Frequency and Risk Factors Associated with Cord Graft Failure after Transplant with Single-Unit Umbilical Cord Cells Supplemented by Haploidentical Cells with Reduced-Intensity Conditioning.
Frequency and Risk Factors Associated with Cord Graft Failure after Transplant with Single-Unit Umbilical Cord Cells Supplemented by Haploidentical Cells with Reduced-Intensity Conditioning.
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DOI：
10.1016/j.bbmt.2016.02.010
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
Artz AS
中科院分区：
文献类型：
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作者：
Tsai SB;Liu H;Shore T;Fan Y;Bishop M;Cushing MM;Gergis U;Godley L;Kline J;Larson RA;Martinez G;Mayer S;Odenike O;Stock W;Wickrema A;van Besien K;Artz AS
移植延迟和脐带移植失败（CGF）是无关脐带血（UCB）造血干细胞移植（HSCT）后的严重并发症，特别是使用低细胞剂量UCB单位时。单倍脐带HSCT方法允许通过共输注CD 34+选择的单倍相合移植物来使用较低剂量的单个UCB单位，这提供了早期瞬时植入，同时等待持久的UCB植入。我们描述了降低强度预处理单脐带HSCT后CGF的发生率、并发症和危险因素。在107例接受单脐带HSCT的患者中，94例可评估CGF，定义为第60天髓系和CD 3室中<5%的脐带血嵌合体，而不考虑中性粒细胞和血小板计数。94例可评估患者中有14例发生CGF（15%）。CGF治疗后的中位生存期为12.7个月，7例存活者持续半相合或混合半相合-自体造血。CGF治疗后的中位无进展生存期为7.7个月，与无CGF的患者（10.47个月; P = 0.18）无统计学差异。在单变量分析中，没有UCB因素与CGF相关，包括细胞剂量，细胞活力，受体主要ABO与UCB单位不匹配，或HLA匹配程度。我们还发现CGF与受体巨细胞病毒血清状态、单倍相合供体年龄或30天单倍相合嵌合体无关。然而，较高的单倍体相合的总有核和CD 34+细胞剂量和第30天骨髓或CD 3区室中UCB嵌合体< 5%与CGF的风险较高相关。我们的结论是，在第30天评估嵌合体可能预示即将发生CGF，避免高单倍体相合细胞剂量可能会降低单倍脐带HSCT后CGF的风险。然而，由于主要的单倍相合或混合嵌合体和造血功能，CGF后的长期生存是可能的。
Delayed engraftment and cord graft failure (CGF) are serious complications after unrelated cord blood (UCB) hematopoietic stem cell transplantation (HSCT), particularly when using low-cell-dose UCB units. The haplo-cord HSCT approach allows the use of a lower dose single UCB unit by co-infusion of a CD34+ selected haploidentical graft, which provides early transient engraftment while awaiting durable UCB engraftment. We describe the frequency, complications, and risk factors of CGF after reduced-intensity conditioning haplo-cord HSCT. Among 107 patients who underwent haplo-cord HSCT, 94 were assessable for CGF, defined as <5% cord blood chimerism at day 60 in the myeloid and CD3 compartments, irrespective of neutrophil and platelet counts. CGF occurred in 14 of 94 assessable patients (15%). Median survival after CGF was 12.7 months with haploidentical or mixed haploidentical–autologous hematopoiesis persisting in the 7 surviving. Median progression-free survival after CGF was 7.7 months and was not statistically different from those without CGF (10.47 months; P = .18). In univariate analyses, no UCB factors were associated with CGF, including cell dose, cell viability, recipient major ABO mismatch against the UCB unit, or degree of HLA match. We also found no association of CGF with recipient cytomegalovirus serostatus, haploidentical donor age, or day 30 haploidentical chimerism. However, higher haploidentical total nucleated and CD34+ cell doses and day 30 UCB chimerism < 5% in either the myeloid or CD3 compartments were associated with greater risk of CGF. We conclude that assessing chimerism at day 30 may foretell impending CGF, and avoidance of high haploidentical cell doses may reduce risk of CGF after haplo-cord HSCT. However, long-term survival is possible after CGF because of predominant haploidentical or mixed chimerism and hematopoietic function.