Antifugal Effect of Recombinant Human Granulocyte-macrophage Stimulating Factor (rhGM-CSF) in Patients Post Allo-HSCT

Phase 4

Completed

Interventions: Drug: rhG-CSF group
Drug: rhGM-CSF group
Drug: rhG-CSF+rhGM-CSF group

Brief Summary: We conducted a prospective, multicenter, open-label randomized trial to compare the antifungal effect of Recombinant Human Granulocyte-macrophage Stimulating Factor (rhGM-CSF), Recombinant Human Granulocyte Stimulating Factor (rhG-CSF) or a combination of rhGM-CSF and rhG-CSF for neutropenic patients undergoing allogeneic stem cell transplantation.

Detailed Description: From Sept 2009 to Dec 2012, we recruited consecutive patients with hematological diseases undergoing allogeneic stem cell transplantation at 5 institutions in China. Recipients between ages of 14 to 60 years old were eligible. Eligible patients were randomized to receive once daily subcutaneous 5-7μg/kg/d GM-CSF (Molgramostim, TOPLEUCON®; Xiamen Amoytop Biotech Co., Ltd., China) (GM-CSF group), 5-7μg/kg/d G-CSF (G-CSF group), or a combination of 2-3μg/kg/d GM-CSF and 2-3μg/kg/d G-CSF each (G-CSF+GM-CSF group). Administration of CSFs was started on day 5 post-transplant and continued until recovery from neutropenia (absolute neutrophil count \[ANC\] \> 1.5×10(9)/L for 2 consecutive days). If absolute neutrophil count (ANC) decreased to \< 1.5×10(9)/L within 5 days after withdrawal of CSFs, the same CSF would be resumed until the absolute neutrophil count (ANC) reached 1.5×10(9)/L again. All patients received antimicrobial prophylaxis with oral levofloxacin 500 mg daily and antifungal prophylaxis with oral fluconazole 200 mg daily.

Recruitment & Eligibility

Inclusion Criteria

Age 14~60 years old
Allogenic hematological stem cell transplantation(HSCT) patients.
Cardiac ejection factor ≥ normal upper limit, Aspartate aminotransferase and/or Alanine aminotransferase < 2 upper limit of normal, and/or total bilirubin < 2.5 upper limit of normal, creatinine < upper limit of normal.
Informed consent.

Exclusion Criteria

Evidence of proven, probable or possible fungal infection at the time of enrollment.
Patients were receiving anti-fungal treatment with proven SFI before transplantation.
A history of hypersensitivity to G-CSF or GM-CSF.

Arm && Interventions

Group	Intervention	Description
rhG-CSF group	rhG-CSF group	subcutaneous 5-7μg/kg/d Recombinant Human Granulocyte Stimulating Factor (rhG-CSF) once daily
rhGM-CSF group	rhGM-CSF group	subcutaneous 5-7μg/kg/d Recombinant Human Granulocyte-macrophage Stimulating Factor (rhGM-CSF) once daily
rhG-CSF+rhGM-CSF group	rhG-CSF+rhGM-CSF group	a combination of 2-3μg/kg/d Recombinant Human Granulocyte-macrophage Stimulating Factor (rhGM-CSF) and 2-3μg/kg/d Recombinant Human Granulocyte Stimulating Factor (rhG-CSF) each

Primary Outcome Measures

Name	Time	Method
Incidences of Invasive Fungal Diseases (IFD)	100 day post transplant	The incidence of proven and probable Invasive fungal diseases (IFD) within 100 days post transplantation

Secondary Outcome Measures

Name	Time	Method
Hematological Engraftment	100 days post transplant	The median time of neutrophil and platelet recovery .
Hemorrhage Related Mortality	3-1099 days	Hemorrhage related mortality after a median follow-up of 600 days
Incidence of Ⅱ- Ⅳ Acute Graft Versus Host Disease (aGVHD)	100 days post transplant	Incidence of Ⅱ- Ⅳacute graft versus host disease (aGVHD) within 100 days after allogeneic stem cell transplantation (Allo-HSCT).The severity of acute GVHD in the three main target organs (skin, liver, gastrointestinal tract) was assigned stage 1 to 4 based on accepted criteria (Consensus Conference on Acute GVHD Grading).
IFD Related Mortality	3-1099 days	IFD-related mortalities after a median follow-up of 600 days.
Transplant Related Mortality	100 days post transplant	Transplant related mortality within 100 days after Allogeneic Stem Cell Transplantation (Allo-HSCT).
Infection Related Mortality	3～1099 days)	Infection related mortality after a median follow-up of 600 days.
Relapse Related Mortality	3～1099 days	Relapse related mortality after a median follow-up of 600 days.
Graft Versus Host Disease (aGVHD) Related Mortality	3-1099 days	Graft versus host disease (aGVHD) related mortality after a median follow-up of 600 days .

Locations (5): The First Affiliated Hospital of Guangxi Medical University
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Nanning, Guangxi, China
Henan Cancer Hospital
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Zhengzhou, Henan, China
The First Affiliated Hospital of Xinjiang Medical University
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Urumqi, Xinjiang, China
Wuhan Tongji Hospital
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Wuhan, Hubei, China
Shanghai First People's Hospital
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Shanghai, Shanghai, China