[Cutaneous and systemic T-cell lymphoma treated with haploidentical bone marrow transplantation]. / Lymphome T cutané et systémique traité avec succès par greffe haplo-identique.

BACKGROUND: Herein, we report a case of systemic cutaneous T-cell lymphoma refractory to standard therapy, the course of which resulted in haplo-identical bone marrow grafting. PATIENTS AND METHODS: A 53-year-old woman consulted for facial erythema with infiltration, keratotic lesions on the trunk, and adenopathies measuring around 1cm on the axilla and inguinal folds. A diagnosis was made of Sézary syndrome (SS), a leukaemic form of epidermotropic cutaneous T-cell lymphoma. After three years of treatment with methotrexate, the patient developed transformed SS with visceral involvement. Given the high risk of relapse and the absence of an HLA-compatible donor, haploidentical bone marrow grafting was performed. The patient was still in complete remission two and a half years later. The disease course was nevertheless marked by the emergence one year after grafting of a Blaschko-distributed lichenoid eruption having histological features consistent with chronic graft-versus-host disease (GVHD); treatment with topical betamethasone proved efficacious. DISCUSSION: To our knowledge, this is the first reported case of haploidentical grafting for systemic and transformed cutaneous T-cell lymphoma. This approach could henceforth represent a therapeutic option for patients requiring an allograft in the absence of compatible donors. The Blaschko-distributed lichenoid lesions attributed to chronic GVHD could be the result of reduced immune tolerance to abnormal embryological clones leading to a T-lymphocyte-mediated inflammatory reaction.

Hematopoietic Stem Cell Transplant for Mycosis Fungoides and Sézary Syndrome.

Mycosis fungoides (MF) and Sézary syndrome (SS) are common types of primary cutaneous T-cell lymphoma. Early-stage MF has a favorable prognosis and responds well to skin-directed regimens. Patients with advanced-stage MF, transformed MF, and SS are treated with combined systemic and skin-directed therapies. However, the disease is incurable with standard regimens, and frequent relapses are common. Owing to the lack of improvement in overall survival with standard regimens, hematopoietic stem cell transplant (HSCT) has been explored as a potential curative option. This article reviews the role of HSCT in MF/SS and discusses data regarding conditioning regimens, treatment-related complications, and outcomes.

Minimal residual disease monitoring with high-throughput sequencing of T cell receptors in cutaneous T cell lymphoma.

Mycosis fungoides (MF) and the leukemic presentation Sézary syndrome (SS) are clonal T cell lymphomas arising from the skin and are considered noncurable with standard therapies. To develop a specific and sensitive monitoring tool, we tested the ability of high-throughput sequencing (HTS) of T cell receptors (TCRB) to monitor minimal residual disease (MRD) after allogeneic hematopoietic cell transplantation. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs) or skin samples. The rearranged TCRß loci were amplified using Vß- and Jß-specific primers, followed by HTS, to generate up to 1,000,000 reads spanning the CDR3 region of individual cells. Malignant clones were identified in diagnostic samples in all cases by a dominant CDR3 sequence. Before transplant, four patients had circulating Sézary cells by the routine flow cytometry, which was confirmed by TCRB HTS. Although the flow cytometry found no detectable Sézary cells, malignant clones were detected by TCRB HTS in all other six cases. Five patients achieved "molecular remission" in blood between +30 and +540 days after transplant. Four of these patients also achieved molecular clearance in skin after transplant. Experiments using blood samples spiked with purified Sézary cells demonstrated that TCRB HTS can detect Sézary cells at the level of 1 in 50,000 PBMCs, which is more sensitive than standard diagnostics. We have thus demonstrated the utility of TCRB HTS to assess MRD with increased sensitivity and specificity compared to other current methodologies, and to monitor response to therapy in this MF/SS patient population.

Allogeneic hematopoietic cell transplantation for patients with mycosis fungoides and Sézary syndrome: a retrospective analysis of the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.

PURPOSE: To analyze the outcome of allogeneic transplantation for mycosis fungoides and Sézary syndrome (MF/SS) in terms of nonrelapse mortality (NRM), relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) and to identify factors associated with the outcome. PATIENT AND METHODS: Sixty patients with MF (n = 36) and SS (n = 24) who received a first allogeneic hematopoietic cell transplantation (HCT) from a matched related (mRD; n = 45) or unrelated donor (mUD; n = 15) between 1997 and 2007 and who were registered in the European Group for Blood and Marrow Transplantation database were analyzed: 37 men and 23 women, median age 46.5 years (range, 22 to 66 years). Forty-four patients had TNM stage IV, and 40 patients were at advanced phase at transplantation. Forty-four patients received reduced-intensity conditioning (RIC) regimens, and 25 underwent T-cell depletion (TCD). RESULTS: Allogeneic transplantation in MF/SS offers an estimated OS of 66% at 1 year and 54% at 3 years, primarily driven by donor type, disease phase, and type of conditioning. RIC decreased NRM (relative risk [RR] = 4.7; P = .008) without increasing REL, leading to a higher OS (RR = 2.8; P = .03). Advanced-phase disease increases REL (RR = 3.0; P = .03) and reduces PFS (RR = 4.4; P = .002) and OS (RR = 3.5; P = .023). Recipients of mRD allogeneic HCT had better PFS (RR = 2.7; P = .006) and OS (RR = 4.0; P = .001) than their mUD counterparts. The risk of REL increases with TCD (RR = 3.2; P = .005). Some patients who experience relapse can successfully undergo rescue treatment with donor lymphocyte infusions. CONCLUSION: Allogeneic transplantation is a valid therapeutic alternative for high-risk patients with advanced-stage MF/SS. Our data also suggest the existence of a clinically relevant graft-versus-lymphoma effect in MF/SS.

Total skin electron beam and non-myeloablative allogeneic hematopoietic stem-cell transplantation in advanced mycosis fungoides and Sezary syndrome.

PURPOSE: Transformed mycosis fungoides (MF) and Sézary syndrome (SS) are currently incurable. We studied the safety and efficacy of total skin electron beam with allogeneic hematopoietic stem-cell transplantation (HSCT) in patients with cutaneous T-cell lymphoma (CTCL). PATIENTS AND METHODS: Nineteen patients with advanced CTCL (median age, 50 years; four prior therapies) underwent total skin electron beam radiation followed by allogeneic HSCT between July 2001 and July 2008. Sixteen patients were conditioned with fludarabine (125 mg/m(2)) and melphalan (140 mg/m(2)) plus thymoglobulin (for mismatched donors). Graft-versus-host disease (GVHD) prophylaxis was with tacrolimus/mini methotrexate. RESULTS: Eighteen patients experienced engraftment, and one died as a result of sepsis on day 16. Median time to recovery of absolute neutrophil count (ANC) was 12 days. Fifteen achieved full donor chimerism, 12 had acute GVHD, and 12 were treated for chronic GVHD. The overall intent-to-treat response was 68%, and the complete response rate was 58%. Four of six patients died in complete remission as a result of bacterial sepsis (n = 2), chronic GVHD and fungal infection (n = 1), or lung cancer (n = 1); only two died as a result of progressive disease. Eight experienced relapse in skin; five regained complete response with reduced immunosuppression or donor lymphocyte infusions. Eleven of 13 are currently in complete remissions, with median follow-up of 19 months (range, 1.3 to 8.3 years). Median overall survival has not been reached. CONCLUSION: Total skin electron beam followed by allogeneic stem-cell transplantation merits additional evaluation for a selected group of patients with refractory, advanced, cutaneous T-cell lymphoma with evidence for graft-versus-tumor effect.