Allogeneic Hematopoietic Stem Cell Transplantation in Cutaneous T-Cell Lymphomas

Abstract

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.

Sézary Syndrome: Different Erythroderma Morphological Features with Proposal for a Clinical Score System

“…Traditionally, these patients have been treated with chemotherapy, (i.e., gemcitabine, liposomal doxorubicine, CHOP, and CHOP-like polychemotherapy), but considering the low response and the high toxicity, it should not be taken into account as a primary treatment [15]. To date, allogeneic hematopoietic stem cell transplantation (HSTC), particularly using reduced-intensity conditioning, is the only curative treatment, although intended for only few selected patients [16][17][18]. Overall, SS patients have an unmet clinical need for effective treatments, due to low response rates, short-lived improvements, concomitant immunosuppression, and often severe drug-related side effects [19].…”

Management of relapsed cutaneousT‐Celllymphoma following allogeneic hematopoietic stem cell transplantation: Review with representative patient case

“…Patients with severe relapsed CTCL can be managed through a general approach that is used for most patients with relapsed leukemia or non-Hodgkin lymphoma after stem cell transplant. [5][6][7] Abbreviations:…”

“…Patients with severe relapsed CTCL can be managed through a general approach that is used for most patients with relapsed leukemia or non‐Hodgkin lymphoma after stem cell transplant 5–7 . First, reduction of posttransplant immunosuppression and infusion of donor lymphocytes can help enhance the antitumor immune function of the graft.…”

“…In terms of pre‐transplant treatments, bridge therapy is important to achieve complete or near complete remission of CTCL prior to allo‐HSCT. Bridge therapies often include TSEBT for skin debulking as well as systemic treatments such as brentuximab vedotin 5 . Some bridge regimens have been associated with adverse events that should be considered.…”

“…Moreover, transplanted immune cells may directly attack tumor cells in what is termed a graft‐versus‐lymphoma (GVL) effect. Several studies have described encouraging long‐term outcomes with allo‐HSCT in high‐risk, younger CTCL patients with good performance status who have achieved complete remission or minimal residual disease at time of transplant 2–33 …”