scholarly journals Etoposide, Cytarabine and Mitoxantrone- or Fludarabine, Cytarabine and Granulocyte Colony-Stimulating Factor-Based Intensive Reinduction Chemotherapy Is Recommended for Children with Relapsed Acute Myeloid Leukemia: The Results from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05R Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-6
Author(s):  
Hiroshi Moritake ◽  
Shiro Tanaka ◽  
Takako Miyamura ◽  
Hideki Nakayama ◽  
Norio Shiba ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myeloid Leukemia ◽  
Survival Rates ◽  
Study Group ◽  
Overall Survival Rate ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Pediatric Leukemia ◽  
Lymphoma Study Group ◽  
Stimulating Factor

Background:The current event-free survival rates of children with acute myeloid leukemia (AML) approach 60%, with hematopoietic cell transplantation (HCT) as an effective second-line therapy and improvements in supportive care; however, the overall survival rates of children with relapsed AML still remains 70%, which is an unsatisfactory situation that urgently needs to be solved. Patients & Methods:In order to identify prognostic factors and improve their prognosis, we analyzed 111 patients with relapsed disease after treatment with the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 protocol, who were registered in the retrospective JPLSG AML-05R study. We collected the following data: age at relapse, time from the diagnosis to relapse, site of relapse, FAB classification, chromosomal analysis results, reinduction chemotherapy regimen, rate of achieving a second complete remission (CR2) after initial reinduction therapy, detailed information on HCT, outcome and cause of death. Moreover, ninety-three leukemic samples obtained from 111 patients at the time of their diagnosis were available for a genetic analysis. Mutational analyses ofFLT3-ITD,KIT, N-andK-RAS, NPM1,WT1,andKMT2A-partial tandem duplication were performed. Screening ofNUP98-NSD1was also performed. The high or low expression ofMECOMandPRDM16were determined based on theABL1ratio. Results:The 5-year overall survival rate was 36.1%. t(8;21) was found in 27 patients and inv(16) was found in 5 patients.KMT2Arearrangement was found in 23 patients (24.7%).KITmutations were found in 17 patients (17.5%). The following mutations were also detected:FLT3-ITD (n=10),N-RAS(n=10),WT1(n=7),K-RAS(n=4),NUP98-NSD1(n=2),KMT2A-PTD (n=2), andNPM1(n=2). The high expression ofMECOMandPRDM16was found in 24 (25.8%) and 32 (34.4%) patients, respectively. A genetic analysis revealed the prognostic significance ofFLT3-ITD as a poor prognostic marker (p=0.04) and core binding factor-AML, t(8;21) and inv(16), as a good prognostic marker (p<0.01). The five-year overall survival rate in the AML-05 risk groups were as follows: high risk, 14.7%; intermediate risk, 32.3%; and low risk 61.7% (p<0.01). The major determinant of survival was duration from the diagnosis to relapse. The mean duration in the non-surviving group (10.1±4.1 months) was shorter than that in the surviving group (16.3±8.3 months) (p<0.01). Moreover, achieving CR2 prior to HCT was associated with a good prognosis (p<0.01). "Etoposide, cytarabine and mitoxantrone" (ECM)- or "fludarabine, cytarabine and granulocyte colony-stimulating factor" (FLAG)-based regimens were therefore recommended for reinduction therapy (p<0.01). Conclusions:Achieving CR2 prior to HCT by intensive reinduction chemotherapy, ECM, or FLAG, is important for improving the prognosis of patients with relapsed pediatric AML. Liposomal daunorubicin or 3 fractionated doses of gemtuzumab ozogamicin is an attractive option which is under consideration for addition to FLAG. Moreover, recent molecular targeted therapeutics, such as FLT3 inhibitors, may contribute to improving the prognosis of these patients. Larger prospective investigations are needed in order to establish individualized treatment strategies for patients with relapsed childhood AML. Disclosures No relevant conflicts of interest to declare.

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.

Leukostasis in Children and Adolescents with Chronic Myeloid Leukemia: Japanese Pediatric Leukemia/Lymphoma Study Group

2015 ◽  
Vol 63 (3) ◽  
pp. 406-411 ◽  
Author(s):  
Hidemitsu Kurosawa ◽  
Akihiko Tanizawa ◽  
Chikako Tono ◽  
Akihiro Watanabe ◽  
Haruko Shima ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Children And Adolescents ◽  
Myeloid Leukemia ◽  
Study Group ◽  
Pediatric Leukemia ◽  
Lymphoma Study Group

Use of nab-paclitaxel and gemcitabine in pancreatic cancer without granulocyte colony-stimulating factor: A multicenter real-world experience

2021 ◽  
pp. 107815522110386
Author(s):  
Angela Chen ◽  
Vincent H Ha ◽  
Sunita Ghosh ◽  
Carole R Chambers ◽  
Michael B Sawyer
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Free Survival ◽  
Colony Stimulating Factors ◽  
Median Progression Free Survival ◽  
Stimulating Factor

Introduction The metastatic pancreatic adenocarcinoma clinical trial (MPACT) trial established gemcitabine (gem) and nab-paclitaxel (nab) as a standard treatment for pancreatic cancer utilizing granulocyte colony-stimulating factors to manage neutropenia. This was a challenge for jurisdictions that do not use granulocyte colony-stimulating factors in palliative settings. We developed dosage guidelines to dose modify gem and nab without granulocyte colony-stimulating factors. We undertook a retrospective review to determine the efficacy and safety of these dose adjustment guidelines in the real world. Methods A multi-centered, retrospective chart review was performed on pancreatic patients between December 1, 2014, and August 21, 2018. Provincial electronic medical health records were reviewed. Using Log-rank statistics we determined the patient's progression-free survival and overall survival. Results Of 248 patients, 209 met patient selection criteria. Patients were excluded if they were lost to follow-up, on gem alone prior to nab/gem combination therapy or did not receive nab or gem. Patients who received nab/gem as first-line therapy had a median progression-free survival of 6.3 months (95% CI, 5.1–7.4), and median overall survival of 11.1 months (95% CI, 9.5–12.8). Those who received gem/nab in the second line had a median progression-free survival of 4.6 months (95% CI, 2.8–6.5), and median overall survival of 19.3 months (95% CI, 12.6–26.0). Conclusions The patient’s progression-free survival and overall survival taking nab/gem using our dose modification algorithm were equivalent or superior to the MPACT trial's progression-free survival and overall survival. Gem/nab can be given by our dose modification scheme without granulocyte colony-stimulating factor.

scholarly journals Granulocyte Colony-Stimulating Factor Treatment Before Radiotherapy Protects Against Radiation-Induced Liver Disease in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Isalira Peroba Rezende Ramos ◽  
Marlon Lemos Dias ◽  
Alan Cesar Nunes De Moraes ◽  
Fernanda Guimarães Meireles Ferreira ◽  
Sergio Augusto Lopes Souza ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Disease Model ◽  
Survival Rates ◽  
Radiotherapy Planning ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Before And After ◽  
Radiation Induced ◽  
Stimulating Factor

Radiation-induced liver disease (RILD) remains a major problem resulting from radiotherapy. In this scenario, immunotherapy with granulocyte colony-stimulating factor (G-CSF) arises as an attractive approach that might improve the injured liver. Here, we investigated G-CSF administration’s impact before and after liver irradiation exposure using an association of alcohol consumption and local irradiation to induce liver disease model in C57BL/6 mice. Male and female mice were submitted to a previous alcohol-induced liver injury protocol with water containing 5% alcohol for 90 days. Then, the animals were treated with G-CSF (100 μg/kg/d) for 3 days before or after liver irradiation (18 Gy). At days 7, 30, and 60 post-radiation, non-invasive liver images were acquired by ultrasonography, magnetic resonance, and computed tomography. Biochemical and histological evaluations were performed to verify whether G-CSF could prevent liver tissue damage or reverse the acute liver injury. Our data showed that the treatment with G-CSF before irradiation effectively improved morphofunctional parameters caused by RILD, restoring histological arrangement, promoting liver regeneration, preserving normal organelles distribution, and glycogen granules. The amount of OV-6 and F4/80-positive cells increased, and α-SMA positive cells’ presence was normalized. Additionally, prior G-CSF administration preserved serum biochemical parameters and increased the survival rates (100%). On the other hand, after irradiation, the treatment showed a slight improvement in survival rates (79%) and did not ameliorate RILD. Overall, our data suggest that G-CSF administration before radiation might be an immunotherapeutic alternative to radiotherapy planning to avoid RILD.

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.

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