OBJECTIVE: Use of high-dose cyclophosphamide without hematopoietic stem cell transplant to treat severe aplastic anemia (SAA) has been controversial due to concern for increased infectious toxicity as compared with antithymocyte globulin and cyclosporine A. As children often tolerate dose-intensive therapy better than adults, we sought to perform a detailed retrospective analysis of both treatment response and toxicity in 28 patients younger than 22 years of age treated with 29 courses of high-dose cyclophosphamide as the sole form of immunosuppression. STUDY DESIGN: Children and adolescents with SAA who lacked an human leukocyte antigen-matched sibling donor were treated with cyclophosphamide 50 mg/kg/d for 4 consecutive days then received daily granulocyte colony stimulating factor until neutrophil recovery, transfusion support, and antimicrobial prophylaxis. RESULTS: Overall survival was 85%, with hematologic response of 79% and complete response of 66%. Cumulative incidences of bacterial infection (86%) and fungal infection (62%) were high but deaths due to infection were rare, as were clonal evolution (1/28), clinically relevant paroxysmal nocturnal (1/28), and relapse (2/28). CONCLUSIONS: Response rates and survival following high-dose cyclophosphamide in pediatric patients with SAA exceed those seen in adults and compare favorably to antithymocyte globulin/cyclosporine A with manageable infectious toxicity.
OBJECTIVE: Use of high-dose cyclophosphamide without hematopoietic stem cell transplant to treat severe aplastic anemia (SAA) has been controversial due to concern for increased infectious toxicityas compared with antithymocyte globulin and cyclosporine A. Aschildren often tolerate dose-intensive therapy better than adults, we sought to perform a detailed retrospective analysis of both treatment response and toxicity in 28 patients younger than 22 years of age treated with 29 courses of high-dose cyclophosphamideas the sole form of immunosuppression. STUDY DESIGN:Children and adolescents with SAA who lacked an human leukocyte antigen-matched sibling donor were treated with cyclophosphamide 50 mg/kg/d for 4 consecutive days then received daily granulocyte colony stimulating factor until neutrophil recovery, transfusion support, and antimicrobial prophylaxis. RESULTS: Overall survival was 85%, with hematologic response of 79% and complete response of 66%. Cumulative incidences of bacterial infection (86%) and fungal infection (62%) were high but deaths due to infection were rare, as were clonal evolution (1/28), clinically relevant paroxysmal nocturnal (1/28), and relapse (2/28). CONCLUSIONS: Response rates and survival following high-dose cyclophosphamide in pediatric patients with SAA exceed those seen in adults and compare favorably to antithymocyte globulin/cyclosporine A with manageable infectious toxicity.
Authors: Ben De Pauw; Thomas J Walsh; J Peter Donnelly; David A Stevens; John E Edwards; Thierry Calandra; Peter G Pappas; Johan Maertens; Olivier Lortholary; Carol A Kauffman; David W Denning; Thomas F Patterson; Georg Maschmeyer; Jacques Bille; William E Dismukes; Raoul Herbrecht; William W Hope; Christopher C Kibbler; Bart Jan Kullberg; Kieren A Marr; Patricia Muñoz; Frank C Odds; John R Perfect; Angela Restrepo; Markus Ruhnke; Brahm H Segal; Jack D Sobel; Tania C Sorrell; Claudio Viscoli; John R Wingard; Theoklis Zaoutis; John E Bennett Journal: Clin Infect Dis Date: 2008-06-15 Impact factor: 9.079
Authors: J C Marsh; R M Pearce; M B C Koh; Z Lim; A Pagliuca; G J Mufti; J Perry; J A Snowden; A J Vora; R T Wynn; N Russell; B Gibson; M Gilleece; D Milligan; P Veys; S Samarasinghe; M McMullin; K Kirkland; G Cook Journal: Bone Marrow Transplant Date: 2013-08-05 Impact factor: 5.483
Authors: Emma M Groarke; Bhavisha A Patel; Fernanda Gutierrez-Rodrigues; Olga Rios; Jennifer Lotter; Daniela Baldoni; Annie St Pierre; Ruba Shalhoub; Colin O Wu; Danielle M Townsley; Neal S Young Journal: Br J Haematol Date: 2021-01-07 Impact factor: 8.615