Lymphocyte Crossmatch Testing or Donor HLA-DP and -DQ Allele Typing Effectiveness in Single Cord Blood Transplantation for Patients With Anti-HLA Antibodies Other Than Against HLA-A, -B, -C, and -DRB1.

Anti-human leukocyte antigen (HLA) antibodies other than those against HLA-A, -B, -C, and DRB1 are a risk factor for engraftment delay and failure, especially in cord blood transplantation (CBT). The primary objective of this study was to assess the impact of the presence of anti-HLA antibodies on CBT and to evaluate the utility of lymphocyte crossmatch testing or additional HLA-DP and -DQ typing of CB units in improving transplant outcomes. We retrospectively assessed the engraftment rates and transplant outcomes of 772 patients who underwent their first CBT at our hospital between 2012 and 2021. Donors were routinely typed for HLA-A, -B, -C, and-DRB1 alleles, and the anti-HLA antibodies of recipients were screened before donor selection in all cases. Among patients who had antibodies against other than HLA-A, -B, -C, and DRB1 (n = 58), lymphocyte crossmatch testing (n = 32) or additional HLA-DP/-DQ alleles typing of CB (n = 15) was performed to avoid the use of units with corresponding alleles. The median patient age was 57 years (16 to 77). Overall, 75.7% had a high-risk disease status at transplantation, 83.5% received myeloablative conditioning regimens, and >80% were heavily transfused. Two hundred twenty-nine of the 772 recipients (29.6%) were positive for anti-HLA antibodies. There were no statistical differences in the number of infused CD34-positive cells between the anti-HLA antibody-positive and the anti-HLA antibody-negative patients. Of the 229 patients with anti-HLA antibodies, 168 (73.3%) had antibodies against HLA-A, -B, -C, and-DRB1 (Group A), whereas 58 (25.3%) had antibodies against HLA-DP, HLA-DQ, or -DRB3/4/5 with or without antibodies against HLA-A, -B, -C, and -DRB1 (Group B). No patients in both Groups A and B exhibited donor-specific anti-HLA antibodies against HLA-A, -B, -C, and -DRB1. The neutrophil engraftment rate was lower in patients with anti-HLA antibodies than in those without antibodies (89.9% versus 94.1%), whereas nonrelapse mortality (NRM) before engraftment was higher in antibody-positive patients (9.6% versus 4.9%). In patients who received 2 or more HLA allele-mismatched CB in the host-versus-graft (HVG) direction (n = 685), the neutrophil engraftment rate was lower in the anti-HLA antibody-positive recipients than in the antibody-negative recipients with significant differences (88.8% versus 93.8%) (P = .049). Similarly, transplant outcomes were worse in the antibody-positive patients with respect to 2-year overall survival (OS) (43.1% versus 52.3%) and NRM (44.0% versus 30.7%) than in the antibody-negative patients. In contrast, the results of Group B were comparable to those of the antibody-negative patients, while those of Group A were statistically worse than the antibody-negative patients in terms of all engraftment rate (88.6%), OS (34.2%), and NRM (49.0%). The presence of anti-HLA antibodies negatively impacts engraftment, NRM, and OS in CBT. However, HLA-DP/-DQ allele typing of CB units or lymphocyte crossmatch testing could be a useful strategy to overcome poor engraftment rates and transplant outcomes, especially in patients with anti-HLA antibodies against HLA-DP, HLA-DQ, or -DRB3/4/5.

Fluorescence enhancement of benzimidazolium derivative on clay nanosheets by surface-fixation induced emission (S-FIE).

The photophysical behaviors of benzimidazolium derivative [4-(1,3-dimethylbenzimidazol-3-imu-2-yl)-N, N-diphenylaniline (2-(4-(diphenylamino)phenyl)-1,3-dimethyl-1H-benzo[d]imidazol-3-ium)] (BID) in water, organic solvents and on synthetic saponite were investigated. The fluorescence quantum yield (Φf) of BID was 0.91 on the saponite surface under the optimal condition, while that in water was 0.010. Such fluorescence enhancement on the inorganic surface is called "surface-fixation induced emission (S-FIE)". This fluorescence enhancement ratio for BID is significantly high compared to that of conventional S-FIE active dyes. From the values of Φf and the excited lifetime, the non-radiative deactivation rate constant (knr) and radiative deactivation rate constant (kf) of BID on the saponite surface and in water were determined. Results showed that the factors for fluorescence enhancement were both the increase of kf and the decrease of knr on the saponite surface; especially, knr decreased by more than two orders due to the effect of nanosheets.

[Fulminant Clostridioides difficile infection during treatment with FLT3 inhibitor for acute myeloid leukemia].

An 80-year-old man with FLT3-TKD mutation-positive acute myeloid leukemia (AML) relapsed during consolidation therapy with venetoclax/azacitidine and was started on gilteritinib as salvage therapy. On the day after treatment initiation, febrile neutropenia was observed, but the fever resolved promptly after initiation of antimicrobial therapy. On the fifth day after completion of antimicrobial therapy, the patient experienced fever and watery diarrhea over 10 times a day, and a diagnosis of Clostridioides difficile infection (CDI) was made based on stool examination. The patient was treated with intravenous metronidazole, but renal dysfunction, hypotension, and hypoxemia developed, and a CT scan showed pleural and intraperitoneal effusion, significant intestinal wall thickening, and intestinal dilatation. Fidaxomicin was started under general monitoring in the intensive care unit and response was achieved. The patient was discharged from the intensive care unit on the 18th day after the onset of CDI. We report this case not only due to the rarity of fulminant CDI during AML treatment, but also because it is a valuable example of effective treatment of fulminant CDI with fidaxomicin.

Fatal outcome of BK virus encephalitis in an allogeneic stem cell transplantation recipient.

BK virus (BKV) encephalitis is a rare complication after hematopoietic stem cell transplantation (HSCT). A 43-year-old woman with recurrent follicular lymphoma after autologous HSCT received allogeneic bone marrow transplantation from a human leukocyte antigen-matched related donor. Neutrophil engraftment was achieved on post-transplant day 13. Memory loss and noncooperative attitude toward the medical staff were observed on day 16, and her mental status worsened progressively. Magnetic resonance imaging (MRI) showed nonspecific findings on day 19; however, cerebrospinal fluid (CSF) analysis including real-time polymerase chain reaction on day 20 revealed elevated levels of BKV 4.67 × 104 copy/mL. BKV encephalitis was diagnosed based on CSF findings, intravenous administration of immunoglobulin and cidofovir was started, and the immunosuppressive agent dose was reduced. Diffusion-weighted MRI on day 28 showed signal abnormalities in the bilateral periventricular white matter. Although the follow-up CSF analysis on day 35 was negative for BKV, her mental status and MRI findings did not improve, and she died on day 55 because of respiratory failure. This case emphasizes the importance of considering BKV encephalitis as a differential diagnosis of post-transplant encephalitis, considering the central nervous system-associated immune reconstitution inflammatory syndrome in patients with worsening central nervous system findings after eradication of BKV in the CSF.

Structural Transformation of Azonia[5]helicene Photoproduct via Reaction Field Function of Layered Inorganic Material.

In an attempt to generalize "on surface synthesis", which has unique potential in the area of organic synthesis, the focus was placed on layered silicates having a highly flat surface. The photoreaction of (±)-13-bromo-6a-azonia[5]helicene (AHHBr) and (±)-2-bromo-13-methyl-6a-azonia[5]helicene (AHBrMe) in solution and within the layers was examined. In the case of AHBrMe, the photoproduct was different from that in solution. 1H nuclear magnetic resonance (NMR), Fourier transform-infrared spectroscopy (FT-IR), and electrospray ionization-mass spectrometry (ESI-MS) measurements revealed that the photoproduct obtained within the layers was a benzo-perylene molecule with a completely flat lactone structure (AL). This study is the first example of the successful conversion of a chemical reaction path due to the steric effect of the flat surface of layered silicate.

Long-term lymphocyte subset number reconstitution is unique but comparable between umbilical cord blood and unrelated bone marrow transplantation.

The number of umbilical cord blood transplantation (U-CBT) procedures has been growing annually, but little research has been done on long-term immune recovery after U-CBT. Infection risk is high in U-CBT recipients, and this can be partially attributed to immature immunocompetent cells in umbilical cord blood. In this study, we analyzed lymphocyte subset (LST) number to determine the long-term recovery timeline. We included 36 U-CBT and 10 unrelated bone marrow transplantation (U-BMT) recipients who survived more than 2 years after transplantation, and followed them for up to 10 years post-transplant. Recovery kinetics in the early phase post-transplant was different for each LST. Recovery of CD19+ B cells was faster after U-CBT than after U-BMT in the first 5 years after transplantation. Although CD4+ T cells increased in the first several months after U-CBT, long-term cell count recovery was impaired in approximately 20% of patients. Thus, although the LST recovery pattern after U-CBT was unique, LST number recovery was statistically comparable between U-CBT and U-BMT past 5 years post-transplantation.

Monolayer Modification of Spherical Amorphous Silica by Clay Nanosheets.

Clay-silica nanocomposite materials (CSiN) were prepared by an electrostatic interaction between negatively charged clay nanosheets and positively charged spherical silica, which was modified with an alkyl ammonium group by silane coupling. By optimization of the preparation conditions, 84% coverage of the silica surface by the clay nanosheets was achieved. Adsorption experiments using cationic porphyrin dyes on the CSiN revealed that the clay nanosheet covers the spherical silica as a single layer and does not detach from the silica surface under aqueous conditions. In addition, it turned out that the cationic porphyrin dye did not penetrate the space between the silica surface and the clay nanosheet. Porphyrin molecules were adsorbed only at the outer surface of the clay nanosheet without molecular aggregation even under the high-density adsorption conditions. By combining spherical silica and clay nanosheets, it is possible to prepare novel hybrid materials where the surface can act as a unique adsorption field for dyes.

A case report of a truncated ABL1 mutation in 2 cases with Philadelphia chromosome-positive B cell precursor acute lymphoblastic leukemia.

Acquired point mutations in the ABL1 gene are widely recognized as a cause of Philadelphia chromosome-positive B cell precursor acute lymphoblastic leukemia (Ph+ B-ALL) that is resistant to tyrosine kinase inhibitors, whereas there are few reports about other types of the ABL1 mutation. Here, we report 2 cases of Ph+ B-ALL gaining a partial deletion type mutation of the ABL1 gene (Δ184-274 mutation), which resulted in truncation of the ABL1 molecule and loss of kinase activity. In both cases, the disease was refractory to multiple agents in the recurrent phase after allogeneic hematopoietic cell transplantation. This is a case report of a truncated ABL1 mutation in 2 patients with Ph+ B-ALL.

Decoration of Gold and Platinum Nanoparticle Catalysts by 1 nm Thick Metal Oxide Overlayer and Its Effect on the CO Oxidation Activity.

Exfoliated M-Al layered double hydroxide (M-Al LDH; M = Mg, Co, Ni, and Zn) nanosheets were adsorbed on Au/SiO2 and calcined to transform LDH into mixed metal oxides (MMOs) and yield Au/SiO2 coated with a thin MMO overlayer. These catalysts showed a higher catalytic activity than pristine Au/SiO2. In particular, the 50% CO conversion temperature decreased by more than 250 °C for Co-Al MMO-coated Au/SiO2. In contrast, the deposition of CoAlOx on Au/SiO2 by impregnation or the deposition of Au on Co-Al MMO-coated SiO2 resulted in a worse catalytic activity. Moreover, the presence of a thick MMO overlayer decreased the catalytic activity, suggesting that the control of the overlayer thickness to less than 1 nm is a requisite for obtaining a high catalytic activity. Moreover, the thin Co-Al MMO overlayer on Au/SiO2 possessed abundant oxygen vacancies, which would play an important role in O2 activation, resulting in a highly active interface between Au and the defect-rich MMO on the Au NP surface. Finally, this can be applied to Pt/SiO2, and the obtained Co-Al MMO-coated Pt/SiO2 also exhibited a much improved catalytic activity for CO oxidation.

Evaluation of the pharmacokinetics of liposomal amphotericin B and analysis of the relationship between pharmacokinetics, efficacy and safety in patients with hematological diseases.

INTRODUCTION: This study aimed to identify factors responsible for changes in blood concentrations of a liposomal formulation of amphotericin B (AMPH-B, L-AMB) and analyze the relationships between blood concentrations and efficacy or toxicity. METHODS: L-AMB was administered to 30 patients being treated for hematological diseases. AMPH-B plasma concentrations were determined right before the initiation (Cmin) and at the end (Cmax) of infusion on at least 1 day, beginning on Day 3 of L-AMB treatment. The relationships of Cmin divided by dose (C/D ratio) to body weight, age, hepatic function, renal function, serum albumin, C-reactive protein (CRP), response, hypokalemia, and renal impairment were evaluated. RESULTS: C/D ratio was not correlated with age, hepatic function, renal function, or serum albumin. Body weight adjusted C/D ratio was negatively correlated with CRP. Cmax and Cmin were compared between responders and non-responders, those with or without hypokalemia, and those with or without renal impairment. A higher Cmax in patients with hypokalemia was the only significant difference seen. CONCLUSIONS: The negative correlation between CRP and plasma concentrations was likely caused by higher distribution of L-AMB from the blood to infected tissue in patients with a greater degree of infection, with a resulting decrease in plasma concentrations. AMPH-B plasma concentrations were not related to response. Higher Cmax of AMPH-B were observed in patients with hypokalemia, but no relationship between plasma concentration and renal toxicity was observed, suggesting that AMPH-B plasma concentrations appear to be minimally related to PD when used as L-AMB.

A Case of Closed Pilon Fracture Resulting in Soft-Tissue Necrosis and Treated with Reverse Sural Artery Flap and Circular External Fixation.

Tibial pilon fractures are difficult to treat due to articular comminution and soft-tissue injuries caused by high-energy trauma. Open reduction and internal fixation is a commonly used method of treatment. However, it has a high risk of infection and soft-tissue complications due to the extensive detachment of soft tissue. We report on a case with a tibial pilon fracture and soft-tissue necrosis that we treated using limited internal fixation combined with a circular external fixator (LIFCEF) and reverse sural artery flap (RSAF) as part of an orthoplastic approach within the orthopedic surgery department alone, which obtained good results. A 51-year-old man was injured in a motorcycle accident and transported to a nearby hospital. X-rays at the time of injury showed tibial pilon fractures (AO Foundation/Orthopedic Trauma Association 43c3.3, Ruedi-Allgower: Type III). Soft-tissue necrosis with blisters on the medial side of the lower leg (AO soft-tissue classification: IC3-MT1-NV1) was observed. In addition, the patient was referred to our hospital on day 10 of the injury. LIFCEF was chosen for treating the fracture because plate fixation was accompanied by the risk of plate exposure, soft-tissue complications, and an increased skin defect area, and RSAF was chosen to reconstruct the soft tissue defect. Four years after the surgery, the American Orthopedic Foot and Ankle Score was 92 points. X-ray alignment evaluation showed mLDTA 93° and aADTA 91°. Stage 2 arthrosis was present according to the Takakura ankle osteoarthritis classification, but the patient was able to walk without pain. Tibial pilon fractures are difficult to treat due to articular comminution and soft-tissue injuries caused by high-energy trauma. The timing and choice of treatment are crucial concerning the soft tissue.

Gold/Substituted Hydroxyapatites for Oxidative Esterification: Control of Thin Apatite Layer on Gold Based on Strong Metal-Support Interaction (SMSI) Results in High Activity.

Gold nanoparticles (Au NPs) deposited on various cation- and anion-substituted hydroxyapatites (Au/sHAPs) show oxidative strong metal-support interaction (SMSI), wherein a thin layer of the sHAP covered the surface of the Au NPs by heat treatment in an oxidative atmosphere. Calcination of Au/sHAPs at 300 °C caused a partial SMSI and that at 500 °C gave fully encapsulated Au NPs. We investigated the influence of the substituted ions in sHAP and the degree of the oxidative SMSI on the catalytic performance of Au/sHAPs for oxidative esterification of octanal or 1-octanol with ethanol to obtain ethyl octanoate. The catalytic activity depends on the size of the Au NPs but not on the support used, owing to the similarity of the acid and base properties of sHAPs except for Au/CaFAP. The presence of a large number of acidic sites on CaFAP lowered the product selectivity, but all other sHAPs exhibited similar activity when the Au particle size was almost the same, owing to the similarity of the acid and base properties. Au/sHAPs_O2 with SMSI exhibited higher catalytic activity than Au/sHAPs_H2 without SMSI despite the fact that the number of exposed surface Au atoms was decreased by the SMSI. In addition, the oxidative esterification reaction proceeded even though the Au NPs were fully covered by the sHAP layer when the thickness of the layer was controlled to be less than 1 nm. The substrate can access the surfaces of the Au NPs covered by the thin sHAP layer (<1 nm), and the presence of the sHAP structure in close contact with the Au NPs resulted in significantly higher catalytic activity compared with that for fully exposed Au NPs deposited on the sHAPs. This result suggests that maximizing the contact area between the Au NPs and the sHAP support based on the SMSI enhances the catalytic activity of Au.

Post-traumatic Aeromonas hydrophila Osteomyelitis caused by an Infected Gustilo-Anderson Grade 3B Tibial Fracture: A Case Report with a 7-year Follow-up.

Introduction: Post-traumatic osteomyelitis (OM) is often caused by Staphylococcus aureus. However, occasionally, it is caused by an infection with a rare bacterium. A case of OM caused by Aeromonas hydrophila was first reported in 1975. Since then, only nine cases have been reported, making it a rare disease. Here, we report a case of rare A. hydrophila OM that developed following open tibial fracture (classified as Gustilo-Anderson 3B) caused by an injury in a river. Case Report: The patient was a 50-year-old male who got injured in a river and was diagnosed with open tibial fracture. Debridement in the first surgery happened at a leisurely pace. Purulent discharge from the wound persisted despite external fixation; however, no bacterium was detected in the bacterial culture. The patient underwent multiple debridement procedures; A. hydrophila was detected in the bone marrow. Despite the appropriate administration of antibacterial drugs and debridement, infection persisted until radical bone resection and tissue reconstruction were performed. In the present case, OM following an open fracture caused by an injury in a river was suspected, which was caused by the rare bacterium A. hydrophila. Conclusion: In cases of OM occurring after underwater trauma, A. hydrophila should be considered as a causative pathogen. In addition, in cases of post-traumatic OM accompanied by bone and soft-tissue defects, the orthoplastic approach is required.

Rituximab/bendamustine/cytarabine for transplant-eligible patients with mantle cell lymphoma: A retrospective study.

BACKGROUND: Mantle cell lymphoma is considered an aggressive B-cell lymphoma. The optimal induction regimen remains controversial as no randomized controlled trial has compared the efficacy of different induction therapies. METHOD: Herein, we performed a retrospective analysis of the clinical characteristics of 10 patients who received induction treatment consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, bendamustine, and cytarabine (R-BAC) at Toranomon Hospital between November 2016 and February 2022. RESULT: Although one patient discontinued R-BAC therapy due to a rash, the other nine completed the scheduled chemotherapy. All patients achieved complete response, underwent high-dose chemotherapy and autologous stem cell transplantation, and maintained complete remission with a median follow-up of 15 months. Hematological adverse events (AEs) occurred in all patients; however, none developed documented infection. There were also no fatal non-hematological AEs specific to R-BAC. CONCLUSION: R-CHOP/R-BAC may be a good induction therapy for transplant-eligible patients with mantle cell lymphoma.

Predictive scoring system for distinguishing Stenotrophomonas maltophilia bacteremia from Pseudomonas aeruginosa bacteremia in patients with hematological malignancies.

Difficulties in immediately distinguishing Stenotrophomonas maltophilia (SM) bacteremia from Pseudomonas aeruginosa (PA) bacteremia in the clinical setting can lead to treatment delay. We aimed to develop a scoring system to immediately distinguish SM bacteremia from PA bacteremia using clinical indicators. We enrolled cases of SM and PA bacteremia in adult patients with hematological malignancies between January 2011 and June 2018. The patients were randomized into derivation and validation cohorts (2:1), and a clinical prediction tool for SM bacteremia was developed and verified. In total, 88 SM and 85 PA bacteremia cases were identified. In the derivation cohort, the following independent predictors of SM bacteremia were identified: no evidence of PA colonization, antipseudomonal ß-lactam breakthrough bacteremia, and central venous catheter insertion. We scored each of the three predictors according to their regression coefficient (2, 2, and 1, respectively). Receiver operating characteristic curve analysis confirmed the score's predictive performance, with an area under the curve of 0.805. The combined sensitivity and specificity (0.655 and 0.821) was highest with a cut-off value of 4 points. Positive and negative predictive values were 79.2% (19/24) and 69.7% (23/33), respectively. This novel predictive scoring system is potentially useful for distinguishing SM bacteremia from PA bacteremia, which would facilitate immediate administration of appropriate antimicrobial therapy.

[Allogeneic hematopoietic cell transplantation for myelofibrosis: current status and future challenges].

Remarkable progress has been made in the field of myelofibrosis recently. Along with the use of driver gene mutations for diagnosis of myelofibrosis, non-driver gene mutations that affect its prognosis have also been identified, and new prognostic models based on them have been proposed. Furthermore, several important findings have been reported across diverse research fields, such as determining the appropriate modality for reducing splenomegaly before transplantation either by splenectomy or drug therapy, pre-transplant conditioning and donor selection, and long-term follow-up after transplantation. However, due to the relative rarity of myelofibrosis, it is difficult to keep up with the latest findings and develop the best clinical treatment regimens for patients. The purpose of this study is to summarize the current status and recent findings in transplantation therapy for myelofibrosis and to identify the challenges faced during treatment.

Clinical and microbiological characteristics of bacterial meningitis in umbilical cord blood transplantation recipients.

Bacterial meningitis is a rare but severe infectious complication after hematopoietic stem cell transplantation. However, its clinical features were previously not clear. We reviewed the cases of 7 patients diagnosed with bacterial meningitis with a positive cerebrospinal fluid culture among 1147 patients who underwent cord blood transplantation (CBT) at our institution between September 2007 and September 2020. The diagnosis was made on day + 5- + 45, and 5 patients developed bacterial meningitis before neutrophil engraftment. The causative organisms were all Gram-positive cocci: Enterococcus faecium and Enterococcus gallinarum (2 patients each), and Staphylococcus haemolyticus, Streptococcus mitis/oralis, and Rothia mucilaginosa (1 patient each). Six patients developed bacterial meningitis secondary to prior or concomitant bacteremia caused by the same bacterium. Five patients had received anti-MRSA agents at onset: vancomycin in 3, teicoplanin in 1, and daptomycin in 1. After diagnosis of bacterial meningitis, linezolid was eventually used for 6 patients. Two patients with E. gallinarum were alive at day + 1380 and + 157 after CBT, respectively, whereas 5 patients died 17-53 (median 43) days after the onset of bacterial meningitis. Breakthrough meningitis in CBT can occur even during the use of anti-MRSA drugs, and intensive antibiotic treatment is necessary.

Factors Associated with Breakthrough Fungemia Caused by Candida, Trichosporon, or Fusarium Species in Patients with Hematological Disorders.

Limited data are available on breakthrough fungemia, defined as fungemia that develops on administration of antifungal agents, in patients with hematological disorders. We reviewed the medical and microbiological records of adult patients with hematological diseases who had breakthrough fungemia between January 2008 and July 2019 at Toranomon Hospital and Toranomon Hospital Kajigaya in Japan. A total of 121 cases of breakthrough fungemia were identified. Of the 121 involved patients, 83, 11, 5, and 22 were receiving micafungin, voriconazole, itraconazole, and liposomal amphotericin B, respectively, when the breakthrough occurred. Of the 121 causative breakthrough fungal strains, 96 were Candida species, and the rest were 13 cases of Trichosporon species, 7 of Fusarium species, 2 of Rhodotorula mucilaginosa, and 1 each of Cryptococcus neoformans, Exophiala dermatitidis, and Magnusiomyces capitatus. The crude 14-day mortality rate of breakthrough fungemia was 36%. Significant independent factors associated with the crude 14-day mortality rate were age of ≥60 years (P = 0.011), chronic renal failure (P = 0.0087), septic shock (P < 0.0001), steroid administration (P = 0.0085), and liposomal amphotericin B breakthrough fungemia (P = 0.0011). An absolute neutrophil count of >500/µL was significantly more common in candidemia in the multivariate analysis (P = 0.0065), neutropenia and nonallogeneic hematopoietic stem cell transplants were significantly more common in Trichosporon fungemia (P = 0.036 and P = 0.033, respectively), and voriconazole breakthrough fungemia and neutropenia were significantly more common in Fusarium fungemia (P = 0.016 and P = 0.016, respectively). The epidemiological and clinical characteristics of breakthrough fungemia of patients with hematological disorders were demonstrated. Some useful factors to predict candidemia, Trichosporon fungemia, and Fusarium fungemia were identified.

Clinical and Microbiological Characteristics of Proven Invasive Aspergillosis Due to Rare/Cryptic Species in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

There are few reports on the clinical course of proven invasive aspergillosis (IA) due to rare/cryptic species in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. We retrospectively reviewed the electronic medical records of patients who underwent allo-HSCT between January 2012 and December 2018. Of 934 allo-HSCT recipients, 10 were diagnosed with proven IA and 61 were diagnosed with probable IA. DNA sequencing was performed in cases of proven IA, and Aspergillus could be identified to the species level in 8 of the 10 cases. Three were due to A. fumigatus, and 5 were due to rare/cryptic Aspergillus species, namely, A. turcosus, A. felis, A. viridinutans, A. nidulans, and A. calidoustus. In these 8 patients, no patients with IA due to A. fumigatus died, whereas 3 of the 5 with IA due to rare/cryptic species died within 12 weeks. The 2 surviving cases of IA due to rare/cryptic species were treated with surgical resection and antifungal treatment. Susceptibility testing for cryptic species in 4 cases showed an amphotericin B MIC > 1 mg/L in 3 cases, itraconazole MIC > 1 mg/L in 2 cases, and voriconazole MIC > 1 mg/L in 2 cases. In conclusion, more than half of the causative pathogens of proven IA were rare/cryptic species, so it is important to accurately identify the Aspergillus species. In addition, surgical treatment might be an important option in cases of proven IA, given the possibility that the causative organisms are azole-resistant A. fumigatus or rare/cryptic species.