Advanced Chronic Myelogenous Leukemia Research Articles

Recombinant interferon-alpha therapy of Philadelphia chromosome-negative myeloproliferative disorders with thrombocytosis

purpose: The clinical course of patients with myeloproliferative disorders and excessive thrombocytosis may be complicated by serious hemorrhagic or thrombotic events. We have previously reported that interferon-alpha can control severe refractory thrombocytosis in patients with advanced chronic myelogenous leukemia. Therefore, we treated a group of thrombocythemic patients with Ph-negative myeloproliferative disorders, including polycythemia vera and essential thrombocythemia, with recombinant and interferon-alpha ( rIFN- α 2 a ). patients and methods: Eight patients with profound elevations in platelet counts received a median induction dose of 5.4 × 10 6 U/day (rante, 5.0 to 10.0 × 10 6 U/day) of rIFN- α 2 a administered intramuscularly or subcutaneously. result: We observed a significant decline in platelet counts from a median baseline value of 1,929 × 10 9/L (range, 960 to 2,960 × 10 9/L) to a median posttreatment value of 431 × 10 9/L (range, 71 to 1,150 × 10 9/L) ( p <0.01). Concomitantly, white blood cell counts declined from a median baseline value of 20.8 × 10 9/L (range, 10.5 to 40.8 × 10 9/L) to a median posttreatment value of 6.1 × 10 9/L (range, 2.9 to 29.0 × 10 9/L) ( p <0.02). Correction of thrombocytosis was rapid, with a median of only eight days from the start of therapy to the achievement of a platelet count less than 1,000 × 10 9/L. Six of eight patients have shown an ongoing response with a median follow-up period of 11 months (range, one to 30 months). There have been no bleeding or thrombotic events during the study. Side effects of rIFN- α 2 a therapy consisted of fever and flu-like symptoms, with tachyphylaxis developing after one to two weeks of therapy. conclusion: Our observations suggest that alpha interferon may be a promising therapeutic agent for myeloproliferative disorders characterized by thrombocytosis.

Human leukocyte interferon to control thrombocytosis in chronic myelogenous leukemia.

Nine patients with refractory chronic myelogenous leukemia and severe symptomatic thrombocytosis (greater than or equal to 1 X 10(6) platelets/mm3) were given partially purified human leukocyte interferon-alpha. A significant decline in platelet counts, from a mean (+/- SE) of 1.71 +/- 0.53 X 10(6)/mm3 to a mean of 0.52 +/- 0.24 X 10(6)/mm3 (p less than 0.01), resulted in all patients. Maintenance of low platelet counts was achieved in two patients for more than 143 and 300 days, respectively. Treatment with human leukocyte interferon-alpha was stopped in the remaining patients because of increases in the leukocyte count, toxicity, or both. Our preliminary observations suggest that human leukocyte interferon-alpha may significantly alleviate progressive thrombocytosis in advanced chronic myelogenous leukemia. Further studies of human leukocyte interferon-alpha and chemotherapeutic agents are indicated.

Cytogenetic Conversion Following Allogeneic Bone Marrow Transplantation for Advanced Chronic Myelogenous Leukemia

We performed a pilot study to test the effectiveness of allogeneic bone marrow transplantation in the treatment of chronic myelogenous leukemia. Five patients in the advanced stages of chronic myelogenous leukemia (four in blast crisis, one in accelerated phase) with abnormal chromosomes underwent matched-sibling allogeneic bone marrow transplantation after preparation with busulfan, vincristine, cyclophosphamide, and fractionated total body irradiation. Engraftment and conversion to normal chromosome patterns after transplantation occurred in all five patients. None of the patients reverted to an abnormal chromosome pattern of demonstrated clinical or hematologic evidence of recurrent disease during the course of this study; however, longest survival from transplant was 248 days. Allogeneic bone marrow transplantation can eradicate the abnormal clone even in far advanced chronic myelogenous leukemia and can provide normal hematopoiesis. We suggest that clinical complications of chemotherapeutic toxicity and infection were responsible for the short survival in this group of patients, and that these complications could be decreased by performing transplantation in the chronic phase or early accelerated phase of the disease.

Cytogenetic conversion following allogeneic bone marrow transplantation for advanced chronic myelogenous leukemia

We performed a pilot study to test the effectiveness of allogeneic bone marrow transplantation in the treatment of chronic myelogenous leukemia. Five patients in the advanced stages of chronic myelogenous leukemia (four in blast crisis, one in accelerated phase) with abnormal chromosomes underwent matched-sibling allogeneic bone marrow transplantation after preparation with busulfan, vincristine, cyclophosphamide, and fractionated total body irradiation. Engraftment and conversion to normal chromosome patterns after transplantation occurred in all five patients. None of the patients reverted to an abnormal chromosome pattern of demonstrated clinical or hematologic evidence of recurrent disease during the course of this study; however, longest survival from transplant was 248 days. Allogeneic bone marrow transplantation can eradicate the abnormal clone even in far advanced chronic myelogenous leukemia and can provide normal hematopoiesis. We suggest that clinical complications of chemotherapeutic toxicity and infection were responsible for the short survival in this group of patients, and that these complications could be decreased by performing transplantation in the chronic phase or early accelerated phase of the disease.