Abstract

Simple SummaryAdvanced-stage cutaneous T-cell lymphomas are aggressive diseases with frequent disease relapses and a reduced overall survival. Most treatment regimens fail to induce long-term remissions. Allogeneic hematopoietic stem cell transplantation has been associated with treatment-free long-term remissions and holds a potential for cure in this disease but is associated with frequent complications, mostly linked to the development of graft-versus-host disease and infections. Herein, we review the current evidence supporting the use of allogeneic stem cell transplantation in advanced-stage cutaneous T-cell lymphomas. Cutaneous T-cell lymphomas (CTCLs) are non-Hodgkin lymphomas that develop primarily in the skin. They account for almost 80% of primary cutaneous lymphomas. Epidermotropic CTCLs (mycosis fungoides (MF) and Sézary syndrome (SS)) are the most common form of CTCL. The course of the disease ranges from an indolent clinical behavior in early-stage disease to an aggressive evolution in the advanced stages. Advanced-stage disease is defined by the presence of tumors, erythroderma, or significant blood, nodal or visceral involvement. Advanced-stage disease is characterized by frequent disease relapses, refractory disease, a severely impaired quality of life and reduced overall survival. In the last twenty-five years, allogeneic hematopoietic stem cell transplantation (HSCT) has led to prolonged remissions in advanced CTCL, presumably linked to a graft-versus-lymphoma effect and is thus emerging as a potential cure of the disease. However, the high post-transplant relapse rate and severe morbidity and mortality associated with graft-versus-host disease and infections are important issues. Allogeneic HSCT is thus mostly considered in young patients with no comorbidities and an aggressive, advanced-stage CTCL. Allogeneic HSCT gives the best results in patients with a pre-transplant complete remission of the lymphoma. For this reason, one of the challenges is to define the best time to consider allogeneic HSCT in the disease course. Early identification of patients at high risk for progression is important to identify candidates who may benefit from allogeneic HSCT before their disease becomes treatment-refractory. This review describes the role of allogeneic HSCT in CTCL, summarizes the published data and future perspectives in this area.

Highlights

  • Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of lymphoproliferative disorders Cancers2 of Health defined by 2020, the EuropeanOrganization for Research and Treatment of Cancer (EORTC)-WorldOrganization (WHO) classification [1]

  • The flare reaction was correlated with a high PD1 expression on Sézary cells but did not associate with the subsequent clinical response or lack of response. These data suggest that immune checkpoint inhibitors could be used as a salvage treatment after allo-hematopoietic stem cell transplantation (HSCT) in relapsed CTCL, patients should be carefully monitored for GVHD, as observed with post-allo-HSCT nivolumab used as a salvage therapy in Hodgkin lymphoma [63]

  • New therapeutic approaches are being studied in CTCL such as targeted therapies, combination treatments and immunotherapy, but none to date have a proven curative effect

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Summary

Introduction

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of lymphoproliferative disorders. The various CTCL subtypes are defined by their clinico-pathological characteristics disorders defined by the European Organization for Research and Treatment of Cancer (EORTC)and differ terms of prognosis. Advanced-stage disease defined bycourse the presence of tumors Independent prognostic markers have been identified for patients with (stage IIB, Figure 1A), erythroderma (stage III, Figure 1B), or significant blood (Figure 1C), nodal or advanced. In advanced-stage disease, with frequent relapses to multiple successive treatment lines [6]. The results of recommendations presented here are mostly based on retrospective studies with a lack of a recent meta-analysis might represent the best supportingmight the use of allo-HSCT an effective randomized controlled data. Prolongedasremissions allo-HSCT suggest a graft-versus-lymphoma supporting the use of allo-HSCT an effective with treatment for CTCL [8]. IV).with erythroderma (stage III); (C) Sézary syndrome with significant blood involvement (stage IV)

Selection of Patients for Allo-HSCT
Bridging Therapies to Allo-HSCT
Different Conditioning Approaches and Types of Donors
Evolution Post Allo-HSCT
Best Practice Set of Recommendations
Findings
Conclusions and Perspectives
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