Mitoxantrone and high-dose cytosine arabinoside for the treatment of refractory acute lymphocytic leukemia

Article Abstract:

Although great advances in the treatment of acute lymphocytic leukemia (ALL) have been made over the past two decades, its prognosis still depends strongly on several host and tumor attributes. Characteristics like patient age, degree of leukocytosis, and chromosome abnormalities of the tumor cells all influence the relative chances for long-term remission, which range from 40 to 50 percent in patients at average risk and less than 20 percent for patients with greater risk factors. Refractory ALL, which doesn't respond to conventional treatment, has been treated with high doses of cytosine arabinoside (ara-C), and response rates of between 20 and 60 percent have been reported. Likewise, mitoxantrone has been used in these patients and similar response rates have been found. Since the toxic effects of ara-C and mitoxantrone do not overlap, there is little reason not to try both drugs simultaneously, and there may, in fact, be some beneficial antileukemic effects as a result of combining them. To examine this combination of drugs, 25 patients with a diagnosis of refractory ALL were treated with 5mg per square meter (of body surface) mitoxantrone over one hour daily for five days, and 3mg ara-C over two hours every twelve hours for six doses. For purposes of this study, complete remission was defined on the basis of bone marrow examination. A percentage of blast cells, immature, undifferentiated cells, under 5 percent was regarded as complete remission (CR). Complete remission was observed in 9 of 25 patients (36 percent). Eight patients had disease which was resistant to this treatment, and another eight died during the treatment, primarily of complications induced by chemotherapy. The overall median survival time for the 25 patients was 10 weeks, while among the patients achieving remission, the median survival period was 16 weeks. Although the improvement in survival seems promising, the deaths due to the suppression of the bone marrow were higher than seen with some other treatments, suggesting that some sort of additional support for immune function be provided patients treated with mitoxantrone and high-dose cytosine arabinoside. (Consumer Summary produced by Reliance Medical Information, Inc.)

Leukemia, Lymphocytic leukemia, Mitoxantrone hydrochloride, Mitoxantrone

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Fatal pulmonary failure complicating high-dose cytosine arabinoside therapy in acute leukemia

Article Abstract:

The treatment of relapsed cancer patients poses a problem for the clinician; conservative treatment is likely to fail, and aggressive treatment brings with it more severe side effects. This is the case in acute and chronic leukemia, for which intermediate- and high-dose cytosine arabinoside have become popular in recent years. In an evaluation of the use of high-dose cytosine arabinoside in the treatment of relapsed acute leukemia or chronic myeloid leukemia, 103 patients were treated. They received three grams per square meter of body area over a two-hour period every 6 to 12 hours for 6 to 12 doses, or two 2-hour infusions followed by a continuous infusion of 1.5 grams per square meter per day for three or four days. Thirteen patients developed adult respiratory distress syndrome. This syndrome includes the development of pulmonary edema (fluid accumulation) without a recognized cause. Only four of the patients recovered; the condition was fatal for nine. Pathological examination revealed exudate without any signs of inflammation, and pathological signs seen in other tissues, such as the intestines, hinted at a problem involving capillary leakage in these patients. The data suggest that the pulmonary edema in these patients may be the result of capillary leakage stemming from the high dose of cytosine arabinoside. While previous studies have reported sporadic incidents of pulmonary failure associated with aggressive cytosine arabinoside treatment, only one noted an incidence similar to that seen in this study. The reason for the discrepancy is uncertain, but may involve the schedule on which the drug is administered. Since the pathogenesis of pulmonary failure among these patients is unclear, the high rate of mortality demands awareness of the problem and the investigation of possible pathogenic mechanisms. (Consumer Summary produced by Reliance Medical Information, Inc.)

Health aspects, Development and progression, Acute respiratory distress syndrome, Adult respiratory distress syndrome, Pulmonary edema

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Fludarabine therapy in hairy cell leukemia

Article Abstract:

Hairy-cell leukemia is a B-cell lymphoproliferative disorder, cancer involving the lymph tissue, and also affects the bone marrow, spleen, and liver. The condition gets its name from the cytoplasmic protrusions visible on the surface of the cells when viewed under the microscope. Removal of the spleen results in improvement in three-quarters of cases, and some chemotherapeutic agents have shown some promising effects. These chemotherapeutic agents include alpha-interferon, deoxycoformycin, and 2-chlorodeoxyadenosine. Variant forms of hairy cell leukemia are generally resistant to chemotherapy, however. Patients who progress after chemotherapy and then relapse after achieving a remission may be resistant to further drug treatment. Fludarabine monophosphate has shown promise in treating chronic lymphocytic leukemia and other types of lymphomas. This drug has now been used in the experimental treatment of three patients with hairy cell leukemia; one patient had a variant form of hairy cell leukemia. The patients were previously treated with alpha-interferon. Two patients achieved partial responses and the third achieved a minor response when treated with fludarabine. The patient with the minor response has remained stable for over 14 months, and one of the partially responding patients has been in remission for over 13 months. The remaining patient with variant hairy cell leukemia had an 18 month remission after treatment; eight additional courses of fludarabine after relapse has induced a second remission, which has now lasted over 15 months. These results suggest that fludarabine may deserve further investigation for the treatment of hairy cell leukemia, particularly for relapsed patients or for patients with variant disease. (Consumer Summary produced by Reliance Medical Information, Inc.)

Interferon alpha, Fludarabine, Leukemia, Hairy cell, Hairy cell leukemia

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