scholarly journals Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by the Eastern Cooperative Oncology Group (E1996)

Blood ◽  
2009 ◽  
Vol 114 (12) ◽  
pp. 2393-2400 ◽  
Author(s):  
Peter L. Greenberg ◽  
Zhuoxin Sun ◽  
Kenneth B. Miller ◽  
John M. Bennett ◽  
Martin S. Tallman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Eastern Cooperative Oncology Group ◽  
Flow Cytometric Analysis ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Phase 3 ◽  
Stimulating Factor ◽  
Acute Myeloid

Abstract This phase 3 prospective randomized trial evaluated the efficacy and long-term safety of erythropoietin (EPO) with or without granulocyte colony-stimulating factor plus supportive care (SC; n = 53) versus SC alone (n = 57) for the treatment of anemic patients with lower-risk myelodysplastic syndromes. The response rates in the EPO versus SC alone arms were 36% versus 9.6%, respectively, at the initial treatment step, 47% in the EPO arm, including subsequent steps. Responding patients had significantly lower serum EPO levels (45% vs 5% responses for levels < 200 mU/mL vs ≥ 200 mU/mL) and improvement in multiple quality-of-life domains. With prolonged follow-up (median, 5.8 years), no differences were found in overall survival of patients in the EPO versus SC arms (median, 3.1 vs 2.6 years) or in the incidence of transformation to acute myeloid leukemia (7.5% and 10.5% patients, respectively). Increased survival was demonstrated for erythroid responders versus nonresponders (median, 5.5 vs 2.3 years). Flow cytometric analysis showed that the percentage of P-glycoprotein+ CD34+ marrow blasts was positively correlated with longer overall survival. In comparison with SC alone, patients receiving EPO with or without granulocyte colony-stimulating factor plus SC had improved erythroid responses, similar survival, and incidence of acute myeloid leukemia transformation.

scholarly journals Efficacy and Safety of DAC Combined with CAG Regimen (decitabine in combined with aclacinomycin, cytarabine and G-CSF) As a Second Induction Regimen Compared with Non-DAC Regimen for Acute Myeloid Leukemia Who Failed the First Course of Standard Induction IA Chemotherapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5104-5104
Author(s):  
Yili Chen ◽  
Min Dai ◽  
Qifa Liu
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Granulocyte Colony Stimulating Factor ◽  
Efficacy And Safety ◽  
Colony Stimulating Factor ◽  
Induction Regimen ◽  
Stimulating Factor ◽  
Acute Myeloid ◽  
Intermediate Dose

BACKGROUND: Acute myeloid leukemia (AML) patients who failed the first course of standard induction chemotherapy remain a challenge owing to poor response to the second induction regimen. We retrospectively compared the efficacy and safety of DAC+CAG regimen with non-DAC regimen in AML patients who failed the first course of standard induction regimen. MATERIALS AND METHODS: The three regimens consisted of (1) DAC combined with CAG regimen (decitabine, cytarabine, aclarubicin and granulocyte colony stimulating factor, n=25) ; (2) the repeated first course (IA 3+7, n=30); (3) Intermediate-dose AraC -based chemotherapy including IA 3+3 (idarubicin, Ara-C n=14) or CLAG (cladribine, aclarubicin and granulocyte colony stimulating factor, n=15). RESULTS: Our data indicate that after the second course, the overall response (OR, complete remission [CR]+partial remission [PR]) rates in DAC+CAG group was higher than the Intermediate-dose AraC -based group (80% vs 48.3%, P= 0.049), whereas the CR rates among 3 groups were not statistically different (P = 0.09). The overall survival (OS) of DAC+CAG group is longer than IA 3+7 group and Intermediate-dose AraC -based group with significance (21 months VS 18.5 months, P=0.038 and 21 months VS 10 months, P=0.023, respectively), the relapse-free survival (RFS) of DAC+CAG group is longer than Intermediate-dose AraC-based group (16 months VS 8.5 months, P=0.016), though there was no significant difference in overall survival (OS) of the transplanted patients among the 3 groups (P = 0.064). The median duration of thrombocytopenia in the DAC+CAG group is shorter than IA 3+7 group and Intermediate-dose AraC-based group (10 days vs 12 days, P<0.001 and 10 days vs 14 days P=0.023, respectively). Fewer incidence of lung infection and febrile neutropenia in the DAC+CAG group than other two groups (P=0.018 and P=0.025, respectively) were observed, no patients died within 4 weeks after initiating the second induction course in the DAC+CAG group whereas 2 patients died in the Intermediate-dose AraC -based group. CONCLUSION: Our data indicate that DAC combined with CAG regimen may represent a better alternative option with good response and safety for AML patients who failed the first course of standard induction chemotherapy. Disclosures No relevant conflicts of interest to declare.

Granulocyte Colony-Stimulating Factor (G-CSF) Treatment of Childhood Acute Myeloid Leukemias That Overexpress the Differentiation-Defective G-CSF Receptor Isoform IV Is Associated With a Higher Incidence of Relapse

2010 ◽  
Vol 28 (15) ◽  
pp. 2591-2597 ◽  
Author(s):  
Stephanie Ehlers ◽  
Christin Herbst ◽  
Martin Zimmermann ◽  
Nicole Scharn ◽  
Manuela Germeshausen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Children And Adolescents ◽  
Cumulative Incidence ◽  
Myeloid Leukemia ◽  
Cell Surface Expression ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor ◽  
Acute Myeloid ◽  
Factor G

Purpose This prospective, multicenter Acute Myeloid Leukemia Berlin-Frankfurt-Muenster (AML-BFM) 98 study randomly tested the ability of granulocyte colony-stimulating factor (G-CSF) to reduce infectious complications and to improve outcomes in children and adolescents with acute myeloid leukemia (AML). However, a trend toward an increased incidence of relapses in the standard-risk (SR) group after G-CSF treatment was observed. Patients and Methods Of 154 SR patients in the AML-BFM 98 cohort, 50 patients were tested for G-CSF receptor (G-CSFR) RNA isoform I and IV expression, G-CSFR cell surface expression, and acquired mutations in the G-CSFR gene. Results In patients randomly assigned to receive G-CSF after induction, 16 patients overexpressing the G-CSFR isoform IV showed an increased 5-year cumulative incidence of relapse (50% ± 13%) compared with 14 patients with low-level isoform IV expression (14% ± 10%; log-rank P = .04). The level of G-CSFR isoform IV had no significant effect in patients not receiving G-CSF (P = .19). Multivariate analyses of the G-CSF–treated subgroup, including the parameters G-CSFR isoform IV overexpression, sex, and favorable cytogenetics as covariables, revealed the prognostic relevance of G-CSFR isoform IV overexpression for 5-year event-free survival (P = .031) and the 5-year cumulative incidence of relapse (P = .049). Conclusion Our results demonstrate that children and adolescents with AMLs that overexpress the differentiation-defective G-CSFR isoform IV respond to G-CSF administration after induction, but with a significantly higher incidence of relapse.

scholarly journals A point mutation in the granulocyte colony-stimulating factor receptor (G-CSF-R) gene in a case of acute myeloid leukemia results in the overexpression of a novel G-CSF-R isoform

Blood ◽  
1995 ◽  
Vol 85 (4) ◽  
pp. 902-911 ◽  
Author(s):  
F Dong ◽  
M van Paassen ◽  
C van Buitenen ◽  
LH Hoefsloot ◽  
B Lowenberg ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Point Mutation ◽  
Myeloid Leukemia ◽  
Receptor Gene ◽  
Splice Donor Site ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Cytoplasmic Region ◽  
Stimulating Factor ◽  
Acute Myeloid

A novel human granulocyte colony-stimulating factor (G-CSF) receptor isoform, designated SD, has been identified in which the distal C- terminal cytoplasmic region, previously shown to be essential for maturation signalling, is substituted by an altered C-terminus. The SD receptor has a high affinity for G-CSF and retains the membrane- proximal cytoplasmic region known to be sufficient for proliferative signalling. Nonetheless, the SD isoform lacks the ability to transduce growth signals in murine BAF3 cells and, in contrast to the wild-type G- CSF receptor, is scarcely capable of activating JAK2 kinase. Expression of SD receptor was found to be low in normal granulocytes, but was significantly increased in a patient with acute myeloid leukemia (AML). The leukemic cells of this patient harbour a point mutation in the SD splice donor site of the G-CSF receptor gene. These findings provide the first evidence that mutations in the G-CSF receptor gene can occur in certain cases of clinical de novo AML. The possible contribution of defective G-CSF receptor signalling to leukemogenesis is discussed.

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