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 clinical trial of the oral form of VP 16-213 (NSC-141540), a semisynthetic podophyllotoxin, was undertaken. In 20 patients, treatment was started at 200 mg/day p.o. for 5 days; courses were repeated after a rest period of 16 days. Five patients were treated at the same dose, repeated with only 9-day rest periods. Subsequently, 65 patients were given 300-400 mg/day for 5 days, with rest periods of 9 days between courses. The side effects encountered included anorexia, nausea and vomiting, stomatitis, diarrhea, leukopenia, thrombocytopenia, alopecia, and pruritus. Substernal discomfort with or without palpitations was reported by 18 patients; no explanation for this symptom could be found. No complete remissions (CR) were observed. Parital remissions (PR) and improvement (IMP) were seen as follows: small cell carcinoma, lung (10 patients)--2 PR, 3 IMP; adenocarcinoma, lung (4 patients)--1 PR; alveolar cell carcinoma, lung (1 patient)--1 IMP; mesothelioma (4 patients)--1 IMP; ovarian cancer (12 patients)--3 PR, 3 IMP; breast cancer (20 patients)--4 IMP; colon cancer (8 patients)--2 IMP; bladder cancer (4 patients)--2 IMP; histiocytic lymphoma (7 patients)--2 PR, 3 IMP; chronic myeloid leukemia (1 patient)--1 IMP.
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PMID:A clinical trial of the oral form of 4'-demethyl-epipodophyllotoxin-beta-D ethylidene glucoside (NSC 141540) VP 16-213. 16 75

Forty patients with Ph-positive blastic phase (BP) (28 patients) or chronic phase (CP)-CML (3 patients) and relapsed adult acute lymphoblastic leukemia (ALL) (9 patients) with cytogenetical translocations [t(8;14):2 patients; t(4;8):2 patients; t(4;11):3 patients; t(9;22):2 patients], received an intensive conventional chemotherapy. During early recovery from marrow aplasia, when WBC reached 0.3-1.5 x 10--9/L, peripheral blood stem cells (BSC) were collected by 4-8 leukapheresis consecutively. BSC collected from the 2/3 patients with CP-CML resulted Ph-negative and PCR negative. In 8 out of 26 BP-CML patients, BSC resulted Ph-negative and in two cases PCR negative. Of the nine ALL patients, 6 patients lost the cytogenetic translocations, one patient died during aplasia, two patients did not have cytogenetic modifications and died in few weeks of leukemia and one patient out of six responding patients relapsed before transplant. After complete recovery, 15 patients (BP-CML:8 patients; CP-CML:2 patients; ALL:5 patients) were subsequently given high-dose therapy (VP-16 +/- Cy+TBI in single dose) followed by reinfusion of "normal" BSC. Both the patients in CP-CML and 5/5 patients with ALL maintain clinical and cytogenetic remission; all the patients transplanted in BP-CML relapsed 5-18 months post-transplant. It is concluded that intensive conventional chemotherapy employed in CML and ALL can lead to a precocious overshoot of cytogenetically normal BSC.
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PMID:Intensive conventional chemotherapy can lead to a precocious overshoot of cytogenetically normal blood stem cells (BSC) in chronic myeloid leukemia and acute lymphoblastic leukemia. 135 2

10 patients between the ages of 5 and 40 yrs with myeloid leukemia (4 acute, 6 chronic) in early (5 cases) or intermediate stage of the disease were given Cyclophosphamide and Busulfan (6 cases) or Cyclophosphamide, Busulfan and VP-16 (4 cases with CML) and bone marrow transplants from HLA-matched donors (in 9 cases from siblings and in one case from HLA phenotypically matched father). There was one transplant related death and 3 relapses in CML cases. In cases which relapsed GvHD was not observed. Altogether acute GvH and chronic GvHD was seen in 2 and 4 cases, respectively. All grafted cases with AML survive in continuous remission lasting more than 2 years (median 30.5 month).
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PMID:[Allogeneic bone marrow transplantation in myeloid leukemia: chemical conditioning, clinical course and results]. 148 72

Fifteen patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who were ineligible for allogeneic bone marrow transplantation (BMT) or alpha-interferon therapy were included in this study. Eight patients were in the first late chronic phase, five were in the second chronic phase, one was in the accelerated phase, and one was in the blastic phase. Autologous bone marrow cells (median, 2.5 x 10(8) nucleated cells/kg) were stored at a median of 30 months after diagnosis. Patients were treated with cyclophosphamide (1.5 g/m2 daily for 4 days), carmustine (BCNU) (300 mg/m2), and etoposide (VP-16) (250 mg/m2 daily for 3 days) (CBV), followed by reinfusion of autologous bone marrow. Hematopoietic recovery was rapid, and toxicity was mild to moderate in 14 patients. One patient died of cytomegalovirus pneumonitis. Eight of 15 patients showed Ph suppression to less than 90% Ph-positive metaphases after autologous BMT. Major cytogenetic responses (Ph suppression to less than 35% Ph-positive metaphases) developed in four patients. Cytogenetic responses were observed in 4 of 11 patients infused with 100% Ph-positive marrows, and in all 4 patients infused with Ph-mosaic marrows (mixture of diploid and Ph-positive cells). Better results were observed when autologous BMT was performed in the chronic phase compared with the advanced phases. The major cytogenetic responses have lasted for 3, 4, 12, and 15+ months, whereas minor cytogenetic responses lasted for only a short time (less than 2 months). Three of seven patients (43%) in the chronic phase with previous resistance to alpha-interferon therapy became sensitive to alpha-interferon therapy after autologous BMT. The authors concluded that intensive chemotherapy followed by autologous BMT produced cytogenetic remissions in patients with Ph-positive CML and reinduced disease sensitivity to alpha-interferon therapy in patients previously resistant to it. This is particularly useful when treatment is given during the chronic phase and stem cells are collected at a time of previous cytogenetic remission.
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PMID:Intensive combination chemotherapy and autologous bone marrow transplantation leads to the reappearance of Philadelphia chromosome-negative cells in chronic myelogenous leukemia. 167 51

The aim of this work is to evaluate the relationship between P-glycoprotein expression in circulating blasts and clinical response in patients suffering from acute lymphoblastic leukemia, acute non-lymphoblastic leukemia, and chronic myeloid leukemia in either lymphoid or myeloid blastic crisis. The results obtained show that: a) patients whose blasts express P-glycoprotein are resistant towards protocols including Doxorubicin, Daunorubicin, Etoposide, Mithramycin, Vincristine; b) P-glycoprotein can be expressed constitutively in some cases; c) P-glycoprotein does not appear to be the only mechanism responsible for resistance towards anthracyclines and Etoposide.
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PMID:P-glycoprotein and drug resistance in acute leukemias and in the blastic crisis of chronic myeloid leukemia. 198 99

Diaziquone (AZQ) and etoposide (VP-16) were administered as simultaneous 5-day continuous infusions to 27 patients with acute leukemia (22 with acute myeloid leukemia (AML), three with chronic myeloid leukemia in blast crisis (CML-B), and two with acute lymphocytic leukemia) at four different doses in a phase I trial. Gastrointestinal toxicity, primarily stomatitis, was dose limiting, occurring in six of 10 patients at the highest dose level. Diarrhea was the only other grade 3 toxicity noted (three of 10 at the highest dose level). The duration of bone marrow aplasia was excessive at the highest dose (median 48 days to granulocytes greater than 500/mm3, range 33-67) but acceptable (31 days) at the maximum tolerated dose: AZQ 28 mg/m2/day x 5 days, VP-16 150 mg/m2/day x 5 days. Complete remissions were seen in seven patients (six AML, one CML-B) and a partial remission in one patient with AML. The median duration of unmaintained complete remission was 3 months (range 1.5-26+).
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PMID:Continuous infusion diaziquone and etoposide: a phase I study in adult patients with acute leukemia. 231 18

Nine patients with myeloid blast crisis of Philadelphia chromosome-positive chronic myelocytic leukemia received 1-3 courses of intensive induction chemotherapy with DAT (daunomycin, cytosin-arabinoside and 6-thioguanin) or DAV (daunomycin, cytosin-arabinoside and VP-16). Eight patients responded with clearing of blasts from peripheral blood giving a response rate of 89%. However, bone marrow aplasia with less than 5% blasts was seen in only 2 patients. These 2 patients subsequently received an allogeneic bone marrow transplant and achieved complete remissions of 3 and 6 month duration. All patients died due to progression of blast crisis. Median survival of the group was 164 days. These results were compared to a historical control group of 31 patients with myeloid blast crisis treated with vincristine and prednisone. Despite a significantly better response rate with DAV or DAT (8 of 9 versus 9 of 31, p = 0.01) survival was not significantly different than that of the control group.
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PMID:Daunomycin, cytosin-arabinoside and VP-16 (DAV) for myeloid blast crisis of CML. 266 Sep 27

Etoposide, an epipodophyllotoxin structurally related to vincristine, is active in solid tumors. Trials of etoposide in hematologic malignancies, particularly leukemia and lymphoma, were initiated in 1973. Subsequent studies indicate that etoposide, either as a single agent or in combination with other drugs, is active in acute myelogenous leukemia, non-Hodgkin and Hodgkin lymphoma. Etoposide may be effective in acute lymphoblastic leukemia, but it is inactive in chronic myelogenous leukemia. The major toxicity of etoposide is myelosuppression. Non-hematologic toxicity is relatively mild at doses up to 2000 mg/m2. This feature favors its use in high dose regimens such as those employed before bone marrow transplantation. Preliminary studies of etoposide in autologous bone marrow transplantation in lymphoma and Hodgkin disease are promising. Studies of high dose etoposide in combination with other chemotherapeutic agents or in the context of bone marrow transplantation are in progress.
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PMID:Etoposide in leukemia, lymphoma and bone marrow transplantation. 267 26

Thirty-eight patients (median age, 21 years) with acute nonlymphoblastic leukemia (ANLL) (17 patients), acute lymphoblastic leukemia/lymphoma (ALL) (18 patients), chronic myelogenous leukemia (two patients), and refractory anemia received allogeneic bone marrow transplants from HLA-identical sibling donors or a one-antigen-mismatched brother (one patient) after a preparatory regimen consisting of fractionated total body irradiation and high-dose VP 16-213 (60 to 70 mg/kg body weight). Of the 33 patients with acute leukemia who received grafts from HLA-identical donors, three patients with ANLL received transplants in first remission and one patient with standard-risk ALL received a graft while in second remission. All other patients were in more advanced stages of their disease or exhibited other high-risk features. At the time of analysis, 20 of the 33 patients were alive, with 19 of them remaining in continued complete remission for 6 to 35 months (median, 18 months). The 3-year actuarial disease-free survival rate of 56.6% +/- 9.7% (SE) and the actuarial relapse rate of 11.9% +/- 6.8% (SE) demonstrate that the combination of fractionated total body irradiation and high-dose VP 16 is an effective mode of therapy in patients with advanced leukemias. Preliminary experience cautions against the use of VP 16 instead of cyclophosphamide in any clinical situation carrying an increased risk of graft rejection because the immunosuppressive potency of VP 16 is largely untested but may be inferior to that of cyclophosphamide.
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PMID:Fractionated total body irradiation and high-dose VP 16-213 followed by allogeneic bone marrow transplantation in advanced leukemias. 305 26

VP-16 was used to treat newly diagnosed elderly (greater than or equal to 65 yr) patients with acute nonlymphocytic leukemia (ANLL) and patients with blast crisis of chronic granulocytic leukemia (BI-CGL). Our pilot study indicated that VP-16 160 mg/m2 intravenously daily for 5 days was well tolerated and suggested a direct dose-response correlation. Thirty additional ANLL patients and 11 CGL patients were studied. Among 26 evaluable ANLL patients, we observed ten responses (38%) (seven complete remission and three partial remission), but none of 11 patients with CGL in blast crisis had meaningful responses. In patients who responded to treatment, myelosuppression was always reversed by day 25. Stomatitis was the major nonhematologic toxicity and appeared more severe with advancing age. We conclude that VP-16 is active against ANLL and is well tolerated at doses higher than have been previously described. It remains to be shown that the present schedule is superior to the intermittent high-dose or continuous low-dose infusion schedules, which have been recently described.
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PMID:Phase I-II trial of VP-16 in the treatment of acute nonlymphocytic leukemia and blast crisis of chronic granulocytic leukemia. 346 1


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