Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Children and Adolescents with Fanconi Anemia.
We describe haploidentical bone marrow transplantation with post-transplant cyclophosphamide (PT-CY) for 30 patients with Fanconi anemia (FA). Twenty-six patients were transplanted upfront, and the preparatory regimens included fludarabine 150 mg/m2+ total body irradiation 200 to 300 cGy ± CY 10 mg/kg without (n = 12) or with rabbit antithymocyte globulin (r-ATG) 4 to 5 mg/kg (n = 14). Four patients were rescued after primary or secondary graft failure after related or unrelated donor transplantation with the above regimen with (n = 2) or without r-ATG (n = 2). PT-CY at 25 mg/kg/day (total dose, 50 mg/kg) followed by cyclosporine and mycophenolate mofetil was given to all patients. All patients engrafted in the subgroup of patients who did not receive r-ATG (n = 14), but their transplant course was complicated by high rates of acute and chronic graft-versus-host disease (GVHD), and only 8 patients are alive. In the subgroup that received r-ATG (n = 16), 14 patients had sustained engraftment, severe GVHD rates were lower, and 13 patients are alive. Hemorrhagic cystitis occurred in 50% of patients, whereas cytomegalovirus reactivation occurred in 75%. One-year overall survival for the entire cohort was 73% (95% CI, 64% to 81%), and all surviving patients achieved full donor chimerism. In conclusion, haploidentical donor transplantation with PT-CY is a suitable option for FA patients without a matched related or unrelated donor.
Hospital de Clinicas, Federal University of Parana, Curitiba, Brazil. Electronic address: carmembonfim@gmail.com.
Carmem
C
Bonfim
Hospital de Clinicas, Federal University of Parana, Curitiba, Brazil.
Lisandro
L
Ribeiro
Hospital de Clinicas, Federal University of Parana, Curitiba, Brazil.
Samantha
S
Nichele
Hospital de Clinicas, Federal University of Parana, Curitiba, Brazil.
Gisele
G
Loth
Hospital de Clinicas, Federal University of Parana, Curitiba, Brazil.
Marco
M
Bitencourt
Hospital de Clinicas, Federal University of Parana, Curitiba, Brazil.
Adriana
A
Koliski
Hospital de Clinicas, Federal University of Parana, Curitiba, Brazil.
Cilmara
C
Kuwahara
Hospital de Clinicas, Federal University of Parana, Curitiba, Brazil.
Ana Luiza
AL
Fabro
Hospital de Clinicas, Federal University of Parana, Curitiba, Brazil.
Noemi F
NF
Pereira
Hospital de Clinicas, Federal University of Parana, Curitiba, Brazil.
Daniela
D
Pilonetto
Department of Pediatric Hematology Oncology, Blood and Marrow Transplantation Program, Medical College of Wisconsin, Milwaukee, Wisconsin.
Monica
M
Thakar
Cell and Gene Therapy Program, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Hans-Peter
HP
Kiem
Department of Pediatrics, Pediatric Blood and Marrow Transplant Program, Duke University Medical Center, Durham, North Carolina.
Kristin
K
Page
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Ephraim J
EJ
Fuchs
Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
Mary
M
Eapen
Hospital de Clinicas, Federal University of Parana, Curitiba, Brazil.
Ricardo
R
Pasquini
D000293:Adolescent; D064591:Allografts; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use*; D003586:Cytomegalovirus Infections / Q000150:complications; D020031:Epstein-Barr Virus Infections / Q000150:complications; D005199:Fanconi Anemia / Q000150:complications / Q000188:drug therapy / Q000628:therapy*; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007958:Leukocyte Count; D052016:Mucositis / Q000209:etiology; D009504:Neutrophils; D055031:Primary Graft Dysfunction / Q000453:epidemiology; D012189:Retrospective Studies; D016879:Salvage Therapy; D014019:Tissue Donors; D014123:Toxoplasmosis / Q000150:complications; D019172:Transplantation Conditioning; D014775:Virus Activation
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide
Fanconi anemia; Haploidentical; Inherited bone marrow failure syndromes