Colony-stimulating Factors for Prevention and Treatment of Infectious Complications in Patients with Acute Myelogenous Leukemia

Overview

Journal Cochrane Database Syst Rev

Publisher Wiley

Specialties General Medicine
Health Services

Date 2012 Jun 15

PMID 22696376

Citations 12

Authors

Ronit Gurion

Yulia Belnik-Plitman

Anat Gafter-Gvili

Mical Paul

Liat Vidal

Isaac Ben-Bassat

Ofer Shpilberg

Pia Raanani

Affiliations

Soon will be listed here.

Abstract

Background: Acute myelogenous leukemia (AML) is a fatal bone marrow cancer. Colony-stimulating factors (CSFs) are frequently administered during and after chemotherapy to reduce complications. However, their safety with regard to disease-related outcomes and survival in AML is unclear. Therefore, we performed a systematic review and meta-analysis to evaluate the impact of CSFs on patient outcomes, including survival.

Objectives: To assess the safety/efficacy of CSFs with regard to disease-related outcomes and survival in patients with AML.

Search Methods: We conducted a comprehensive search strategy. We identified relevant randomized clinical trials by searching the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 7), MEDLINE (January 1966 to July 2010), LILACS (up to December 2009), databases of ongoing trials and relevant conference proceedings.

Selection Criteria: Randomized controlled trials that compared the addition of CSFs during and following chemotherapy to chemotherapy alone in patients with AML. We excluded trials evaluating the role of CSFs administered for the purpose of stem cell collection and/or priming (e.g. before and/or only for the duration of chemotherapy).

Data Collection And Analysis: Two review authors appraised the quality of trials and extracted data. For each trial, we expressed results as relative risk (RR) with 95% confidence intervals (CI) for dichotomous data. We analyzed time-to-event outcomes as hazard ratios (HRs).

Main Results: The search yielded 19 trials including 5256 patients. The addition of CSFs to chemotherapy yielded no difference in all-cause mortality at 30 days and at the end of follow up (RR 0.97; 95% CI 0.80 to 1.18 and RR 1.01; 95% CI 0.98 to 1.05, respectively) or in overall survival (HR 1.00; 95% 0.93 to 1.08). There was no difference in complete remission rates (RR 1.03; 95% CI 0.99 to 1.07), relapse rates (RR 0.97; 95% CI 0.89 to 1.05) and disease-free survival (HR 1.00; 95% CI 0.90 to 1.13). CSFs did not decrease the occurrence of bacteremias (RR 0.96; 95% CI 0.82 to 1.12), nor the occurrence of invasive fungal infections (RR 1.40; 95% CI 0.90 to 2.19). CSFs marginally increased adverse events requiring discontinuation of CSFs as compared to the control arm (RR 1.33; 95% CI 1.00 to 1.56).

Authors' Conclusions: In summary, colony-stimulating factors should not be given routinely to acute myelogenous leukemia patients post-chemotherapy since they do not affect overall survival or infectious parameters including the rate of bacteremias and invasive fungal infections.

Citing Articles

Current state and future opportunities in granulocyte colony-stimulating factor (G-CSF).

Link H Support Care Cancer. 2022; 30(9):7067-7077.

PMID: 35739328 PMC: 9225876. DOI: 10.1007/s00520-022-07103-5.

Neutropenia and Infection Prophylaxis in Childhood Cancer.

Villeneuve S, Aftandilian C Curr Oncol Rep. 2022; 24(6):671-686.

PMID: 35230594 PMC: 8885776. DOI: 10.1007/s11912-022-01192-5.

Strategies to generate functionally normal neutrophils to reduce infection and infection-related mortality in cancer chemotherapy.

Abdel-Azim H, Sun W, Wu L Pharmacol Ther. 2019; 204:107403.

PMID: 31470030 PMC: 6881549. DOI: 10.1016/j.pharmthera.2019.107403.

A CD123-targeting antibody-drug conjugate, IMGN632, designed to eradicate AML while sparing normal bone marrow cells.

Kovtun Y, Jones G, Adams S, Harvey L, Audette C, Wilhelm A Blood Adv. 2018; 2(8):848-858.

PMID: 29661755 PMC: 5916008. DOI: 10.1182/bloodadvances.2018017517.

A phase I study of selinexor in combination with high-dose cytarabine and mitoxantrone for remission induction in patients with acute myeloid leukemia.

Wang A, Weiner H, Green M, Chang H, Fulton N, Larson R J Hematol Oncol. 2018; 11(1):4.

PMID: 29304833 PMC: 5756334. DOI: 10.1186/s13045-017-0550-8.

References

Heil G, Hoelzer D, Sanz M, Lechner K, Noens L, Szer J . Long-term survival data from a phase 3 study of Filgrastim as an adjunct to chemotherapy in adults with de novo acute myeloid leukemia. Leukemia. 2006; 20(3):404-9. DOI: 10.1038/sj.leu.2404090. View

Takeshita A, Ohno R, Hirashima K, Toyama K, Okuma M, Saito H . [A randomized double-blind controlled study of recombinant human granulocyte colony-stimulating factor in patients with neutropenia induced by consolidation chemotherapy for acute myeloid leukemia. (rG.CSF clinical study group)]. Rinsho Ketsueki. 1995; 36(6):606-14. View

Lowenberg B, Salem M, Delwel R . Effects of recombinant multi-CSF, GM-CSF, G-CSF and M-CSF on the proliferation and maturation of human AML in vitro. Blood Cells. 1988; 14(2-3):539-49. View

Zittoun R, Suciu S, Mandelli F, de Witte T, Thaler J, Stryckmans P . Granulocyte-macrophage colony-stimulating factor associated with induction treatment of acute myelogenous leukemia: a randomized trial by the European Organization for Research and Treatment of Cancer Leukemia Cooperative Group. J Clin Oncol. 1996; 14(7):2150-9. DOI: 10.1200/JCO.1996.14.7.2150. View

Bernell P, Kimby E, Hast R . Recombinant human granulocyte-macrophage colony-stimulating factor in combination with standard induction chemotherapy in acute myeloid leukemia evolving from myelodysplastic syndromes: a pilot study. Leukemia. 1994; 8(10):1631-9. View

Takeyama H, Yamada H, Emi N, Saito H, Takeshita A, Ohno R . [Efficacy of early administration of G-CSF after intensive chemotherapy in acute leukemia: a randomized controlled trial. Tokai Infection Study Group on Hematological Disorders]. Rinsho Ketsueki. 1995; 36(11):1257-65. View

Kern W, Aul C, Maschmeyer G, Kuse R, Kerkhoff A, Eimermacher H . Granulocyte colony-stimulating factor shortens duration of critical neutropenia and prolongs disease-free survival after sequential high-dose cytosine arabinoside and mitoxantrone (S-HAM) salvage therapy for refractory and relapsed acute myeloid.... Ann Hematol. 1998; 77(3):115-22. DOI: 10.1007/s002770050425. View

DerSimonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials. 1986; 7(3):177-88. DOI: 10.1016/0197-2456(86)90046-2. View

Dekker A, Bulley S, Beyene J, Dupuis L, Doyle J, Sung L . Meta-analysis of randomized controlled trials of prophylactic granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor after autologous and allogeneic stem cell transplantation. J Clin Oncol. 2006; 24(33):5207-15. DOI: 10.1200/JCO.2006.06.1663. View

10.

Bennett J, Catovsky D, Daniel M, Flandrin G, GALTON D, Gralnick H . Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol. 1976; 33(4):451-8. DOI: 10.1111/j.1365-2141.1976.tb03563.x. View

11.

Higgins J, Thompson S . Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21(11):1539-58. DOI: 10.1002/sim.1186. View

12.

Park L, Waldron P, Friend D, Sassenfeld H, Price V, Anderson D . Interleukin-3, GM-CSF, and G-CSF receptor expression on cell lines and primary leukemia cells: receptor heterogeneity and relationship to growth factor responsiveness. Blood. 1989; 74(1):56-65. View

13.

Lowenberg B, van Putten W, Theobald M, Gmur J, Verdonck L, Sonneveld P . Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia. N Engl J Med. 2003; 349(8):743-52. DOI: 10.1056/NEJMoa025406. View

14.

Lowenberg B, Suciu S, Archimbaud E, Ossenkoppele G, Verhoef G, Vellenga E . Use of recombinant GM-CSF during and after remission induction chemotherapy in patients aged 61 years and older with acute myeloid leukemia: final report of AML-11, a phase III randomized study of the Leukemia Cooperative Group of European.... Blood. 1997; 90(8):2952-61. View

15.

Ohno R, Naoe T, Kanamaru A, Yoshida M, Hiraoka A, Kobayashi T . A double-blind controlled study of granulocyte colony-stimulating factor started two days before induction chemotherapy in refractory acute myeloid leukemia. Kohseisho Leukemia Study Group. Blood. 1994; 83(8):2086-92. View

16.

Beksac M, Ali R, Ozcelik T, Ozcan M, Ozcebe O, Bayik M . Short and long term effects of granulocyte colony-stimulating factor during induction therapy in acute myeloid leukemia patients younger than 65: results of a randomized multicenter phase III trial. Leuk Res. 2010; 35(3):340-5. DOI: 10.1016/j.leukres.2010.07.005. View

17.

Inoue C, Murate T, Hotta T, Saito H . Response of leukemic cells to the sequential combination of GM-CSF and G-CSF. Int J Cell Cloning. 1990; 8(1):54-62. DOI: 10.1002/stem.5530080107. View

18.

Lehrnbecher T, Zimmermann M, Reinhardt D, Dworzak M, Stary J, Creutzig U . Prophylactic human granulocyte colony-stimulating factor after induction therapy in pediatric acute myeloid leukemia. Blood. 2006; 109(3):936-43. DOI: 10.1182/blood-2006-07-035915. View

19.

Buchner T, Berdel W, Hiddemann W . Priming with granulocyte colony-stimulating factor--relation to high-dose cytarabine in acute myeloid leukemia. N Engl J Med. 2004; 350(21):2215-6. DOI: 10.1056/NEJM200405203502124. View

20.

Maslak P, Weiss M, Berman E, Yao T, Tyson D, Golde D . Granulocyte colony-stimulating factor following chemotherapy in elderly patients with newly diagnosed acute myelogenous leukemia. Leukemia. 1996; 10(1):32-9. View