Induction of Graft-Versus-Host Disease After Autologous Bone Marrow Transplantation

Jones, Richard J.; Hess, Allan D.; Mann, Risa B.; Piantadosi, Steven; Vogelsang, Georgia B.; Farmer, Evan R.; Geller, Robert B.; Santos, George W.

doi:10.1016/s0140-6736(89)92575-0

Cited by 182 publications

(91 citation statements)

References 12 publications

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“…This frequency is comparable with the data of studies in adults with a reported frequency of histologically proven GVHD of the skin between 33% 15 and 100%. 13 Our results indicate that GVHD can be safely and reproducibly induced by 1.5 mg/kg/day CsA intravenously for 28 days following ABMT and APBSCT in childhood. In agreement with previous studies, [13][14][15][16][17][18] CsA-induced GVHD was mild, self-limiting, and confined to the skin.…”

Section: Discussionmentioning

confidence: 53%

“…Interestingly, Barredo et al 26 recently reported an unusual case of severe and progressive GVHD following ABMT and CsA therapy. Corresponding to the data in adults, [13][14][15][16][17][18][19] histologically proven CsA-induced GVHD developed after a conditioning regimen that included chemotherapy alone and chemotherapy with total body irradiation and was observed following both ABMT and APBSCT (Table 1). In all cases, acute GVHD of the skin developed during the initial phase of engraftment while the patients were receiving CsA.…”

Section: Discussionmentioning

confidence: 85%

“…This is the first study to be conducted in people of this age; all previous studies have been carried out only in adults. [13][14][15][16][17][18][19] Fischer et al 25 evaluated the effect of age on the induction of syngeneic GVHD after syngeneic bone marrow transplantation and CsA therapy in rats. They found a dramatic decline in the incidence of syngeneic GVHD with increasing age of the animals.…”

Section: Discussionmentioning

confidence: 99%

“…This finding corresponds with the data of previous clinical studies with a reported onset of CsA-induced GVHD during CsA treatment in the majority of patients. [13][14][15] In contrast, in animal studies, CsA-induced GVHD was not seen while rats were receiving CsA but was observed 12-40 days after cessation of CsA therapy. 8 The difference between clinical and animal studies suggests that species-specific differences exist in the clonal expansion of autoreactive T cells.…”

Section: Discussionmentioning

confidence: 99%

“…CsA-induced GVHD has been reported after ABMT in adults with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease, 13,14 acute myeloid leukemia (AML), [15][16][17] acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia, 14 and breast cancer. 18 Recently, CsA-induced GVHD has been described in adult patients with lymphoma following autologous peripheral blood stem cell transplantation (APBSCT).…”

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confidence: 99%

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Cyclosporin A-induced graft-versus-host disease following autologous bone marrow and stem cell transplantation in hematological malignancies of childhood

Gruhn

Häfer

Kosmehl³

et al. 1998

Bone Marrow Transplant

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Summary:Cyclosporin A (CsA) can induce graft-versus-host disease (GVHD) following autologous bone marrow transplantation (ABMT) and autologous peripheral blood stem cell transplantation (APBSCT) in adults. We investigated whether GVHD can be induced following ABMT and APBSCT in childhood, and which cells are involved in the pathogenesis of this syndrome. We conducted a prospective study of 20 children and adolescents with hematological malignancies receiving CsA after ABMT and APBSCT. Skin biopsies were obtained on day 21 after transplantation or in the event of a rash. Immunophenotypic analysis of peripheral blood lymphocytes was performed on days 14, 21, 28 and 60 after transplantation. Clinical GVHD of the skin, confirmed by histological criteria, occurred in five patients. Five patients had no clinical GVHD but had acute GVHD alterations on routine skin biopsy. In all 10 patients with a positive skin biopsy for GVHD, CD4 + lymphocytes were the predominant cells in the epidermis. Immunophenotypic analysis of peripheral blood lymphocytes revealed a significantly increased CD4/CD8 ratio in patients with a positive skin biopsy (P Ͻ 0.01). Our findings indicate that it is possible to induce acute GVHD following ABMT and APBSCT in childhood. In addition, CD4 + lymphocytes play an important role in the pathogenesis of CsA-induced GVHD. Keywords: cyclosporin A; graft-versus-host disease; bone marrow transplantation; hematopoietic stem cell transplantation Despite the increased morbidity and mortality in patients with graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT), GVHD is associated with a clinically significant antitumor effect. 1,2 It has been shown that mature T cells from the donor contaminating the bone marrow inoculum are responsible for the development of GVHD. 3 T cell depletion of donor marrow for allogeneic BMT leads to a markedly reduced incidence of GVHD in the marrow recipients. Unfortunately, T cell depletion is also associated with an increased incidence of marrow graft failure and an increase in relapse rate. 4 The procedure-related toxicity is lower after autologous bone marrow transplantation (ABMT) than after allogeneic BMT. In contrast, the higher relapse rates after autologous and syngeneic BMT than after allogeneic BMT are at least partly due to the absence of graft-versus-tumor effect associated with GVHD. 5,6 A syndrome that clinically resembles acute GVHD has been observed spontaneously in 8% of patients receiving autologous or syngeneic BMT. 7 This syndrome appears to involve only the skin, is generally mild, and is self-limiting. Due to the rarity of this phenomenon, it has not been possible to determine its effects on leukemic relapse rates.In ABMT, further significant dose escalation with the current conditioning protocols is limited due to unacceptable toxicity. Therefore, interest has focused on methods stimulating immunologically mediated antitumor activity. In animal models, GVHD was induced by treatment with cyclosporin A (CsA) in rats or mice un...

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Cyclosporin A-induced graft-versus-host disease following autologous bone marrow and stem cell transplantation in hematological malignancies of childhood

Gruhn

Häfer

Kosmehl³

et al. 1998

Bone Marrow Transplant

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Lichenoid Graft-vs-Host Disease in an Autologous Bone Marrow Transplant Recipient

et al. 1995

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Malignant neoplasms in cyclosporin A-induced autoimmunity (CyA-AI)

et al. 1997

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Lethally X-irradiated LEW rats reconstituted with synge-neic bone marrow and given low-dose Cyclosporine A (CyA) for 5 weeks develop, after withdrawal of CyA, symptoms of disease resembling graft-vs.-host disease (GVHD) as seen after allogeneic bone-marrow transplantation. Symptoms of disease may include acute dermatitis and chronic disease resembling scleroderma. Since anti-class II MHC cytotoxic lymphocytes are generated in this model, it has been proposed as an anti-tumor regimen in humans. We now report that LEW rats treated according to this protocol may, after cessation of CyA administration, paradoxically develop malignant neoplasms. Of 48 experimental animals, 31 developed rapidly progressive subcutaneous and/or intracutaneous tumors commencing at 6 weeks, 13 weeks and 6 months after cessation of CyA. Tumors were of mesenchymal origin, usually high-grade sarcoma, adenocarcinoma or both mesen-chymal and epithelial tumors. Such tumor incidence exceeded the incidence of tumor growth in X-irradiated controls , and in rats subjected to thymectomy prior to X-irradiation and CyA administration. CyA by itself induced no tumors. Our results show that total body X-irradiation is required for tumor development but that the presence of CyA-induced autoimmune disease increases the incidence significantly. Int.

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Induction of Graft-Versus-Host Disease After Autologous Bone Marrow Transplantation

Cited by 182 publications

References 12 publications

Cyclosporin A-induced graft-versus-host disease following autologous bone marrow and stem cell transplantation in hematological malignancies of childhood

Cyclosporin A-induced graft-versus-host disease following autologous bone marrow and stem cell transplantation in hematological malignancies of childhood

Lichenoid Graft-vs-Host Disease in an Autologous Bone Marrow Transplant Recipient

Malignant neoplasms in cyclosporin A-induced autoimmunity (CyA-AI)

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