High-dose chemotherapy and unpurged autologous bone marrow transplantation for acute leukemia in second or subsequent remission

Article Abstract:

Adults with acute leukemia often achieve complete remission after chemotherapy, but it is uncommon for this remission to persist. After a relapse, chemotherapeutic salvage may be attempted, but long-term disease-free survival is rare. While the dose-response curve of many chemotherapeutic agents indicates that a greater percentage of survivors could be achieved, the practical dose is usually limited by the toxic side effects of these drugs. The bone marrow is often the most critical site of toxic side effects. For this reason, numerous clinicians and researchers have attempted to exploit the therapeutic effects of higher drug dosages by following chemotherapy treatments with bone marrow transplantation, thereby reducing the impact of the toxic side effects. The problems of transplantation may be avoided through the use of autologous transplantations of the patient's own bone marrow. This method was used in the treatment of 22 adults with acute myelogenous leukemia or acute lymphoblastic leukemia. Bone marrow cells were collected from the patients during remission after treatment; the cells were stored and frozen in liquid nitrogen. The median period between the collection of the cells and relapse was 10 months. After relapse, the patients were placed on a high-dose regimen of cyclophosphamide, BCNU or carmustine, and VP-16 or etoposide. To compensate for their bone-marrow repression, the patients were given prophylactic doses of antibiotics, antifungal agents, and antiviral drugs. Six days after the start of the chemotherapy, the patients' bone marrow cells were thawed and infused into the bone. The bone marrow was not treated in any way; although taken from the patient at remission, the bone marrow itself might well have contained leukemic cells. Nevertheless, long-term disease-free survival was achieved in 14 percent of the cases. It is interesting to note that some of the remissions were longer than those achieved previously by the same patient. It is difficult to make comparisons between studies examining salvage procedures, since there may be considerable bias in the selection of patients. The authors propose that achieving a longer second, or subsequent, remission (an event they term inversion) may be a suitable basis for the comparison of chemotherapeutic studies. (Consumer Summary produced by Reliance Medical Information, Inc.)

Complications and side effects, Dosage and administration, Autografts

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Intensive combination chemotherapy and autologous bone marrow transplantation leads to the reappearance of Philadelphia chromosome-negative in chronic myelogenous leukemia

Article Abstract:

In chronic myelogenous leukemia (CML), the patient enjoys an average of three to four years of fairly normal active life. This chronic phase is followed by the so-called accelerated and blastic phases during which the patient deteriorates rapidly and generally dies of complications, such as internal bleeding or infection. Chemotherapy can induce a second ''chronic'' phase in patients with accelerated disease, but it is short-lived and relapse occurs after three to nine months. CML is characterized by an unusual genetic finding known as the Philadelphia chromosome. Somewhere in the ancestry of some blood cells, pieces of chromosomes 9 and 22 became interchanged. This translocation, as the geneticists call it, is easily observed under the microscope and is called the Philadelphia chromosome. Evidence suggests that abnormal bone marrow cells with the Philadelphia chromosome are capable of suppressing normal cells. However, there is some indication that the suppressed normal cells are not gone, and researchers have now shown that a combination of chemotherapy and autologous bone marrow transplantation can bring out these normal cells in patients with CML. In autologous bone marrow transplantation, some of the patient's own bone marrow is removed and stored during a period of remission following chemotherapy. When the patient relapses after the remission, a very high dose of chemotherapy may be used; the stored bone marrow may then be used to replace the bone marrow destroyed by the chemotherapy. This method was used in the treatment of 15 patients with CML. One patient died of infection during the treatment. Four patients achieved major cytogenetic responses, which means the percent of the cells with the Philadelphia chromosome was reduced to less than 35 percent. Three of these patients suffered relapses after 3, 4, and 12 months. One patient's response has continued for over 15 months. Curiously, of the seven patients who were known to be insensitive to alpha-interferon therapy before the procedure, three became sensitive to alpha-interferon therapy as a result of the autologous bone marrow transplantation. (Consumer Summary produced by Reliance Medical Information, Inc.)

Care and treatment, Identification and classification, Cancer cells, Philadelphia chromosome, Myeloid leukemia, Philadelphia-positive, Philadelphia-positive myeloid leukemia

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Mitoxantrone and high-dose etoposide for patients with relapsed or refractory acute leukemia

Article Abstract:

Acute myelogenous leukemia (AML) carries a grim prognosis. While 65 to 75 percent of patients may be expected to respond to chemotherapy, the majority will relapse and ultimately die of their disease. New drugs must be evaluated for efficacy in attempts to induce a second remission in patients who have relapsed, as well as to potentially salvage patients who failed to respond to conventional treatment. Mitoxantrone and etoposide are two drugs that have been shown to have some activity against acute myelogenous leukemia, both alone and in combination with each other. A study was undertaken to evaluate the efficacy of mitoxantrone with etoposide in the treatment of 35 patients with AML. All 35 patients had either failed to respond to initial therapy or had relapsed after a previous treatment or treatments. Eight patients achieved complete responses. Four patients died within two weeks of therapy and eight patients died of aplasia, or the inability to make new blood cells. Of those who managed not to die, 13 patients had mild to moderate inflammation of the mucous membranes, a side effect of some chemotherapeutic treatments. Ten more patients had severe mucositis. Among the patients who responded to treatment, the response endured a median of seven months. The median survival of these patients was eight months, in contrast with the patient group as a whole, which had a median survival time of two months. At present, a single patient remains free of disease at more than 23 months. The results confirm that although mitoxantrone and etoposide are effective agents against acute myelogenous leukemia, the toxicity of this combination is high. It may be possible to achieve better tolerance to the treatment if strategies are used to reduce the inflammation of the mucous membrane. (Consumer Summary produced by Reliance Medical Information, Inc.)

Etoposide, Mitoxantrone hydrochloride, Mitoxantrone

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