Induction and Maintenance Therapy for Patients with Mycosis Fungoidus (MF) and Sezary Syndrome (SS) in Large Cell Transformation Phase.

To determine the frequency of transformation of cutaneous T-cell tumors (CTCL) and effect of different therapies.

Retrospective analysis of treatment results for 68 patients with two types of CTCL, MF and SS, selected from 263 patients T-cell lymphoma/leukemia treated at NCH during 9 years. All 68 patients have CD 3 +, CD 4+, CD 7-, CD 8-, CD 30- immunophenotype and T-cell clonality (rearranged genes for T-cell receptor). MF was diagnosed in 48 patients (24 men, 24 women) with median age 52 years (26 - 77), SS in 20 patients (12 men, 8 women), median age 61 years (23 -87). Half of the MF patients started surveillance at III - IV stages, 15 of 20 patients with SS - at stage IV. Treatment of CTCL in the indolent phase was conducted in accordance with their stage: monochemotherapy (leukeran or methotrexate) and biologically active agents (interferons, retinoids, monoclonal antibody) were used. Appearance of transformation to large cell lymphoma was consistent with tumor progression as determined by presence of two or more of the following: 1. rapid growth of tumors in MF or leukemization in SS; 2. presence of large anaplastic cells in blood or tumor biopsy; 3. increase in expression of Ki-67 (10-70%); 4. appearance of activation markers (CD30, CD25) in tumor cells, and 5. loss of certain linear T-cell markers. For treatment of patients in large cell transformation phase Promace-Cytabom or FNC protocols were used in 7 patients. Five patients received A-CHOP-14 (with alemtuzumab) and subsequent maintenance therapy (methotrexate 20 mg per week, 6-mercaptopurine 50-100 mg/day in combination with alpha interferon 3 million daily).

The overall median time of observation (before and during treatment) in 48 patients with MF was 96 months (8-264). For 13 patients who died it was 76 months (8-264), mortality rate was 27%. The overall median observation (before and during treatment) in 20 patients with SS was 60 months (6-123), for 8 who died, it was 62 months (6-94), mortality 40%. The median observation for treatment of MF was 30 months (from 3-122) for the SS, it was 18 months (1 - 85). Restraining aggressive therapy for an indolent process resulted in complete or partial remission, while maintaining a good quality of life. Large cell transformation phase was observed in 12 patients (7 of 48 patients with MF (14.5%) and 5 of 20 patients with SS (25%). Seven of the 12 patients died within 2-4 months due to septic complications during Promace-Cytabom or FNC protocols. The remaining 5 patients received A-CHOP-14 (6-7 courses) which reduced tumor formation and /or leukemization. However, the persistence of patches, plaque or erythrodermia was the reason for maintenance therapy. This combination led to further regression of skin manifestations and full or partial remission within 4-12 months.

Because of the lack of a generally accepted treatment for GM and SS in Large Cell Transformation phase, even small successes should be discussed. The effectiveness of combining of polychemotherapy with maintenance therapy may be effective due to the presence of several distinct clones of tumor cells with different properties. Keywords: treatment of cutaneous T-cell lymphoma, Mycosis Fungoidus, Sezary Syndrome, Large Cell Transformation Phase, immunohistochemical markers of T-cell lymphomas.

No relevant conflicts of interest to declare.