BACKGROUND: The combination of cyclophosphamide (CY) and antithymocyte globulin (ATG) has been used as a standard conditioning regimen for matched related donor transplantation in patients with severe aplastic anemia. PROCEDURE: To decrease the regimen-related toxicity while maintaining appropriate engraftment and survival rates, fludarabine (FLU) was added to the regimen. Four pediatric patients received matched related donor bone marrow transplantation with CY (50 mg/kg×2) (instead of the 50 mg/kg×4 standard dosing), equine ATG (30 mg/kg×3), with the addition of FLU (30 mg/m×4). Graft versus host disease (GvHD) prophylaxis included a calcineurin inhibitor and methotrexate. RESULTS: No grade 4 acute toxicities occurred during the first 30 days after transplant. All patients engrafted with normalization of peripheral blood counts and transfusion independence. One patient developed grade 1 to 2 acute GvHD, followed by chronic GvHD that resolved. With a median follow-up of 41.7 months, all 4 patients are alive and transfusion free, with complete donor chimerism. This combination of a low-dose CY/ATG+FLU regimen was overall very well tolerated and contributed toward a successful outcome including engraftment, chimerism, and survival. CONCLUSION: This small pilot study shows that this cytoreductive regimen could be considered as the standard of care for transplantation of pediatric patients with aplastic anemia from HLA-matched siblings.
BACKGROUND: The combination of cyclophosphamide (CY) and antithymocyte globulin (ATG) has been used as a standard conditioning regimen for matched related donor transplantation in patients with severe aplastic anemia. PROCEDURE: To decrease the regimen-related toxicity while maintaining appropriate engraftment and survival rates, fludarabine (FLU) was added to the regimen. Four pediatric patients received matched related donor bone marrow transplantation with CY (50 mg/kg×2) (instead of the 50 mg/kg×4 standard dosing), equine ATG (30 mg/kg×3), with the addition of FLU (30 mg/m×4). Graft versus host disease (GvHD) prophylaxis included a calcineurin inhibitor and methotrexate. RESULTS: No grade 4 acute toxicities occurred during the first 30 days after transplant. All patients engrafted with normalization of peripheral blood counts and transfusion independence. One patient developed grade 1 to 2 acute GvHD, followed by chronic GvHD that resolved. With a median follow-up of 41.7 months, all 4 patients are alive and transfusion free, with complete donor chimerism. This combination of a low-dose CY/ATG+FLU regimen was overall very well tolerated and contributed toward a successful outcome including engraftment, chimerism, and survival. CONCLUSION: This small pilot study shows that this cytoreductive regimen could be considered as the standard of care for transplantation of pediatric patients with aplastic anemia from HLA-matched siblings.
Authors: Judith C Marsh; Vikas Gupta; Ziyi Lim; Aloysius Y Ho; Robin M Ireland; Janet Hayden; Victoria Potter; Mickey B Koh; M Serajul Islam; Nigel Russell; David I Marks; Ghulam J Mufti; Antonio Pagliuca Journal: Blood Date: 2011-04-25 Impact factor: 22.113
Authors: R Storb; G Longton; C Anasetti; F R Appelbaum; P Beatty; W Bensinger; S Crawford; H J Deeg; K Doney; A Fefer Journal: Bone Marrow Transplant Date: 1992 Impact factor: 5.483
Authors: A Bacigalupo; F Locatelli; E Lanino; J Marsh; G Socié; S Maury; A Prete; A Locasciulli; S Cesaro; J Passweg Journal: Bone Marrow Transplant Date: 2005-12 Impact factor: 5.483
Authors: Madan H Jagasia; Hildegard T Greinix; Mukta Arora; Kirsten M Williams; Daniel Wolff; Edward W Cowen; Jeanne Palmer; Daniel Weisdorf; Nathaniel S Treister; Guang-Shing Cheng; Holly Kerr; Pamela Stratton; Rafael F Duarte; George B McDonald; Yoshihiro Inamoto; Afonso Vigorito; Sally Arai; Manuel B Datiles; David Jacobsohn; Theo Heller; Carrie L Kitko; Sandra A Mitchell; Paul J Martin; Howard Shulman; Roy S Wu; Corey S Cutler; Georgia B Vogelsang; Stephanie J Lee; Steven Z Pavletic; Mary E D Flowers Journal: Biol Blood Marrow Transplant Date: 2014-12-18 Impact factor: 5.742
Authors: S R McCann; A Bacigalupo; E Gluckman; W Hinterberger; J Hows; P Ljungman; P Marin; C Nissen; E van't Veer Kerthof; A Raghavachar Journal: Bone Marrow Transplant Date: 1994-03 Impact factor: 5.483
Authors: R E Champlin; M M Horowitz; D W van Bekkum; B M Camitta; G E Elfenbein; R P Gale; E Gluckman; R A Good; A A Rimm; C Rozman Journal: Blood Date: 1989-02 Impact factor: 22.113
Authors: Joseph Hai Oved; Yash B Shah; Kimberly Venella; Michele E Paessler; Timothy S Olson Journal: Front Pediatr Date: 2022-07-28 Impact factor: 3.569