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At least 847 records · Page 47Linked to original sources
PubMed1998

An in vitro model for cytogenetic conversion in CML. Interferon-alpha preferentially inhibits the outgrowth of malignant stem cells preserved in long-term culture.

IFN-alpha has been shown to prolong survival in chronic myeloid leukemia patients, but its mechanism of action is still not understood. The human cobblestone area-forming cell (CAFC) assay allows for the measurement of the concentration of normal as well as malignant stem cells, while their progeny can be measured in parallel long-term culture (LTC) in flasks. Using CAFC and LTC assays, we have examined direct effects of IFN-alpha (500; 5,000 IU/ml) on the maintenance and outgrowth of CD34-enriched normal and malignant stem cells, obtained from six patients with an established major cytogenetic response to IFN-alpha and from four nonresponding patients. CAFC concentrations were not affected by IFN-alpha. In contrast, IFN-alpha strongly inhibited the clonogenic output in flask LTC. Nucleated cells (NC) produced in LTC were evaluated by fluorescent in situ hybridization (FISH) for the presence of the Philadelphia (Ph) translocation. After 8 wk of LTC, the percentage of Ph+ NCs produced was significantly more inhibited by IFN-alpha in responding patients than in nonresponders. Control LTC without IFN-alpha showed no significant differences of Ph+ NC production between responders and nonresponders. These findings provide the first in vitro model for cytogenetic conversion and suggest that direct antiproliferative effects of IFN-alpha account for the cytogenetic response observed clinically.

Adult↗
PubMed2003

The burden and outcomes associated with four leukemias: AML, ALL, CLL and CML.

Given the recent advances in the treatment of hematologic malignancies and the many other treatments on the horizon, physicians and payers will be faced with the critical decisions of when to use new treatments in the clinical pathway and how to allocate healthcare resources. This review will provide an overall context for the clinical, economic and quality of life burden of leukemia, as well as provide cross-analysis among the four major types of leukemia: acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia and chronic myeloid leukemia.

Animals↗
PubMed1993

Treatment of chronic myeloid leukemia with interferon alpha (Roferon): results of the Israeli Study Group on CML.

Thirty patients with chronic myeloid leukemia from 11 Israeli medical centers entered this study. Their ages ranged from 16-65 (median 41) and time from diagnosis to treatment was 1-16 months (median 4 months). After cytoreductive therapy with hydroxyurea (22 patients) or busulphan (8 patients), patients received 9 million units/day of recombinant interferon alpha-2 alpha (Roferon A) subcutaneously. Side effects included arthralgia or low back pain in 7 patients, thrombocytopenia in 9, weight loss in four, neurologic disturbances in 4 and leukopenia in 3 cases. Seventeen patients achieved complete hematologic remission (CHR) and 6 partial hematologic remission (PHR). Six patients achieved major cytogenetic response, 4 of them lost all Ph1 chromosome positive cells and 4 had minimal cytogenetic response. Frequency of relapse was high: 8 patients with CHR and 6 with PHR relapsed, but patients with major cytogenetic response did not relapse. Patients who had received prior therapy with busulphan had a higher remission rate but a lower quality of cytogenetic response. Escalation of Roferon to 12 million units per day in relapsing or nonresponding patients induced PHR in 2/7. Neutralizing anti-interferon antibodies occurred in 7 relapsing or nonresponding patients. The cytoreductive induction with hydroxyurea enhanced the hematologic remissions to a median of 6 weeks. Further studies should define the role of combination therapy in order to improve response and prevent relapses.

Adolescent↗
PubMed1986

Rapidly progressive myelomonocytic leukemia (juvenile CML).

A rare type of rapidly fatal childhood leukemia, generally called juvenile chronic myelogenous leukemia, is characterized by absence of the Philadelphia chromosome and a predominantly monocytic proliferation, among other features. Unlike Philadelphia chromosome positive chronic myelogenous leukemia, this disease is neither chronic nor principally a disorder of granulocytic cell lines. A case is presented, with several clinical and laboratory parameters useful in establishing the correct diagnosis, and a change in terminology to "rapidly progressive juvenile myelomonocytic leukemia" is proposed.

Child↗