Epidemiology and Factors Associated with Treatment Success of Invasive Fungal Infections Among Newly Hematologic Malignancy Patients Receiving Chemotherapy or Hematopoietic Stem Cell Transplant in Thailand.

Purpose: Invasive fungal infection (IFI) causes disability/death in patients with hematologic malignancy (HM) receiving chemotherapy or hematopoietic stem cell transplant (HSCT). There is limited epidemiological data, treatment outcomes, and factors associated with IFI treatment success in Thailand. This study aimed to identify factors associated with IFI treatment success among new HM patients receiving chemotherapy or HSCT, determine IFI incidence among HM patients receiving chemotherapy or HSCT, and the IFI incidence of a breakthrough in patients receiving primary antifungal prophylaxis, and identify antifungal drugs susceptibility. Patients and Methods: This study reviewed the charts of patients aged ≥ 15 years with newly HM who received chemotherapy or HSCT between January 2016 and June 2021 at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. The 2020 EORTC/MSG criteria were used to diagnose IFI. IFI treatment success factors were evaluated using logistic regression. Results: Ninety-two patients with 107 episodes of IFI met the inclusion criteria. IFI incidence on proven and probable cases among newly HM patients receiving chemotherapy or HSCT was 7%. Most infections (38.3%) occurred during the induction-phase chemotherapy. Aspergillosis (35.5%) was the commonest IFI, followed by candidiasis (11.2%), Pneumocystis jirovecii pneumonia (8.4%), mucormycosis (3.7%), and others, respectively. The 12-week IFI treatment success rate was 67.3%. It was associated with age < 60 years, absence of coinfection, and the receipt of appropriate empirical therapy on the first day of IFI diagnosis. The incidence of breakthrough IFI from proven and probable cases in patients receiving primary antifungal prophylaxis was 6.1%. Most fungal pathogen isolates were still highly susceptible to antifungal drugs. Conclusion: The IFI treatment success in patients with HM or HSCT in our study was high. Close monitoring of coinfected patients aged ≥ 60 is recommended. Appropriate antifungal drugs are essential for clinical outcomes.

Post-transplant Lymphoproliferative Disorder of Naso-orbital Region in Adult Renal Transplant Recipients: A Case Report and Literature Review.

Post-transplant lymphoproliferative disorder (PTLD) is an uncommon but fatal complication following both solid organ and hematologic stem cell transplantations. Epstein-Barr virus (EBV) has been considered a main etiologic agent causing PTLD, especially in the first year after transplantation. Extranodal manifestations are frequently found in PTLD; however, naso-orbital involvement in adults is rare. We report a case of EBV-associated PTLD of the naso-orbital region in a 72-year-old patient that occurred 10 years after kidney transplant. Six additional adults with naso-orbital PTLD were identified after completing this literature review, including 2 cases with eyelid swelling, 3 cases with proptosis, and 1 case with facial numbness. The majority of cases occurred after 1 year of transplantation and were associated with EBV. This report emphasizes recognizing PTLD as differential diagnosis in transplant recipients who present with naso-orbital symptoms.

Common viral infections in kidney transplant recipients.

Infectious complications have been considered as a major cause of morbidity and mortality after kidney transplantation, especially in the Asian population. Therefore, prevention, early detection, and prompt treatment of such infections are crucial in kidney transplant recipients. Among all infectious complications, viruses are considered to be the most common agents because of their abundance, infectivity, and latency ability. Herpes simplex virus, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, hepatitis B virus, BK polyomavirus, and adenovirus are well-known etiologic agents of viral infections in kidney transplant patients worldwide because of their wide range of distribution. As DNA viruses, they are able to reactivate after affected patients receive immunosuppressive agents. These DNA viruses can cause systemic diseases or allograft dysfunction, especially in the first six months after transplantation. Pretransplant evaluation and immunization as well as appropriate prophylaxis and preemptive approaches after transplant have been established in the guidelines and are used effectively to reduce the incidence of these viral infections. This review will describe the etiology, diagnosis, prevention, and treatment of viral infections that commonly affect kidney transplant recipients.

B-cell activating factor, a predictor of antibody mediated rejection in kidney transplantation recipients.

AIM: Donor-specific antibody (DSA) is a widely-used biomarker for antibody-mediated rejection (ABMR) but correctly indicates only 30-40% of patients with ABMR. Additional biomarkers of ABMR in kidney transplant recipients are needed. METHODS: All 68 kidney transplanted-recipients enrolled in this study were negative for graft rejection as determined by surveillance-biopsy ELISA at day 7 post-transplantation. Allograft biopsy was then performed at 6 months post-transplantation for subclinical-ABMR detection. Recipients were stratified by pre-transplant DSA and BAFF at day 7 into four groups. RESULTS: During the study period, 13.2% of the recipients demonstrated subclinical-ABMR at 6 months, without patient with clinical ABMR presentations. Overall mean BAFF at day 7 was 393 pg/mL (95% CI = 316-471 pg/mL). The optimal cut-off value for low vs. high BAFF level was 573 pg/mL, with sensitivity and specificity at 77.8% and 88.1%, respectively. Fifty percent of recipients with high BAFF at day 7 (14 patients) and only 3.7% of patients with low BAFF demonstrated ABMR (P < 0.05). Indeed, ABMR was more common in patients high BAFF level (hazard ratio = 7.30; 95% CI = 3.77-14.15). The prevalence of ABMR among negative pre-transplant DSA/low BAFF, positive DSA/low BAFF, negative DSA/high BAFF, and positive DSA/ high BAFF recipients were 4.4, 0, 37.5 and 66.7%, respectively (P < 0.05). CONCLUSIONS: Post-transplant ABMR can be predicted by perioperative serum BAFF level. Together with DSA testing, BAFF provides additional predictive value for ABMR.

Anti-GM-CSF autoantibodies in patients with cryptococcal meningitis.

Cryptococcal meningitis has been described in immunocompromised patients, as well as in those for whom no immune defect has been identified. GM-CSF regulates the function of phagocytes and pulmonary alveolar macrophages, critical elements in cryptococcal control. We performed clinical histories, immunological evaluation, and anticytokine autoantibody screening in four current patients with cryptococcal meningitis and identified and tested 103 archived plasma/cerebrospinal fluid samples from patients with cryptococcal meningitis. We assessed the ability of anti-GM-CSF autoantibody-containing plasmas to inhibit GM-CSF signaling. We recognized anti-GM-CSF autoantibodies in an otherwise healthy female with cryptococcal meningitis who later developed pulmonary alveolar proteinosis (PAP). Her diagnosis prompted screening of patients with cryptococcal meningitis for anticytokine autoantibodies. We identified seven HIV-negative patients with cryptococcal meningitis who tested positive for high-titer anti-GM-CSF autoantibodies. Two of the seven later developed evidence of PAP. Plasma from all patients prevented GM-CSF-induced STAT5 phosphorylation and MIP-1α production in normal PBMCs. This effect was limited to their IgG fraction. Anti-GM-CSF autoantibodies are associated with some cases of cryptococcal meningitis in otherwise immunocompetent patients. These cases need not have associated PAP.

Basal ganglia and brainstem encephalitis, optic neuritis, and radiculomyelitis in Epstein-Barr virus infection.

The neurologic complications of Epstein-Barr virus (EBV) infection are rare. We describe a healthy adult with acute EBV meningoencephalomyeloradiculitis. The clinical manifestations, a serologic study, and a dynamic change of EBV DNA in the cerebrospinal fluid with spontaneous recovery confirmed the diagnosis of EBV infection of the nervous system. In addition, we provide other clinical clues for suspicion of EBV infection in patients with encephalitis. These include bilateral basal ganglia and brainstem lesions on magnetic resonance imaging, optic neuritis, or involvement of all levels of the nervous system.