Prophylactic and Preemptive Anti-Fungal Therapy after Cord Blood Transplantation: A Retrospective Analyses of 188 Adult Patients.

Background: Therapeutic outcomes for hematological diseases have recently been markedly improved due to the introduction of hematopoietic stem cell transplantation (HSCT), improvement of therapeutic regimens, and advancement of support therapy. Although invasive fungal infections have been one of the major causes of morbidity and mortality after cord blood transplantation(CBT), proper prophylactic and therapeutic approach to them has not been clearly established yet. To address this, we performed retrospective analysis to assess the effectiveness and safety of various antifungal agents for prevention and treatment of invasive fungal infections.

Patients and Methods: Medical records of a total of 188 patients who underwent umbilical CBT at Toranomon hospital between March 2002 and December 2005 were reviewed. The diagnosis included AML (n=53), ML (n=32), MDS (n=25), ALL (n=24), ATL (n=22), CML (n=7), AA (n=5), MM (n=3), and others (n=17). The median age was 54 (range; 17–79). The conditioning regimen consisted of fludarabine (125mg/m²), melphalan (80 mg/m²) and 4 Gy TBI for most of the patients. The incidence of breakthrough invasive fungal infection within 50 days after transplant was analysed.

Results: Forty-eight of the 188 were administered prophylactic anti-fungal agents other than fluconazole (FLCZ) due to prior mold infection, intorelant to FLCZ, and so on, were excluded. Remaining 140 patients who received FLCZ categolized into 2 groups; those who had empirically switched FLCZ to micafungin (MCFG) and/or amphotericin B (AMPH) and/or itraconazole (ITCZ) capsule at the first sign of infection (group A, n=69), and those who had continued FLCZ (group B, n=71). Four breakthrough invasive fungal infections were observed, 3 of them were invasive pulmonary aspergillosis (IPA), and 1 of them was tricosporon sepsis. Interestingly, all of these 4 were in group B, whereas no breakthrough infections were observed in those who were in group A. All 3 diagnosed IPA died of its exacerbation despite MCFG and/or AMPH treatment.

Conclusion: Proper administration of prophylactic anti-fungal agents can reduce the incidence of invasive fungal infection early after CBT. Although FLCZ has less activity to aspergillus, prophylactic FLCZ is effective enough to prevent breakthrough fungal infection. Immediate switch to other agents at the first sign of infection, such as MCFG, AMPH, ITCZ which are active against aspergillus could be recommended to prevent breakthrough infections.