Successful transplantation despite cerebral and pulmonary invasive aspergillosis using combination antifungal therapy and granulocyte transfusions in refractory AML

F.R. Schuster (1), H.J. Laws (1), M. Printz (1), F. Babor (1), L. Tramsen (2), T. Lehrnbecher (2), A. Borkhardt (1), R. Meisel (1)

Author address: 

(1)Clinic of Pediatric Oncology, Haematology and Clinical Immunology (Dusseldorf, DE); (2)Clinic of Pediatric Haematology and Oncology (Frankfurt, DE)

Abstract: 

Introduction: Historically diagnosis of active, invasive aspergillosis was considered as a contraindication to alloSCT. New antifungal agents like improved azoles and echinocandines have opened novel treatment options with reduced side effects. Additionally, combinations of antifungal agents employing different modes of action become increasingly attractive. Method: We report on a seven year old girl with acute myeloid leukemia (AML M2)-relapse, who developed biopsy-proven cerebral and pulmonary aspergillosis during relapse treatment (BFM relapsed AML 01). At both sites of fungal infection surgical excision was performed and A. fumigatus could be detected. Despite FLAG and FLAG-DNX reinduction treatment the patient did not reach remission. Therefore, SCT was carried out from her HLA-identical brother after additional chemotherapy using low dose ARA-C and CD33-antibody mylotarg. Conditioning regiment consisted of reduced FLAMSA, Bu and CYC. The transplanted BM contained 6 x 10 6 /kg CD34 + cells. CSA and MMF were employed for GvHD-prophylaxis. After onset of grade III aGvHD, steroids and extrocorporal photopheresis were added. Two granulocyte transfusions (GT) were administered until early neutrophil engraftment on day + 12. Immunosuppression was stopped on day + 160. Antifungal treatment was carried out with voriconazole and caspofungin before and after SCT and caspofungin monotherapy during conditioning. Combination therapy was continued until day + 131 and then switched to oral voriconazole, when Aspergillus-specifi c T-cells became readily detectable in peripheral blood. Result: The child is alive and in remission ten months after SCT. Hemilobectomy was carried out on day + 70. The fi nal eradication of the cerebral infection site is planned. Conclusion: Combination therapy including azoles and echonicandines may lead to synergistic effects because different fungal structures are targeted. GT up to the engraftment may be helpful in patients suffering from aspergillosis undergoing SCT. There is evidence that voriconazole achieves high drug levels S393 in central nervous system and in the lung. However, it remains unclear, whether azoles alone or in combination with echinocandines and/or the addition of GT were the critical agents providing treatment success in this patient suffering from cerebral and pulmonary aspergillosis. Nevertheless, this regimen might prove highly effective in aplastic patients during SCT, thus warranting prospective evaluation in clinical trials.
2010

abstract No: 

R1269

Full conference title: 

Annual Meeting of the EBMT, 36th
    • EBMT 36th (2010)