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异基因干细胞移植后移植物功能不良患者中,无需进一步预处理即可增强CD34+选择的外周血细胞。

Boost of CD34+-selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation.

作者信息

Larocca Alessandra, Piaggio Giovanna, Podestà Marina, Pitto Anna, Bruno Barbara, Di Grazia Carmen, Gualandi Francesca, Occhini Domenico, Raiola Anna Maria, Dominietto Alida, Bregante Stefania, Lamparelli Teresa, Tedone Elisabetta, Oneto Rosi, Frassoni Francesco, Van Lint Maria Teresa, Pogliani Enrico, Bacigalupo Andrea

机构信息

Divisione Ematologia, Ospedale San Gerardo, Monza, Milano, Italy

出版信息

Haematologica. 2006 Jul;91(7):935-40.

Abstract

BACKGROUND AND OBJECTIVES

A proportion of patients develop poor graft function (PGF) following an allogeneic hemopoietic stem cell transplant (HSCT). It is uncertain whether a boost of donor marrow or blood cells is beneficial in terms of trilineage recovery and non-relapse-related mortality (NRM).

DESIGN AND METHODS

The aim of this study was to compare outcomes in patients with PGF and full donor chimerism following an allogeneic HSCT who did or did not receive a boost of donor stem cells. The study included patients with primary PGF--i.e. those failing to achieve sustained graft function- and secondary PGF--i.e. those developing PGF after complete hematologic recovery. We studied 54 patients with PGF: 20 patients received no further donor cell infusion (group A), 14 received a boost of unmanipulated marrow or blood cells from the original donor, without further conditioning (group B), and 20 received donor cells after CD34 selection without conditioning (group C). The three groups were comparable for disease phase, patients' age, donor type, primary or secondary PGF, full donor chimerism and duration of PGF.

RESULTS

Trilineage recovery was seen in 40%, 36% and 75% of the patients in, respectively, groups A, B and C (p=0.02). In multivariate Cox analysis trilineage recovery was more frequent in patients with secondary PGF (RR of complete recovery 2.82, p=0.01) and in patients receiving CD34+-selected cells (RR of complete recovery 3.0; p=0.007). There was no effect of donor type on hematologic recovery. The rate of NRM was 55%, 64%, 20% in groups A, B and C, respectively (p=0.06) and was highly correlated with trilineage recovery (RR 0.36, p<0.0001). PGF was the primary cause of death in 30%, 21% and 10% of the patients in the three groups, graft-versus-host disease (GVHD) in 5%, 36%, and 10%.

INTERPRETATIONS AND CONCLUSIONS

In patients with poor graft function (a) a boost of CD34+-selected peripheral blood donor cells is associated with a high chance of trilineage recovery and a low risk of acute GVHD; (b) a boost of unmanipulated donor cells does not seem to offer a survival advantage over no infusion of cells; and (c) NRM is lower when using peripheral blood cells for the boost. These data may be useful when discussing second stem cell donations for patients with poor graft function.

摘要

背景与目的

一部分患者在接受异基因造血干细胞移植(HSCT)后会出现移植物功能不良(PGF)。目前尚不确定增加供体骨髓或血细胞输入对于三系造血恢复及非复发相关死亡率(NRM)是否有益。

设计与方法

本研究旨在比较异基因HSCT后出现PGF且为完全供体嵌合状态的患者,接受或未接受供体干细胞增加输入的预后情况。研究纳入原发性PGF患者,即未能实现持续移植物功能的患者,以及继发性PGF患者,即血液学完全恢复后出现PGF的患者。我们研究了54例PGF患者:20例患者未接受进一步的供体细胞输注(A组),14例接受了来自原供体的未处理骨髓或血细胞增加输入,未进行进一步预处理(B组),20例在未进行预处理的情况下接受了CD34选择后的供体细胞(C组)。三组在疾病分期、患者年龄、供体类型、原发性或继发性PGF、完全供体嵌合状态及PGF持续时间方面具有可比性。

结果

A组、B组和C组患者的三系造血恢复率分别为40%、36%和75%(p = 0.02)。在多因素Cox分析中,继发性PGF患者的三系造血恢复更为常见(完全恢复的相对风险为2.82,p = 0.01),接受CD34+选择细胞的患者也是如此(完全恢复的相对风险为3.0;p = 0.007)。供体类型对血液学恢复无影响。A组、B组和C组的NRM率分别为55%、64%和20%(p = 0.06),且与三系造血恢复高度相关(相对风险0.36,p < 0.0001)。PGF是三组中30%、21%和10%患者的主要死亡原因,移植物抗宿主病(GVHD)则分别导致5%、36%和10%患者死亡。

解读与结论

对于移植物功能不良的患者,(a)增加输入经CD34选择的外周血供体细胞与三系造血恢复的高概率及急性GVHD的低风险相关;(b)增加输入未处理的供体细胞似乎并不比不输入细胞具有生存优势;(c)使用外周血细胞进行增加输入时NRM较低。这些数据在讨论为移植物功能不良患者进行第二次干细胞捐献时可能会有所帮助。

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