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

Abstract

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.

Engraftment Syndrome after Autologous Stem Cell Transplantation: An Update Unifying the Definition and Management Approach

“…Survival outcomes are rarely reported in the ES literature. In a single case report, Byrne et al reported a possible graft-versus-myeloma effect, as evidenced by a reduction in Bence-Jones protein excretion to 0.08 g/dl and less than 2% plasma cell infiltration in a bone marrow aspirate 59 . In sharp contrast to this case, a review of 461 lymphoma patients by Keung et al failed to show improved survival in patients that developed ES, and, instead, revealed an association between ES/AGVHD and the development of a secondary myelodysplastic syndrome 31 .…”

Graft-versus-myeloma

“…Thus, while this report shows that induction of autologous GVHD is feasible and reasonably well-tolerated in myeloma patients, it is not possible to assess the antitumor effect. Byrne et al 66 described apparent response of myeloma in a patient who developed spontaneous 'autologous' GVHD following an autograft. However, it is possible that the administration of corticosteroids as therapy of GVHD contributed to the response.…”

Autoreactive antibodies following autologous peripheral blood stem cell transplantation

“…Graftversus-myeloma effect has also been shown in a patient presenting with autologous GVHD. 9 In addition to an antitumor effect, autoreactive antibodies have been detected transiently in patients with autologous GVHD. 3 Moreover, Deliliers et al 2 reported that patients who developed autoreactive antibodies after autologous BMT achieved better long-term survivals.…”