Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new immunomodulating agent, bestatin (INN: ubenimex) has low toxicity after long-term oral administration and significantly modifies immunological responses. Prolongation of remission duration and survival was achieved in adult acute nonlymphocytic leukemia with bestatin immunotherapy combined with remission maintenance chemotherapy. Patients with myelodysplatic syndrome (MDS) and chronic myelogenous leukemia (CML) responded to bestatin, and it is noted that cytogenetic remission was obtained in CML. MDS and CML are thought to be a family of clonal malignant disorders in which malignant transformations occurs at the level of the pluripotent stem cell. Bestatin may be capable of modifying the biological-proliferative disequilibrium of the disease, and the therapy opens new and promising prospects in the treatment of both MDS and CML. Randomized controlled studies of bestatin immunotherapy were performed in solid tumors including malignant melanoma, carcinoma of the lung, stomach, bladder, head and neck, and esophagus, and therapeutic benefits on disease free-interval or survival were observed in certain types of these cancers. However, the adjuvant activity of bestatin immunotherapy for these cancers should be further investigated to confirm its activity.
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PMID:Clinical trials of bestatin for leukemia and solid tumors. 159 4

A high remission rate (56%) was achieved in a preliminary study using Bestatin in patients with myelodysplastic syndromes. In particular, 9 out of 13 patients (69%) in the high blast group achieved hematologic remission. After Bestatin treatment, intrinsic hematopoietic stem cell abnormalities as well as hematologic findings were markedly improved. The success of Bestatin therapy in MDS led us to investigate the clinical activity of Bestatin in CML. In the current study the busulfan and Bestatin combination therapy resulted in complete hematologic remission in all of the patients. The most exciting result was the suppression of the Philadelphia chromosomes among the responding patients. Complete cytogenetic response was obtained in 3 patients (21%), partial cytogenetic response in 1 (7%), and minor cytogenetic response in 5 (36%). In particular, the majority of early chronic phase CML patients achieved significant cytogenetic response with sustained Ph1 negativity. The results are very encouraging and warrant further studies.
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PMID:Bestatin treatment of myelodysplastic syndromes and chronic myelogenous leukemia. 191 73

The effects of bestatin was studied in 17 patients with acute and chronic leukemia, and three patients with malignant lymphoma with or without concomitant chemotherapy. Complete remission was obtained in eight patients with acute leukemia and in three patients with malignant lymphoma. Definite effects on both clinical and hematological findings have not been observed in patients with chronic myelogenous leukemia. The PPD and PHA skin reactions increased in about 60 percent of the patients examined. Effects of bestatin on hematological and immunological parameters were obtained at a daily dose of from 30 to 90 mg of bestatin everyday for more than 2 weeks. Bestatin appeared to be useful for the maintenance therapy of hematological malignancies. No side effects due to bestatin were detected.
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PMID:The effect of bestatin on patients with acute and chronic leukemia and malignant lymphoma. 693 Jan 19

We proposed a new approach to treat chronic myelogenous leukemia using a combination of busulfan and Bestatin. Twenty-three patients with Ph1 positive CML including 20 in the chronic phase and 3 in the accelerated phase, were treated with the combination therapy. Complete hematologic remission was obtained in all patients. Complete cytogenetic response (CCR) was obtained in 6 patients (26%), partial cytogenetic response (PCR) in 1 (4%), and minor cytogenetic response (MCR) in 6 (26%). In particular, of 13 patients in early chronic phase, 5 (39%) achieved CCR, 1 PCR, 3 MCR. Complete suppression of Ph1+clone was further confirmed by molecular analysis. Cytogenetic conversion to a normal diploid state persisted for 6-41+ months (median 22 months+). Three year survival rate was 86.6 +/- 9.0% (95% confidence limit). Furthermore, the long-term complete hematologic remission in the accelerated phase patients without progression of the disease may be indicative of a long-term survival. We conclude that Bestatin effectively controls CML and allows reappearance of diploid hemopoietic cells in some patients. The rationale for this combination therapy is that busulfan suppresses the proliferation of leukemic progenitors and decreases tumor burden to the level where Bestatin exhibits its antiproliferative effects. Bestatin is not merely antiproliferative but provides more complex biological properties capable of enhancing repopulation of normal residual stem cells.
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PMID:[Bestatin therapy of chronic myelogenous leukemia]. 843 58