In spite of the remarkable progress in diagnostic technology and the introduction of more effective and less toxic antifungal agents, invasive fungal infections (IFIs) remain one of the most serious complications after hematopoietic stem cell transplantation (HSCT). The accurate evaluation of patient’s immune status and surrounding environment hold important clues to success in the management of post-transplant IFIs, because host factors have become more diversified and complicated by the expanding indications for HSCT. Balance between efficacy and toxicity of antifungal prophylaxis and treatment should be also maintained, by fully understanding the characteristics of each antifungal agent and targeted pathogen, and by assessing patient’s medical conditions over time. Further improvement of clinical outcome will be achieved by optimizing diagnostic, prophylactic and therapeutic approach based on individual patient’s risk and situation. This review summarizes recent advances in the management of IFIs in HSCT recipients.
Invasive fungal disease (IFD) is one of the life-threatening infectious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Major fungal species are Candida and Aspergillus. Candidiasis mainly develops in the early post-transplant period with neutropenia and mucositis, while Asperigillosis both in the early and later periods. Protective environment effectively prevents aspergillosis and is recommended in the early post-transplant period. Therefore, in the setting of HSCT in protective environment, early-post transplant prophylaxis of IFD should focus mainly on candidiasis. In the later period when acute and chronic graft-versus-host disease develop and the exposure of systemic glucocorticoid would increase the risk of IFD, prophylaxis should focus on aspergillosis. Evidences based on the studies having evaluated the efficacy and safety of several anti-fungal agents in the prophylaxis of IFD after allo-HSCT have been accumulated. In this review, the results of studies of each anti-fungal agent were summarized, and the current status and limitation of prophylaxis of IFD after allo-HSCT in Japan were discussed.
In the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI), the diffusion capacity of carbon monoxide (DLCO) is used for judging the risk of pulmonary disorder. Originally the HCT-CI used the Dinakara equation to adjust DLCO for hemoglobin (Hb). However, the Cotes equation is recommended as the standard method for adjusting DLCO and is more widely used. Recently, it has been reported that the choice between these 2 methods of adjusting DLCO has a significant impact on the HCT-CI results. Therefore we performed a retrospective analysis to determine the influence of the 2 methods of adjusting DLCO for Hb as part of risk assessment by HCT-CI. Correction of DLCO calculated using the Cotes equation showed significantly lower values than using the Dinakara equation. In our study, 75.3% of the cases were judged to have pulmonary dysfunction using the Cotes equation, whereas 77.4% were judged normal using the Dinakara equation. Regarding risk assessment by HCT-CI, 63.4% of the cases were categorized as being higher risk when using the Cotes equation than when using the Dinakara equation. Using different methods for the correction of DLCO makes it difficult to compare the results of clinical studies involving HCT-CI and impairs the credibility of databases.
A 50-year-old male developed acute lymphoblastic leukemia 100 months after allogeneic peripheral blood stem cell transplantation from his HLA-identical sister. A cytogenetic analysis of bone marrow cells revealed a normal karyotype of 46, XX. Therefore, this recipient was diagnosed with donor cell-derived acute lymphoblastic leukemia (DC-ALL). He did not achieve complete remission following chemotherapy, and subsequently underwent unrelated cord blood transplantation (CBT) using myeloablative conditioning. Thirty-four days after CBT, he achieved complete remission for DC-ALL and complete second donor-type engraftment. However, hemodialysis was initiated due to progressive renal failure. He died due to acute circulatory failure 362 days after CBT while maintaining complete remission for DC-ALL. In conclusion, CBT for DC-ALL may represent a promising therapeutic option. However, the further development of supportive care is particularly important in donor cell-derived leukemia patients because fatal complications following second transplantation may develop in these patients.