Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inhibitory effects on some immunological responses and MethA fibrosarcoma in the double grafted tumor system in mice were compared between 6-mercaptopurine (6-MP) and its novel water-soluble derivative, gamma-(9H-purine-6-yl)thiomethyl L-glutamate (6-MPG). The dose-dependent inhibitory effects by 6-MPG on the hemagglutinin response to SRBC, DTH reaction to MBSA, contact sensitivity to oxazolone, GVH response and growth of the primary tumor were 3-10 times weaker than those by 6-MP, probably reflecting the difference in their cytotoxicities antimetabolites. However, the two drugs were nearly equipotent in reproducing inhibition of the secondary tumor growth, which is a host-mediated immunological response to tumor antigen as shown by its dependency on the primary inoculation with 1 x 10(4) or more MethA cells and by the production of anti-tumor splenocytes in tumor-bearing animals (the Winn assay). Thus, 6-MPG may point to the direction of derivatization towards anti-tumor immunopotentiators with an improved therapeutic index.
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PMID:Augmentation of tumor immunity by 6-MPG, a water-soluble derivative of 6-mercaptopurine, in mice. 893 10

Host conditioning prior to allogeneic bone marrow transplantation (BMT) has traditionally involved the use of high-dose, myeloablative chemotherapy and irradiation, focusing on maximal tumor cytoreduction as well as adequate immunosuppression to allow engraftment of allogeneic stem cells. High-dose chemoradiation conditioning regimens have been associated with a significant incidence of organ toxicity and acute and chronic graft-versus-host disease (GVHD). Recent efforts to diminish the acute transplant-associated toxicities have focused on the development of relatively nontoxic, nonmyeloablative, or less myeloablative conditioning regimens, with the emphasis being predominantly on induction of immunosuppression to enable engraftment. Without ablative chemotherapy, disease control in these regimens is largely relegated to the graft-versus-leukemia/lymphoma (GVL) effect. While the evolution these regimens has resulted in successful engraftment of allogeneic stem cells with minimal toxicity, acute and chronic GVHD occurs in 20% to 50% of patients and remains a major cause of transplant-associated morbidity. Strategies to lower the incidence of acute GVHD have primarily focused on more precise molecular donor/recipient matching, alternative stem cell sources, and T-cell depletion of the graft. While successful in lowering the frequency and severity of GVHD, T-cell-depleted grafts have been associated with compromised the graft-versus-disease effect. Recent studies have suggested that, in addition to T-effector cells within the graft, donor and host dendritic cells may play a role in GVHD. Purine analogues have been evaluated as part of these regimens. While fludarabine and cladribine have been shown to be effective, these agents have been associated with an increased incidence of serious infection and severe acute GVHD. Pentostatin has a different mechanism of action and was also investigated as part of these preparative regimens. Regimens using pentostatin/extracorporeal photopheresis (ECP)/total body irradiation (TBI) have been shown to be well tolerated and associated with early full donor engraftment with a predominance of donor dendritic cell (DC)2 cells and a low incidence of acute GVHD. Further investigation evaluating this preparative regimen is warranted.
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PMID:The role of purine analogues in low-intensity regimens with allogeneic hematopoietic stem cell transplantation. 1654 13

Purine analogs are often used for conditioning preceding allogeneic hematopoietic stem cell transplantation (HCT). We prospectively tested fludarabine (Flu) 40 mg/m(2)/day x 5 days vs cladribine (Clad) 10 mg/m(2)/day x 5 days plus oral busulfan (1 mg/kg q6 h x 2 days) and total body irradiation 200 cGy in 32 recipients of matched sibling and unrelated donor (URD) HCT. Patients were similar in age (median 52 years), diagnosis, extensive pre-HCT therapy (56 vs 63%), and high-risk disease status (81 vs 93%). Neutrophil engraftment was prompt (median 11 vs 12 days), but early graft failure using Clad halted randomization. Platelet recovery was prompt (median Flu 18 vs Clad 24 days). Graft-versus-host disease (GVHD) after Flu vs Clad was similar; (acute grade II/IV 56 vs 69%, P=0.26; chronic 50 vs 31%, P=0.27). Nonrelapse mortality (Flu 25 vs Clad 38%, P=0.47) and progression-free survival at 3 years were similar as well. Multivariate analyses showed slightly, but not significantly lower relative risk (RR) of neutrophil engraftment with Clad (RR 0.6 (95% CI 0.2-1.3) P=0.16) and with URD RR 0.4 (0.2-1.0) P=0.04). Older patients with advanced hematologic malignancies achieve satisfactory outcomes using either of these reduced intensity conditioning regimens.
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PMID:Fludarabine vs cladribine plus busulfan and low-dose TBI as reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation: a prospective randomized trial. 1722 Sep 5