Cyclosporine-induced graft-versus-host disease after autologous bone marrow transplantation in hematological malignancies

Carella, Angelo Michele; Gaozza, Eugenia; Congiu, A; Carlier, P; Nati, S; Truini, Mauro; Castellaneta, A.; Viale, Maurizio

doi:10.1007/bf01703140

Cited by 25 publications

(12 citation statements)

References 14 publications

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“…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. No patients exhibited extracutaneous manifestations of GVHD.…”

Section: Discussionsupporting

confidence: 92%

“…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: 90%

“…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%

“…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: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 90%

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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“…[5][6][7] It is thought eral studies have reported the successful induction of autologous GVHD using cyclosporin A and/or ␣-interferon. 8,9 However, although in vitro studies have shown that the although attempts to reduce the dose of prednisolone below 10 mg daily have been unsuccessful and he continues to effector cells of autologous GVHD can have a graft-versustumour effect, 10 significant in vivo antitumour activity of have some mild chronic changes.…”

mentioning

confidence: 99%

Autologous GVHD following PBSCT, with evidence for a graft-versus-myeloma effect

Byrne

Carter

Ellis

et al. 1997

Bone Marrow Transplant

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Summary:Case reportA 48-year-old man with refractory kappa light chain myeThe development of GVHD following allogeneic BMT is known to be closely associated with significant antiloma underwent tandem PBSC transplants in 1996. He had presented in August 1995 (urinary Bence-Jones protein leukaemic activity. Immunological graft-versus-leukaemia (GVL) effects are now well established and are (BJP) excretion 2.4 g/l; plasma cell infiltration, 94%; ␤2-microglobulin, 10.8 mg/l) and failed to respond to three commonly exploited in the treatment of leukaemic relapse following allogeneic transplantation by the use courses of VAD chemotherapy followed by a further three courses of cyclophosphamide-VAMP chemotherapy (BJP of donor lymphocyte infusions. More recently a graftversus-myeloma (GVM) effect following allogeneic excretion, 2.8 g/l; plasma cell infiltration, Ͼ50%). He therefore went on to receive two courses of a cyclosporin Atransplantation has been documented, suggesting that eradication of haematological malignancies following VAD regimen in an attempt to block the presumed MDR phenotype. This treatment led to a partial response (BJP allogeneic transplantation is achieved at least in part by immunological mechanisms. It is now also established excretion, 0.84 g/l; 15% plasma cell infiltration). PBSC mobilisation was then performed using cyclophosphamide that spontaneous GVHD can occur following autologous transplantation and can be induced by cyclosporin A 3 g/m 2 and G-CSF 300 g daily and sufficient CD34-positive cells were collected for a tandem transplant. Some of administration. However, there is only limited evidence that the development of autologous GVHD has an antithe cells collected were stored unmanipulated for use after the first transplant whilst the remainder underwent CD34 ϩ tumour effect. We report for the first time the development of autologous GVHD following PBSC transplanselection using the Ceprate (Cellpro, St Pierre, Belgium) column method for use following the second high-dose protation for myeloma apparently resulting in a GVM effect.cedure. PCR on the apheresis products revealed contamination with myeloma as demonstrated by PCR for a known Keywords: autologous graft-versus-host disease (GVHD); multiple myeloma; graft-versus-myeloma (GVM) IgH framework III rearrangement even after CD34 ϩ selection. effect; PBSC transplantation He proceeded to the first unselected PBSCT in March 1996, following conditioning with high-dose melphalan Evidence for a graft-versus-myeloma (GVM) effect following allogeneic transplantation has recently been reported. 1,2 It is known that clinical and histological changes consistent with GVHD can arise in recipients of syngeneic and autologous grafts, but as yet there has been little direct evidence that this can lead to an antitumour effect. We report a patient who spontaneously developed grade II GVHD following a tandem PBSCT which resulted in a significant GVM effect.

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Autologous Graft‐vs.‐Host Disease

Hess¹,

Jones²

2003

Thomas' Hematopoietic Cell Transplantation

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Cyclosporine-induced graft-versus-host disease after autologous bone marrow transplantation in hematological malignancies

Cited by 25 publications

References 14 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

Autologous GVHD following PBSCT, with evidence for a graft-versus-myeloma effect

Autologous Graft‐vs.‐Host Disease

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