Minimal Residual Disease Status Before Allogeneic Bone Marrow Transplantation Is an Important Determinant of Successful Outcome for Children and Adolescents With Acute Lymphoblastic Leukemia

Minimal Residual Disease Status Before Allogeneic Bone Marrow Transplantation Is an Important Determinant of Successful Outcome for Children and Adolescents With Acute Lymphoblastic Leukemia
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同种异体骨髓移植前的最小残留疾病状态是急性淋巴细胞白血病儿童和青少年成功结果的重要决定因素

DOI:
10.1182/blood.v92.11.4072.423k33_4072_4079
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发表时间:
1998
期刊:
影响因子:
20.3
通讯作者:
A. Oakhill
A. Oakhill
中科院分区:
医学1区
文献类型:
--
作者:
C. Knechtli;N. Goulden;J. Hancock;V. Grandage;Emma L. Harris;R. Garland;Claire G. Jones;A. Rowbottom;L. Hunt;A. Green;E. Clarke;A. Lankester;J. Cornish;D. Pamphilon;C. Steward;A. Oakhill

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急性淋巴细胞白血病(ALL)同种异体移植的疗效很大程度上受到移植时缓解状态的影响。使用基于聚合酶链反应 (PCR) 的微小残留病 (MRD) 分析,我们回顾性研究了亚显微白血病对 64 名因儿童 ALL 接受同种异体骨髓移植 (BMT) 的患者结果的影响。移植前 6 至 81 天(中位数 23 天)采集缓解期 BM 标本。所有患者均接受类似的调理治疗; 50 例接受了来自无关捐赠者的移植物,14 例接受了来自相关捐赠者的移植物。 19 名患者在第一次完全缓解 (CR1) 时接受移植,45 名患者在第二次或后续 CR 时接受移植。通过 Ig 或 T 细胞受体 δ 或 γ 重排的 PCR、电泳和等位基因特异性寡聚探针分析来分析 MRD。样品被评为高水平阳性(电泳后克隆带明显;灵敏度 10−2 至 10−3)、低水平阳性(仅在寡探针检测后检测到 MRD;灵敏度 10−3 至 10−5)或阴性。排除 8 例因孤立性髓外复发而移植到 CR2 的患者(均为 MRD−),12 例患者中 MRD 检测到高水平,11 例患者检测到低水平,33 例检测不到 MRD。这些组的两年无事件生存率分别为 0%、36% 和 73% ( P < .001)。持续缓解的患者的随访时间为 20 至 96 个月(中位数为 35 个月)。这些结果表明 MRD 分析可以在这种情况下常规使用。这将有助于识别耐药性白血病患者(他们可能受益于创新的 BMT 方案)和疾病反应更佳的患者(他们可能是 BMT 与现代强化复发化疗随机试验的候选者)。
The efficacy of allografting in acute lymphoblastic leukemia (ALL) is heavily influenced by remission status at the time of transplant. Using polymerase chain reaction (PCR)-based minimal residual disease (MRD) analysis, we have investigated retrospectively the impact of submicroscopic leukemia on outcome in 64 patients receiving allogeneic bone marrow transplantation (BMT) for childhood ALL. Remission BM specimens were taken 6 to 81 days (median, 23) before transplant. All patients received similar conditioning therapy; 50 received grafts from unrelated donors and 14 from related donors. Nineteen patients were transplanted in first complete remission (CR1) and 45 in second or subsequent CR. MRD was analyzed by PCR of Ig or T-cell receptor δ or γ rearrangements, electrophoresis, and allele-specific oligoprobing. Samples were rated high-level positive (clonal band evident after electrophoresis; sensitivity 10−2 to 10−3), low-level positive (MRD detected only after oligoprobing; sensitivity 10−3 to 10−5), or negative. Excluding 8 patients transplanted in CR2 for isolated extramedullary relapse (all MRD−), MRD was detected at high level in 12 patients, low level in 11, and was undetectable in 33. Two-year event-free survival for these groups was 0%, 36%, and 73%, respectively ( P < .001). Follow-up in patients remaining in continuing remission is 20 to 96 months (median, 35). These results suggest that MRD analysis could be used routinely in this setting. This would allow identification of patients with resistant leukemia (who may benefit from innovative BMT protocols) and of those with more responsive disease (who may be candidates for randomized trials of BMT versus modern intensive relapse chemotherapy).
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DOI: --
发表时间: 1995
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影响因子: 20.3
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白血病祖细胞的移植前负担作为急性淋巴细胞白血病骨髓移植后复发的预测因子。
DOI: 10.1056/nejm199310283291802
发表时间: 1993
期刊: The New England journal of medicine
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