Chemotherapy-induced B-cell depletion in hepatoblastoma patients undergoing ABO-incompatible living donor liver transplantation
Chemotherapy-induced B-cell depletion in hepatoblastoma patients undergoing ABO-incompatible living donor liver transplantation
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DOI：
10.1111/petr.12675
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发表时间：
2016-05-01
影响因子：
1.3
通讯作者：
Kasahara, Mureo
中科院分区：
文献类型：
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作者：
Kanazawa, Hiroyuki;Fukuda, Akinari;Kasahara, Mureo
来自ABO-I供体的LT需要预处理方案以防止术后灾难性AMR。已知用于HBL的NAC会引起骨髓抑制，导致淋巴细胞数量和功能减少。我们通过参考B、T细胞和抗ABO血型同种凝集素滴度的动力学，研究了来自ABO-I供体的因LT列出的HBL患者中化疗诱导的骨髓抑制。在2005年至2015年期间，在我们研究所接受LDLT的319例患者中，有12例适用于不可切除的HBL。本研究纳入了3例接受ABO-I供体LDLT的不可切除HBL患者。免疫抑制包括他克莫司和低剂量类固醇的标准方案，如ABO相容/相同LDLT。未使用额外的B细胞耗竭术前治疗。在LDLT前和术后检测淋巴细胞绝对计数、淋巴细胞亚群（包括CD20 + B细胞、CD3 + CD4 + T细胞和CD3 + CD8 + T细胞）和抗ABO血型同种凝集素滴度。诊断时的中位年龄为19个月（范围，3 - 31个月）。中位随访时间为7个月（范围：6 - 15个月）。末次NAC至LDLT的中位间隔时间为33天（范围：25 - 52天）。LDLT至辅助化疗的中位间隔为28天（范围，22 - 36天）。LDLT前的CD 20 + B细胞计数降至中位数5个细胞/mm（3）（范围0 - 6个细胞/mm（3））。第7天CD 20 + B细胞计数出现短暂反弹（最大值为82个细胞/mm3），随后在LDLT后14天开始下降，并持续至辅助化疗期间。抗ABO血型同种凝集素滴度在LDLT前降低至1：1至1：16之间，并在本研究的随访期间保持较低水平。所有三名患者在LDLT后均保持良好的健康状况，无急性细胞或AMR。基于顺铂的HBL化疗后发生的B细胞耗竭可能有助于在儿童中实现安全的ABO-I LDLT，而无需使用额外的预处理方案来预防AMR。
LT from ABO-I donors requires preconditioning regimens to prevent postoperative catastrophic AMR. NAC for HBL is known to cause myelosuppression leading to a reduction in the number and function of lymphocytes. We investigated this chemotherapy-induced myelosuppression in HBL patients listed for LT from ABO-I donors with reference to the kinetics of B, T cells, and anti-ABO blood type isoagglutinin titers. Between 2005 and 2015, of the 319 patients who underwent LDLT at our institute, 12 were indicated for unresectable HBL. Three patients with unresectable HBL who underwent LDLT from ABO-I donors are included in this study. Immunosuppression consisted of a standard regime of tacrolimus and low-dose steroids as in ABO compatible/identical LDLT. No additional preoperative therapies for B-cell depletion were used. Absolute lymphocyte counts, lymphocyte subsets (including CD20+ B cells, CD3+CD4+ T cells and CD3+CD8+ T cells), and anti-ABO blood type isoagglutinin titers were measured before LDLT and postoperatively. The median age at diagnosis was 19 months (range, 3-31 months). The median follow-up was seven months (range, 6-15 months). The median interval from the last NAC to LDLT was 33 days (range, 25-52 days). The median interval from LDLT to adjuvant chemotherapy was 28 days (range, 22-36 days). The counts of CD20+ B cells before LDLT were depleted to median 5 cells/mm(3) (range, 0-6 cells/mm(3)). There was a transient rebound in the CD20+ B cell counts on day seven (maximum of 82 cells/mm(3)) followed by a decline starting at 14 days after LDLT that was sustained for the duration of adjuvant chemotherapy. Anti-ABO blood type isoagglutinin titers were lowered to between 1:1 and 1:16 before LDLT and remained low for the duration of follow-up in this study. All of the three patients remained in good health without either acute cellular or AMR after LDLT. The B-cell depletion that occurs after cisplatin-based chemotherapy for HBL may help accomplish safe ABO-I LDLT in children without the use of additional conditioning regimens for prevention of AMR.