Toxicity of high-dose sequential chemotherapy and purged autologous hematopoietic cell transplantation precludes its use in refractory/recurrent non-Hodgkin's lymphoma.

We conducted a pilot study in 20 patients with high-risk or recurrent/refractory non-Hodgkin's lymphoma (NHL) using high-dose sequential chemotherapy (HDSC) and autologous hematopoietic cell transplantation (AHCT). After cytoreduction with standard salvage therapy, HDSC/AHCT was administered in 4 phases at 2- to 4-week intervals. Phase 1 consisted of cyclophosphamide 7 g/m2 followed by granulocyte colony-stimulating factor (G-CSF) at 10 microg/kg per day and leukapheresis upon recovery from white blood cell nadir. The hematopoietic cell product was enriched by Percoll gradient separation and purged with a B-cell or T-cell monoclonal antibody panel and complement. Phase 2 consisted of methotrexate 8 g/m2 with leucovorin rescue and vincristine 1.4 mg/m2. Phase 3 was etoposide 2 g/m2 with G-CSF 5 microg/kg per day. In phase 4, the preparative regimen of mitoxantrone 60 mg/m2 and melphalan 180 mg/m2 was administered followed by AHCT. The NHL histologies were diffuse large cell, follicular/diffuse mixed, small noncleaved cell, T-cell-rich B-cell, lymphoblastic, and peripheral T cell. The remission status was first partial remission (PR1; n = 1) or beyond first complete remission (post-CR1; n = 19). Of the 20 patients enrolled, 11 proceeded through all 4 phases. Nine were removed from the study after the first or second phase because of progressive disease (n = 5), poor hematopoietic cell mobilization (n = 1), excessive toxicity (n = 2), and chronic active hepatitis C (n = 1). Treatment-related toxicities in the remaining 11 transplant recipients were cardiomyopathy, hemorrhagic cystitis, persistent cytopenias, acute renal failure, abnormal liver function test results, and infectious complications. There were no treatment-related deaths. Eight of the 11 transplant recipients were alive, 6 without disease, at a median follow-up of 2.7 years. The estimated median 2-year event-free survival was 55%, and overall survival was 70%. We conclude that HDSC/AHCT in refractory/recurrent NHL is associated with considerable acute and chronic toxicities. Given the toxicity profile, efficacy data were not sufficiently promising to warrant further study.

Overview of treatment of localized low-grade lymphomas.

The results of treatment of localized low-grade lymphoma have been reviewed with particular emphasis on the results of long-term follow-up of patients treated with radiation therapy at Stanford University. These data and results from numerous other centers suggest that 40% to 50% of patients with stage I and II follicular low-grade lymphomas can expect to achieve clinical cure of their disease with radiation therapy. Randomized trials published to date do not support the use of adjuvant chemotherapy. Although a policy of initial observation with deferral of treatment until the occurrence of disease progression is a well established approach to patients with advanced disease, no randomized studies exist that support this as a safe alternative to radiation therapy for early stage disease. New systemic therapies are required for the treatment of occult disease to prevent the occurrence of relapse outside of irradiated volumes.

PUVA treatment of erythrodermic and plaque-type mycosis fungoides. Ten-year follow-up study.

Since our preliminary report of psoralen plus long-wave ultraviolet A (PUVA) therapy in ten patients with erythroderma-type or plaque-type mycosis fungoides (MF), we have treated 38 patients with biopsy-proved MF. Approximately one third, mostly patients with erythroderma, received PUVA as primary therapy; the remainder had recurrent disease following electron beam irradiation or topical mechlorethamine (Mustargen) hydrochloride. Follow-up data are presented in 29 patients who completed an initial course of PUVA given two to three times weekly. A complete clinical response was observed in ten patients with plaque-type MF and seven with erythroderma without Sézary syndrome. The PUVA therapy was palliative for patients with advanced disease, in combination with other therapies. The mean observation period was approximately five years. Despite maintenance PUVA, most patients relapsed between ten and twenty months and were treated with another intensive course. Long-term maintenance therapy with PUVA was necessary to control the disease.

Cutaneous malignancies and metastatic squamous cell carcinoma following topical therapies for mycosis fungoides.

Specific treatments for mycosis fungoides, including electron beam irradiation, topical mechlorethamine, and psoralen plus ultraviolet A (PUVA) may be associated with the development of skin cancers after a variable latency period. Because these treatments are often not curative, topical therapies for mycosis fungoides, administered sequentially or concomitantly, are being used increasingly in order to control recurrent disease. This report documents the development of multiple cutaneous tumors, including squamous cell carcinoma, basal cell carcinoma, actinic keratoses, keratoacanthomas, and one case of lentigo maligna, in seven patients who received topical therapies for mycosis fungoides. In contrast to the usual latency period between ionizing radiation therapy and the development of skin cancer, two of our patients who had received prior PUVA therapy developed multiple skin tumors upon completion of electron beam irradiation. The development of metastatic squamous cell carcinoma in two of the other seven patients with multiple cutaneous neoplasms suggests that this potential hazard must be considered in the evaluation and treatment of patients with mycosis fungoides.

PUVA treatment of erythrodermic and plaque type mycosis fungoides.

Five patients with plaque type mycosis fungoides (MF) and five patients with erythrodermic MF responded favorably to oral psoralen photochemotherapy (PUVA). The mean total UVA irradiation dose was less for erythrodermic than for plaque type MF, but the mean number of treatments to achieve clearing was greater in the erythrodermic patients. Histologic examination at clearing revealed persistence of an inflammatory infiltrate in the lower dermis in most cases. Subsequent recurrent lesions in five patients revealed a more extensive dermal inflammatory infiltrate, although findings were not always diagnostic of MF due to a lack of epidermal involvement. Resumption of more intensive PUVA therapy again resulted in clinical clearing in all five patients. The follow-up period for six patients who received long-term PUVA maintenance ranged from 1 1/2 to 3 1/2 years. During PUVA therapy, five of ten patients developed epithelial malignancies or premalignancies, and one patient developed a malignant fibrous histiocytoma. Most of these patients had received prior treatment with electron beam and topical nitrogen mustard.