Treosulfan-based conditioning regimen in a second matched unrelated peripheral blood stem cell transplantation for a pediatric patient with CGD and invasive aspergillosis, who experienced initial graft failure after RIC
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by a defect of phagocyte NADPH-oxidase and characterized by severe, recurrent bacterial and fungal infections. Invasive aspergillosis (IA) is the leading cause of mortality in patients with CGD. We report the case of a 3-year-old boy with CGD, who developed IA despite antifungal prophylaxis. His treatment consisted of a 10-month-long multi-drug antifungal therapy, together with surgery, but these did not cause any substantial clinical improvement. BMT in high-risk patients with CGD remains a challenge due to both, higher risk of graft rejection and inflammatory flare in the course of immune recovery. Our patient rejected the first matched unrelated donor (MUD) allograft after RIC regimen recommended by the EBMT Inborn Errors Working Party for high-risk patients. After treosulfan-based conditioning and second MUD peripheral blood stem cell transplantation both, full reconstitution of the granulocytic series and complete recovery from IA, were achieved.
KeywordsTreosulfan Peripheral blood stem cell transplantation Invasive aspergillosis Primary immunodeficiency
- 14.Walsh TJ, Goodman JL, Pappas P, Bekersky I, Buell DN, Roden M, et al. Safety, tolerance and pharmacokinetics of high-dose liposomal amphotericin B (AmBisome) in patients infected with Aspergillus sp. and other filamentous fungi: maximum tolerated dose study. Antimicrob Agents Chemother. 2001;45:3487–96.CrossRefPubMedGoogle Scholar
- 19.Ozsahin H, von Planta M, Müller I, Steinert HC, Nadal D, Lauener R, et al. Successful treatment of invasive aspergillosis in chronic granulomatous disease by bone marrow transplantation, granulocyte colony-stimulating factor-mobilized granulocytes, and liposomal amphotericin-B. Blood. 1998;92(8):2719–24.PubMedGoogle Scholar
- 21.Greystoke B, Bonanomi S, Carr TF, Gharib M, Khalid T, Coussons M, et al. Treosulfan-containing regimens achieve high rates of engraftment associated with low transplant morbidity and mortality in children with non-malignant disease and significant co-morbidities. Br J Haematol. 2008;142:257–62.CrossRefPubMedGoogle Scholar
- 22.Bernardo ME, Zecca M, Piras E, Vacca A, Giorgani G, Cugno, et al. Treosulfan-based conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with thalassemia major. Br J Haematol. 2008;143(4): 548–51.Google Scholar
- 24.Beelen DW, Trenschel R, Casper J, Freund M, Hilger RA, Scheulen ME, et al. Dose-escalated treosulphan in combination with cyclophosphamide as a new preparative regimen for allogeneic haematopoietic stem cell transplantation in patients with an increased risk for regimen-related complications. Bone Marrow Transplant. 2005;35:233–41.CrossRefPubMedGoogle Scholar