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 combination of eight cytotoxic drugs, administered simultaneously, has been used in 86 cases of acute leukemia. The regimen, designated TRAMPCOL, incorporated thioguanine, rubidomycin, (daunorubicin), cytosine arabinoside, methotrexate, prednisolone, cyclophosphamide, vincristine, and usually L-asparaginase. Treatment was administered in five-day pulses with treatment-free intervals varying from nine to 23 days. Subjective and objective toxic effects were not more severe than those seen with two- and four-drug regimens previously employed. Substantial clinical and hematologic improvement occurred in 8/19 patients with chronic granulocytic leukemia (CGL) in acute transformation. Complete clinical and hematologic remission (CR) was achieved in 3/7 patients with untreated acute myeloid leukemia (AML), 5/19 patients with AML who had failed to achieve CR with other therapy, and 4/18 patients with AML in relapse after CR obtained with regimens other than TRAMPCOL. CR occurred in 15/17 patients with acute lymphocytic leukemia (ALL), most of whom had had multiple previous relapses. CR was not achieved in four patients with AML superimposed on pre-existing myeloproliferative disorders. The TRAMPCOL regimen merits further evaluation in CGL after acute transformation, as a primary treatment for AML, and as therapy for ALL 1) in relapse, 2) in adults, 3) in children with adverse prognostic features, and 4) in T-cell ALL.
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PMID:Multiple-drug chemotherapy for acute leukemia The TRAMPCOL regimen: results in 86 patients. 26 3

Thirty-seven patients with Philadelphia-chromosone-positive (Ph'+) chronic myelogenous leukemia who were untreated or minimally pretreated were entered on the L-5 protocol. This protocol consisted of sequential treatment with splenic irradiation, splenectomy, arabinosylcytosine and 6-thioguanine, and L-asparaginase. Maintenance therapy was hydroxyurea or a multiple-drug regimen. The median survival of the 37 patients is 50 mo. Twelve patients showed a temporary reduction in the percentage of Ph'+ marrow metaphases to less than one-third of the initial values and in 7 of these patients none were found. The duration of the Ph'+ chromosome reduction ranged from 1 to 43 mo. The median survival of the responders has not yet been reached. It is concluded that whereas overall survival is not appreciably extended, patients who have a reduction in Ph'+ cells in the marrow may survive longer than the average; also, the reduction occurs most frequently in patients who have relatively small spleens at diagnosis. The reduction is difficult to maintain, and it may be reinduced in some patients with intensive chemotherapy.
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PMID:Results of treatment of Ph'+ chronic myelogenous leukemia with an intensive treatment regimen (L-5 protocol). 28 22

A patient with Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) who was treated with alpha-interferon (alpha-IFN) is reported. After the treatment, the number of Ph+ bone marrow (BM) cells decreased gradually and the intensity of the rearranged major breakpoint cluster region (M-BCR) gene became faint; however, a lymphoblastic crisis developed about 1 year later. At the time of the blast crisis, the rearranged M-BCR band was detected, indicating that the blast crisis clone was derived from CML cells. The patient was treated with a combination of vincristine, prednisolone, daunorubicin, and L-asparaginase, and a hematologic remission was obtained. During the remission status, no rearranged M-BCR fragment was detected by conventional Southern analysis. Thus, the hematologic and genetic alteration in this case appeared to be identical to Ph+ acute leukemia with M-BCR rearrangement. The current case therefore indicates that alpha-IFN can reduce the proportion of Ph+ cells, but is unable to prevent blast crisis. Furthermore, the quantitative reduction of the cell population with a Ph chromosome may have some effects in modifying the genetic manifestations and clinical features of Ph+ CML, e.g., the delay in the appearance of the blast crisis.
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PMID:Restoration of cytogenetically normal marrow cells after remission of lymphoblastic crisis in a case of Ph positive CML treated with alpha-interferon. 155 Oct 82

Two patients with hematological malignancies were successfully treated with monomethoxypolyethylene glycol-conjugated Escherichia coli L-asparaginase (PEG2-ASP), which reportedly lacks both antigenicity and immunogenicity but retains catalytic activity as well as slow clearance in an experimental animal model. A 20-year-old male patient with leukemic lymphoma was refractory to conventional chemotherapy but responsive to L-asparaginase (L-ASP) followed, however, by severe adverse effects. On relapse, an intravenous infusion of 100-200 IU/day dose of PEG2-ASP alone led to a complete remission 2 months later without hypersensitivity or other significant adverse reactions. Surprisingly, he remained in a complete remission for over one year with a regular weekly infusion of PEG2-ASP, combined with a weekly small dose of Ara-C. During this period, blood asparagine was not detectable. The other patient, a 64-year-old woman with chronic myelogenous leukemia in blast crisis achieved, within 6 weeks, a complete remission with twice-weekly infusions of PEG2-ASP. Thus, PEG2-ASP is a highly effective antitumor agent overcoming the limitations in therapeutic use of L-ASP.
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PMID:High efficacy of monomethoxypolyethylene glycol-conjugated L-asparaginase (PEG2-ASP) in two patients with hematological malignancies. 186 35

Ten patients with lymphoid-type blast crisis of chronic myeloid leukemia were treated with combination chemotherapy comprising doxorubicin, vincristine, L-asparaginase, and prednisone. Once remission was achieved in 9 (90%), consolidation with doxorubicin, vincristine and cyclophosphamide was given, and then maintenance chemotherapy with 6-mercaptopurine and methotrexate. Median remission duration was 12 months (range 2-18) and survival 17 (range 3-29). Drug-related toxicity was manageable, leading to a major schedule alteration in 3 cases. These data suggest that combination chemotherapy including doxorubicin improves the prognosis of lymphoid blast crisis in chronic myeloid leukemia.
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PMID:Treatment of the lymphoid blast crisis of chronic myeloid leukemia. 347 57

The treatment of an allergic reaction to L-asparaginase is discussed in the presentation of a case of a 26-year-old man with chronic myelogenous leukemia who was undergoing methotrexate-L-asparaginase rescue therapy. The possible mechanism of action of L-asparaginase is reviewed, and precautions for use of L-asparaginase in combination therapy with methotrexate are presented.
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PMID:Treatment of L-asparaginase allergic reaction. 657 33

The blast cells of a 14-year-old patient in the blastic phase of chronic myelogenous leukemia (CML) were studied. Cellular morphology, presence of the enzyme terminal deoxynucleotidyl transferase (TdT), and reactivity to the common acute lymphoblastic leukemia antiserum (CALLA) substantiated a lymphoid blast cell line. Immunologic surface markers were nonreactive for E-rosette (T) cells and immunoglobulin-bearing (B) cells. Cytogenetic, studies revealed persistance of the Philadelphia chromosome and a near-haploid cell line, i.e., 28,XY,t(9;22), +14, +15, +21, +22(GTG). The patient responded to chemotherapy with vincristine, prednisone, and L-asparaginase, first line drugs used for remission-induction of acute lymphoblastic leukemia in childhood. We suggest that severe hypodiploidy or near-haploidy, along with TdT and CALLA, may provide more accurate prognostic information in patients with CML and the lymphoid blastic crisis.
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PMID:Near-haploid cell line in the blastic crisis of chronic myelogenous leukemia: a possible marker for lymphoid malignancy. 660 58

The different sensitivity of myeloid progenitor cells (CFUc) to chemotherapeutic agents was measured with an in vitro clonogenic assay. Normal marrow and peripheral blood CFUc and blood CFUc obtained from patients with chronic myelogenous leukemia (CML) were tested for their sensitivity to medications used currently in the management of CML. The drugs tested were adriamycin, L-asparaginase, busulfan, beta-cytosine arabinoside (Ara-C), daunorubicin, hydroxyurea, melphalan, and thioguanine. CML CFUc were significantly more sensitive to Ara-C [drug dose required for 90% inhibition of CFUc growth (LD90) = 0.015 +/- 0.003 microgram/ml] than were normal CFUc (LD90 = 0.038 +/- 0.009 microgram/ml). A shift to enhanced sensitivity to L-asparaginase was detected in patients studied sequentially who entered blast transformation during this study. In vitro and in vivo pharmacokinetic data are compared.
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PMID:Sensitivity of myeloid progenitor cells in healthy subjects and patients with chronic myeloid leukemia to chemotherapeutic agents. 694 Oct 40

Thirteen adult patients with histologically confirmed lymphoblastic lymphoma were treated with an intensive chemotherapy program consisting of induction with cyclophosphamide, adriamycin, vincristine, and prednisone (modified CHOP); consolidation and central nervous system (CNS) prophylaxis with methotrexate intrathecally and by high-dose intravenous injection, citrovorum factor and L-asparaginase; reinforcement with CHOP; and maintenance with 6-mercaptopurine and methotrexate. Treatment duration was 1 yr. A 14th patient with T-cell acute lymphoblastic leukemia was also treated at presentation by the same regimen. Thirteen patients had at least a mediastinal mass or abnormal cells in the bone marrow; one presented with CNS disease. The median age was 22 yr (range 16--50), and male--female ratio was 2.5:1. All patients had a rapid complete clinical response. Of the 13 patients without initial CNS disease, 4 have relapsed, 3 with primary CNS relapse and 1 with a recurrent abdominal mass. Five patients have died, 2 from drug toxicity, 2 from CNS relapse, and 1 from chronic myelogenous leukemia, which was diagnosed simultaneously with the lymphoblastic lymphoma. The median follow-up is 19 mo, and all patients have completed their planned therapy. At 3 yr, the actuarial survival is 61% and relapse-free survival is 56%.
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PMID:Lymphoblastic lymphoma in adults: results of a pilot protocol. 697 May 98

Between June 1991 and September 1992, 80 patients with adult acute lymphoblastic leukemia (ALL) (newly diagnosed, n = 68; relapsed or refractory ALL, n = 7; lymphoid blast transformation of Philadelphia chromosome-positive chronic myelogenous leukemia [LT-CML], n = 5) were managed with a combination regimen consisting of idarubicin 36, 20, or 10 mg/m2 plus vincristine, L-asparaginase, and prednisolone (IVAP-1, -2, -3). Three patients with LT-CML and four with relapsing ALL had a complete remission. In the group of newly diagnosed patients aged 15 to 60 years treated with IVAP-1, the complete remission rate was only 44% due to the high incidence of toxic deaths. In contrast, 39 of 44 cases who subsequently received IVAP-2 achieved a complete remission (89%, P = .001), as did 62% of elderly patients who received IVAP-3. Hematologic and nonhematologic toxicity was significantly reduced with IVAP-2 compared with IVAP-1. The use of recombinant human granulocyte colony-stimulating factor in 24 patients was not associated with a reduced duration of granulocytopenia less than 0.5 x 10(9)/L, although there was a lower incidence of documented infections in patients receiving granulocyte colony-stimulating factor than in controls. Post-remission intensification with idarubicin-based courses, high-dose therapy with autologous bone marrow stem cell rescue, and rotational weekly therapy was feasible and its toxicity was manageable. These preliminary findings indicate that IVAP-2 (idarubicin 20 mg/m2) is a highly effective and well-tolerated regimen for remission induction of adult ALL.
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PMID:Intensive therapy for adult acute lymphoblastic leukemia: preliminary results of the idarubicin/vincristine/L-asparaginase/prednisolone regimen. 750 63


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