title: Chemotherapy-induced B-cell depletion in hepatoblastoma patients undergoing ABO-incompatible living donor liver transplantation.
abstract: 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.
authors.affiliation: Transplantation Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kanazawa
authors.affiliation: Transplantation Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Akinari
authors.initials: A
authors.lastname: Fukuda
authors.affiliation: Transplantation Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Vidyadhar Padmakar
authors.initials: VP
authors.lastname: Mali
authors.affiliation: Transplantation Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Tri Hening
authors.initials: TH
authors.lastname: Rahayatri
authors.affiliation: Transplantation Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hirata
authors.affiliation: Transplantation Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Transplantation Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Uchida
authors.affiliation: Transplantation Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Shigeta
authors.affiliation: Transplantation Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Seisuke
authors.initials: S
authors.lastname: Sakamoto
authors.affiliation: Department of Pediatric Hematology and Oncology Research, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Transplantation Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Mureo
authors.initials: M
authors.lastname: Kasahara
mesh_terms: D000017:ABO Blood-Group System; D018951:Antigens, CD20 / Q000097:blood; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D001787:Blood Group Incompatibility; D017252:CD3 Complex / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D017024:Chemotherapy, Adjuvant / Q000379:methods; D002675:Child, Preschool; D002945:Cisplatin / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000150:complications; D005260:Female; D018197:Hepatoblastoma / Q000097:blood / Q000188:drug therapy / Q000601:surgery*; D006801:Humans; D007113:Immunity, Innate; D007165:Immunosuppression Therapy; D007223:Infant; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects* / Q000379:methods; D019520:Living Donors; D016131:Lymphocyte Subsets; D008297:Male; D012306:Risk; D000069283:Rituximab / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use; D019172:Transplantation Conditioning; D016896:Treatment Outcome
chemical_list: D000017:ABO Blood-Group System; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D017252:CD3 Complex; D000069283:Rituximab; D002945:Cisplatin; D016559:Tacrolimus
keywords: ABO blood type incompatible; SIOPEL; chemotherapy; hepatoblastoma; living donor liver transplantation