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Int J Clin Exp Pathol 2011;4(6):596-605
Original Article
Dynamics of early histopathological changes in GVHD after
busulphan/cyclophosphamide conditioning regimen
Sulaiman Al-Hashmi, Zuzana Hassan, Behnam Sadeghi, Björn Rozell, Moustapha Hassan
Experimental Cancer Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Clinical Research Centre,
Karolinska University Hospital, Stockholm, Sweden; Department of Veterinary Disease Biology, Faculty of Life Sciences, University of
Copenhagen, Copenhagen, Denmark.
Received July 13, 2011; accepted July 27, 2011; Epub July 31, 2011; published August 15, 2011
Abstract: Hematopoietic stem cell transplantation (HSCT) is a curative treatment for otherwise incurable diseases. Conditioning regimen is an
important part of HSCT and consists of chemotherapy with or without irradiation. Conditioning exerts myelosuppressive, immunosuppressive
and antitumor effects, but also contributes to HSCT-related complications including graft-versus-host disease (GVHD). Since almost 50% of
the transplanted patients are conditioned with cytostatics without irradiation; we developed and characterized a GVHD mouse model following
conditioning with busulphan and cyclophosphamide. Recipient Balb/c female mice were treated with busulphan (20 mg/kg/day for 4 days) and
cyclophosphamide (100 mg/kg/day for two days). After one day rest, recipient mice were transplanted with 2x107 bone marrow and 3x107
spleen cells from male C57BL/6 (allogeneic group) or female Balb/c (syngeneic/control group) mice. The allogeneic, but not syngeneic
transplanted mice developed GVHD. Histopathology of the major internal organs (liver, pancreas, spleen, lungs, heart and kidney) was
examined before conditioning start, after conditioning’s end and 5, 7 and 21 days after transplantation using hematoxylin-eosin staining.
Decreased spleen cellularity and diminished glycogen content in the liver were observed after conditioning regimen. Histopathological
changes such as vasculitis, inflammation and apoptotic cell forms in liver, spleen, pancreas, lungs and heart were observed in allogeneic
transplanted mice, however, only hypocellular spleen and extramedullar hematopoiesis were detected in syngeneic transplanted animals. No
morphological changes were observed in kidney in both HSCT settings. This is the first study describing early histopathological changes after
conditioning regimen with busulphan/cyclophosphamide and dynamics of GVHD development in several major internal organs.
(IJCEP1107002).
Keywords: Graft-versus-host disease; hematopietic stem cell transplantation; mouse; conditioning regimen; busulphan; cyclophosphamide
Full text PDF
Address all correspondence to:
Zuzana Hassan, MD, PhD
Experimental Cancer Medicine
Clinical Research Centre, floor 6th
Novum
Karolinska University Hospital Huddinge
141 86 Stockholm
Sweden
Tel:+46 8 58583862
Fax: +46 8 58583800
Email: Zuzana.hassan@ki.se
Original Article
Dynamics of early histopathological changes in GVHD after
busulphan/cyclophosphamide conditioning regimen
Sulaiman Al-Hashmi, Zuzana Hassan, Behnam Sadeghi, Björn Rozell, Moustapha Hassan
Experimental Cancer Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Clinical Research Centre,
Karolinska University Hospital, Stockholm, Sweden; Department of Veterinary Disease Biology, Faculty of Life Sciences, University of
Copenhagen, Copenhagen, Denmark.
Received July 13, 2011; accepted July 27, 2011; Epub July 31, 2011; published August 15, 2011
Abstract: Hematopoietic stem cell transplantation (HSCT) is a curative treatment for otherwise incurable diseases. Conditioning regimen is an
important part of HSCT and consists of chemotherapy with or without irradiation. Conditioning exerts myelosuppressive, immunosuppressive
and antitumor effects, but also contributes to HSCT-related complications including graft-versus-host disease (GVHD). Since almost 50% of
the transplanted patients are conditioned with cytostatics without irradiation; we developed and characterized a GVHD mouse model following
conditioning with busulphan and cyclophosphamide. Recipient Balb/c female mice were treated with busulphan (20 mg/kg/day for 4 days) and
cyclophosphamide (100 mg/kg/day for two days). After one day rest, recipient mice were transplanted with 2x107 bone marrow and 3x107
spleen cells from male C57BL/6 (allogeneic group) or female Balb/c (syngeneic/control group) mice. The allogeneic, but not syngeneic
transplanted mice developed GVHD. Histopathology of the major internal organs (liver, pancreas, spleen, lungs, heart and kidney) was
examined before conditioning start, after conditioning’s end and 5, 7 and 21 days after transplantation using hematoxylin-eosin staining.
Decreased spleen cellularity and diminished glycogen content in the liver were observed after conditioning regimen. Histopathological
changes such as vasculitis, inflammation and apoptotic cell forms in liver, spleen, pancreas, lungs and heart were observed in allogeneic
transplanted mice, however, only hypocellular spleen and extramedullar hematopoiesis were detected in syngeneic transplanted animals. No
morphological changes were observed in kidney in both HSCT settings. This is the first study describing early histopathological changes after
conditioning regimen with busulphan/cyclophosphamide and dynamics of GVHD development in several major internal organs.
(IJCEP1107002).
Keywords: Graft-versus-host disease; hematopietic stem cell transplantation; mouse; conditioning regimen; busulphan; cyclophosphamide
Full text PDF
Address all correspondence to:
Zuzana Hassan, MD, PhD
Experimental Cancer Medicine
Clinical Research Centre, floor 6th
Novum
Karolinska University Hospital Huddinge
141 86 Stockholm
Sweden
Tel:+46 8 58583862
Fax: +46 8 58583800
Email: Zuzana.hassan@ki.se
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