Gemtuzumab ozogamicin for treatment of relapsing/refractory acute myelogenous leukemia (AML)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 16531-16531
Author(s):  
D. C. Case ◽  
M. A. Boyd ◽  
J. A. Hedlund ◽  
T. J. Ervin
Keyword(s):  
Complete Remission ◽  
Acute Myelogenous Leukemia ◽  
Single Agent ◽  
Liver Function Tests ◽  
Initial Therapy ◽  
Gemtuzumab Ozogamicin ◽  
Myelogenous Leukemia ◽  
Acute Myelogenous ◽  
Blast Cells ◽  
Age Range

16531 Background: Gemtuzumab ozogamicin is a calicheamicin-conjugated anti-CD 33 monoclonal antibody studied and utilized in relapsed and refractory acute myelogenous leukemia. Methods: At our center we treated a series of refractory patients (<60 years old) and relapsed patients (>60 years old) with gemtuzumab ozogamicin over a 3 year period. We treated 20 patients: 14 males and 6 females with an age range of 21 to 77 years (median 64 years). Seven patients were refractory to multiple regimens (<60 years old) and 13 were relapsing from initial therapy (>60 years old). Cytogenetic analysis revealed 60% were intermediate-risk and 40% were poor-risk. The goal of therapy was complete remission (≤ 5% leukemia blast cells in the marrow. ≥ 9 g/dl hemoglobin, ≥1500/ul absolute neutrophil count, and platelet count ≥100,000/ul). Patients received gemtuzumab ozogamicin 9 mg/m2 I.V. days 1 and 5. All patients received at least one dose. Patients achieving complete remission were eligible to receive monthly doses of gemtuzumab ozogamicin after complete remission was obtained. Results: Of the 7 refractory patients (<60 years old), there were no complete remissions. Of 13 relapsing patients (>60 years old) there were 2 complete remissions. One patient was 64 and the other 67 years old. Both remissions lasted 2 months. All patients were treated in the hospital. Chills/fever with treatment occurred in 40% of patients. Fever/neutropenia was universal. Thirty percent had elevation of liver function tests. Conclusions: Gemtuzumab ozogamicin as a single agent is capable of producing complete remission in a small number of relapsing patients >60 years old. Remissions are short. No significant financial relationships to disclose.

scholarly journals Phase II Trial of Vorinostat With Idarubicin and Cytarabine for Patients With Newly Diagnosed Acute Myelogenous Leukemia or Myelodysplastic Syndrome

2012 ◽  
Vol 30 (18) ◽  
pp. 2204-2210 ◽  
Author(s):  
Guillermo Garcia-Manero ◽  
Francesco Paolo Tambaro ◽  
Nebiyou B. Bekele ◽  
Hui Yang ◽  
Farhad Ravandi ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Acute Myelogenous Leukemia ◽  
Single Agent ◽  
Complete Response ◽  
Myelogenous Leukemia ◽  
Platelet Recovery ◽  
Free Survival ◽  
Binding Factor ◽  
Deacetylase Inhibitor ◽  
Acute Myelogenous

Purpose To evaluate the safety and efficacy of the combination of the histone deacetylase inhibitor vorinostat with idarubicin and ara-C (cytarabine) in patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Patients and Methods Patients with previously untreated AML or higher-risk MDS age 15 to 65 years with appropriate organ function and no core-binding factor abnormality were candidates. Induction therapy was vorinostat 500 mg orally three times a day (days 1 to 3), idarubin 12 mg/m2 intravenously (IV) daily × 3 (days 4 to 6), and cytarabine 1.5 g/m2 IV as a continuous infusion daily for 3 or 4 days (days 4 to 7). Patients in remission could be treated with five cycles of consolidation therapy and up to 12 months of maintenance therapy with single-agent vorinostat. The study was designed to stop early if either excess toxicity or low probability of median event-free survival (EFS) of more than 28 weeks was likely. Results After a three-patient run-in phase, 75 patients were treated. Median age was 52 years (range, 19 to 65 years), 29 patients (39%) were cytogenetically normal, and 11 (15%) had FLT-3 internal tandem duplication (ITD). No excess vorinostat-related toxicity was observed. Induction mortality was 4%. EFS was 47 weeks (range, 3 to 134 weeks), and overall survival was 82 weeks (range, 3 to 134 weeks). Overall response rate (ORR) was 85%, including 76% complete response (CR) and 9% in CR with incomplete platelet recovery. ORR was 93% in diploid patients and 100% in FLT-3 ITD patients. Levels of NRF2 and CYBB were associated with longer survival. Conclusion The combination of vorinostat with idarubicin and cytarabine is safe and active in AML.

scholarly journals Chemotherapy for acute myelogenous leukemia in children and adults: VAPA update

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 315-319 ◽  
Author(s):  
HJ Weinstein ◽  
RJ Mayer ◽  
DS Rosenthal ◽  
FS Coral ◽  
BM Camitta ◽  
...  
Keyword(s):  
Complete Remission ◽  
Maintenance Therapy ◽  
Induction Chemotherapy ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Kaplan Meier ◽  
High Incidence ◽  
Acute Myelogenous ◽  
Leukemia In Children

Abstract We designed a protocol (VAPA) that featured 14 mo of intensive postremission induction chemotherapy in an effort to improve remission durations for patients with acute myelogenous leukemia (AML). One hundred and seven patients under 50 yr of age were entered into this study. The rate of complete remission is 70%. A Kaplan-Meier analysis of patients entering remission predicts that 56% +/- 7% (+/-SE) of patients less than 18 yr and 45% +/- 9% of patients aged 18–50 yr will remain in remission at 3 yr (median follow-up is 43 mo). Patients with the monocytic subtype had a statistically significant shorter duration of remission (2-sided p less than 0.05). There was a high incidence of primary CNS relapse in children. Thirty-one of 41 patients who completed the regimen remain in remission without maintenance therapy. We conclude that the VAPA protocol continues to offer a promising approach to treatment of AML.

Survivorship in AML – a landmark analysis on the outcomes of acute myelogenous leukemia patients after maintaining complete remission for at least 3 years

2020 ◽  
Vol 61 (13) ◽  
pp. 3120-3127 ◽  
Author(s):  
Catherine Kendall Major ◽  
Hagop Kantarjian ◽  
Koji Sasaki ◽  
Gautam Borthakur ◽  
Tapan Kadia ◽  
...  
Keyword(s):  
Complete Remission ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Landmark Analysis ◽  
Acute Myelogenous

Heterogeneity in the specific activity and methotrexate sensitivity of dihydrofolate reductase from blast cells of acute myelogenous leukemia patients.

1985 ◽  
Vol 3 (11) ◽  
pp. 1545-1552 ◽  
Author(s):  
S Dedhar ◽  
D Hartley ◽  
D Fitz-Gibbons ◽  
G Phillips ◽  
J H Goldie
Keyword(s):  
Dihydrofolate Reductase ◽  
Acute Myelogenous Leukemia ◽  
Specific Activity ◽  
Reductase Activity ◽  
Myelogenous Leukemia ◽  
Mechanisms Of Resistance ◽  
Clinical Resistance ◽  
Dihydrofolate Reductases ◽  
Acute Myelogenous ◽  
Blast Cells

Dihydrofolate reductase activity was found to be highly heterogeneous in terms of its specific activity and methotrexate sensitivity in the blast cells of patients with acute myelogenous leukemia. None of the patients had previously been treated with methotrexate (MTX). The blast cells of four of 12 patients studied contained methotrexate-insensitive forms of dihydrofolate reductase, and the blast cells of three (distinct from the four mentioned previously) of the 12 had significantly higher dihydrofolate reductase activities than the rest. The presence of MTX-insensitive dihydrofolate reductases and high levels of enzyme activity represent intrinsic mechanisms of resistance and may explain the apparent clinical resistance of acute myelogenous leukemia to methotrexate.

scholarly journals Autologous leukemia-specific T-cell-mediated lymphocytotoxicity in patients with acute myelogenous leukemia.

1978 ◽  
Vol 147 (3) ◽  
pp. 912-922 ◽  
Author(s):  
S K Lee ◽  
R T Oliver
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Blast Cell ◽  
Third Party ◽  
Myelogenous Leukemia ◽  
Target Antigen ◽  
Leukemic Blast ◽  
Crossover Studies ◽  
Acute Myelogenous ◽  
Blast Cells ◽  
Short Term Culture

Short-term culture of acute myelogenous leukemia patient's remission lymphocytes with inactivated autologous leukemic blast cells plus allogeneic lymphocytes, generated effector T lymphocytes which were cytotoxic for the specific autologous blast cell in 11 of 14 patients studied. Experiments using Daudi and Molt 4 lymphoblastoid cell lines as third-party helper cell suggest that an HLA D locus incompatability is necessary to provide effective help in this system. Cold target inhibition experiments, crossover studies between pairs of patients, and experiments with allogeneic leukemic blast cells as priming stimulus suggest that the target antigen is only present on the specific autologous blast cell.

scholarly journals Mutation of the p53 gene in human acute myelogenous leukemia

Blood ◽  
1991 ◽  
Vol 77 (7) ◽  
pp. 1500-1507 ◽  
Author(s):  
JM Slingerland ◽  
MD Minden ◽  
S Benchimol
Keyword(s):  
Acute Myelogenous Leukemia ◽  
P53 Protein ◽  
Point Mutations ◽  
P53 Gene ◽  
Myelogenous Leukemia ◽  
Wild Type ◽  
P53 Expression ◽  
Coding Sequence ◽  
Acute Myelogenous ◽  
Blast Cells

Abstract Heterogeneity of p53 protein expression is seen in blast cells of patients with acute myelogenous leukemia (AML). p53 protein is detected in the blasts of certain AML patients but not in others. We have identified p53 protein variants with abnormal mobility on gel electrophoresis and/or prolonged half-life (t 1/2). We have sequenced the p53 coding sequence from primary blast cells of five AML patients and from the AML cell line (OCIM2). In OCIM2, a point mutation in codon 274 was identified that changes a valine residue to aspartic acid. A wild type p53 allele was not detected in these cells. Two point mutations (codon 135, cysteine to serine; codon 246, methionine to valine) were identified in cDNA from blasts of one AML patient. Both mutations were present in blast colonies grown from single blast progenitor cells, indicating that individual leukemia cells had sustained mutation of both p53 alleles. The cDNAs sequenced from blast samples of four other patients, including one with prolonged p53 protein t 1/2 and one with no detectable p53 protein, were fully wild type. Thus, the heterogeneity of p53 expression cannot be explained in all cases by genetic change in the p53 coding sequence. The prolonged t 1/2 of p53 protein seen in some AML blasts may therefore reflect changes not inherent to p53. A model is proposed in which mutational inactivation of p53, although not required for the evolution of neoplasia, would confer a selective advantage, favoring clonal outgrowth during disease progression.

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