Browse
Submit Data
Databases
API
Help

Dataset Information

30 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Outcomes following hematopoietic stem cell transplantation in patients treated with standard chemotherapy with or without gemtuzumab ozogamicin for acute myeloid leukemia.

ABSTRACT: The phase 3 ALFA-0701 trial demonstrated improved outcomes with fractionated-dose gemtuzumab ozogamicin (GO) combined with standard chemotherapy vs. standard chemotherapy alone in adults with de novo acute myeloid leukemia (AML). We examined post-transplant outcomes and occurrence of hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) in patients who received hematopoietic stem cell transplantation (HSCT) as follow-up therapy in ALFA-0701. Patients aged 50-70 years were randomized to standard chemotherapy with or without GO (3 mg/m2 on days 1, 4, and 7 of induction and day 1 on each of two consolidation courses). Allogeneic HSCT was recommended for patients in first complete remission with matched (related or unrelated) donor, except those with core-binding factor AML or normal karyotype and either NPM1+/FLT3-ITDwt or CEBPA+ AML. Eighty-five patients (GO: n = 32; control: n = 53) received HSCT in first complete remission or after relapse/primary induction failure. Three patients (GO: n = 2; control: n = 1 [received GO as follow-up therapy]) developed VOD/SOS after HSCT or conditioning. Post-transplant survival, non-relapse mortality, and relapse were not different between arms. Results indicate fractionated-dose GO as part of induction and consolidation chemotherapy for AML does not induce excess post-transplant VOD/SOS or mortality and thus does not preclude the use of HSCT as consolidation treatment.

SUBMITTER: Pautas C

PROVIDER: S-EPMC8189917 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Veno-occlusive disease risk in pediatric patients with acute myeloid leukemia treated with gemtuzumab ozogamicin before allogeneic hematopoietic cell transplantation.

Project description:BackgroundGemtuzumab ozogamicin (GO) administered before allogeneic hematopoietic cell transplantation (alloHCT) has been linked to an increased risk of hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS).ProcedureThis retrospective analysis examined VOD/SOS risk and clinical outcomes in pediatric patients with acute myeloid leukemia who received myeloablative alloHCT in 2008-2011 with (n = 148) and without (n = 348; controls) prior GO exposure and were reported to the Center for International Blood and Marrow Transplant Research.ResultsCumulative incidences (95% confidence interval [CI]) of VOD/SOS and severe VOD/SOS, respectively, at 100 days were 16% (11-23%) and 8% (4-13%) for GO-exposed patients and 10% (7-13%) and 3% (2-5%) for controls. With a median follow-up of approximately 7 years, the 5-year adjusted overall survival probability (95% CI) after alloHCT was 51% (43-58%) and 55% (50-60%) for GO-exposed patients and controls, respectively; three (4%) and one (<1%) deaths were attributed to VOD/SOS. In multivariate analyses, GO exposure was observed to be associated with an increased risk of VOD/SOS at 100 days, but was not associated with overall survival, disease-free survival, relapse, or nonrelapse mortality.ConclusionsResults suggest that GO treatment prior to alloHCT in pediatric patients may increase the risk of VOD/SOS but not death.

| S-EPMC8324076 | biostudies-literature

Gemtuzumab ozogamicin for the treatment of acute myeloid leukemia.

Project description:IntroductionGemtuzumab ozogamicin (GO) is an antibody-drug conjugate consisting of a monoclonal antibody targeting CD33 linked to a cytotoxic derivative of calicheamicin. Despite the known clinical efficacy in relapsed/refractory acute myeloid leukemia (AML), GO was withdrawn from the market in 2010 due to increased early deaths witnessed in newly diagnosed AML patients receiving GO + intensive chemotherapy. In 2017, new data on the clinical efficacy and safety of GO administered on a fractionated-dosing schedule led to re-approval for newly diagnosed and relapsed/refractory AML. Areas covered: Addition of fractionated GO to chemotherapy significantly improved event-free survival of newly diagnosed AML patients with favorable and intermediate cytogenetic-risk disease. GO monotherapy also prolonged survival in newly diagnosed unfit patients and relapse-free survival in relapsed/refractory AML. This new dosing schedule was associated with decreased incidence of hepatotoxicity, veno-occlusive disease, and early mortality. Expert commentary: GO represents the first drug-antibody conjugate approved (twice) in the United States for AML. Its re-emergence adds a valuable agent back into the armamentarium for AML. The approval of GO as well as three other agents for AML in 2017 highlights the need for rapid cytogenetic and molecular characterization of AML and incorporation into new treatment algorithms.

| S-EPMC6661897 | biostudies-literature

Therapeutic Targeting of Acute Myeloid Leukemia by Gemtuzumab Ozogamicin.

Project description:Acute myeloid leukemia (AML) is a complex hematological malignancy characterized by genetic and clinical heterogeneity and high mortality. Despite the recent introduction of novel pharmaceutical agents in hemato-oncology, few advancements have been made in AML for decades. In the last years, the therapeutic options have rapidly changed, with the approval of innovative compounds that provide new opportunities, together with new challenges for clinicians: among them, on 1 September, 2017 the Food and Drug Administration granted approval for Gemtuzumab Ozogamicin (GO) in combination with daunorubicin and cytarabine for the treatment of adult patients affected by newly diagnosed CD33+ AML. Benefits of GO-based regimens were also reported in the pre- and post-transplantation settings. Moreover, several biomarkers of GO response have been suggested, including expression of CD33 and multidrug resistance genes, cytogenetic and molecular profiles, minimal residual disease and stemness signatures. Among them, elevated CD33 expression on blast cells and non-adverse cytogenetic or molecular risk represent largely validated predictors of good response.

| S-EPMC8469571 | biostudies-literature

Clinical significance of CD33 nonsynonymous single-nucleotide polymorphisms in pediatric patients with acute myeloid leukemia treated with gemtuzumab-ozogamicin-containing chemotherapy.

Project description:The purpose of this study was to evaluate clinical implications of CD33 single-nucleotide polymorphisms (SNP) in pediatric patients with acute myeloid leukemia (AML) treated with gemtuzumab-ozogamicin (GO)-based therapy.We genotyped four CD33 SNPs: rs35112940 (G>A; Arg304Gly), rs12459419 (C>T; Ala14Val), rs2455069 (A>G; Arg69Gly), and rs1803254 (G>C; 3'UTR) in pediatric patients undergoing induction chemotherapy containing GO (COG-AAML03P1 trial; n = 242) or not containing GO (St. Jude AML02 trial; n = 172).CD33 SNPs were correlated significantly with clinical characteristics and treatment outcome. The coding SNPs, rs35112940 and rs12459419, were significantly associated with clinical endpoints in COG-AAML03P1 but not in the St. Jude AML02 trial. Specifically, among white patients in COG-AAML03P1, the 3-year overall survival (OS) rate from remission was 84% ± 8% for those homozygous (GG) for rs35112940 versus 68% ± 15% for the other genotypes (P = 0.018); these patients also had a lower relapse risk and superior disease-free survival. Likewise, patients homozygous for variant allele (TT) for rs12459419 were more likely to have favorable risk disease than CC and CT genotypes (52% vs. 31%, P = 0.034) and significantly lower diagnostic blast CD33 expression than other genotypes (P < 0.001).Our data suggest that genetic variations in CD33 could impact clinical outcome of GO-based therapy in pediatric AMLs.

| S-EPMC3602123 | biostudies-literature

Antibody-based therapy of acute myeloid leukemia with gemtuzumab ozogamicin.

Project description:Antibodies have created high expectations for effective yet tolerated therapeutics in acute myeloid leukemia (AML). Hitherto the most exploited target is CD33, a myeloid differentiation antigen found on AML blasts in most patients and, perhaps, leukemic stem cells in some. Treatment efforts have focused on conjugated antibodies, particularly gemtuzumab ozogamicin (GO), an anti-CD33 antibody carrying a toxic calicheamicin-g 1 derivative that, after intracellular hydrolytic release, induces DNA strand breaks, apoptosis, and cell death. Serving as paradigm for this strategy, GO was the first anti-cancer immunoconjugate to obtain regulatory approval in the U.S. While efficacious as monotherapy in acute promyelocytic leukemia (APL), GO alone induces remissions in less than 25-35% of non-APL AML patients. However, emerging data from well controlled trials now indicate that GO improves survival for many non-APL AML patients, supporting the conclusion that CD33 is a clinically relevant target for some disease subsets. It is thus unfortunate that GO has become unavailable in many parts of the world, and the drug's usefulness should be reconsidered and selected patients granted access to this immunoconjugate.

| S-EPMC3683663 | biostudies-literature

Biomarkers of Gemtuzumab Ozogamicin Response for Acute Myeloid Leukemia Treatment.

Project description:Gemtuzumab ozogamicin (GO, Mylotarg®) consists of a humanized CD33-targeted antibody-drug conjugated to a calicheamicin derivative. Growing evidence of GO efficacy in acute myeloid leukemia (AML), demonstrated by improved outcomes in CD33-positive AML patients across phase I to III clinical trials, led to the Food and Drug Administration (FDA) approval on 1 September 2017 in CD33-positive AML patients aged 2 years and older. Discrepancies in GO recipients outcome have raised significant efforts to characterize biomarkers predictive of GO response and have refined the subset of patients that may strongly benefit from GO. Among them, CD33 expression levels, favorable cytogenetics (t(8;21), inv(16)/t(16;16), t(15;17)) and molecular alterations, such as NPM1, FLT3-internal tandem duplications and other signaling mutations, represent well-known candidates. Additionally, in depth analyses including minimal residual disease monitoring, stemness expression (LSC17 score), mutations or single nucleotide polymorphisms in GO pathway genes (CD33, ABCB1) and molecular-derived scores, such as the recently set up CD33_PGx6_Score, represent promising markers to enhance GO response prediction and improve patient management.

| S-EPMC7460695 | biostudies-literature

Gemtuzumab ozogamicin for treatment of newly diagnosed CD33-positive acute myeloid leukemia.

Project description:In September 2017, the US FDA announced re-approval of gemtuzumab ozogamicin (GO), a CD33-targeting immunoconjugate, for treatment of newly diagnosed and relapsed/refractory acute myeloid leukemia (AML). This is a very significant step toward defining new treatment regimens in AML, as the treatment has essentially stayed unchanged with the '7 + 3 induction regimen' (7 days cytarabine and 3 days of anthracycline) since 1973. GO is the first antibody-drug conjugate to receive FDA approval for treating cancer. This review article discusses the challenges faced and lessons learned during the journey of GO for AML treatment. Selected trials that have made significant contribution in our understanding of the most efficacious and safe use of GO for treating AML patients as well as factors influencing GO response are highlighted in this article.

| S-EPMC6331698 | biostudies-literature

Gemtuzumab ozogamicin can reduce minimal residual disease in patients with childhood acute myeloid leukemia.

Project description:Gemtuzumab ozogamicin (GO) is an active agent for the treatment of CD33-postive acute myeloid leukemia (AML) and may improve the outcome of specific patient subgroups when combined with conventional chemotherapy. However, to the best of the authors' knowledge, the effects of GO on levels of minimal residual disease (MRD) are unknown.Pediatric patients with AML who received GO, either alone or in combination with chemotherapy on the AML02 multicenter trial, were analyzed to determine the effects of GO on MRD and outcome.Among 17 patients who received GO alone because of persistent leukemia, 14 had a reduction in their MRD level and 13 became MRD negative. Of the 29 who received chemotherapy in combination with GO after responding poorly to chemotherapy, 28 demonstrated reduced MRD and 13 became MRD negative. Treatment with GO effectively reduced MRD before hematopoietic stem cell transplantation and was not found to be associated with increased treatment-related mortality after transplantation.GO is effective in reducing MRD levels in pediatric patients with AML and may improve the outcome of those patients at high risk of disease recurrence.

| S-EPMC4271731 | biostudies-literature

Gemtuzumab ozogamicin and novel antibody-drug conjugates in clinical trials for acute myeloid leukemia.

Project description:Targeted agents are increasingly used for the therapy of acute myeloid leukemia (AML). Gemtuzumab ozogamicin (GO) is the first antibody-drug conjugate (ADC) approved for induction therapy of AML. When used in fractionated doses, GO combined with the conventional cytarabine/anthracycline-based induction chemotherapy significantly improves the outcome of previously untreated AML patients. Single-agent GO is effective and safe for AML patient ineligible for intensive chemotherapy. Multiple combination regimens incorporating GO have also been recommended as potential alternative options. In addition, several novel ADCs targeting CD33, CD123 and CLL-1 are currently undergoing preclinical or early clinical investigations. In this review, we summarized the efficacy and limitations of GO as well as novel ADCs for adult AML patients.

| S-EPMC6824118 | biostudies-literature

Mcl-1 dependence predicts response to vorinostat and gemtuzumab ozogamicin in acute myeloid leukemia.

Project description:Older adults with acute myeloid leukemia (AML) are commonly considered for investigational therapies, which often only benefit subsets of patients. In this study, we assessed whether BH3 profiling of apoptotic functionality could predict outcomes following treatment with vorinostat (histone deacetylase inhibitor) and gemtuzumab ozogamicin (GO; CD33-targeted immunoconjugate). Flow cytometry of BH3 peptide priming with Noxa (anti-apoptotic protein Mcl-1 modulator) correlated with remission induction (p=.026; AUC=0.83 [CI: 0.65-1.00; p=.00042]: AUC=0.88 [CI:0.75-1.00] with age adjustment) and overall survival (p=.027 logistic regression; AUC=0.87 [0.64-1.00; p=.0017]). This Mcl-1-dependence suggests a pivotal role of Bcl-2 family protein-mediated apoptosis to vorinostat/GO in AML patients.

| S-EPMC4104771 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data