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)

Twenty children with various hematological malignancies (nine with acute lymphoblastic leukemia, eight with acute non-lymphoblastic leukemia, two with chronic myelogenous leukemia, one with malignant lymphoma and one with 7-monosomy) and four with severe aplastic anemia were treated with allogeneic or syngeneic bone marrow transplantation (BMT) between September 1977 and September 1988. Eleven patients are surviving currently and ten are disease free 8 to 51 months after BMT. Conditioning regimen consisted of total body irradiation (TBI) and cyclophosphamide in twenty patients. Two patients did not receive TBI. Graft failure was observed in five patients and complete recovery of recipient marrow was seen in two of them. Eleven patients developed acute graft-versus-host disease (GvHD) with grade I-II in eight patients. Three patients suffered from chronic GvHD. Seven patients with acute leukemia relapsed and all but one died of leukemia. Early death occurred in two undergone BMT in poor clinical conditions. Performance status in 100% in surviving patients except one. Efforts to improve these results are that BMT should be considered early in the course of their disease for patients who are at risk for relapse with conventional chemotherapy and improved conditioning regimens to reduce leukemia relapse after BMT for patient with the second or subsequent remission.
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PMID:[Treatment results of bone marrow transplantation in Kyushu Cancer Center. Bone Marrow Transplantation Team]. 236 34

The Southeastern Cancer Study Group conducted a phase I-II trial of sequentially administered 5-azacitidine and amsacrine in patients with refractory adult acute leukemia from September 1980 to March 1983. The 5-azacitidine was administered by continuous iv infusion on Days 1-4 at doses ranging from 112 to 200 mg/m2/day, while amsacrine was given at doses ranging from 75 to 150 mg/m2/day on Days 5-8. The doses of 5-azacitidine and amsacrine were alternately escalated through six dose levels during the phase I portion of the trial. Of 128 patients entered, 102 (80%) were evaluable for response. Remission was achieved in 13 of 80 evaluable patients with acute myeloid leukemia, in one of 12 evaluable patients with acute lymphoid leukemia, and in none of 11 patients with blastic transformation of chronic granulocytic leukemia. Three remissions occurred in patients with acute myeloid leukemia who were refractory to initial induction chemotherapy with cytarabine and anthracycline combination chemotherapy. Remissions were relatively durable, lasting a median of 28 weeks in the 13 patients with refractory acute myeloid leukemia (range, 14-54 weeks). Toxic effects included universal severe myelosuppression, hyperbilirubinemia at a frequency and severity similar to those seen with amsacrine used as a single agent, moderately severe stomatitis and diarrhea, three incidents of amsacrine-related cardiac dysrhythmia, and a single case of probable drug-related cardiomyopathy. This combination has activity in the treatment of myeloid leukemia, which is primarily resistant to cytarabine and anthracyclines, and could have a role in primary management.
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PMID:Sequentially administered 5-azacitidine and amsacrine in refractory adult acute leukemia: a phase I-II trial of the Southeastern Cancer Study Group. 241 Jan 19

A Phase II study of recombinant granulocyte colony-stimulating factor (G-CSF) in allogeneic bone marrow transplantation (BMT) was performed. The recovery of leukocytes and neutrophils was markedly accelerated in G-CSF-administered recipients. The days to WBC count greater than 1,000/microliters (11.5 +/- 1.9) and the days to neutrophil count greater than 500/microliters (11.5 +/- 1.4) were significantly shorter than those of the monocyte-CSF (M-CSF) and CSF(-) groups. In the G-CSF group the WBC count at nadir was higher than in other groups, and neutrophil recovery preceded monocyte recovery. After the discontinuation of G-CSF, the WBC count first decreased for a few days and then increased again slowly. The short duration of leukopenia brought about a reduction in the number of febrile (greater than 38 degrees C) days which, until day 30, were 1.8 +/- 1.9 in the G-CSF group, also significantly shorter than in others. Acute graft-versus-host disease (greater than grade II) appeared in two of eight patients from the G-CSF group, this incidence being comparable to those found in the other groups. A side effect of G-CSF-mild bone pain-was observed in one patient, but it was tolerable. Six of eight patients in the G-CSF group survived for between five and 13 months after BMT with a Karnofsky score greater than 90%. No relapses were observed in the six, including one patient with chronic myelogenous leukemia and two with acute non-lymphoblastic leukemia. To determine the final influence of G-CSF on myeloid leukemia, further long-term follow-up studies are needed. G-CSF was well tolerated and seemed promising against allogeneic BMT.
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PMID:Granulocyte colony-stimulating factor in allogeneic bone marrow transplantation. 248 58

Amsacrine with high-dose cytarabine is effective therapy for Philadelphia chromosome (Ph1)-negative acute lymphoblastic leukemia (ALL). We examined the effectiveness of this regimen in 19 patients with Ph1-positive lymphoblastic leukemia. Four had an antecedent chronic phase of chronic myelogenous leukemia and 15 presented with ALL. There were no complete responders in either group. All 14 patients whose bone marrow could be assessed after completion of therapy showed persistent leukemia. We conclude that patients with Ph1-positive lymphoblastic leukemia have a disease that is resistant to treatment that is highly effective in patients with Ph1-negative ALL.
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PMID:Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL) is resistant to effective therapy for Ph1-negative ALL. 250 96

Thirty patients with malignant hematological disease underwent allogeneic bone marrow transplantation following Busulphan (Bu) and Cyclophosphamide (Cy). The diseases were chronic myelogenous leukemia, acute lymphoblastic and non lymphoblastic leukemia, myelofibrosis and multiple myeloma in complete remission and in relapse. A sustained disease-free survival (DFS) was achieved in 0/5 acute leukemia patients transplanted in relapse, in 5/7 acute leukemia patients transplanted in remission (600-1550 days) and in 6/9 CML patients transplanted in the chronic phase of the disease (500-950 days). A sustained DFS was also achieved in one 2nd BMT for relapsed CML. The data suggest that the Bu-Cy protocol combines high tumor ablative capability with toxicity comparable to previously described conditioning regimens for allogeneic BMT, particularly in diseases involving a great expansion of the bone marrow.
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PMID:Allogeneic bone marrow transplantation for hematological malignancies following therapy with high doses of busulphan and cyclophosphamide. 251 Nov 15

We examined activities of procoagulant and fibrinolysis in homogenate of leukemic cells. Procoagulant activity (PCA) was increased in patients with acute myelocytic leukemia (AML) and acute promyelocytic leukemia (APL), but it was significantly decreased in patients with chronic myelocytic leukemia (CML) and adult T cell leukemia. In CML, PCA was increased in the blastic phase. Plasminogen activator activity (PLGAA) was also increased in patients with AML, APL and acute lymphocytic leukemia (ALL) associated with disseminated intravascular coagulation (DIC). Elastase-like activity, trypsin-like activity and chymotrypsin-like activity (CTLA) were increased in those with myelocytic leukemia, but they were low in those with lymphocytic leukemia. PCA, PLGAA and CTLA were significantly higher in patients with DIC than in those without DIC. Measurement of procoagulant and fibrinolytic activity in leukemic cells homogenate may be useful not only for studying hemostatic abnormalities but also for classification of leukemic cells.
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PMID:[Activity of procoagulant and fibrinolysis in homogenate of leukemic cells]. 259 44

Bone marrow transplantation (BMT) offers potentially curable treatment for patients with high-risk hematologic malignancies. However, relapse remains the major cause for failure of autologous BMT in these diseases and of allogeneic BMT in subsets of patients with these diseases. With our current preparative regimens, relapse rates following autologous BMT are over 30% for patients with intermediate or high-grade non-Hodgkin lymphoma and relapsed Hodgkin's disease in sensitive relapse and over 50% following autologous BMT for patients with acute non-lymphoblastic leukemia (ANLL) and acute lymphoblastic leukemia (ALL). Relapse rates exceed 80% in patients treated with autologous BMT for non-Hodgkin lymphomas and Hodgkin's disease in drug-resistant relapse. We also see a relapse rate over 50% in patients given allogeneic BMT for ANLL in second or third remission or early relapse, for ALL in third or subsequent remission or early relapse, and for chronic myelogenous leukemia (CML) in accelerated phase or blast crisis. We have explored two new approaches for improving the anti-tumor activity of our BMT preparative regimens. One involves combining etoposide, a chemotherapeutic agent that has excellent activity against leukemias and lymphomas, has shown synergistic activity with cyclophosphamide in vitro, and can be substantially dose-escalated, with busulfan and cyclophosphamide. The other approach attempts to induce graft-versus-host disease (GVHD), which appears to provide a clinical anti-tumor effect following allogeneic BMT, in recipients of autologous BMT. A syndrome similar to mild GVHD has been reported to occur spontaneously in a small number of patients receiving autologous or syngeneic transplants. GVHD can also be induced in rats undergoing syngeneic BMT by treatment with cyclosporine (CSA).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New conditioning regimens for high risk marrow transplants. 262 18

An analysis of the rate of leukocyte reconstitution in 164 recipients of HLA-identical sibling marrow transplants showed two factors to be independently influential. These were the underlying diagnosis and the type of prophylactic regimen used to minimize the risk of graft-versus-host disease. Patients with severe aplastic anemia had a faster rate of reconstitution of the total white blood cell count to levels of both 500 and 1000 x 10(6)/l than patients with acute non-lymphoblastic leukemia (ANL), acute lymphoblastic leukemia (ALL) or chronic myeloid leukemia (CML). Patients with severe aplastic anemia (SAA), however, did not show a faster rate of reconstitution of blood neutrophils. As well as being slower than patients with SAA for total leukocyte reconstitution, patients with CML were slower than patients with ANL and ALL in attaining a neutrophil count of 500 x 10(6)/l, and slower than patients with ANL in attaining a neutrophil count of 1000 x 10(6)/l. Patients given cyclosporin as the sole immunosuppressant prophylactic regimen post-transplant had faster reconstitution to total leukocyte counts of 500 and 1000 x 10(6)/l and to neutrophils of 1000 x 10(6)/l than patients given methotrexate alone, methotrexate and cyclosporin, or cyclosporin and T cell depletion of the donor marrow. No other factors (including the pretransplant preparative regimen) were significant in influencing the rate of leukocyte or neutrophil reconstitution. When only patients given cyclosporin were analysed, those with severe aplastic anemia continued to show a faster rate of leukocyte reconstitution to WBC 500 x 10(6)/l compared to patients with ANL, ALL or CML, and a faster rate to WBC 1000 x 10(6)/l than patients with CML.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Recipients of HLA-identical sibling marrow transplants with severe aplastic anemia engraft more quickly, and those with chronic myeloid leukemia more slowly, than those with acute leukemia. 264 83

In the present study we have evaluated the efficacy and toxicity of a 6-day continuous constant rate intravenous infusion of anthracyclines added to the standard conditioning regimen for allogeneic bone marrow transplantation (BMT). In 22 consecutive recipients of a lymphocyte depleted bone marrow graft, either demethoxydaunomycin (n = 11) or daunorubicin (n = 11) were added to high-dose cyclophosphamide and total body irradiation. Five patients had acute non-lymphoblastic leukemia in first complete remission, six patients acute lymphoblastic leukemia in first or second complete remission, nine patients chronic myelogenous leukemia in chronic phase and two patients refractory anemia with excess of blasts. After a median observation period of 18 months, only one leukemic relapse has been observed. Six patients died in the post-transplant period. In 17 of the 22 patients a severe, transient mucositis developed. No cardiac toxicity, as assessed with radioisotope studies, was observed. We conclude that anthracyclines may be effectively and safely incorporated in conditioning regimens before BMT, provided that they are administered as long-term continuous infusions in order to avoid toxicity due to excessive plasma levels.
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PMID:Prevention of leukemic relapse after transplantation with lymphocyte depleted marrow by intensification of the conditioning regimen with a 6-day continuous infusion of anthracyclines. 265 Jul 87

Bone marrow purging with cyclophosphamide derivatives (Mafosfamide) requires the establishment of a defined experimental procedure for reliable leukemic cell destruction while sparing normal hematopoietic stem cells to ensure engraftment. We previously defined the granulocyte-macrophage colony-forming unit (CFU-GM) LD95 as being the maximum tolerable dose of drug to use. We now report, in 20 patients with acute non-lymphoblastic leukemia (n = 5), acute lymphoblastic leukemia (n = 5), chronic myelogenous leukemia (n = 5), and non-Hodgkin's lymphoma (n = 5), that the nature of the cells treated (i.e., buffy coat cells or mononuclear cells) significantly influences the accuracy of the LD95 determination, whereas other parameters such as hematocrit or nucleated cell concentration do not. We subsequently define the most reliable experimental procedure for in vitro purging with Mafosfamide: incubation of 2 x 10(7) buffy coat cells/ml with a hematocrit of 5%. We show that the wide individual susceptibility to the drug is not related to any incubation procedure. In a series of 163 patients with hematological malignancies, we confirm the large variation of sensitivity to the drug according to patient susceptibility and diagnosis. These data favor the adjustment of the dose of Mafosfamide on an individual basis, prior to bone marrow purging for autologous bone marrow transplantation.
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PMID:Establishment of a reliable experimental procedure for bone marrow purging with mafosfamide (ASTA Z 7557). 265 56


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