Transplantation of allogeneic hematopoietic stem cells: an emerging treatment modality for solid tumors

Abstract

Allogeneic transplantation of hematopoietic cells from an HLA-compatible donor has been used to treat hematologic malignancies. Allogeneic transplantation not only replaces the marrow affected by the disease, but exerts an immune graft-versus-tumor (GVT) effect mediated by donor lymphocytes. The development of nonmyeloablative conditioning regimens before allogeneic transplantation has allowed this therapy to be used in elderly and disabled patients. An allogeneic GVT effect is observed in a proportion of patients with renal, breast, colorectal, ovarian, and pancreatic cancer treated with allogeneic transplantation. In general, the tumor response is associated with the development of acute and chronic graft-versus-host disease. Further improvements will depend on the identification of the antigen targets of GVT, and on reduction of the toxicity of the procedure. Targeted therapies may complement the immune effect of allogeneic transplantation. We present updated results from the literature and data recently placed on file at the European Bone Marrow Transplantation Solid Tumors Working Party.

Engraftment of unrelated cord blood after reduced-intensity conditioning regimen in children with refractory neuroblastoma: a feasibility trial

“…GVT effect in solid tumors is typically delayed for months after transplant. 1 Given the rapidity of tumor recurrence in our patients, there was not time to establish T-cell mediated GVT activity. Future clinical trails based on this approach should be aimed at transplanting patients in minimal residual disease.…”

“…This GVT effect has been shown in patients with refractory solid tumors. 1 The early trials of matched sibling allogeneic BMT in children with neuroblastoma between 1985 and 1995 reported outcomes similar to those of autologous transplantation. 2,3 Given a higher rate of TRM with allogeneic hematopoietic SCT and the occurrence of GVHD, autologous is the preferred therapeutic option for those in need of hematopoietic SCT: only 25 allogeneic transplantations were therefore performed for neuroblastoma in Europe in 2006.…”

“…[14][15][16][17] Allogeneic hematopoietic transplantation thus appears to be not only an immunotherapeutic modality, but also as a platform for subsequent immunotherapy. 1,11,18 Second, reduced-intensity conditioning regimen (RIC) followed by PBSCT has been shown to induce rapid donor chimerism in adult patients with solid tumors, thereby providing a GVT effect without the toxicity of a myeloablative preparative regimen. 1 Third, partially HLA-mismatched unrelated cord blood transplantation (UCBT) has been shown in childhood hematological malignancies to have outcomes similar to those of HLAmatched BMT.…”

“…1,11,18 Second, reduced-intensity conditioning regimen (RIC) followed by PBSCT has been shown to induce rapid donor chimerism in adult patients with solid tumors, thereby providing a GVT effect without the toxicity of a myeloablative preparative regimen. 1 Third, partially HLA-mismatched unrelated cord blood transplantation (UCBT) has been shown in childhood hematological malignancies to have outcomes similar to those of HLAmatched BMT. [19][20][21][22][23] Furthermore, it has been shown to retain a GVL effect in spite of a lower risk of GVHD.…”

HLA-matched allo-SCT after reduced intensity conditioning with fludarabine/CY in patients with metastatic breast cancer

“…9 The presented data from one single center are supporting recently published promising data of the European Group for Blood and Marrow Transplant registry (EBMT) and MD Anderson Cancer Centre 10 and a recent review reporting relatively high response rates and supporting the role of allo-SCT for solid tumors. 11 …”