Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects
Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects
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DOI：
10.1182/blood.v97.11.3390
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发表时间：
2001-06-01
期刊：
影响因子：
20.3
通讯作者：
Storb, RF
中科院分区：
文献类型：
--
作者：
McSweeney, PA;Niederwieser, D;Storb, RF
毒性限制了异基因造血细胞移植（HCT）的使用，以年轻，医学上合适的患者。在犬HCT模型中，移植后霉酚酸酯（MMF）和环孢素（CSP）的组合允许在低剂量（200 cGy）全身照射（TBI）的最低毒性条件下稳定的同种异体移植。这些发现以及供体白细胞输注（DLI）的已知抗肿瘤作用导致了本试验的设计。治疗了45例患有血液恶性肿瘤、HLA相同的同胞供体和常规HCT相对禁忌症的患者（中位年龄56岁）。免疫抑制包括HCT后200 cGy的TBI和CSP/MMF。对于持续性恶性肿瘤、混合嵌合体或两者，在HCT后给予DLI。方案毒性和骨髓抑制轻微，允许53%的合格患者进行完全门诊移植，20%的患者发生非致命性移植排斥反应。47%的持续植入患者发生II至III级急性移植物抗宿主病（GVHD）。中位随访417天，生存率为66.7%，非复发死亡率为6.7%，复发死亡率为26.7%。53%的持续植入患者为不完全缓解，包括8例分子缓解。这种基于使用移植后免疫抑制来控制移植物排斥和GVHD的新型同种异体移植方法显著降低了同种异体移植的急性毒性，可以在先前不合格的患者中进行HCT，主要是在门诊环境中。未来的方案修改应减少排斥反应和GVHD，从而促进各种恶性肿瘤的同种异体免疫治疗的研究。（血。2001;97：3390-3400）（C）2001由美国血液学学会。
Toxicities have limited the use of allogeneic hematopoietic cell transplantation (HCT) to younger, medically fit patients. in a canine HCT model, a combination of postgrafting mycophenolate mofetil (MMF) and cyclosporine (CSP) allowed stable allogeneic engraftment after minimally toxic conditioning with low-dose (200 cGy) total-body irradiation (TBI). These findings, together with the known antitumor effects of donor leukocyte infusions(DLIs), led to the design of this trial, Forty-five patients (median age 56 years) with hematologic malignancies, HLA-identical sibling donors, and relative contraindications to conventional HCT were treated. Immunosuppression involved TBI of 200 cGy before and CSP/MMF after HCT. DLIs were given after HCT for persistent malignancy, mixed chimerism, or both. Regimen toxicities and myelosuppression were mild, allowing 53% of eligible patients to have entirely outpatient transplantations, Nonfatal graft rejection occurred in 20% of patients. Grades II to III acute graft-versus-host disease (GVHD) occurred in 47% of patients with sustained engraftment. With median follow-up of 417 days, survival was 66.7%, nonrelapse mortality 6.7%, and relapse mortality 26.7%. Fifty-three percent of patients with sustained engraftment were incomplete remission, including 8 with molecular remissions. This novel allografting approach, based on the use of postgrafting immunosuppression to control graft rejection and GVHD, has dramatically reduced the acute toxicities of allografting, HCT with the induction of potent graft-versus-tumor effects can be performed in previously ineligible patients, largely in an outpatient setting. Future protocol modifications should reduce rejection and GVHD, thereby facilitating studies of allogeneic immunotherapy for a variety of malignancies. (Blood. 2001;97:3390-3400) (C) 2001 by The American Society of Hematology.