The efficacy and toxicity of 2-chlorodeoxyadenosine (2-CdA) in cutaneous T-cell lymphoproliferative disorders was examined. Between February 1991 and April 1996, 25 patients with relapsed or refractory cutaneous T-cell lymphoproliferative disorders (24 mycosis fungoides or Sezary syndrome, one Ki-1+ anaplastic large cell lymphoma) were treated with 2-CdA initially administered by continuous intravenous infusion at a dose of 0.1 mg/kg/d for 7 days (13 patients). The infusion duration was subsequently reduced to 5 days (9 patients) because of prohibitive hematologic toxicity. Three patients were treated at the same daily dose by bolus injection over two hours for 5 days. Cycles were administered at 28 day intervals. Seventeen patients received more than one cycle. An overall response rate of 24% was achieved. Three patients (12%) had a complete response with a median duration of 4.5 months (range, 2.5 to 16). Three (12%) had a partial response with a median duration of 2 months (range, 2 to 4). Nineteen patients (76%) had no response. The most significant toxicities encountered were myelosuppression (64%) and infectious complications (64%). 2-CdA has activity as a single agent in patients with previously treated relapsed T-cell lymphoproliferative disorders.

Cytogenetic analysis was performed on peripheral blood lymphocyte cultures from 19 patients with mycosis fungoides (MF)/Sézary syndrome (SS) stimulated with either phytohemagglutinin, a conventional mitogen, or a combination of interleukin-2 (IL-2) plus IL-7. The use of both PHA-stimulated and IL-2 plus IL-7-stimulated cultures enhanced the ability to identify clonal abnormalities. Clonal abnormalities were observed in 11 patients (53%) including one with monosomy for the sex chromosome as the sole abnormality. Five of the 11 patients with clonal abnormalities had normal peripheral white blood cell counts, indicating detectability of clones in the absence of frankly leukemic disease. The presence of clonal abnormalities correlated with advanced stage disease and a significantly reduced survival duration from the time of cytogenetic studies. Clonal abnormalities involving chromosomes 1 and 8 were observed in six cases. In five cases with aberrations of chromosome 1, loss of material involved the region between 1p22 and 1p36. In an additional case, a reciprocal translocation involving 1p33 was observed. Clonal abnormalities involving chromosomes 10 and 17 were observed in 5 cases, clonal abnormalities involving chromosome 2 in 4 cases, and clonal abnormalities involving chromosomes 4, 5, 6, 9, 13, 15, 19, and 20 in 3 cases. In 2 cases a der(8)t(8;17)(p11;q11) was observed. Regions of the genome that encode T-cell receptors were not involved in abnormalities. The region between 1p22 and 1p36 is identified as a region of the genome that requires detailed analysis toward the identification of potential gene(s) involved in the process of malignant transformation and/or progression in MF/SS.

We investigated the efficacy of 2-chlorodeoxyadenosine (2-CdA) therapy in patients with mycosis fungoides (MF) and the Sezary syndrome (SS). Between February 1991 and November 1993, 21 patients with relapsed or refractory MF/SS were treated with 2-CdA. 2-CdA was administered by continuous intravenous infusion at a dose of 0.1 mg/kg/d for 7 days initially (13 patients), but was subsequently reduced to 5 days (nine patients) due to hematologic toxicity. All patients had failed to respond to at least one prior treatment for MF/SS (median number of total prior therapies, five; median number of systemic prior therapies, three) and had an Eastern Cooperative Oncology Group performance status of two or better. Cycles were administered at 28-day intervals. Assessable patients received at least 5 days of 2-CdA. Fourteen patients received more than one cycle of 2-CdA. An overall response rate of 28% was achieved. Three patients (14%) had a complete response with a median duration of 4.5 months (range, 2.5 to 16). Three (14%) had a partial response with a median duration of 2 months (range, 2 to 4). Fifteen patients (72%) had no response. The most significant toxicities encountered were bone marrow suppression (62% of patients) and infectious complications (62% of patients). Thirty-eight percent of patients experienced no toxicity from 2-CdA. 2-CdA has activity as a single agent in patients with previously treated relapsed MF/SS. Studies in less heavily pretreated individuals with 2-CdA alone or in combination will be undertaken.

PURPOSE To investigate the efficacy of combined topical therapy and systemic interferon alfa-2a in patients with mycosis fungoides (MF) and the Sézary syndrome (SS). PATIENTS AND METHODS Between December 1987 and April 1993, 39 patients with all stages of MF and SS were treated with combined phototherapy and systemic interferon alfa-2a as part of two institutional studies. The initial phase I study of 15 patients established the maximum-tolerated dose of interferon and has been previously reported. Subsequently, 24 patients have been entered onto a phase II trial. Long-term follow-up data are provided for both studies. RESULTS The median follow-up duration for the entire cohort is 28 months. Patients with all stages of disease were enrolled (stage IB, n = 14; IIA, n = 5; IIB, n = 6; III, n = 8; IVA, n = 5; IVB, n = 1). Thirty-four patients had received previous therapy. Overall, 36 of 39 patients achieved a complete response (CR; 62%) or partial response (28%) to therapy. The median response duration is 28 months (range, 1 to 64). Twenty-nine of 39 patients are alive, with a median survival duration of 62 months (range, 1 to 66). CONCLUSION Interferon alfa-2a combined with phototherapy is an effective, safe, durable therapy for MF and SS.

BACKGROUND:Mycosis fungoides (MF) is a non-Hodgkin's T-cell lymphoma of the skin that often begins as limited patches and plaques with slow progression to systemic involvement. No studies have been published comparing photochemotherapy (PUVA) with other topical therapies in the treatment of early-stage disease.OBJECTIVE:The purpose of the study was to examine our long-term experience using PUVA to treat early-stage MF and to compare its effectiveness and side-effect profile with other previously reported topical therapies.METHODS:Eighty-two patients with MF (83% stage IA or IB) were treated with PUVA. Clinical and histologic features were observed for a period from 2 months to 15 years (median, 43 months).RESULTS:A response was noted in 78 patients (95%) with complete clinical and histologic clearing in 53 patients (65%) for all stages. The mean duration of total complete response to PUVA for all stages was 43 months (3.6 years). The mean survival of our study group for all stages was 8.5 years. Signs of chronic actinic skin damage were found in 10% of patients, including three patients with basal cell carcinomas and three patients with squamous cell carcinomas. In a nonrandomized comparison with previously reported data for other topical therapies, the efficacy and side-effect profile of PUVA compared favorably.CONCLUSION:PUVA is an effective and safe therapy for MF with prolonged disease-free remissions being achieved. Patients with stage I and II MF respond best to PUVA. Palliative therapy with PUVA is useful in more advanced cases of MF.

A 44-year-old man was diagnosed with cutaneous T-cell lymphoma characterized by a proliferation of CD4-positive cells. In response to alpha-interferon therapy, he experienced rapid regression of his cutaneous disease. This improvement was associated with development of renal failure, characterized by nephrotic-range proteinuria with interstitial nephritis and minimal-change nephropathy. The remarkable finding of renal biopsy was marked proliferation of visceral epithelial cells (podocytes). Renal disease improved significantly in response to discontinuation of interferon and initiation of prednisone therapy. Nephrotic range proteinuria regressed, but never completely resolved. This case is illustrative of the probable role for lymphokine-mediated nephrotoxicity in the setting of lymphoproliferative disease.

The purpose of this study was to investigate the biologic activity of DAB486IL-2 when administered three times daily, in terms of toxicity, pharmacokinetics, and anti-tumor effects in patients with IL-2R expressing hematologic malignancies, especially mycosis fungoides. 20 patients were enrolled in this dose escalation phase I trial. Patient cohorts were treated at levels of 0.03 mg/kg, 0.05 mg/kg, 0.07 mg/kg and 0.09 mg/kg every 8 hours for a total of 12 doses, every 21 days as toxicity and response warranted. Eight patients experienced transient fevers associated with DAB486IL-2 administration. One patient experienced grade 3 hypotension, and a second developed fluid retention manifested as weight gain/pedal edema. Dose limiting toxicity consisted of one episode of transient grade 4 hepatic transaminase elevation, and 8 episodes of transient asymptomatic grade 3 hepatic transaminase elevation. At the maximum tolerated dose DAB486IL-2 exhibited biphasic clearance kinetics; transient receptor saturation may be one mechanism for this observation. Initial serum concentration and apparent steady state level (plateau) directly correlated with the dose administered, but no difference in area under the concentration curve with greater dose was observed. Biologic activity was noted in patients with mycosis fungoides with skin lesion clearing and relief of pruritus. One patient with mycosis fungoides, and one patient with a relapsed intermediate grade non-Hodgkin's lymphoma achieved partial responses. The novel mechanism of action, toxicity profile, and evidence of biologic activity in refractory cancer patients, support development of more active constructs of this agent; such trials are underway.

Journal Article Suppression of Anti-Interferon α-2a Antibody Formation in Patients With Mycosis Fungoides by Exposure to Long-Wave UV Radiation in the A Range and Methoxsalen Ingestion Get access Timothy M. Kuzel, Timothy M. Kuzel * Department of Medicine, Division of Hematology and Oncology, Northwestern University Medical School and Cancer Center and the Veterans Administration Lakeside Medical CenterChicago, III *Correspondence to : Timothy M. Kuzel, M.D., Department of Medicine, Northwestern University Medical School, 303 E. Chicago Ave., Rm. 8524 Olson Pavillion, Chicago, IL 60611. Search for other works by this author on: Oxford Academic PubMed Google Scholar Henry H. Roenigk, Jr., Henry H. Roenigk, Jr. Department of Dermatology, Northwestern University Medical School and Cancer Center and the Veterans Administration Lakeside Medical CenterChicago, III Search for other works by this author on: Oxford Academic PubMed Google Scholar Ellen Samuelson, Ellen Samuelson Department of Medicine, Division of Hematology and Oncology, Northwestern University Medical School and Cancer Center and the Veterans Administration Lakeside Medical CenterChicago, III Search for other works by this author on: Oxford Academic PubMed Google Scholar Steven T. Rosen Steven T. Rosen Department of Medicine, Division of Hematology and Oncology, Northwestern University Medical School and Cancer Center and the Veterans Administration Lakeside Medical CenterChicago, III Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 2, 15 January 1992, Pages 119–121, https://doi.org/10.1093/jnci/84.2.119 Published: 15 January 1992 Article history Received: 02 August 1991 Revision received: 29 October 1991 Accepted: 07 November 1991 Published: 15 January 1992

The pharmacokinetics of Y-90 B72.3 and In-111 B72.3 were compared following single dose injections in patients. Both radiolabeled antibodies were obtained from Cytogen Corporation with the same chelator and the same number of chelators per antibody molecule. Monoexponential plasma clearances were observed in all patients receiving In-111 B72.3 and in most patients receiving Y-90 B72.3 (11 of 13 patients). The mean plasma clearance half-life was significantly faster for Y-90 B72.3, which was 30.6 hours +/- 4.7 hours (s.d.), than for In-111 B72.3, which was 43.7 hours +/- 13.7 hours (s.d.). In addition, in patients receiving In-111 B72.3, slower plasma clearance of activity and a reduction of in vivo radioimmune complexes were observed following the administration of higher levels of antibody (2-20 mg). Size exclusion HPLC analysis of plasma showed greater than 95% of the activity associated with radiolabeled antibody at all time periods tested. The mean urinary clearance was relatively low and not significantly different for both radiolabeled antibodies at 48 hours post-injection. Biopsies of tumor tissue were obtained from selected patients and counted for activity. Mean tumor uptake was 0.0057% ID/gm and 0.0035 % ID/gm for In-111 and Y-90 B72.3, respectively.