Enhanced graft-versus-tumor effect following dose-reduced conditioning and allogeneic transplantation for refractory lymphoid malignancies after high-dose therapy

Abstract

Summary:Non-myeloablative regimens have been proven to allow engraftment following allogeneic stem cells transplantation (allo-SCT) with minimal procedure-related toxicity. Conventional allo-SCT may produce remissions in patients with relapsed and refractory lymphoid malignancies (LM) but these good results may be achieved at the cost of high treatment-related morbidity and mortality. Application of allo-SCT using less intensive regimens may temper the frequency of these complications, allowing a potent graft-versus-tumor effect (GVT). We present our data on 11 patients with LM receiving allo-SCT with a reduced regimen. Ten patients had received previous high-dose therapy, and were at high risk for toxicity, thus precluding the use of allo-SCT. A fludarabine and low-dose busulfan combination facilitated engraftment while exerting GVT. Hematological recovery was quick, and full donor T cell chimerism preceded acute GVHD. GVHD and infections were the major problems. Spontaneous acute GVHD occurred in eight patients (72%). Five patients (45%) achieved complete remission, and the GVT effect was closely associated with GVHD. These results support the concept that GVT is effective against LM in patients who have been heavily pretreated. Further studies are needed to investigate strategies to generate more specific alloreactive effects providing optimal GVT and an acceptable risk of GVHD and infections. Bone Marrow Transplantation the alloreactivity against host tumor cells. 1,2 Non-myeloablative and reduced conditioning regimens have recently been proven to allow engraftment following allo-SCT with minimal procedure-related toxicity in patients with advanced disease. 3 The immune reaction between donorderived immunocompetent T lymphocytes and host-type tumor cells has been well established to be the major antitumor agent in allo-SCT. 1 Evidence supporting the socalled graft-versus-tumor (GVT) effect includes the higher risk of relapse following T cell-depleted or syngeneic transplantation. 4,5 Furthermore, donor lymphocyte infusions (DLI) may re-induce remission in many patients relapsing after allo-SCT. 6 New approaches using non-myeloablative and reduced conditioning regimens aim to extend the use of allo-SCT to patients who are ineligible for high-dose chemotherapy or total body irradiation by prioritizing and increasing the immunosuppressive aspect of the preparation.Multiple myeloma (MM) is a lymphoid malignancy (LM) with a median survival of 3 years. Despite the development of numerous conventional chemotherapy regimens, there has been little progress in improving the survival of patients with MM. High-dose chemotherapy with autologous stem cell transplantation (ASCT) can result in prolonged survival, 7 but unfortunately, few, if any, patients with MM who receive ASCT are cured. 8 Only allo-SCT is curative in MM. However, the very high transplant-related morbidity and mortality limit the application of allo-SCT to younger patients. Allo-SCT has also produced prolonged remissions in patients with relapsed and ref...

MTX or mycophenolate mofetil with CsA as GVHD prophylaxis after reduced-intensity conditioning PBSCT from HLA-identical siblings

“…34,35 Patients with lymphoid malignancies have generally been transplanted in more advanced disease status and have received a greater number of therapy lines than those with myeloid disease. 34,36 Allo-HSCT in this setting is thus a greater challenge for physicians and investigators.…”

Second hematopoietic SCT for lymphoma patients who relapse after autotransplantation: another autograft or switch to allograft?

“…[48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] The rationale behind this strategy is to decrease the high TRM observed after myeloablative allo-SCT, though preserving the GVT effect. In addition, RIC allo-SCT allows patients with significant coexistent medical problems to undergo allo-SCT.…”

Infectious complications following allogeneic HLA-identical sibling transplantation with antithymocyte globulin-based reduced intensity preparative regimen

“…Some observations, including the initial report from our group, suggested that the kinetic and risk factors for infections might be modified after RIC allo-SCT. [17][18][19][20] However, our current knowledge of infectious complications after allo-SCT is still primarily based on results of analyses performed in the standard allo-SCT setting. This report describes an analysis of infectious complications (CMV antigenemia, documented bacteremia and fungal infections) in 101 patients with hematological and nonhematological malignancies, who received an antithymocyte globulin-(ATG), fludarabine-and busulfan-based RIC prior to allo-SCT from HLA-identical siblings.…”