risk treated with IC gained 1.4 QALYs, compared with 2.0 QALYs in patients treated with aza-ven. Patients at adverse risk treated with IC and allogeneic stem cell transplantation (allo-SCT), IC, aza-ven and allo-SCT, or aza-ven gained 2.1, 1.5, 3.0, and 1.9 QALYs, respectively. Meanwhile, patients at intermediate risk treated with IC gained 2.0 QALY, compared with 1.7 QALY in patients treated with aza-ven. Patients at intermediate risk treated with IC and allo-SCT, IC, aza-ven and allo-SCT, and aza-ven gained 2.7, 2.3, 2.6, and 1.8 QALYs, respectively. We have demonstrated that medically fit patients with newly diagnosed adverse-risk AML may benefit from treatment with aza-ven over those treated with IC, whereas IC remains the preferred approach for patients at intermediate risk. Our work challenges the use of the European LeukemiaNet risk classification for patients treated with aza-ven and highlights the need for prospective investigation into aza-ven as induction therapy for medically fit patients.
| S-EPMC10839604 | biostudies-literature
Project description:T-cell lymphomas are rare malignancies that are often found in older individuals. Here we present the case of a 63 year old female that presented with diffuse cervical, inguinal, and axillary lymphadenopathy with associated weight loss and night sweats. The patient underwent excisional lymph node biopsy which revealed a T-cell lymphoma with findings characteristic of peripheral T-cell lymphoma, not otherwise specified.
| S-EPMC7296317 | biostudies-literature