Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment with daunorubicin-DNA (DNR-DNA) or adriamycin-DNA (ADM-DNA) has been evaluated in acute lymphoblastic leukemia of childhood (ALL), acute nonlymphoblastic leukemia (ANLL) and bronchogenic carcinoma (BC). The Five-year survival rate in 69 children with ALL was 73.7% when ADM-DNA was introduced in the treatment and 38% with DNR-DNA (P = 0.03). A randomization between free DNR and DNR-DNA for remission induction in 26 patients with ANLL has shown that the drugs were of equivalent effectiveness. The one-year survival rate was 66% for the DNR group and 64% for the DNR-DNA group. In 59 patients with BC, a randomized trial between ADM-DNA and cyclophosphamide-vinblastine (CTX-VLB) did not show an advantage in favor of one of these treatments. In anaplastic BC (51 patients), there was no difference in survival rate or remission rate between patients treated with ADM or ADM-DNA. No cardiotoxicity was noted among the patients treated with the complexed drugs. ADM-DNA and DNR-DNA are as effective as the free drugs. Cardiotoxicity appears to be reduced.
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PMID:Clinical trials with daunorubicin-DNA and adriamycin-DNA in acute lymphoblastic leukemia of childhood, acute nonlymphoblastic leukemia, and bronchogenic carcinoma. 38 79

Antileukemia sera with "directed" specificity are produced by immunization of rabbits with mouse leukemia cells admixed with normal antigen blocking (NAB) serum. Addition of NAB serum to the leukemia cells inhibits production of antibodies to normal cell components and directs specificity toward leukemia cell antigens. The resulting antileukemia serum (ALK-NABS) was not sufficiently potent to produce more than moderate therapy in the standard L1210 leukemia therapy assay. When given together with noncurative doses of cyclophosphamide (CTX), ALK-NABS acts synergistically. It is most effective when given early after injection of the leukemia cells and prior to injection of CTX. Daily repeated injections of a given dose are more effective than a single injection of that dose. Most important, small doses of ALK-NABS produce a significant prolongation of lifespan in conjunction with CTX. Results of therapy for BW-A leukemia with ALK-NABS in conjunction with CTX were negative.
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PMID:Passive immunotherapy for mouse leukemias with antisera of "directed" specificity: synergism with the action of cyclophosphamide. 92 53

We have identified and partially purified a novel cytolytic factor isolated from enriched plasma membranes prepared from highly purified lymphokine-activated killer cells (adherent-LAK. A-LAK cells) and a large granular lymphocytic NK cell leukemia, CRNK-16. The enriched plasma membranes were shown to be physically devoid of lytic granules and contained no detectable pore-forming protein (PFP, perforin) activity. The plasma membrane-associated cytolytic factor (designated M-CTX) was solubilized in biologically active form and was highly lytic to a large panel of target cells in 2- to 4-hr 51Cr release assays. Characteristics of the M-CTX include: (1) it is plasma membrane- not granule-associated: (2) it is not hemolytic and functions in the absence of Ca2+: (3) nucleated target cells are lysed in 2 to 4 hr at 37 degrees C but not at 4 degrees C: (4) it induces apoptotic cell death with nuclear DNA fragmentation and massive membrane blebbing: (5) it is isolated from the plasma membranes of cultured A-LAK cells, a lytically active LGL leukemia (CRNK-16), and fresh spleen cells but not from thymocytes or L929 fibroblasts: and (6) the lytic activity of the partially purified toxin is inactivated by trypsin, serum, and heat, but is not blocked by antibodies that inactivate TNF-alpha, LT or IFN-gamma. Taken collectively, these data suggest that M-CTX may represent a heretofore undescribed membrane-associated toxin possibly involved in contact-mediated cell killing.
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PMID:Identification and partial characterization of a novel plasma membrane-associated lytic factor isolated from highly purified adherent lymphokine-activated killer cells. 155 54

The anti-tumour effects of methoxyphenyl maleamic acid (MPMA) and cytotoxic drugs, in combination were investigated on P388 leukaemia and S180 (ascites) tumours. Simultaneous administration of MPMA with CTX or HN2 resulted in enhancement of anti-tumour activity. The increased activity was observed against P388 leukaemia, whereas S180 (ascites) tumour was not responsive to the combined treatment. The possible mechanism (s) of action, responsible for the modulation of activity of CTX and HN2 against P388 tumour have been postulated.
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PMID:Methoxyphenyl maleamic acid augments the activity of cytotoxic drugs against murine tumours. 176 80

2(R,S)-D-ribo-(1',2',3',4'-Tetrahydroxybutyl)-thiazolidine-4(R)-ca rboxylic acid (RibCys) is a prodrug of L-cysteine that releases the sulfhydryl amino acid after nonenzymatic ring opening and hydrolysis. The L-cysteine then elevates glutathione (GSH) levels by stimulating its biosynthesis. RibCys was investigated for its ability to protect CDF1 mice from the potent urotoxicity of cyclophosphamide (CTX) without compromising the therapeutic utility of the drug. RibCys induced a significant reduction in weight loss of the animals and in bladder inflammation at 48 h after CTX administration; however, bladder tissue remained inflamed as compared with that in controls. Bladder histology also showed some pathological changes in the presence of RibCys. In contrast, all parameters of toxicity (body weight loss, bladder inflammation, and pathological abnormalities) had been virtually reversed by day 21 after administration. In tests against L1210 leukemia, RibCys did not interfere with CTX anticancer activity. From these preliminary studies, RibCys appears to be a likely candidate for protecting against long-term CTX toxicity, perhaps reversing the original damage caused by a very high dose, without compromising the therapeutic utility of the alkylating agent.
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PMID:L-cysteine prodrug protects against cyclophosphamide urotoxicity without compromising therapeutic activity. 185 73

We tested the value of early intensification of chemotherapy in 68 consecutive children with acute nonlymphocytic leukemia (ANLL) who were admitted to St. Jude Children's Research Hospital from November 1983 through March 1987. Fifty-eight patients (85%) entered complete remission after treatment with etoposide (VP-16)/cytarabine (ara-C) (A), followed by daunorubicin (Dauno)/ara-C/thioguanine (6-TG) (B) and then VP-16/azacytidine (5-AZ) (C). Thirty percent of the complete responders, mainly those with an M4 or M5 leukemia subtype, attained M1 marrow status after component A, 60% after A + B, and 10% after A + B + C. Induction failures resulted primarily from absolute or relative drug resistance; there was only one death during this phase of therapy. Postremission treatment consisted of three pairs of drugs (vincristine [VCR]/amsacrine [m-AMSA], or doxorubicin [Doxo]/6-TG/ara-C, and VP-16/cyclophosphamide [CTX]) administered sequentially in 6-week cycles for 22 months. Despite the high rate of remission induction, only 33% +/- 7% SE of the patients are expected to be failure-free survivors at 2 years. Remission durations were not significantly affected by the majority of factors examined in this study, with the exception of marrow cellularity after VP-16/ara-C induction therapy. Patients with less than or equal to 5% leukemic cells survived relapse-free for a median of 36.1 months, compared with 11.3 months for the group with a larger infiltrate (P = .01). Although postremission therapy did not improve the percentage of long-term failure-free survivors, the induction regimen we used appears highly effective, and its components should be considered for inclusion in other treatment programs.
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PMID:Early intensification of chemotherapy for childhood acute nonlymphoblastic leukemia: improved remission induction with a five-drug regimen including etoposide. 329 13

A series of experiments in DBA/2J mice evaluated the biological and pharmacokinetic interactions of the alkylating agent cyclophosphamide (CTX) and the histamine-H2 antagonists cimetidine (CMT) and ranitidine (RNT). Doses were adjusted to approximate human dose levels: 100 mg/kg for CMT; and 25 mg/kg for RNT. CMT reduced the survival of normal (bone marrow stem cell) colony forming units in a dose dependent fashion. CMT, given 5 or 30 min before CTX (200 mg/kg), significantly increased the survival of leukemia bearing mice, as well as the elimination half-life and plasma area under the curve of total alkylating metabolites of CTX. RNT did not significantly alter CTX antileukemic activity, pharmacokinetics, or toxicity to normal bone marrow stem cells. These results suggest caution in the use of CMT in patients being treated with CTX in order to avoid the possibility of exaggerated CTX toxicities. RNT may comprise a safer histamine-H2 antagonist to use with CTX if a histamine-H2 antagonist is clinically indicated.
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PMID:Interaction of cimetidine but not ranitidine with cyclophosphamide in mice. 394 64

Sixty patients consisting of 56 cases with leukemia, 3 with lymphoma and 1 with neuroblastoma were treated with various kinds of hematopoietic stem cell transplantation. The conditioning regimen consisted of mainly cyclophosphamide (CTX) and total body irradiation (TBI) with the addition of 1-3 doses of other antitumor drugs e.g. cytarabine, daunomycin, etoposide, 6-MP etc. The overall incidence of hemorrhagic cystitis in the course of transplantation was 23.3% (14 out of 60 patients). The time of onset of hematuria in 6 of 14 patients was within 1-4 days following high-dose CTX during conditioning and in the remaining 8 cases occurred 10-30 days after transplantation. The duration of hematuria lasted 2-31 days (mean, 4 days). Thirteen patients recovered and one patient died from the complication.
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PMID:[Hemorrhagic cystitis in the course of hematopoietic stem cell transplantation]. 790 67

In an effort to develop more effective therapy for patients with refractory or relapsed acute myelogenous leukemia (R-AML) we combined three drugs with proven activity in AML, that are not typically used in induction regimens, with cytosine arabinoside (ara-C). Twenty-five patients (3 primary refractory, 22 relapsed) were treated. Patients received 3 days of "CECA" therapy as follows: cyclophosphamide (CTX) 1 g/m2 i.v. over 2 hrs., etoposide (VP-16) 200 mg/m2 i.v. over 3 hr, carboplatin (CBP) 150 mg/m2 i.v. over 24 hours and ara-C 1 g/m2 over 2 hr. Peripheral circulating blasts cleared in 24 cases (96%), and marrow aplasia was achieved in 19 (76%). There were 3 complete remissions (CR), 1 patient died before day 14, 5 died aplastic 14 or more days from the start of therapy, 5 had primary resistant disease, and 10 had secondary resistance i.e., leukemia reappearing after developing aplasia and 1 was lost to follow up 6 weeks into therapy. Two of the patients achieving CR received allogeneic BMT in CR (at 18 and 22 weeks): one died of fungal infection on day 50 and the other, who had CNS involvement at relapse, is alive 24 months post transplant. Toxicity was tolerable: one patient each developed grade III diarrhea and mucositis, another had grade III cardiac toxicity, a fourth developed a grade IV bilirubin elevation. Single, 2, and 3 or more infectious episodes occurred in 10, 5 and 4 patients respectively. This regimen showed definite anti-leukemic activity: the 3 patients achieving CR were among 23 patients with a 1%, 10% or 20% expectation for second CR attainment. The CECA regimen should be investigated in better prognosis salvage groups.
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PMID:CECA-cyclophosphamide, etoposide, carboplatin and cytosine arabinoside--a new salvage regimen for relapsed or refractory acute myelogenous leukemia. 951 8

The combination of a cyclophosphamide (CTX)-based chemotherapy regimen and interleukin-2 (IL-2) has been shown to provide synergistic effects against malignancy in animal models. We therefore conducted a phase I-II trial combining CTX-based combination chemotherapy or CTX alone with high-dose IL-2 in patients with advanced and refractory malignant disease. Fifteen patients with hemato-oncological malignancies (malignant lymphoma 8, multiple myeloma 3, solid tumor 2, leukemia 2) were enrolled in the study. Continuous high-dose IL-2 infusion was shown to be safely administered, starting as soon as recovery of white blood cell count. All patients developed rebound lymphocytosis 24-48 h after termination of IL-2 infusion. Although grade IV toxicity was observed in 5 patients (7 episodes), all side effects completely subsided. Triple chemotherapy (CTX, etoposide and Ara-C) seemed rather toxic (in this group of heavily treated patients) while CTX alone was well tolerated. Four out of 13 (31%) evaluable patients had partial response and another patient (7%) had stabilization of disease progression lasting 2-8 months. Our conclusion is that the combination of CTX and continuous infusion of IL-2 is feasible and should be investigated in patients with various malignant neoplasms.
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PMID:Continuous interleukin-2 infusion combined with cyclophosphamide- based combination chemotherapy in the treatment of hemato-oncological malignancies. Results of a phase I-II study. 979 34


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