Radiation-sparing reduced-intensity unrelated umbilical cord blood transplantation for rare hematological disorders in children

• Published in: International journal of hematology Vol. 115; no. 2; pp. 269 - 277
• Main Authors: Sawada, Akihisa, Shimizu, Mariko, Koyama-Sato, Maho, Higuchi, Kohei, Okada, Yosuke, Goto, Kimitoshi, Inoue, Shota, Yasui, Masahiro, Inoue, Masami
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.02.2022; Springer Nature B.V
• Subjects: Adolescent; Blood; Blood diseases; Bone marrow; Bone Marrow Failure Disorders - therapy; Child; Child, Preschool; Children; Chimerism; Chronic myeloid leukemia; Conditioning; Cord blood; Cord Blood Stem Cell Transplantation - adverse effects; Cord Blood Stem Cell Transplantation - methods; Cyclophosphamide; Disorders; Female; Fetal Blood - transplantation; Fludarabine; Globulins; Graft rejection; Grafts; Hematological diseases; Hematology; Humans; Infant; Irradiation; Juveniles; Leukemia; Leukemia - therapy; Male; Medicine; Medicine & Public Health; Melphalan; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - therapy; Myeloid leukemia; Myelomonocytic leukemia; Oncology; Original Article; Radiation; Retrospective Studies; Thymocytes; Transplantation; Transplantation Conditioning - adverse effects; Transplantation Conditioning - methods; Umbilical cord; Whole-Body Irradiation - adverse effects; Whole-Body Irradiation - methods; Juvenile myelomonocytic leukemia; Myelodysplastic syndrome; Aplastic anemia; Cord blood transplantation; Reduce-intensity conditioning
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-021-03254-z

Graft failure is a major pitfall of unrelated umbilical cord blood transplantation (CBT) in children with rare hematological disorders other than acute leukemia, such as acquired and inherited bone marrow failure, myelodysplastic syndrome, juvenile myelomonocytic leukemia, and chronic myeloid leukemia. We developed a less-toxic conditioning regimen for CBT that achieves a higher rate of complete donor chimerism, and retrospectively compared it against two other conditioning regimens for CBT performed at our single institution. The engraftment rate with complete donor chimerism was 100% and 5-year event-free survival (5y-EFS) was 90.9% in patients using our latest regimen ( n  = 11) of reduced-intensity conditioning (RIC) containing fludarabine (Flu) 180 mg/m 2 , melphalan (MEL) 210 mg/m 2 , and low-dose rabbit anti-thymocyte globulin (LD-rATG) 2.5 mg/kg without irradiation (regimen C). Outcomes were better than in patients ( n  = 10) treated with previous regimens involving irradiation (5y-EFS 30.0%, p  = 0.004): regimen A, consisting of myeloablative conditioning containing cyclophosphamide (CY) and total body irradiation (TBI) with 8–12 Gy, or regimen B, consisting of RIC with Flu, CY, horse ATG, and thoracoabdominal irradiation (TAI) with 6 Gy. In conclusion, Flu/MEL/LD-rATG (regimen C) without TBI/TAI may be preferable as RIC for unrelated CBT in children with rare hematological disorders.