High Rates of Community and Hospital Acquired Infections in Patients with Cellular Immunodeficiencies

Purpose

Patients with primary immunodeficiency diseases (PID) are perceived to be at high risk for acquiring as well as developing complications from infections. There is little data describing the infection type and frequency these patients may acquire in the community or during hospital admissions. Data is critically needed in order to inform best practices on how to protect these vulnerable patients.

Methods

This is a retrospective study which included PID patients who were discharged from Children’s National Health System (CNHS) from January 1, 2011, through August 31, 2017, and were assigned a discharge diagnosis code indicating PID. Hospitalizations that occurred in the study period were reviewed to extract information on the type of infections upon admission and during hospitalization. The rate of hospital acquired infections (HAIs) was calculated by the number of HAIs divided by the total number of days between date of admission and date of discharge or receiving the first bone marrow transplant, whichever the one came first. The rates were then compared to the HAI rate among oncology patients receiving treatment at CNHS during the same study period.

Results

During this study period, 33 PID patients were admitted 80 times for a total of 1855 patient days. Of these 80 admissions, 31 were due to an infection. Ten of the 31 admissions with severe combined immunodeficiency disease (SCID) were infection related, 4/4 in ectodermal dysplasia with immunodeficiency due to gain of function mutation (IkappaBalpha) patients, 8/10 in Wiskott-Aldrich patients, 1/2 in STAT3 mutation patients, 1/1 in Hyper IGM patient, 1/5 in severe chronic active EBV (SCAEBV) patients, 1/1 NK defect, 2/21 in primary hemophagocytic lymphohistiocytosis patients, 3/4 chronic granulomatous disease, and 0/1 congenital neutropenia. HAI occurred in 11 out of 80 admissions (13.75%). Patients with SCID had the highest HAI rate of 13.09 per 1000 patient days, followed by SCAEBV (11.10), IkappaBalpha (6.58), and Wiskott-Aldrich (4.91). Comparing to oncology patients in which the HAI rate was 0.92 per 1000 patient days. SCID patients had 11.7 (95% confidence interval 3.7–29; p?<?0.001) and T cell defects excluding SCID had 4.8 (95% CI 1.0–14.8; p?=?0.03) times greater risk of acquiring an infection during a hospitalization.

Conclusions

Patients with severe T cell defects such as SCID are at greater risk for infections in the community and in hospital settings. Additional infection prevention measures are likely needed when caring for these patients in a clinic or as an inpatient. Further studies are urgently needed to determine the most appropriate measures for these patients.

     

Staging Systems for Newly Diagnosed Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplantation: The Revised International Staging System Shows the Most Differentiation between Groups

The Revised International Staging System (R-ISS) and the International Myeloma Working Group 2014 (IMWG 2014) are newer staging systems used to prognosticate multiple myeloma (MM) outcomes. We hypothesized that these would provide better prognostic differentiation for newly diagnosed multiple myeloma (MM) compared with ISS. We analyzed the Center for International Blood and Marrow Transplant Research database from 2008 to 2014 to compare the 3 systems (N?=?628) among newly diagnosed MM patients undergoing upfront autologous hematopoietic cell transplantation (AHCT). The median follow-up of survivors was 48 (range, 3 to 99) months. The R-ISS provided the greatest differentiation between survival curves for each stage (for overall survival [OS], the differentiation was 1.74 using the R-ISS, 1.58 using ISS, and 1.60 using the IMWG 2014) . Univariate analyses at 3 years for OS showed R-ISS I at 88% (95% confidence interval [CI], 83% to 93%), II at 75% (95% CI, 70% to 80%), and III at 56% (95% CI, 3% to 69%; P < .001). An integrated Brier score function demonstrated the R-ISS had the best prediction for PFS, though all systems had similar prediction for OS. Among available systems, the R-ISS is the most optimal among available prognostic tools for newly diagnosed MM undergoing AHCT. We recommend that serum lactate dehydrogenase and cytogenetic data be performed on every MM patient at diagnosis to allow accurate prognostication.     

Primary gastroesophageal-ileal hodgkin lymphoma

Primary Hodgkin lymphoma of the gastrointestinal tract is exceedingly rare to the point that some authors regard with skepticism the existence of this entity. Cases of gastrointestinal Hodgkin lymphoma have been reported previously; however, most of these cases represented secondary involvement of the digestive tract in the context of systemic disease. Other cases have been reclassified in retrospective studies as non-Hodgkin lymphomas after the application of immunohistochemical techniques. We report a case of primary Hodgkin lymphoma of the gastrointestinal tract in a patient who presented with obstructive symptoms at the site of a gastroileal bypass; the bypass had been performed years earlier because of morbid obesity. Some non-Hodgkin lymphomas may morphologically mimic Hodgkin lymphoma and vice versa; therefore, an accurate pathologic diagnosis is important, since the therapeutic approach and prognostic implications differ significantly for these diseases. In this context, immunohistochemistry should be used to confirm or to exclude the histologic diagnosis of Hodgkin lymphoma.     

Serum TABM produced during anterior chamber-associated immune deviation passively transfers suppression of delayed-type hypersensitivity to primed mice

Injection of soluble protein antigen into the anterior chamber of the eye of primed mice induces anterior chamber-associated immune deviation (ACAID) which is manifested by suppression of delayed-type hypersensitivity (DTH) to the antigen. Recently, we found that ACAID induced in primed mice also results in a rapid rise in serum of soluble T lymphocyte-derived proteins specific for nominal antigen (TABM). Here, we demonstrate that serum TABM induced in primed mice during ACAID will transfer the suppression of DTH to mice primed to the same antigen. Sera from TNP-BSA-primed mice that received an anterior chamber injection of TNP-BSA, but not BSA alone, suppressed the DTH response to TNP when injected into other TNP-BSA-primed mice. Sera absorbed with Sepharose beads conjugated with either anti-TCR C(alpha), anti-TCR C(beta), anti-TABM or TNP-BSA did not contain TNP-specific TABM and did not transfer suppression of DTH. These results suggest that the antigen-specific, TCR C(alphabeta)+ TABM that appear in serum during ACAID are able to confer on or amplify the capacity of sensitized T cells to suppress DTH. We believe this to be the first demonstration of an in vivo immunologic function that is specifically associated with TABM produced in vivo.      

ThinPrep evaluation of fluid samples aspirated from cystic ovarian masses

The cytological evaluation of ovarian cystic fluid using ThinPrep has not been reported. To determine the diagnostic accuracy of ThinPrep cytology in distinguishing between benign and nonbenign ovarian cystic lesions, we examined 65 fluid samples aspirated during intraoperative consultation with subsequent histologic correlation. One ThinPrep slide was prepared from each sample aspirated from surgically removed ovarian cystic masses and reviewed blindly by a panel of three cytopathologists. The parameters used in cytological evaluation were cellularity, cell types, cellular arrangement, and background. Four samples were acellular and excluded from the study. The consensus cytologic diagnoses were compiled for 61 cases which were assigned to one of the following diagnostic categories: negative for malignant cells (40 cases), atypical cytology (13 cases), and suspicious or positive for malignancy (8 cases). Histologic correlation of the cytological benign/negative cases showed that 26/40 (65%) were histologically benign and 14/40 were false-negative (35%, 5 carcinomas and 9 borderline tumors) with 10 of these cases being mucinous tumors. Most false-negative cytologic samples (11/14 or 79%) did not have an epithelial component. Of the 21 cytological nonbenign diagnoses (atypical/suspicious/positive), 15 (71%) were confirmed on histology (10 carcinomas and 5 borderline tumors). However, a nonbenign cytologic diagnosis was rendered in 6 histologically benign cases, including 2 serous cystadenomas, 1 mucinous cystadenoma, 1 serous cystadenofibroma, 1 endometriosis, and 1 corpus luteal cyst. The diagnostic sensitivity by ThinPrep evaluation of ovarian cystic masses is 81% (26/32) for benign and 52% (15/29) for nonbenign lesions. Our results concluded that ThinPrep examination of ovarian cystic fluid is not accurate in distinguishing benign from malignant cysts, given the significant number of false-negative diagnoses. Major contributing factors include sparse cellularity of the fluid samples and mucinous differentiation of the tumors.