[12] In contrast, a randomised phase III study evaluating granulocyte transfusions in neutropaenic cancer patients with febrile neutropaenia

and pulmonary or soft-tissue infiltrates after conventional or high-dose chemotherapy demonstrated no impact on the course and outcome of infection.[13] Unfortunately, no sub-analyses are available for patients suffering from mucormycosis, which is most likely due to the low number of patients included with these infections. Beside neutrophils, lymphocytes, in particular CD4+ T cells, may also provide critical defence mechanisms against mucormycosis (Fig. 2). This hypothesis is supported by the clinical PF-02341066 in vitro observation that mucormycoses often occur several months after allogeneic HSCT, at a time, when neutropaenia and mucositis have already resolved, but adaptive immune responses are still hampered. A recent study reported that the median time of diagnosis of mucormycosis was 173 days (range, 7–2254) after transplantation; this time frame is comparable to the findings in invasive aspergillosis, which occurs at a median of 82 days (3–6542) after allogeneic HSCT.[14]

Notably, allogeneic HSCT transplant recipients have a low number of anti-Aspergillus TH1 cells for months after transplantation,[15] and it has been demonstrated that TH1-biased immunity correlates with protection and a better outcome in invasive aspergillosis.[16] These observations formed the rationale of transferring functionally active Aspergillus-specific EX 527 manufacturer TH1 cells to allogeneic HSCT recipients at high-risk for or suffering from invasive

aspergillosis. In fact, a proof of principle study in 10 patients after haploidentical HSCT with evidence of invasive aspergillosis demonstrated that transfusion of anti-Aspergillus TH1 cells resulted in a clinical benefit.[17] In patients receiving adoptive immunotherapy, galactomannan as a surrogate marker for the invasive fungal disease new decreased significantly earlier as compared to patients not receiving immunotherapy, and only one of 10 patients receiving immunotherapy died as compared to six of the 13 controls. This observation might be transferred to invasive mucormycosis and suggests that the reconstitution of the cellular immunity by the administration of donor-derived antifungal-TH1 cells against mucormycetes could improve the prognosis of allogeneic HSCT recipients suffering from mucormycosis. Our in vitro studies showed that in all healthy individuals tested, a cellular immune response against Rhizopus oryzae could be detected.[18] These interferon (IFN)-γ producing T cells could be enriched and cultivated, and according to the phenotype and cytokine secretion upon restimulation with R.