On August 22–23, 2025, the 13th Ludaopei Hematology Conference was held in Beijing, jointly organized by the Beijing Health Promotion Association and the Guangzhou Kapok Oncology and Rare Disease Foundation, and hosted by the Beijing Ludaopei Hematology Institute. This high-level meeting brought together world-leading hematology experts, focusing on hematopoietic stem cell transplantation, cellular therapy, and precision treatment of hematologic malignancies, and attracted more than one thousand attendees.
During the conference, Professor Cao Xingyu of Beijing Ludaopei Hospital delivered an insightful lecture on advances in the treatment of cutaneous T-cell lymphomas (CTCL) and hematopoietic stem cell transplantation (HSCT). Oncology Frontier – Hematology Frontier has summarized the academic highlights to provide important clinical guidance and theoretical references for optimizing management strategies.
I. Overview of Cutaneous T-Cell Lymphoma (CTCL: Mycosis Fungoides and Sézary Syndrome)
Extranodal lymphomas account for 30% of non-Hodgkin lymphomas (NHL), with the gastrointestinal tract most commonly involved, followed by the skin. Primary cutaneous lymphomas are classified by WHO/EORTC into cutaneous T/NK-cell lymphomas (CTCL) and cutaneous B-cell lymphomas (CBCL). CTCL, which originates from skin-homing or resident T cells, accounts for 70–82% of primary cutaneous lymphomas. Among these, mycosis fungoides (MF) and Sézary syndrome (SS) together comprise 70–75% of newly diagnosed CTCL cases.
MF, the most common CTCL, represents about 50% of primary cutaneous lymphomas and is typically indolent. SS, by contrast, is rare (<5% of CTCL), aggressive, and historically considered a leukemic variant of MF; however, WHO/EORTC now recognizes MF and SS as distinct diseases due to differences in clinical presentation and cell of origin. Both usually arise from Th2-biased helper T cells, with Th2 dominance increasing as disease progresses.
The TNMB (tumor–node–metastasis–blood) staging system remains the most important prognostic tool for MF/SS. Approximately 70% of patients present with early-stage disease (IA–IIA). Five-year overall survival (OS) rates are 96–99% for stage IA and 75–86% for stage IB. Early-stage disease is usually managed with skin-directed therapies such as topical corticosteroids, mechlorethamine, phototherapy, and radiotherapy. Advanced CTCL (≥IIB) carries a much poorer prognosis and requires systemic therapies such as bexarotene, vorinostat, romidepsin, brentuximab vedotin (for CD30+ MF), or mogamulizumab. However, response rates are modest (30–40%), and remissions are often short-lived.
MF originates from tissue-resident memory T cells (TRM) (CCR4+, CLA+, CCR7−, L-selectin−) restricted to fixed skin patches, while SS originates from central memory T cells (Tcm) (CCR4+, CCR7+, L-selectin+), which infiltrate the skin, lymph nodes, and peripheral blood. These molecular phenotypes correlate with clinical features and therapeutic targets.
II. Clinical and Pathologic Features of MF and SS
MF was first described in 1806 by Jean-Louis-Marc Alibert, named for its mushroom-like nodules. Histologically, it is characterized by epidermotropic CD4+ T lymphocytes with cerebriform nuclei. It primarily affects adults (male:female ≈ 2:1), with an incidence of about 10 cases per million population, though rates are higher among Black patients. Risk factors may include environmental exposures, obesity, and long-term smoking.
Clinically, classic MF begins with scaly erythematous patches that evolve over years into plaques and tumors, usually on non-sun-exposed areas. Fewer than one-third of patients develop lymph node/visceral involvement or large-cell transformation. Disease often follows a protracted course spanning decades.
Sézary syndrome (SS), first described in 1938, is the leukemic variant of CTCL, predominantly affecting men over 60 years. It is defined by the triad of erythroderma, lymphadenopathy, and circulating Sézary cells with cerebriform nuclei. Other features include pruritus, alopecia, ectropion, palmoplantar keratoderma, and nail dystrophy. Due to immune dysregulation, SS patients have increased risk of secondary skin and systemic malignancies. SS carries a poor prognosis, with a median survival of ~32 months and 5-year OS of only 10–30%.
Diagnostic criteria for SS include:
- ≥1000 Sézary cells/µL in peripheral blood,
- Immunophenotype abnormalities (CD4/CD8 >10, CD4+CD7− ≥40%, or CD4+CD26− >30%),
- Clonal TCR gene rearrangements in both skin and blood.
Early MF can be diagnosed using the ISCL/EORTC point-based scoring system (≥4 points).
Staging integrates T (skin), N (nodes), M (viscera), and B (blood), guiding treatment and prognosis.
III. Prognosis
Analysis of 525 patients demonstrated stark survival differences by stage. Only 2% of stage T1 and 15% of stage T2 patients died of disease, compared to ~50% of T3/T4. Only 4% of T4 patients achieved long-term remission.
A multinational prognostic index for advanced MF/SS identified four risk factors: stage IV, age >60, large-cell transformation, and elevated LDH. Five-year survival rates ranged from 67.8% (low-risk) to 27.6% (high-risk).
IV. Treatment Strategies
Non-HSCT Therapy
Skin-directed therapies: potent topical corticosteroids, bexarotene gel, mechlorethamine, imiquimod, tazarotene, phototherapy (UVB/PUVA), local electron beam, and total skin electron beam therapy (TSEBT).
Systemic therapies: pralatrexate, gemcitabine, oral bexarotene, low-dose methotrexate, interferon, HDAC inhibitors, brentuximab vedotin, mogamulizumab, as well as immunotherapies (alemtuzumab, lacutamab, pembrolizumab, nivolumab).
Early trials of CD5 CAR-T therapy in refractory T-cell lymphomas (including MF/SS) showed a 44% overall response rate, but further validation is needed.
HSCT Therapy
Autologous HSCT: While capable of inducing remission, relapse occurs rapidly (median 2.3 months), and long-term outcomes are poor.
Allogeneic HSCT (allo-HSCT): Multiple studies confirm allo-HSCT as the only potentially curative option for advanced MF/SS. EBMT follow-up of 60 patients found relapse/progression as the main cause of failure; however, donor lymphocyte infusion (DLI) and salvage therapies offered durable benefit for some. Reduced-intensity conditioning (RIC) regimens were associated with lower non-relapse mortality (NRM) compared to myeloablative regimens.
Key prognostic factors include:
- Performance status: poor Karnofsky scores → higher NRM.
- Donor type: unrelated donors associated with worse OS.
- Disease status at transplant: achieving CR/VGPR prior to allo-HSCT strongly predicts improved OS (74% 2-year OS).
- TBI-based regimens reduce relapse risk.
Bridging strategies (to achieve remission before HSCT): brentuximab + bendamustine, TSEBT, or sequential auto-HSCT followed by allo-HSCT.
Caution: Pre-HSCT use of mogamulizumab or PD-1 inhibitors markedly increases GVHD risk due to prolonged Treg depletion or checkpoint dysregulation.
V. Non-HSCT vs HSCT
The CUTALLO trial, a multicenter matched cohort study in France, confirmed superior PFS and a trend toward improved OS in advanced MF/SS patients receiving allo-HSCT versus non-HSCT therapies. Quality of life also improved over time in the transplant group.
Conclusion
Current evidence indicates that MF ≥ stage IIB and all SS patients require aggressive management. While conventional therapies may control symptoms, they are rarely curative. Allo-HSCT remains the only strategy with potential for long-term remission or cure and should be considered early in eligible patients.
RIC regimens are generally preferred for their lower NRM. Achieving remission before HSCT is essential, with bridging strategies like TSEBT playing a key role. Post-transplant relapse should be managed promptly with DLI to harness graft-versus-tumor effects. Auto-HSCT is not recommended.
Expert Profile
Professor Cao Xingyu Beijing Ludaopei Hospital MD, Chief Physician, Director of the Department of Hematopoietic Stem Cell Transplantation (Deputy Director level, Hebei Yanda Ludaopei Hospital)
- Committee Member, Hematology Branch, Beijing Medical Association
- Committee Member, HSCT Section, Beijing Cancer Prevention Society
- Standing Committee Member, HSCT Section, Hebei Society of Experimental Hematology
- Youth Member, Translational Hematology Committee, Chinese Anti-Cancer Association
Prof. Cao specializes in hematopoietic stem cell transplantation for hematologic malignancies, with particular expertise in cutaneous T-cell lymphomas, graft-versus-host disease, and transplant-related complications.
