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A successful case of allogeneic bone marrow transplantation for osteosarcoma with multiple metastases of lung and bone

Bone Marrow Transplantation volume 37, pages 115–116 (2006)Cite this article

The prognosis of osteosarcoma, not only localized but also with limited lung metastasis, has remarkably improved through intensified chemotherapy and surgical resection. However, patients who have bone metastases or multiple lung metastases still have a poor prognosis. High-dose chemotherapy with autologous SCT (auto-SCT) has also been performed with unsatisfactory outcome for advanced or relapsed osteosarcoma.1, 2 In the treatment of hematologic malignancies and certain forms of solid tumors, allogeneic SCT (allo-SCT) has been shown to offer the potential for applying marrow ablative doses of chemoradiotherapy, as well as inducing a curative graft-versus-tumor (GVT) effect. We report here a case of metastatic osteosarcoma successfully treated with allogeneic BMT (allo-BMT) from an HLA-identical sibling.

Antigens capable of serving as targets for a GVT effect after HLA-matched allo-SCT are mHAs and cancer antigens. CD8+ CTLs recognize these antigens presented as small peptides in the groove of HLA class I molecules. In contrast to neuroblastoma, primary osteosarcoma cells and cell lines are known to possess considerably high levels of HLA class I antigen expression,3 suggesting that osteosarcoma can at least express a variety of mHAs. mHAs are peptides of limited polymorphism encoded by genes on the Y-chromosome or by autosomal genes, and show either ubiquitous or restricted tissue expression. To date, six human H–Y epitopes on the Y-chromosome restricted to HLA-A1, A2, B7, B8, B60, and DQ5 have been reported. Although known H–Ys are not expressed in our patient's HLA types, some H–Ys not clarified yet might play a role as one of mHAs in our patient. As H–Ys are ubiquitously expressed in human tissues, these mHAs are expected to be the targets for both GVHD and GVT effect.4 In fact, Gratwohl had reported that male recipients of female marrow are at an increased risk for GVHD and benefit for GVL effect when compared with other donor/recipient gender combinations.5 A variety of human cancer antigens, the other targets of GVT effects, are also restricted by HLA-class I. Of these, MAGE family antigens originally identified in melanomas are highly expressed in osteosarcoma cell lines and fresh tumor tissues.6 HLA-A24 restricted SART1 and SART3 antigens are also detected in osteosarcoma.7, 8 In fact, SART3-derived peptides are reported to induce HLA-A24-restricted specific-specific CTLs from PBL of osteosarcoma patients.8 These cancer antigens could also be the targets for a GVT effect in our HLA-A24 positive patient.

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Authors and Affiliations

  1. Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan

    K Goi, K Sugita, T Tezuka, H Sato, K Uno, T Inukai & S Nakazawa

  2. Department of Orthopedics, University of Yamanashi, Yamanashi, Japan

    Y Hamada

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  1. K Goi
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  2. K Sugita
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Goi, K., Sugita, K., Tezuka, T. et al. A successful case of allogeneic bone marrow transplantation for osteosarcoma with multiple metastases of lung and bone. Bone Marrow Transplant 37, 115–116 (2006). https://doi.org/10.1038/sj.bmt.1705209

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