Meningeal carcinomatosis from breast carcinoma responsive to trastuzumab.
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Biomedical subjects
Publications and source records attributed to S Suki.
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We have previously proposed a staging system for large cell lymphoma using the two serum markers beta-2-microglobulin (B2M) and lactate dehydrogenase (LDH). We recently tested this model in a different cohort of patients with large cell lymphoma and also examined the possible contribution of thymidine kinase (TK), a previously reported serologic prognostic factor. Using an inclusion criteria in the multivariate analysis for both forward and backward selection of p < 0.15, only LDH, B2M, and TK were significant independent prognostic factors for both time to treatment failure (TTF) and survival. Inclusion of TK in the serologic model resulted in three significantly different risk groups for both TTF and survival. Corresponding endpoints at three years were: 1) good risk (no markers elevated, n = 43): 78%, 91%; 2) intermediate risk (1 or 2 markers elevated, n = 47): 41%, 36%; 3) poor risk (3 markers elevated, n = 11): 0%, 0%. This analysis extends the observation of the independent prognostic significance of B2M and LDH. The addition of TK permits a more precise estimate of risk, contributing to the utility of a serological staging system for large cell lymphoma.
Forty-eight adult patients with recurrent or refractory intermediate grade or immunoblastic lymphoma received high-dose carmustine (BCNU), etoposide, Ara C and cyclophosphamide (BEAC), followed by autologous bone marrow transplantation (BMT). Median follow-up is 906 days (range 613-2067 days). The complete remission rate was 42% and 22% had a partial response. Actuarial failure-free survival is 30% +/- 6.6%. Twenty one patients relapsed or progressed. Only one relapse occurred > 1 year after autologous BMT. Adverse prognostic factors for failure-free survival include high LDH at the time of autologous BMT, chemotherapy-refractory disease and multiple prior relapses. Patients with chemotherapy responsive first salvage (those achieving first CR only with salvage chemotherapy and those with first relapse, responding to salvage chemotherapy) had a failure-free survival of 52% +/- 10% vs 12% +/- 6% for those with more advanced disease. Of 13 patients who had no adverse factors, only two relapsed. Treatment-related mortality occurred in 23%, including infection (n = 4), cardiac toxicity (n = 4), pulmonary toxicity (n = 2) and hemorrhage (n = 1). Pulmonary toxicity was more common among patients who had received prior radiation-therapy to the chest. BEAC chemotherapy with autologous BMT is an effective but relatively toxic regimen for patients with relapsed or refractory lymphomas. The combination of chemotherapy-responsive disease after failure of one chemotherapy regimen and normal LDH identifies patients with a favorable prognosis. Alternative cytotoxic regimens require evaluation, with the goal of reducing treatment related mortality. More effective cytoreductive therapy is required for patient with poor prognostic features.
BACKGROUND: The objectives of the study were to evaluate the antileukemic efficacy and toxicity profiles of the combination of fludarabine and intermediate-dose cytosine arabinoside (ara-C) in refractory or relapsed adult acute lymphocytic leukemia (ALL). PATIENTS AND METHODS. Thirty adults with refractory or relapsed ALL were treated. Their median age was 45 years, 60% were in second or subsequent relapse, and 37% had Philadelphia chromosome-positive disease. Treatment consisted of ara-C 1 g/m2 during a period of 2 hours daily for 6 days, and fludarabine 30 mg/m2 during a period of 30 minutes daily for 5 days on days 2-6. Fludarabine was given 4 hours before ara-C to increase the rate of ara-C 5'-triphosphate (ara-CTP) accumulation in leukemic cells. Courses were repeated every 3 weeks or longer, depending on patient response and side effects. RESULTS: Nine (30%) patients achieved a complete remission (CR), 8 (27%) died during remission induction, and 13 (43%) had resistant disease. The median CR duration was 22 weeks, and the median survival was 12 weeks for all patients, and 34 weeks for those who had a response to treatment. Except for low platelet counts, which predicted shorter survival time, no other prognostic factors were demonstrated, considering the small number of patients treated. Myelosuppression-associated febrile episodes were the most common side effects, occurring in 28 (93%) patients. Neurotoxicity was noted in two (7%) patients. CONCLUSIONS: Fludarabine and ara-C are an active and relatively safe antileukemic combination in refractory or relapsed ALL. Future studies will incorporate other anti-ALL agents, such as topoisomerase II-reactive drugs, to improve the overall efficacy, and growth factors, to reduce myelosuppression-related complications.