Graft-versus-myeloma effect in two cases

Verdonck, LF; Lokhorst, H. M.; Dekker, AW; Nieuwenhuis, H. K.; Petersen, Eefke

doi:10.1016/s0140-6736(96)90871-5

Cited by 227 publications

(123 citation statements)

References 10 publications

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“…However, the presence of lung cancer more than 2 months after transplantation clearly indicates that the conditioning regime was unable to eradicate the tumour completely. In addition, there is considerable evidence of a GVT effect after allogeneic BMT in several haematological malignancies, apparently related to the development of severe GVHD (Weiden et al, 1979;Butturini et al, 1987;Horowitz et al, 1990;Verdonk et al, 1996;van Besien et al, 1997;Collins et al, 1997). This has been the rationale for the successful use of donor lymphocyte infusions (DLI) for treatment of relapse after allogeneic BMT (Collins et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…It contributes to the elimination of residual disease and the achievement of durable remissions in several haematological malignancies, particularly chronic myeloid leukaemia (Weiden et al, 1979;Butturini et al, 1987;Horowitz et al, 1990;Verdonk et al, 1996;van Besien et al, 1997;Collins et al, 1997). However, information about the possible clinical role of GVT in solid tumours is lacking.…”

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confidence: 99%

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Graft‐versus‐tumour effect in non‐small‐cell lung cancer after allogeneic peripheral blood stem cell transplantation

Moscardó¹,

Martı́nez²,

Sanz³

et al. 2000

Br J Haematol

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Summary. Clinical evidence of a graft-vs.-tumour effect in solid tumours after haematopoietic stem cell transplantation is lacking. We report for the first time a complete and durable regression of a stage IB non-small-cell lung carcinoma in a patient who had received an allogeneic peripheral blood haematopoietic stem cell transplant for acute myeloblastic leukaemia in first complete remission. Disappearance of the tumour coincided with development of graft-vs.-host disease. This suggests that simultaneous generation of cytotoxic T lymphocytes against lung carcinoma cells could have been responsible for the regression. This unique clinical observation broadens the possibility of using allogeneic haematopoietic stem cell transplantation in treating neoplasias lacking significant sensitivity to chemotherapy.Keywords: graft-vs.-tumour-effect, lung cancer, allogeneic stem cell transplantation.The graft-vs.-tumour effect (GVT) after allogeneic bone marrow transplantation (BMT) is closely related to the development of graft-vs.-host disease (GVHD). It contributes to the elimination of residual disease and the achievement of durable remissions in several haematological malignancies, particularly chronic myeloid leukaemia (Weiden et al, 1979;Butturini et al, 1987;Horowitz et al, 1990;Verdonk et al, 1996;van Besien et al, 1997;Collins et al, 1997). However, information about the possible clinical role of GVT in solid tumours is lacking.We describe here a patient with acute myeloblastic leukaemia (AML) allografted with peripheral blood stem cells (PBSCs) from his HLA-identical sister, in whom a limited squamous cell lung cancer was detected early after transplant. The lung cancer lesion disappeared. This coincided with the development of acute and chronic GVHD, without specific treatment. This suggests that a GVT effect could eliminate tumour cells in such cases. CASE REPORTA 52-year-old man, a heavy smoker (40 cigarettes/d for the past 35 years), with AML M5a in first complete remission (CR), received a non-manipulated allogeneic PBSC transplant from his HLA-identical sister. The conditioning regimen consisted of busulphan and cyclophosphamide, and cyclosporin and prednisone were given for GVHD prophylaxis. Engraftment was fast, and he developed a grade III acute GVHD that responded to prednisone. The patient was admitted to hospital on d 74 because of cytomegalovirus antigenaemia, fever, left basal lobar pneumonia and flares of GVHD on his skin. A bronchoscopy revealed an unexpected infiltrative and ulcerated lesion in the division between the left lobar superior and inferior bronchi (Fig 1A). Cytology suggested squamous cell carcinoma of the lung, and a transbronchial lung biopsy confirmed this diagnosis (Fig 2). The clinical staging of the tumour was IB (Mountain, 1997). Given his clinical condition, surgery and chemotherapy were ruled out. The patient was managed with intravenous antibiotics, gancyclovir and high-dose methylprednisolone, with resolution of the pneumonia and partial response of the GVHD. A bronchoscop...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Graft‐versus‐tumour effect in non‐small‐cell lung cancer after allogeneic peripheral blood stem cell transplantation

Moscardó¹,

Martı́nez²,

Sanz³

et al. 2000

Br J Haematol

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“…[3][4][5]8,9] In initial studies, 50-70% of patients receiving donor lymphocyte infusions for relapsed multiple myeloma have been reported to achieve complete responses. [5,10,11] A more recent survey of 25 patients at 15 centers reported complete responses in only seven patients (28%) who received one or more infusions of donor lymphocytes.…”

Section: Graft Versus Myelomamentioning

confidence: 99%

“…[7] Small series of patients with multiple myeloma who developed post-allograft relapses and who subsequently were infused with allogeneic leukocytes from their original stem-cell donors have clearly demonstrated a graft-versus-myeloma effect that was associated with GVHD. [3][4][5]8,9] In initial studies, 50-70% of patients receiving donor lymphocyte infusions for relapsed multiple myeloma have been reported to achieve complete responses. [5,10,11] A more recent survey of 25 patients at 15 centers reported complete responses in only seven patients (28%) who received one or more infusions of donor lymphocytes.…”

Section: Graft Versus Myelomamentioning

confidence: 99%

“…In patients with multiple myeloma this effect has been well documented. [3][4][5] In contrast, stem-cell transplantation from autologous or syngeneic donors provides little or no immunologic effect against the myeloma cell. Thus autologous or syngeneic stem-cell transplants are mainly a form of supportive care and require intensive chemotherapy with or without radiation to accomplish eradication of the disease or alternative strategies designed to duplicate or mimic the graftversus-myeloma effect.…”

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Is there still a role for allogeneic stem-cell transplantation in multiple myeloma?

Bensinger

2007

Best Practice & Research Clinical Haematology

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Despite significant improvements in survival for multiple myeloma patients through autologous stem-cell transplantation (SCT) and the introduction of novel drugs, the disease remains incurable for all but a small fraction of patients. Only allogeneic SCT is potentially curative, due in part to a graft-versus-myeloma effect. High transplant-related mortality with allogeneic SCT is currently the major limitation to wider use of this potentially curative modality. Mortality can be reduced through the use of lower-intensity conditioning regimens which allow engraftment of allogeneic stem cells, but this comes at a cost of higher rates of disease progression and relapse. Promising studies to improve outcomes of allogeneic transplants include the use of more intensive nonmyeloablative conditioning regimens, tandem transplants, peripheral blood cells, graft engineering to improve the graft-versus-myeloma activity while reducing graft-versus-host disease (GVHD), post-transplant maintenance, and targeted conditioning therapies such as bone-seeking radioisotopes. Keywords multiple myeloma; allogeneic stem-cell transplantationThe treatment of multiple myeloma has dramatically improved in the last 10 years. Highdose therapy followed by autologous stem-cell support has emerged as a promising means for increasing remission rates and improving survival. As such, autologous stem-cell transplantation has become the standard of care for many patients with multiple myeloma. In addition, insights into the biology and genetics of myeloma cells have resulted in the rapid introduction of new drugs with unique mechanisms of action. These drugs -which include thalidomide, lenalidomide and bortezomib -have shown significant activity in multiple myeloma, and when these new agents are combined with more traditional drugs, the response and complete remission rates are as high as responses achieved with autologous stem-cell transplantation. [1,2] Despite these advances, long-term survival after treatment with stem-cell transplantation or the newly developed drugs is rare, and disease recurs in virtually all patients.Stem-cell transplantation from allogeneic donors may be curative for 10-20% of patients with chemotherapy-resistant, refractory hematologic malignancies, and for up to 80% of . E-mail address: wbensing@fhcrc.org. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. patients who are transplanted in remission. Much of the high response and curative potential of allografts is attributed to a 'graft-versus-tumor' effect. In patients with multiple myeloma this effect has been well documented...

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Use of nonmyeloablative preparative regimens for allogeneic blood stem cell transplantation: Induction of graft-vs.-malignancy as treatment for malignant diseases

Champlin¹,

Khouri²,

Giralt

1999

J. Clin. Apheresis

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Graft-versus-myeloma effect in two cases

Cited by 227 publications

References 10 publications

Graft‐versus‐tumour effect in non‐small‐cell lung cancer after allogeneic peripheral blood stem cell transplantation

Graft‐versus‐tumour effect in non‐small‐cell lung cancer after allogeneic peripheral blood stem cell transplantation

Is there still a role for allogeneic stem-cell transplantation in multiple myeloma?

Use of nonmyeloablative preparative regimens for allogeneic blood stem cell transplantation: Induction of graft-vs.-malignancy as treatment for malignant diseases

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