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)

Immune responses, specific to the stored donor tissue, were measured in 26 recipients over 4,000 days. CML positive crossmatches were associated with accelerated rejections (three cases). LDA positive crossmatches resulted in primary non-functioning kidneys (three cases). Post-transplantation. CML (16 hour inculation) was associated with rejection (p equals 0.001), highly predictive of rejection (p equals 0.001), and when positive after rejection treatment, was associated with a failure to respond (p equals 0.005 - 0.01). 51Cr-CDA was also associated with rejection (p equals 0.002). Recovery of these immunologic participants from the explanted kidney substantiated that they were important effector mechanisms in vivo.
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PMID:Transplant monitoring: patterns of the immune response. 77 32

The influence of 2-CDA and interferon alpha (IFN-alpha) on the CFU-GM cells from ten normal individuals as well as on the CFU-GM from ten patients with chronic myeloid leukemia (CML) and on clonogenic leukemic blasts (CFU-L) from ten patients with acute myeloid leukemia (AML) in semi-solid cultures in vitro was investigated. The agents were added to the cultures alone and in combinations at concentrations of 20, 40 and 80 nM/l of 2-CDA and 10(2), 10(3) and 10(4) U/ml of IFN-alpha. A dose-dependent growth inhibition of CFU-GM as well as of CFU-L was observed. The inhibitory effect of both drugs used alone was significantly greater on the CFU-GM cells from patients with CML than on cells from normal donors. However, 2-CDA and IFN-alpha used together showed greater additive effect on the CFU-L than on the CFU-GM from normal donors and from CML patients.
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PMID:The interaction of 2-chlorodeoxyadenosine (2-CDA) and interferon alpha (IFN-alpha) on normal and myeloid leukemia hematopoiesis in vitro. 790 73

In vitro studies suggest that nucleoside analogs have an antileukemic effect against chronic myelogenous leukemia (CML). We investigated the antileukemia effect of deoxycoformycin (DCF) and fludarabine in patients with CML. Four patients with Philadelphia chromosome (Ph)-positive CML were treated with DCF at 4 mg/m2 every week for 4 weeks, then every other week for four doses, and then every month as maintenance. Two patients were in late chronic phase and two in accelerated phase. All had previously failed therapy with interferon-alpha (IFN-A). Nine patients were treated with fludarabine 30 mg/m2/day for 5 days every 28 days. Three had Ph-positive CML, and six Ph-negative disease. Five patients were in accelerated phase and four in late chronic phase. Three patients treated with DCF had normalization of WBC counts while on the weekly schedule but progressed when changed to every other week. The fourth patient had no objective response. There were no cytogenetic responses. DCF was well tolerated with only mild nausea and vomiting in all patients. Patients treated with fludarabine received a median of two courses (range 1-4). In two patients (both Ph-positive), disease progressed to blastic phase upon recovery. Two other patients died of hemorrhagic complications secondary to thrombocytopenia. In all other cases fludarabine produced a transient reduction of WBC counts, but counts recovered to levels equal to or greater than the pre-treatment values. There were no cytogenetic responses. These results, together with previous experience with 2-CDA producing only hematologic responses, suggest that nucleoside analogs may not have a significant role in the management of CML.
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PMID:Treatment of chronic myelogenous leukemia with nucleoside analogs deoxycoformycin and fludarabine. 917 28

The high-dose chemotherapy and radiation typically used as the preparative regimen for bone marrow transplantation produces considerable morbidity and mortality. An alternative strategy is to utilize a low-dose, non-myeloablative, preparative regimen designed not to eradicate the malignancy, but to provide sufficient immunosuppression to achieve engraftment of an allogeneic hematopoietic graft and allow subsequent development of a graft-vs.-malignancy effect. We studied this approach in patients who were ineligible for standard myeloablative preparative regimens because of advanced age or comorbidities and demonstrated that purine analog (fludarabine or 2-CDA) containing non-myeloablative chemotherapy allows engraftment of HLA-compatible hematopoietic progenitor cells, and extended remissions were observed in approximately half of chemosensitive patients with recurrent AML or CML. Patients with CLL or lymphoma have been effectively treated using a non-myeloablative regimen of fludarabine/cyclophosphamide of fludarabine, cytarabine, cisplatin. This chemotherapy is known to be non-myeloablative and mixed chimerism was anticipated. All patients with engraftment have responded and 67% have achieved complete remission. Maximal responses are slow to develop and occur gradually over a period of several months to one year. Long-term efficacy must still be determined and controlled trials are necessary comparing this approach with alternative therapies as well as standard transplantation regimens.
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PMID:Graft-vs.-malignancy with allogeneic blood stem cell transplantation: a potential primary treatment modality. 1058 72