Graft-versus-lymphoma effect in refractory cutaneous T-cell lymphoma after reduced-intensity HLA-matched sibling allogeneic stem cell transplantation

Abstract

Summary:Cutaneous T-cell lymphomas (CTCL) are rare diseases that, in their advanced stages or in transformation, have a poor prognosis. Autologous stem cell transplantation (Au-SCT) after high-dose therapy has yielded disappointing results. Allogeneic transplantation (allo-SCT) provides the potential advantage of an immune-mediated graftversus-lymphoma (GVL) effect. Reduced-intensity allo-SCT potentially offers a GVL effect, but with diminished toxicity related to the induction regimen; however, published experience with this approach in CTCL is limited. We report a series of three patients (age 35-49) with advanced, refractory (n ¼ 2) or transformed (n ¼ 1) CTCL who underwent reduced-intensity allo-SCT in the context of active disease. All three survived the peritransplant period and, despite later having disease relapse, all exhibited evidence of a GVL effect. Relapses of the disease were in the context of immune suppression for graft-versus-host disease (GVHD), and when immune suppression was reduced, responses were regained. A comparison is made of these results to those in a review of the published literature to date. We conclude that while a GVL can be achieved for CTCL with reduced-intensity allogeneic transplantation, the clinical benefits are short lived and novel approaches are required to obtain sustained remissions.

Expression of T-plastin, FoxP3 and other tumor-associated markers by leukemic T-cells of cutaneous T-cell lymphoma

“…Similarly the suppressive effects of low dose cyclophosphamide or fludarabine on Treg cells might not selectively target Treg-like neoplastic T-cells vis-á-vis normal Treg cells [80][81][82]. At the present time, a non-myeloblative allogeneic bone marrow transplantation with the intent of generating a graft-versus-lymphoma effect may provide the best therapeutic option to gain long-term survival in these patients [83][84][85][86].…”

The role of high-dose therapy and stem cell rescue in the management of T-cell malignant lymphomas: a BSBMT and ABMTRR study

“…Moreover, there are a number of reports of a GvLy effect for cutaneous T-cell lymphoma, and further investigation is warranted to establish if this effect extends to other PTCL. 23 One potential way to reduce the high transplant-related mortality rate would be to employ an RIC, which would facilitate engraftment as a platform upon which to develop the GvLy effect, including the programmed use of donor lymphocyte infusions. 19,24 Corradini et al 12 reported prospectively on 17 patients with relapsed/primary refractory T-cell lymphomas treated with RIC Allo-SCT.…”

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“…[104][105][106] Investigators have been evaluating reduced-intensity conditioning for MF/SS and transplantation-related mortality is low, time to relapse is variable, and durable remissions are observed. 107,108 We recommend that allogeneic transplantation be considered in younger patients with advanced-stage disease if not responding to agents such as IFN-␣, bexarotene, HDACi, or denileukin diftitox.…”