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

Fifty percent of patients with the myelodysplastic syndrome, frequently following treatment by radiation or chemotherapy, have prognostically unfavorable deletions of the long arms of chromosomes 5 and 7, or trisomy 8, as have the 25% of patients with acute myeloblastic leukemia where remissions last 6-12 months, and where relapse cannot be prevented. In contrast, patients with prognostically favorable cytogenetics (translocation 15; 17 or 8; 21 or inversion 16) maintenance chemotherapy may prevent relapses. Of chronic myelocytic leukemia patients, 85% can achieve hematological remission with interferon alpha, and 40% a partial cytogenetic remission, which probably delays relapse.
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PMID:Prevention of chemotherapy-induced leukemia and of leukemia relapses. 172 55

We have used recombinant human erythropoietin (rHuEPO) in a phase I/II clinical trial to evaluate its ability to reverse refractory anemia in hematologic disorders. rHuEPO was administered subcutaneously 5 days per week at escalating doses (50 to 150 U/kg per day). The aim of treatment was a hemoglobin (Hb) level greater than or equal to 10 g/dL without blood transfusion. Of 25 patients treated, 17 were evaluable, most of them with a regular need for transfusion. Eight of these had lymphoproliferative disorders (three cases of malignant lymphoma and five of monoclonal gammopathy) and were exposed to cytotoxic therapy. The other nine patients had hematopoietic stem cell disorders (four cases of myelodysplastic syndrome, three of idiopathic myelofibrosis, and two of chronic myelogenous leukemia). All patients with lymphoproliferative disorder had serum EPO levels inappropriately low for the degree of anemia, while patients with stem cell disorder showed variable values. Erythroid marrow activity was inadequate in all cases. Seven of eight patients with lymphoproliferative disorder responded to treatment maintaining Hb above 10 g/dL without transfusion. The median dose of rHuEPO required for correction of anemia was 75 U/kg. In four cases response was maintained with 50 U/kg, three times per week. There was no complete response among patients with hematopoietic stem cell disorder, although transfusion requirement was eliminated or reduced in four cases. Four patients developed functional iron deficiency during rHuEPO treatment and required iron supplementation to obtain response. Aggravation of splenomegaly was observed in two cases of myeloproliferative disorder. We conclude that: (1) subcutaneous administration of rHuEPO can be effective and safe in patients with lymphoproliferative disorder exposed to chemotherapy and showing inappropriate EPO response to anemia; (2) this is less likely in hematopoietic stem cell disorders, although favorable responses may be observed in occasional patients; and (3) functional iron deficiency as a cause of nonresponse to rHuEPO is frequent also in nonrenal anemia.
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PMID:Subcutaneous erythropoietin for treatment of refractory anemia in hematologic disorders. Results of a phase I/II clinical trial. 163 33

Relapse continues to be a problem after bone marrow transplantation (BMT) for hematologic malignancies, particularly in recipients of autologous or T-cell-depleted allogeneic grafts and in patients with advanced disease. Interferon (IFN) has shown antiproliferative activity in several malignant hematologic diseases and potentially may be of benefit when administered early after BMT when the number of residual cells is minimal. We tested in a phase I study the maximum tolerated daily dose of recombinant IFN alpha-2b in patients who had received a transplant for a disease at high risk for relapse (acute myeloid leukemia or non-Hodgkin's lymphoma beyond first remission, advanced myelodysplastic syndrome, acute lymphoblastic leukemia at any stage, chronic myeloid leukemia in accelerated or blast phase. Recombinant IFN alpha-2b was started at a dose of 0.5 x 10(6) IU/m2 and escalated by 0.5 x 10(6) IU/m2 in groups of three or four patients. The intention was to administer IFN as soon as stable engraftment after BMT was achieved (defined as an absolute neutrophil count of greater than 2.0 x 10(9)/L and platelet count greater than 100 x 10(9)/L for 5 consecutive days) and continued for 2 months. A total of 14 patients were enrolled after autologous (n = 3) or allogeneic (n = 11) BMT. Dose-limiting toxicity was myelosuppression. Significant (grade 2 to 4) neutropenia and thrombocytopenia led to discontinuation or dose reduction in five of eight patients receiving 1.5 x 10(6) or 2 x 10(6) IU/m2 IFN. Mild to moderate (grade 1 or 2) anorexia, weight loss, and fatigue occurred in the majority of patients independent of the IFN dose. De novo acute GVHD responsive to steroid treatment developed in 3 of 11 allograft recipients. Natural killer (NK) cell function was low before IFN treatment and was not improved with the cytokine. Conversely, interleukin-2-activated NK cells showed normal function even before starting IFN and no change was seen during IFN treatment. Clonogenic hematopoietic progenitor studies showed depression of all progenitor lines (colony-forming unit [CFU]-granulocyte, erythroid, monocyte, megakaryocyte, CFU granulocyte-macrophage, burst-forming unit-erythroid) by IFN at all dose levels except at 0.5 x 10(6) IU/m2. Considering this result and the incidence and severity of marrow depression seen at doses greater than 1.0 x 10(6) IU/m2, we would consider this the maximum dose safely tolerated if IFN alpha-2b is administered in this setting for a prolonged course on a daily basis.
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PMID:Treatment with recombinant interferon (alpha-2b) early after bone marrow transplantation in patients at high risk for relapse [corrected]. 174 91

A case of trisomy 13 is presented: a 73-year-old man with acute nonlymphocytic leukemia (ANLL), FAB borderline M1/M2, and peripheral leukocyte and platelet counts that were difficult to control with chemotherapy. A literature review shows that 35 cases of trisomy 13 are known at present. They are characterized by male predominance (76%), preferentially myeloid disorders (ANLL, myelodysplastic syndromes, chronic myeloid leukemia), leucocytosis, and relatively high platelet counts and hemoglobins. It is suggested that trisomy 13 is a specific nosologic entity with male predominance and characterized by interference with proliferation and differentiation in the myeloid differentiation series.
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PMID:Trisomy 13: a preferentially male chromosome aberration interfering specifically with myeloid proliferation and differentiation? Report of a case and review of the literature. 175 88

Three patients, one with Philadelphia (Ph) chromosome positive chronic myelocytic leukemia (CML) and two with primary acquired myelodysplastic syndromes (MDS), have been identified to have a t(3;21)(q26;q22). In the patient with CML, the t(3;21) was detected only in the blast phase. The t(3;21) as the sole abnormality appeared at presentation of MDS [refractory anemia with excess blasts (RAEB)] in one patient and remained as such when progression to RAEB in transformation (RAEB-t) occurred. The other patient with MDS had the t(3;21), in addition to other changes, during the progression of the disease. Thus, t(3;21) may characterize myeloid crises of clonal hematopoietic stem cell disorders (HSCD) and indicates a poor prognosis. As a primary cytogenetic event it may be also involved in the genesis of myelodysplasia with subsequent leukemic transformation.
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PMID:Translocation (3;21) characterizes crises in myeloid stem cell disorders. 175 92

More than 50% cure can be obtained with allogeneic bone marrow transplantation (BMT) when patients are transplanted in first remission of AML and ALL or chronic phase of CML. On the other hand, considerable progress has been made recently in treating acute leukemia with chemotherapy. Recent studies of intensive chemotherapy in adults with AML report approximately 40-50% 3-year disease-free survival (DFS). Accordingly, several prospective randomized clinical trials have been conducted on the use of BMT versus intensive chemotherapy in the treatment of AML. Significant differences in DFS were found only in a few studies though the results of BMT appear to be comparable or superior to chemotherapy. Therefore, the overall advantage of BMT in first remission AML is smaller than expected. We should know not whether to transplant or to perform chemotherapy, but rather whether to transplant in first remission or to perform chemotherapy first and reserve transplantation as salvage therapy. Recently acute promyelocytic leukemia has been successfully treated with differentiation therapy using all-trans retinoic acid. Low-dose aclarubicin has also been reported to be effective as differentiation therapy in some patients with myelodysplastic syndrome and atypical AML. With the advance of molecular biology of cytokines, several of them are now available for clinical use. G-CSF, GM-CSF and M-CSF are potent stimulators for the granulocyte-macrophage production; they are very effective for accelerating hematologic recovery after chemotherapy-induced myelosuppression or BMT. Interferon-alpha (IFN-alpha) has been used in the several studies. Furthermore, Ph chromosome positivity can be reduced with long-term administration of IFN-alpha; Ph-positive clone can be undetectable in some patients. Thus, IFN-alpha will be the choice of treatment for CML even if BMT is planned.
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PMID:[New trends in the treatment of leukemia]. 177 64

The authors report two cases of secondary myelodysplasia and acute myeloid leukemia with t(3;21)(q26.3;q22) as the only cytogenetic abnormality in neoplastic bone marrow. This translocation was identified as a rare, recurring, non-random aberration in chronic myeloid leukemia less than five years ago and in secondary acute myeloid leukemia and myelodysplasia in 1990. The known and suspected cases in the literature are reviewed.
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PMID:Translocation (3;21)(q26;q22) in secondary leukemia. Report of two cases and literature review. 180 36

The activity of alkaline phosphatase and peroxidase was measured in polymorphonuclears in 20 cases of myelodysplasia syndromes, 10 cases of chronic myeloid leukaemia. Reduced phosphatase activity was found in 5 cases and peroxidase activity in 3 cases of myelodysplasia syndromes. No evident correlation was noted between the activity of these enzymes and prognosis. Increased proportion of peroxidase-negative granulocytes was observed, moreover, in most cases of chronic myeloid leukaemia. The observations will be continued in larger material.
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PMID:[Results of selected cytochemical studies of mature granulocytes in myelodysplastic syndromes and various other hematologic diseases]. 182 68

In human cancer, lysosomal hydrolases contain increased amounts of phosphorylated sugar chains. Sugar chains of the hydrolases undergo post-translational processing which is catalyzed by N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) at the first step. In the present study we estimated serum GlcNAc-phosphotransferase in 50 adults suffering from leukemia and myelodysplastic syndrome. The serum GlcNAc-phosphotransferase was increased to moderate or high levels in patients with acute nonlymphocytic leukemia (ANLL), acute lymphoblastic leukemia and chronic myelogenous leukemia, suggesting that the serum transferase is released from leukemic cells. In many cases of ANLL examined, activity of the transferase was decreased concomitantly with reduction of peripheral blastic cells by effective chemotherapy.
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PMID:Increased N-acetylglucosamine-1-phosphotransferase activity in sera from patients with leukemia. 184 3

The pattern of immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements was determined in 87 patients with acute and chronic leukaemias and myelodysplastic syndromes by Southern blot hybridisation. All 31 cases of common, B cell and null cell acute lymphoblastic leukaemia, and B cell chronic lymphocytic leukaemia showed Ig heavy chain (JH) rearrangement, and TCR (beta-chain) rearrangement was seen in all 5 cases of T cell acute lymphoblastic leukaemia. Inappropriate JH and TCR (beta) rearrangements were present in some cases of T-ALL (60%) and common acute lymphoblastic leukaemia (18%), respectively. For the 19 patients with acute leukaemias following chronic myeloid leukaemia, blastic transformation, all 4 with lymphoid transformation and 3 of the 15 with myeloid transformation had JH rearrangement, and 3 CD10-positive lymphoid transformation and 2 myeloid transformation had their TCR (beta) genes rearranged. In conclusion, the pattern of Ig and TCR gene rearrangements correlated well with the cell lineage. However, cross-lineage rearrangements were more commonly seen in patients with acute leukaemias following chronic myeloid leukaemia blastic transformation, as compared to the de novo cases.
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PMID:Rearrangement of immunoglobulin and T cell receptor genes in acute and chronic leukaemias. 185 Sep 43


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