Analysis of long-term outcomes of combined modality therapy for cutaneous T-cell lymphoma

J Am Acad Dermatol. 2003 Jul;49(1):35-49. doi: 10.1067/mjd.2003.449.


Background: Although cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF) and Sézary syndrome, is often responsive to treatment, few current therapies increase survival or consistently induce durable remissions, especially in advanced disease.

Objective: In an effort to improve treatment efficacy and outcome in CTCL, a combined modality protocol using 3 to 4 consecutive phases of therapy was initiated in 1987 at M.D. Anderson Cancer Center, Houston, Tex.

Methods: During a period of 15 years between 1987 and 2001, 95 patients with early-stage (Ia-IIa, n = 50) and late-stage (IIb-IVb, n = 45) MF were treated with subcutaneous interferon-alpha and oral isotretinoin, followed by total-skin electron beam therapy, and long-term maintenance therapy with topical nitrogen mustard and interferon-alpha. Patients with late-stage (IIb-IVb) disease also received 6 cycles of combination chemotherapy before electron beam therapy.

Results: Combined modality therapy yielded a response rate of 85% with a 60% complete response rate. Among 38 patients with early-stage disease and 18 patients with late-stage disease achieving complete response, 9 (24%) patients with early-stage MF and 3 (17%) patients with late-stage MF achieved sustained remissions lasting more than 5 years. The median disease-free survival (DFS) for early and late stages of disease was 62 and 7 months, with 5-year Kaplan-Meier estimated rates of 50% and 27%, respectively. Current median overall survival times on combined modality are 145 months for patients with early-stage disease and 36 months for those with late-stage disease. Death was attributable to CTCL disease in 17 (55%) of 31 cases. The Kaplan-Meier estimates for 5-year survival are 94% for early-stage and 35% for late-stage disease. Univariate survival analysis in this patient population reveals statistically significant associations of clinical stage with overall response rates (P =.02), DFS (P =.03), and overall survival (P <.0001); age with DFS (P =.001) and overall survival (P =.04); and T stage (P <.0001) and lactate dehydrogenase (P =.007) with overall survival. By multivariate analysis using a Cox proportional hazards model, only age was significantly associated with DFS (hazard ratio 2.9), and only stage with overall survival (hazard ratio 18.2).

Conclusion: This nonrandomized and uncontrolled CTCL study gives supportive evidence that this multiphased combined modality regimen is well tolerated and may yield higher response rates and DFS than total-skin electron beam therapy alone, but provides no evidence for a change in survival.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Combined Modality Therapy
  • Drug Therapy, Combination
  • Female
  • Humans
  • Interferon-alpha / therapeutic use*
  • Isotretinoin / therapeutic use*
  • Lymphoma, T-Cell, Cutaneous / drug therapy*
  • Lymphoma, T-Cell, Cutaneous / mortality
  • Lymphoma, T-Cell, Cutaneous / pathology
  • Male
  • Middle Aged
  • Mycosis Fungoides / drug therapy*
  • Mycosis Fungoides / mortality
  • Mycosis Fungoides / pathology
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Survival Analysis
  • Treatment Outcome


  • Interferon-alpha
  • Isotretinoin