Fludarabine, cytarabine, granulocyte-colony stimulating factor and amsacrine: an effective salvage therapy option for acute myeloid leukemia at first relapse

2012 ◽  
Vol 54 (2) ◽  
pp. 336-341 ◽  
Author(s):  
Chun Yew Fong ◽  
George Grigoriadis ◽  
Jay Hocking ◽  
John Coutsouvelis ◽  
Jenny Muirhead ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Salvage Therapy ◽  
Myeloid Leukemia ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Therapy Option ◽  
First Relapse ◽  
Stimulating Factor ◽  
Acute Myeloid

scholarly journals Phase I/II Study of CPX-351 Followed by Fludarabine, Cytarabine, and Granulocyte-Colony Stimulating Factor for Children With Relapsed Acute Myeloid Leukemia: A Report From the Children’s Oncology Group

2020 ◽  
Vol 38 (19) ◽  
pp. 2170-2177
Author(s):  
Todd M. Cooper ◽  
Michael J. Absalon ◽  
Todd A. Alonzo ◽  
Robert B. Gerbing ◽  
Kasey J. Leger ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Dose Finding ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
First Relapse ◽  
Grade 3 ◽  
Stimulating Factor ◽  
Relapsed Acute Myeloid Leukemia ◽  
Acute Myeloid

PURPOSE Effective regimens are needed for children with relapsed acute myeloid leukemia (AML). AAML1421 is a phase I/II study of CPX-351, a liposomal preparation of daunorubicin and cytarabine. AAML1421 sought to determine the recommended phase II dose (RP2D) of CPX-351 and the response rate after up to 2 cycles of therapy. PATIENTS AND METHODS Children > 1 and ≤ 21 years of age with relapsed/refractory AML were eligible for dose finding; those in first relapse were eligible for the efficacy phase. Dose-limiting toxicity (DLT) assessment occurred during cycle 1. Two cycles of therapy were offered (cycle 1: CPX-351; cycle 2: FLAG [fludarabine 30 mg/m2/dose on days 1-5; cytarabine 2,000 mg/m2/dose on days 1-5; and granulocyte-colony stimulating factor 5 µg/kg/dose, days 1-5 and day 15 through absolute neutrophil count > 500/µL]). Response was assessed after each cycle. RESULTS Thirty-eight patients enrolled: 6 in the dose-finding phase and 32 in the efficacy phase. During dose finding, 1/6 patients experienced a DLT (grade 3 decrease in ejection fraction). The RP2D was 135 units/m2 on days 1, 3, and 5. Toxicities of grade ≥ 3 during cycle 1 included fever/neutropenia (45%), infection (47%), and rash (40%). There was no toxic mortality. Best responses included 20 complete response (CR; 54%), 5 CR with partial recovery of platelet count (CRp; 14%), and 5 CR with incomplete blood count recovery (14%). Twenty-one of 25 with CR/CRp had no detectable residual disease (RD; 84%) by flow cytometry. Hematopoietic stem cell transplantation (HSCT) was used as consolidation in 29/30 responders (96.7%); 20/25 (80%) had no RD before HSCT. CONCLUSION The RP2D of CPX-351 is 135 units/m2/dose on days 1, 3, and 5. Toxicity was manageable, and protocol therapy was effective. Response rates are superior to prior published North American cooperative group clinical trials for children with AML in first relapse.

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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