Prognostic factor analysis in mycosis fungoides/Sézary syndrome.

BACKGROUND: The influence of prognostic factors on survival in patients with mycosis fungoides/Sézary syndrome (MF/SS) is less well described than for other lymphomas. OBJECTIVE: Our purpose was to evaluate the prognostic value of diverse clinicopathologic and laboratory characteristics in patients with MF/SS. METHODS: All 115 patients with MF/SS seen at the Mycosis Fungoides clinic at M. D. Anderson Cancer Center during the study period who had slides available for pathologic review were analyzed. Univariate and multivariate methodologies were used. RESULTS: Age (> or = 60 years; P = .0002), advanced stage (P < 10(-5)), tumor (T3) stage disease (P < or = 10(-5)), lymphadenopathy (P = .006), bone marrow infiltration (P = .03), high lactate dehydrogenase (LDH; P = .0002), high beta2-microglobulin (> 2 mg/L; P = .009), and transformation to large-cell lymphoma (P = .004) were significant prognostic factors in the univariate analysis and correlated with a poorer survival. The outcome of patients staged as IIB was significantly worse than that of those staged as I or IIA or III (P < .001) and was comparable to that of the patients staged as IV (P = .8). In the multivariate analysis, the factors selected include stage (I to IIA and III vs IIB and IV; P < .0001), LDH (P = .006), and age (> or = 60 vs < 60 years; P = .02). The actuarial median survival of patients with advanced stage, high LDH, or age 60 years or more was 2.5 to 3.5 years, whereas that of patients without any of these parameters was more than 13 years. CONCLUSION: Our results suggest that patients with MF/SS who are staged as IIB or IV, who have a high LDH, or who are 60 years of age or older have an aggressive course and poor survival.

Transformation of mycosis fungoides/Sezary syndrome: clinical characteristics and prognosis.

The occurrence of large cell transformation has been well documented in a subgroup of patients with mycosis fungoides/Sezary syndrome (MF/SS). However, because of the rarity of MF/SS, little is known about the influence of clinicopathologic features in predicting large cell transformation and about outcome in the transformed cases. We evaluated all patients with MF/SS who were registered in our clinic during the study period and for whom pathologic slides for review were available or could be obtained. Disease was classified as transformed if biopsy showed large cells (>/=4 times the size of a small lymphocyte) in more than 25% of the infiltrate or if they formed microscopic nodules. Twenty-six patients with transformation were identified from a total of 115 evaluable cases with a diagnosis of MF/SS. The actuarial cumulative probability of transformation reached 39% in 12 years. The median time from diagnosis of MF/SS to transformation was 12 months (range, 0 to 128 months). Thirty-one percent of all patients with stage IIB-IV disease at presentation eventually transformed versus 14% of those with stage I-IIA (P = . 03), with transformation being especially common in patients with tumors (T3), 46% of whom transformed. Combining elevated beta2 microglobulin and lactic dehydrogenase (neither elevated v one or both elevated) was also predictive for transformation (P = .009). The median survival from initial diagnosis of MF/SS for the transformed patients was 37 months versus 163 months for the untransformed group (P = .0029). The median survival from transformation was 19.4 months (range, 2+ to 138 months). The following characteristics were associated with an inferior survival in transformed patients: (1) early transformation (<2 years from the diagnosis v >/=2 years; P = .011) and (2) advanced stage (IIB-IV v I-IIA; 2-year survival, 23% v 86%; P = .0035). We conclude that MF/SS patients with stages IIB-IV disease and, in particular, those with tumors have a high incidence of large-cell transformation. Patients with transformation have a relatively poor survival, especially if transformation occurs early (within 2 years) in the course of disease or if they are staged as IIB or higher.

Two-phase study of hepatic artery vascular occlusion with microencapsulated cisplatin in patients with liver metastases from neuroendocrine tumors.

OBJECTIVE: We conducted a two-phase trial in which 100-micron polylactic acid microcapsules with a cisplatin payload (manufactured at our institution [the M. D. Anderson Cancer Center]) were used for hepatic artery occlusion therapy for symptomatic patients who had liver metastases from neuroendocrine tumors. SUBJECTS AND METHODS: Between January 1993 and December 1995, 20 patients with advanced, unresectable, symptomatic neuroendocrine tumors with liver metastases received repeated hepatic artery occlusion therapy using encapsulated cisplatin. The dose of encapsulated cisplatin was increased in a stepwise fashion. Selective angiography was used to occlude the portion of the hepatic vasculature that had the most metastases with encapsulated cisplatin microcapsules. In each patient, hepatic artery occlusion therapy was repeated in 6-8 weeks and responses were evaluated. Subsequent vascular occlusions were performed on the basis of the level of palliation achieved and the persistence of symptoms. RESULTS: Of the 20 patients, 17 patients had carcinoid tumors and three had islet cell tumors. The median percentage of liver replacement was approximately 50%. Fifteen of the 20 patients had received prior therapy and 17 patients had hormonal syndrome at the beginning of therapy. One patient had tumor bulk-related symptoms. Nineteen patients had elevated peptides markers that could be followed serially Six patients received encapsulated cisplatin at 50 mg/m2, four patients at 75 mg/m2, and 10 patients at 100 mg/m2 of body surface area. The median number of vascular occlusive procedures per patient was three. All patients were assessable for toxicity and 18 were assessable for response (the other two patients were not assessable because of loss of follow-up). The median follow-up time was 14 months. Twelve (67%) of 18 patients had a median reduction in symptoms of 50%. Eleven (73%) of 15 patients with elevated 24-hr-urine levels of 5-hydroxyindoleacetic acid had a median reduction of 64% for this symptom. We observed objective reduction in the tumors of 14 of the 18 patients. In six of the 14 patients, we noted a partial response. In eight, we observed a minor response. In four of the 18 patients, we noted no response. One treatment-related death resulted from hepatorenal syndrome. Other major complications included hepatic pain (100%), fever (100%), nausea (100%), and vomiting (95%). Also all patients had a transient elevation of liver enzymes. Five of the 20 patients died of disease during our study. CONCLUSION: Hepatic artery vascular occlusion therapy using encapsulated cisplatin is feasible, can palliate symptoms, and can produce biochemical and objective responses in liver metastases from neuroendocrine tumors. The maximum tolerated dose appears to be 100 mg/m2 of body surface area per treatment. Polylactic acid capsules have potential because they can incorporate multiple agents. With surface coating, such capsules can also be used to target specific receptors.

Treatment-related leukemia in breast cancer patients treated with fluorouracil-doxorubicin-cyclophosphamide combination adjuvant chemotherapy: the University of Texas M.D. Anderson Cancer Center experience.

PURPOSE: Adjuvant chemotherapy for breast cancer has been the routine practice in the past decade. A number of studies have observed an increased incidence of treatment-related leukemias following chemotherapy with alkylating agents and/or topoisomerase II inhibitors. We evaluated the incidence of treatment-related leukemias in breast cancer patients treated in four adjuvant and two neoadjuvant chemotherapy trials at The University of Texas M.D. Anderson Cancer Center. PATIENTS AND METHODS: Between 1974 and 1989, 1,474 patients with stage II or III breast cancer were treated in six prospective trials of adjuvant (n = 4) or neoadjuvant (n = 2) chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (CTX) (FAC) with or without other drugs. The median observation time was 97 months. In 1,107 patients, FAC chemotherapy was given postoperatively; 367 patients received induction chemotherapy, as well as postoperative chemotherapy. Eight hundred ten patients had surgery followed by radiotherapy and chemotherapy; 664 patients had surgery and chemotherapy only. Patients in two adjuvant and one neoadjuvant study received higher cumulative doses of CTX compared with those in the other studies. RESULTS: Fourteen cases of leukemia were observed. Twelve of these patients had received radiotherapy and chemotherapy, and two had received chemotherapy only. Six of the reported patients with leukemia were treated with a cumulative CTX dose of greater than 6 g/ m2. Five of these patients had received both radiotherapy and chemotherapy. The median latency period in the 14 patients was 66 months (range, 22 to 113). Six of 10 patients with adequate cytogenetic analyses had abnormalities that involved chromosomes 5 and/or 7. The rest of the patients had nonspecific cytogenetic abnormalities or lacked cytogenetic information. The 10-year estimated leukemia rate was 1.5% (95% confidence interval [CI], 0.7% to 2.9%) for all patients treated, 2.5% (95% CI, 1.0% to 5.1%) for the radiotherapy-plus-chemotherapy group, and 0.5% (95% CI, 0.1% to 2.4%) for the chemotherapy-only group; this difference was statistically significant (P = .01). The 10-year estimated leukemia risk for the higher-dose (> 6 g/m2) CTX group was 2% (95% CI, 0.5% to 5.0%) compared with 1.3% (95% CI, 0.4% to 3.0%) for the lower-dose group, a difference that was not statistically significant (P = .53). CONCLUSION: These data illustrate that patients treated with adjuvant FAC chemotherapy plus radiotherapy have a slightly increased risk of leukemia. This information needs to be considered in the treatment plans for patients with breast cancer. However, for most patients, the benefits of adjuvant therapy exceed the risk of treatment-related leukemia.