METHOTREXATE REGIMENS FOR CONTROL OF GRAFT-VERSUS-HOST DISEASE IN DOGS WITH ALLOGENEIC MARROW GRAFTS

METHOTREXATE REGIMENS FOR CONTROL OF GRAFT-VERSUS-HOST DISEASE IN DOGS WITH ALLOGENEIC MARROW GRAFTS
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DOI:
10.1097/00007890-197003000-00007
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发表时间:
1970-01-01
期刊:
影响因子:
6.2
通讯作者:
THOMAS, ED
THOMAS, ED
中科院分区:
医学2区
文献类型:
--
作者:
STORB, R;EPSTEIN, RB;THOMAS, ED

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在同种异体骨髓移植后1天开始使用高剂量甲氨蝶呤进行免疫抑制治疗,以评价其在预防或延迟犬致死性移植物抗宿主病方面的有效性。移植后6天的甲氨蝶呤短期方案与移植后102天的长期方案进行了比较。使用通过犬组织相容性试验不匹配的无关供体-受体对。接受者接受了供体骨髓和白细胞的联合输注,以提供一个移植物抗宿主综合征是急性和迅速致命的测试系统。受体通过1200 R的全身照射准备用于移植。5只未接受免疫抑制治疗的对照犬在移植后9 - 14天死于移植物抗宿主病。接受短期甲氨蝶呤治疗的9只犬中有8只在14 - 21天内死于移植物抗宿主病,1只犬存活了136天。接受长期甲氨蝶呤治疗的10只狗中有7只在18至68天之间死亡,3只狗在移植后存活超过180天。生存数据的统计学分析证明了长期甲氨蝶呤治疗的优越性。结果表明,当骨髓移植后立即开始强化甲氨蝶呤并持续一段较长的时间时,可以在不匹配的受体犬中实现稳定的长期嵌合体。
Immunosuppressive therapy with high doses of methotrexate beginning 1 day after allogeneic bone marrow transplantation was evaluated for its effectiveness in preventing or delaying the lethal graftversus-host disease in dogs. A short-term regimen of methotrexate for 6 days after transplantation was compared with a long-term regimen during 102 days postgrafting. Unrelated donor-recipient pairs mismatched by canine histocompatibility testing were used. The recipients were given combined infusions of donor marrow and leukocytes to provide a test system in which the graft-versus-host syndrome is acute and rapidly fatal. Recipients were prepared for transplantation by 1200 R of total body irradiation. Five control dogs, not receiving immunosuppressive therapy, died between 9 and 14 days after transplantation with graft-versus-host disease. Eight of the 9 dogs receiving short-term methotrexate treatment died between 14 and 21 days with graft-versus-host disease, and 1 dog lived 136 days. Seven of the 10 dogs given long-term methotrexate treatment died between 18 and 68 days, and 3 dogs are alive more than 180 days after transplantation. Statistical analysis of the survival data demonstrated the superiority of the long-term methotrexate treatment. The results show that stable long-term chimerism can be achieved in mismatched recipient dogs when intensive methotrexate is begun immediately after marrow transplantation and continued for a prolonged period of time.