Transfiion Medicine, 1992, 2, 195-1 99
Transfusion-associated graft-versus-host disease in patients with Hodgkin’s disease and T cell lymphoma T.P. Baglin, V. C. Joysey,** J. Horsford,** R. T. Johnson,? V. Broadbent$ and R.E. Marcus Departments of Haematology. **Tissue Typing, and SPaediatrics, AddenbrookeS Hospital, Cambridge, and the tCRC Mammalian Cell DNA Repair Research Group. University of Cambridge, U.K. Received 29 July 1991; acceptedfor publication 17 December 1991
disease were inconsistent with those of her parents and siblings, but HLA typing of her fibroblasts revealed that her true type was consistent with those of her parents and that her circulating lymphocytes were not genetically her own. The HLA types of the patient with T-cell lymphoma were inconsistent with those of her siblings which suggests, but, in the absence of other evidence, does not prove, chimaerism.
Two patients, one with Hodgkin’s disease and one with peripheral T cell lymphoma, developed transfusion-associated graft-versus-host disease 16 and 8 days after transfusion of red cell and platelet concentrates. Fever and skin rash were followed rapidly by an elevation of liver enzymes and the onset of diarrhoea and pancytopenia. Despite treatment with high-dose methyiprednisolone and anti-lymphocyte globulin, commenced within 7 and 2 days of the onset of rash, grade IV GvHD persisted and both patients died with severe pancytopenia. HLA types of peripheral lymphocytes of the patient with Hodgkin’s SUMMARY.
Key words: graft-versus-host disease, Hodgkin’s disease, T-cell lymphoma, transfusion.
Transfusion-associated graft-versus-host disease (TAGvHD) has now been reported in both immunosuppressed and immunocompetent patients (Hathaway ef al., 1965; von Fliedner et al., 1982; Arsura et al., 1988; Thaler et al., 1989). The development of graft-versushost disease (GvHD) is dependent on histocompatibility differences between donor and recipient, the presence of immunocompetent cells in the graft and the inability of the host to reject the immunocompetent donor cells (Billingham, 1966). In the case of the immunocompetent recipient these criteria are fulfilled in the HLA-heterozygous recipient who shares a haplotype with an HLA-homozygous donor. In the case of the immunosuppressed patient the risk factors for the development of GvHD have been poorly defined and reporting of cases and studies of the recipients’ immune status are required to permit more precise identification of patients a t risk (Anderson & Weinstein, 1990). We report two cases of fatal TAGvHD in patients with Hodgkin’s disease and T-cell lymphoma following transfusion of red cells and random donor platelets in the former and random donor platelets in the latter.
PATIENTS A N D M E T H O D S HLA-typing was performed by the microlymphocytotoxic assay using authenticated anti-HLA antisera obtained from the United Kingdom Transplant Service Support Authority. Tests were performed in duplicate and read either by phase-contrast microscopy after staining with eosin, or by fluorescent microscopy after staining with ethidium bromide and acridine orange. The percentage cell death was determined by two independent observers. Fibroblast cultures were established from skin biopsy by serial propagation of outgrowing cells from tissue fragments. Fibroblasts were grown in Eagle’s Minimal Essential Medium, supplemented with nonessential amino acids and 15% fetal calf serum. HLA typing was performed on early passage cultures (second to fifth) as in Johnson et al. (1989). Graft-versus-host disease was graded according to the Seattle scoring system (Thomas et al., 1975). Patient I
A 14-year-old female with stage I1 nodular sclerosing Hodgkin’s disease had completed six courses of ChlVPP (dose per course: 100 mg Chlorambucil, 10
Correspondence: Dr T. P. Baglin, Department of Haernatology, Addenbrooke’s Hospital, Cambridge CB2 2QQ, U.K.
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196
T. P. Baglin et al.
Fig. 1. Haematological parameters in patient 1 in relation to clinical events and treatment. (-0-) Neutrophils, (-O--) platelets.
mg/m2Vinblastine, 1000mg/m2Procarbazine, 350 mg/ m2 Prednisolone. Twenty days after completion of the final course of chemotherapy two units of packed cells and a platelet transfusion from five random donors were administered (haemoglobin 60 g/l, white cells 1-4x 109/1,platelets 48 x lo9/]). Eight days later a fever of 39.0"C and a widespread maculopapular rash developed and the patient was referred to our institute. The patient developed abdominal pain and diarrhoea, the ALT rose from 25 to 1390 pmols/l over 5 days and pancytopenia rapidly ensued (Fig. 1). Bone marrow aspirate and trephine biopsy indicated severe hypoplasia with large granular lymphocytes and vacuolated macrophages (Fig. 2). Immunophenotyping of bone marrow mononuclear cells, after separation on Ficoll, was performed on a Bekton Dickenson flow cytometer using commercial reagents., A predominant population of activated suppressor/cytotoxic lymphocytes was identified (CD2,93%; CD3,90%; CD4,9%; CD8, 82%; HLADr, 33%; CD19
Transfusion-associated graft-versus-host disease in patients with Hodgkin’s disease and T cell lymphoma T.P. Baglin, V. C. Joysey,** J. Horsford,** R. T. Johnson,? V. Broadbent$ and R.E. Marcus Departments of Haematology. **Tissue Typing, and SPaediatrics, AddenbrookeS Hospital, Cambridge, and the tCRC Mammalian Cell DNA Repair Research Group. University of Cambridge, U.K. Received 29 July 1991; acceptedfor publication 17 December 1991
disease were inconsistent with those of her parents and siblings, but HLA typing of her fibroblasts revealed that her true type was consistent with those of her parents and that her circulating lymphocytes were not genetically her own. The HLA types of the patient with T-cell lymphoma were inconsistent with those of her siblings which suggests, but, in the absence of other evidence, does not prove, chimaerism.
Two patients, one with Hodgkin’s disease and one with peripheral T cell lymphoma, developed transfusion-associated graft-versus-host disease 16 and 8 days after transfusion of red cell and platelet concentrates. Fever and skin rash were followed rapidly by an elevation of liver enzymes and the onset of diarrhoea and pancytopenia. Despite treatment with high-dose methyiprednisolone and anti-lymphocyte globulin, commenced within 7 and 2 days of the onset of rash, grade IV GvHD persisted and both patients died with severe pancytopenia. HLA types of peripheral lymphocytes of the patient with Hodgkin’s SUMMARY.
Key words: graft-versus-host disease, Hodgkin’s disease, T-cell lymphoma, transfusion.
Transfusion-associated graft-versus-host disease (TAGvHD) has now been reported in both immunosuppressed and immunocompetent patients (Hathaway ef al., 1965; von Fliedner et al., 1982; Arsura et al., 1988; Thaler et al., 1989). The development of graft-versushost disease (GvHD) is dependent on histocompatibility differences between donor and recipient, the presence of immunocompetent cells in the graft and the inability of the host to reject the immunocompetent donor cells (Billingham, 1966). In the case of the immunocompetent recipient these criteria are fulfilled in the HLA-heterozygous recipient who shares a haplotype with an HLA-homozygous donor. In the case of the immunosuppressed patient the risk factors for the development of GvHD have been poorly defined and reporting of cases and studies of the recipients’ immune status are required to permit more precise identification of patients a t risk (Anderson & Weinstein, 1990). We report two cases of fatal TAGvHD in patients with Hodgkin’s disease and T-cell lymphoma following transfusion of red cells and random donor platelets in the former and random donor platelets in the latter.
PATIENTS A N D M E T H O D S HLA-typing was performed by the microlymphocytotoxic assay using authenticated anti-HLA antisera obtained from the United Kingdom Transplant Service Support Authority. Tests were performed in duplicate and read either by phase-contrast microscopy after staining with eosin, or by fluorescent microscopy after staining with ethidium bromide and acridine orange. The percentage cell death was determined by two independent observers. Fibroblast cultures were established from skin biopsy by serial propagation of outgrowing cells from tissue fragments. Fibroblasts were grown in Eagle’s Minimal Essential Medium, supplemented with nonessential amino acids and 15% fetal calf serum. HLA typing was performed on early passage cultures (second to fifth) as in Johnson et al. (1989). Graft-versus-host disease was graded according to the Seattle scoring system (Thomas et al., 1975). Patient I
A 14-year-old female with stage I1 nodular sclerosing Hodgkin’s disease had completed six courses of ChlVPP (dose per course: 100 mg Chlorambucil, 10
Correspondence: Dr T. P. Baglin, Department of Haernatology, Addenbrooke’s Hospital, Cambridge CB2 2QQ, U.K.
195
196
T. P. Baglin et al.
Fig. 1. Haematological parameters in patient 1 in relation to clinical events and treatment. (-0-) Neutrophils, (-O--) platelets.
mg/m2Vinblastine, 1000mg/m2Procarbazine, 350 mg/ m2 Prednisolone. Twenty days after completion of the final course of chemotherapy two units of packed cells and a platelet transfusion from five random donors were administered (haemoglobin 60 g/l, white cells 1-4x 109/1,platelets 48 x lo9/]). Eight days later a fever of 39.0"C and a widespread maculopapular rash developed and the patient was referred to our institute. The patient developed abdominal pain and diarrhoea, the ALT rose from 25 to 1390 pmols/l over 5 days and pancytopenia rapidly ensued (Fig. 1). Bone marrow aspirate and trephine biopsy indicated severe hypoplasia with large granular lymphocytes and vacuolated macrophages (Fig. 2). Immunophenotyping of bone marrow mononuclear cells, after separation on Ficoll, was performed on a Bekton Dickenson flow cytometer using commercial reagents., A predominant population of activated suppressor/cytotoxic lymphocytes was identified (CD2,93%; CD3,90%; CD4,9%; CD8, 82%; HLADr, 33%; CD19
