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异基因造血细胞移植的非清髓预处理治疗高危急性淋巴细胞白血病。

Non-myeloablative conditioning with allogeneic hematopoietic cell transplantation for the treatment of high-risk acute lymphoblastic leukemia.

机构信息

Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109, USA.

出版信息

Haematologica. 2011 Aug;96(8):1113-20. doi: 10.3324/haematol.2011.040261. Epub 2011 Apr 20.

Abstract

BACKGROUND

Allogeneic hematopoietic cell transplantation is a potentially curative treatment for patients with acute lymphoblastic leukemia. However, the majority of older adults with acute lymphoblastic leukemia are not candidates for myeloablative conditioning regimens. A non-myeloablative preparative regimen is a reasonable treatment option for this group. We sought to determine the outcome of non-myeloablative conditioning and allogeneic transplantation in patients with high-risk acute lymphoblastic leukemia.

DESIGN AND METHODS

Fifty-one patients (median age 56 years) underwent allogeneic hematopoietic cell transplantation from sibling or unrelated donors after fludarabine and 2 Gray total body irradiation. Twenty-five patients had Philadelphia chromosome-positive acute lymphoblastic leukemia. Eighteen of these patients received post-grafting imatinib.

RESULTS

With a median follow-up of 43 months, the 3-year overall survival was 34%. The 3-year relapse/progression and non-relapse mortality rates were 40% and 28%, respectively. The cumulative incidences of grades II and III-IV acute graft-versus-host disease were 53% and 6%, respectively. The cumulative incidence of chronic graft-versus-host disease was 44%. Hematopoietic cell transplantation in first complete remission and post-grafting imatinib were associated with improved survival (P=0.005 and P=0.03, respectively). Three-year overall survival rates for patients with Philadelphia-negative acute lymphoblastic leukemia in first remission and beyond first remission were 52% and 8%, respectively. For patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in first remission who received post-grafting imatinib, the 3-year overall survival rate was 62%; for the subgroup without evidence of minimal residual disease at transplantation, the overall survival was 73%.

CONCLUSIONS

For patients with high-risk acute lymphoblastic leukemia in first complete remission, non-myeloablative conditioning and allogeneic hematopoietic cell transplantation, with post-grafting imatinib for Philadelphia chromosome-positive disease, can result in favorable long-term survival.

摘要

背景

异基因造血细胞移植是治疗急性淋巴细胞白血病患者的一种潜在根治性治疗方法。然而,大多数老年急性淋巴细胞白血病患者不适合进行清髓性预处理方案。非清髓性预处理方案是该类患者的合理治疗选择。我们旨在确定高危急性淋巴细胞白血病患者接受非清髓性预处理和异基因移植的结果。

设计和方法

51 例患者(中位年龄 56 岁)接受了来自同胞或无关供者的异基因造血细胞移植,预处理方案为氟达拉滨和 2 戈瑞全身照射。25 例患者患有费城染色体阳性急性淋巴细胞白血病。其中 18 例患者在移植后接受伊马替尼治疗。

结果

中位随访 43 个月后,3 年总生存率为 34%。3 年复发/进展和非复发死亡率分别为 40%和 28%。Ⅱ级和Ⅲ级/Ⅳ级急性移植物抗宿主病的累积发生率分别为 53%和 6%。慢性移植物抗宿主病的累积发生率为 44%。首次完全缓解时进行造血细胞移植和移植后接受伊马替尼治疗与生存改善相关(P=0.005 和 P=0.03)。首次完全缓解和缓解后复发的费城阴性急性淋巴细胞白血病患者的 3 年总生存率分别为 52%和 8%。首次缓解时接受移植后伊马替尼治疗的费城染色体阳性急性淋巴细胞白血病患者的 3 年总生存率为 62%;移植时无微小残留病证据的亚组患者的总生存率为 73%。

结论

对于首次完全缓解的高危急性淋巴细胞白血病患者,非清髓性预处理和异基因造血细胞移植,伴费城染色体阳性疾病时移植后应用伊马替尼治疗,可以获得良好的长期生存。

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