• Allogeneic Hematopoietic Stem Cell Transplantation
• Cellular Therapies
• Chimeric Antigen Receptor T Cells
• Cutaneous T cell Lymphoma
• Mycosis Fungoides
• Sezary Syndrome

• Humans
• Skin Neoplasms/therapy
• Skin Neoplasms/pathology
• Lymphoma, T-Cell, Cutaneous/therapy
• Lymphoma, T-Cell, Cutaneous/pathology
• Mycosis Fungoides/therapy
• Mycosis Fungoides/pathology
• Sezary Syndrome/therapy
• Sezary Syndrome/pathology
• Vorinostat/therapeutic use

• Allo-HSCT
• CTCL
• GVHD
• cutaneous T-cell lymphoma
• graft-versus-host disease
• stem cell transplantation

• Graft vs Host Disease/etiology
• Graft vs Host Disease/therapy
• Hematopoietic Stem Cell Transplantation/adverse effects
• Humans
• Lymphoma, T-Cell/pathology
• Mycosis Fungoides/etiology
• Neoplasm Recurrence, Local/therapy
• Skin Neoplasms/complications
• Skin Neoplasms/therapy
• Transplantation, Homologous/adverse effects

• U01 CA253190 NCI NIH HHS

• Allogeneic stem cell transplantation
• Sezary syndrome
• mycosis fungoides

Sezary Syndrome (SS) is a rare leukemic variant of primary cutaneous T-cell lymphoma. Relapsed or refractory disease is generally considered incurable by conventional therapeutic approaches, although durable responses can be achieved with novel monoclonal antibodies. Allogeneic hematopoietic stem cell transplantation (alloHSCT) may have potential value by inducing graft vs-lymphoma (GvL) effects, but there is currently no consensus regarding the timing of alloHSCT or type of conditioning regimen. Here we present the case of a male patient who achieved a complete remission (CR) of primary refractory SS after non-myeloablative alloHSCT. Patient: Two years prior to HSCT, the patient had been refractory to CHOEP-based chemotherapy, interferon, extracorporeal photopheresis (ECP), and bexarotene. Directly prior to alloHSCT brentuximab-vedotin (BV) was applied resulting in a partial remission of the skin compartment and overall in a stable disease. Prior to HSCT, flow cytometry of the bone marrow and peripheral blood showed an infiltration with T-cells positive for CD5, CD4, low CD3, low CD2 and negative for CD7, CD38, HLA-DR and CD8. The trephine biopsy showed a 7% infiltration of SS cells. The CD4:CD8 ratio in peripheral blood (pb) was massively increased at 76.67, with 63.5% of white blood cells expressing a SS immune phenotype. The conditioning regimen included 30 mg/m2 fludarabine on days -5, -4 and -3 and total body irradiation with 2 Gy on day -1. Immunosuppression consisted of cyclosporine A from day-1 and mycophenolate mofetil from day 0. The patient received 6.55x106 CD34+ cells and 1.11x108 CD3+ cells/kg body weight. Bone marrow evaluation on day 28 still showed persistent SS cells by flow cytometry. After tapering immunosuppression until day 169, the CD4:CD8 ratio in pb normalized. CR was documented on day 169 after alloHSCT and is now ongoing for almost 3 years after alloHSCT. Conclusions: We confirm that an alloHSCT can be a curative option for refractory patients with SS. The achievement of a CR after tapering the immunosuppressive therapy indicates a significant role of the GvL effect. In present treatment algorithms for patients with SS, the timing of an alloHSCT and the intensity of conditioning should be further explored.

• Sézary syndrome
• clinical practices statement
• cutaneous T-cell lymphoma
• management
• mycosis fungoides

Advanced-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.

• Sézary syndrome
• allogeneic hematopoietic stem cell transplantation
• cutaneous T-cell lymphomas
• lymphomas
• mycosis fungoides
• review

• Cutaneous T-cell lymphoma
• Erythrodermic
• Investigational therapies
• Leukaemic variants
• Mycosis fungoides
• Supportive care
• Sézary syndrome
• Therapeutic strategies
• Treatment regimen

• Humans
• Immunologic Memory
• Mycosis Fungoides/diagnosis
• Mycosis Fungoides/immunology
• Mycosis Fungoides/pathology
• Mycosis Fungoides/therapy
• Neoplasm Proteins/immunology
• Programmed Cell Death 1 Receptor/immunology
• Receptors, KIR3DL2/immunology
• Sezary Syndrome/diagnosis
• Sezary Syndrome/immunology
• Sezary Syndrome/pathology
• Sezary Syndrome/therapy
• Skin Neoplasms/diagnosis
• Skin Neoplasms/immunology
• Skin Neoplasms/pathology
• Skin Neoplasms/therapy
• T-Lymphocytes/immunology
• T-Lymphocytes/pathology

• P30 CA033572 NCI NIH HHS
• R01 CA229510 NCI NIH HHS

• CART cell therapy
• Immune checkpoint inhibitors
• Immunotherapy
• T cell lymphoma
• T-ALL

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still considered a definitive curative modality for refractory or relapsed non-Hodgkin’s lymphoma (NHL). However, transplant-related morbidity and mortality remain a considerable challenge. The graft-versus-host disease (GVHD)–free with relapse-free survival (GRFS) rate and GRFS-related prognostic factors have not been fully examined for NHL alone. We evaluated 104 consecutive patients with refractory or relapsed aggressive NHL receiving allo-HSCT at a single institution. With a median follow-up of 31.5 months, the estimated 3-year overall survival (OS), disease-free survival (DFS), the cumulative incidence rates of relapse, and non-relapse mortality were 45.9%, 45.9%, 36.0%, and 17.0%, respectively. The patients with overall grades III–IV acute GVHD had markedly inferior OS and DFS (p = 0.040 for OS and p = 0.028 for DFS). However, patients with more than mild stage chronic GVHD showed superior OS and DFS (p = 0.004 and p = 0.008, respectively). The 1- and 3-year GRFS rates were 44.5% and 36.9%, respectively. The negative bone marrow involvement at diagnosis, chemosensitive disease status, and fewer exposure lines of chemotherapy before transplantation significantly increased the GRFS incidence. However, no transplant-associated factors were related to GRFS incidence. Furthermore, applying dynamic GRFS method which excepted patients whose chronic GVHD was fully resolved within short-period, survival rate significantly increased over time (36.9% vs. 41.9%, p = 0.045 for conventional GRFS vs. dynamic GRFS at 3 years after transplantation). In conclusion, these results suggest that GRFS is also a useful endpoint to assess transplant outcomes, and the dynamic GRFS calculation, including rapidly manageable chronic GVHD, is a more practical method for patients with refractory or relapsed heterogenous subtypes of NHL.

• Allogeneic hematopoietic stem cell transplantation
• Endpoint
• Graft-versus-host disease
• Lymphoma

• Adolescent
• Adult
• Aged
• Allografts
• Disease-Free Survival
• Female
• Graft vs Host Disease/mortality
• Hematopoietic Stem Cell Transplantation
• Humans
• Lymphoma, Non-Hodgkin/mortality
• Lymphoma, Non-Hodgkin/therapy
• Male
• Middle Aged
• Predictive Value of Tests
• Retrospective Studies
• Risk Factors
• Survival Rate

• National Foundation of Korea (NRF)