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

Ref ID: 18598

Author:

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)

Full conference title:

Annual Meeting of the EBMT, 36th

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.

Abstract Number: R1269

Conference Year: 2010

Link to conference website: NULL

New link: NULL

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