Post-exchange neutrophil count, but not post-hematocrit, predicts endogenous erythropoiesis in patients with sickle cell disease undergoing chronic red cell exchange.

BACKGROUND: With chronic transfusion in sickle cell disease (SCD), equipoise exists regarding whether increasing the post-procedure hematocrit (Hct) suppresses endogenous erythropoiesis. Reticulocytosis predicts SCD morbidity and mortality, so this study's objective was to clarify the role of the post-procedure Hct in suppressing reticulocytosis and to identify other potential red cell exchange (RCE) parameters predictive of reticulocytosis. STUDY DESIGN AND METHODS: This retrospective analysis of 17 patients who underwent chronic RCE at a single institution between 2014 and 2022 examined both standard red cell exchanges (SRCE) and exchanges preceded by isovolemic hemodilution (IVH-RCE). Post-procedure parameters with biologic plausibility to influence the subsequent procedure's absolute reticulocyte count (sPre-ARC) were examined using regression modeling. RESULTS: Neither post-hematocrit, nor post-hemoglobin (Hb), nor ΔHb/day was associated with sPre-ARC or the change in HbS% per day (ΔHbS%/day). Concurrent Hb was predictive for SRCE but not IVH-RCE, where ARC trended lower than with SRCE. Male gender and post-procedure neutrophil and white cell counts were predictors of sPre-ARC, consistent with their associations with SCD morbidity and mortality. IVH-RCE had a stronger correlation than standard RCE between pre-Hct and neutrophil or white cell depletion. DISCUSSION: Although targeting a post-procedure Hct maintains a higher subsequent pre-procedure Hb and a lower sPre-HbS%, it does not lead to sustained suppression of reticulocytosis as measured by the sPre-ARC or the ΔHbS%/day. IVH-RCE or the addition of hydroxyurea could be considered in those patients with high reticulocyte, white blood cell, or neutrophil counts.

A multi-institutional survey of apheresis services among institutions in the United States.

INTRODUCTION: Apheresis practices in the United States (US) have not been comprehensively characterized to date. This study aimed to address this gap by evaluating apheresis therapy through a national survey. METHODS: A multi-institutional survey was conducted between April and July 2023. The survey, comprising 54 questions, focused on institutional demographics, procedures, equipment, staffing, training, and impacts of the Coronavirus Disease 2019 (COVID-19) pandemic. Responses from 22 institutions, primarily academic medical centers, were analyzed. RESULTS: Therapeutic plasma exchange (TPE) was the most common procedure, followed by hematopoietic progenitor cell collection (HPC-A) and red blood cell exchange (RCE). CAR-T cell collections were widespread, with some institutions supporting over 30 protocols concurrently. Most sites used the Spectra Optia Apheresis System, were managed by a transfusion medicine service, and employed internal apheresis providers. Insufficient staffing levels, exacerbated by the COVID-19 pandemic, were common and most often addressed using overtime. DISCUSSION: The survey highlighted the ubiquity of TPE, expanding cellular collections and staffing challenges. The role of apheresis in supporting cellular therapy, particularly in newly developing cell and gene therapies and clinical trials, was evident. Staffing issues during the pandemic emphasized the need for innovative recruitment strategies. CONCLUSION: This nationwide survey provides the most comprehensive analysis to date of apheresis practices in large US academic centers.

Mixed-field ABO front typing as an early sign of disease recurrence in ABO-matched stem cell transplantation.

ABO group testing is critical for allogeneic stem cell transplantation because mismatches can cause both transfusion and engraftment challenges. Even with ABO-matched donor-recipient pairs, ABO group determination may provide valuable insight into allograft status. Herein, we report a case of a 76-year-old female patient with myeloid neoplasm who underwent ABO-matched stem cell transplantation and in whom mixed-field ABO antigen expression during routine follow-up testing post-transplantation was the first sign of a change in transplant graft status; the mixed-field findings pre-dated changes in formal chimerism testing. This case underscores the potential of mixed-field ABO typing as an early indicator of disease recurrence in ABO-matched stem cell transplants and suggests that, in such cases, more sensitive forms of chimerism testing and/or closer monitoring for disease recurrence, particularly in the clinical setting of myeloid neoplasms, may be warranted.

Prognostic factors associated with COVID-19 related severity in sickle cell disease.

BACKGROUND: Equipoise exists regarding sickle cell disease (SCD) as a risk factor for COVID-19 disease severity and variables that increase risk of COVID-19 severity in SCD. Given our health system's large SCD patient catchment, we analyzed our own experience in this regard. STUDY METHODS: Retrospective analysis of the clinical course and factors associated with need for hospitalization and ICU admission of SCD patients diagnosed with COVID-19 through the Northwell Health system from March 1 to Dec 31, 2020. RESULTS: Of 1098 patients with SCD, 3.3% were diagnosed with COVID-19. Overall rates of hospitalization, ICU admission, cohort mortality, and in-hospital mortality were 80%, 19%, 2.5%,and 3.1%, respectively. By multivariable analysis, hospitalization risk was decreased by 60% for every 1 g/dL increase in admission Hb. ICU admission risk was increased by 84% as a health care worker; increased by 45% for every 1000/uL increase in admission immature granulocyte count; and decreased by 17% with hydroxyurea use. DISCUSSION: High hospitalization rates are compatible with worsened severity upon COVID-19 infection in SCD compared to the general population. Patients should be placed on hydroxyurea to increase their Hb and perhaps lower their neutrophil counts. Health care workers with SCD may warrant special safety precautions.

Therapeutic plasma exchange for hyperviscosity syndrome in IgA multiple myeloma.

Hyperviscosity syndrome (HVS) is defined as the symptomatic presentation of increased blood thickness due to various clinical conditions such as hypergammaglobulinemia. HVS secondary to immunoglobulin (Ig)A multiple myeloma has been infrequently reported. Although the efficiency of IgM or IgG removal by therapeutic plasma exchange (TPE) is well described, the efficiency of IgA removal by TPE is not as well known. Here, we describe a case of HVS due to IgA myeloma in a patient who received 2 TPE treatments, with subsequent symptomatic improvement as well as decrease in IgA and viscosity levels.

Heidenhain variant of Creutzfeldt-Jakob disease masquerading as neuromyelitis optica spectrum disorder: recognizing when apheresis is not the answer.

The Heidenhain variant of Creutzfeld-Jakob disease (CJD) is a rare form that initially presents with visual disturbances. In early stages, the presentation can mimic neuromyelitis optica spectrum disorders (NMOSD) and lead to unnecessary treatment modalities. Herein, we describe a case of a 66-year-old man who presented with bilateral vision loss and retro-orbital discomfort. In addition to immunosuppressive therapy, he received 4 rounds of therapeutic plasma exchange after his preliminary diagnosis of NMOSD. We were surprised to note that his condition did not show improvement but deteriorated, with severe neurocognitive symptoms. Eventually, CJD was suspected, and real-time quaking-induced conversion (RT-QuIC) was performed. By the time the diagnosis of Heidenhain variant of CJD was confirmed, the patient was discharged to hospice care and died shortly after.

Epidermal inclusion cyst in male breast: how to differentiate from other male breast lesions.

Male breast lesions are relatively less common. The most encountered malignant lesion in the male breast is ductal adenocarcinoma; and benign lesions are gynecomastia, fibrocystic disease, intramammary lymph node, fibroadenoma, lipoma and epidermal inclusion cyst (EIC), respectively [5,6]. To date, there had been published only a few cases of EIC of the male breast in literature [3,5,6]. In this case, we aimed to present a new case of EIC with its clinical, radiological and pathological characteristics in the male breast. It had benign sonographic and magnetic resonance imaging findings but had also malignant imaging findings with diffusion restriction on diffusion-weighted imaging.

Utility of TRPS-1 immunohistochemistry in diagnosis of metastatic breast carcinoma in cytology specimens.

INTRODUCTION: At present, GATA binding protein 3 (GATA-3) is the most frequently used diagnostic immunohistochemical (IHC) marker for breast carcinoma (BC). However, it is not specific and has very low sensitivity for triple-negative BC (TNBC). SRY-box transcription factor 10 (SOX-10) and trichorhinophalangeal syndrome type 1 (TRPS-1) have been suggested for inclusion in the diagnostic workup of TNBC. TRPS-1 has not been established in cytology specimens as a diagnostic IHC marker for metastatic BC (MBC). Hence, in the present study we evaluated the utility of TRPS-1 in diagnosing MBC in cytology specimens. MATERIALS AND METHODS: MBC cases diagnosed on cytology specimens from January to October 2020 were included in the present study. Only cases with hormonal status available and ≥20 tumor cells on cell blocks were included in the study. The cell blocks were assessed for TRPS-1, GATA-3, and SOX-10 IHC marker positivity (intensity and percentage of tumor cells). The results were correlated with the specimen type (fine needle aspiration [FNA] versus body fluid) and various BC prognostic subgroups. RESULTS: We analyzed 61 cases, including 33 body fluid and 28 FNA (13 lymph node, 10 bone, 2 liver, 2 soft tissue, and 1 lung) specimens. TRPS-1 had 97.2% positivity in ER/PR+ (estrogen receptor/progesterone receptor-positive) MBC compared with GATA-3, which had 100% positivity in the same group. TRPS-1 showed high positivity in 35 of 37 cases (94.6%) and intermediate positivity in 1 (2.6%) and was negative/low positive in 1 case (2.7%). In contrast, GATA-3 showed high positivity for all 37 cases (100%). SOX-10 showed positivity in only 1 of 37 cases (2.7%), with intermediate positivity. In the HER2+ (human epidermal growth factor receptor 2-positive) group, TRPS-1 showed high positivity in 5 of 7 cases (71.4%), intermediate positivity in 1 case (14.3%), and negativity in 1 case (14.3%). However, GATA-3 showed high positivity in 6 of 7 cases (85.7%) and negative/low positivity in 1 case (14.3%). SOX-10 was negative in all 7 cases. In TNBC, TRPS-1 showed high positivity in 16 of 17 cases (94%) and intermediate positivity in 1 (5.9%), and GATA-3 showed high positivity in 9 (53%), intermediate positivity in 2 (11.8%), and low positive/negative in 6 of the 17 cases (35.3%). TRPS-1 expression was significantly higher than GATA-3 expression for the number of positive cases (P = 0.07), mean percentage of positive tumor cells (P = 0.005), and intensity of reactivity (P = 0.005). SOX-10 expression was present in only 5 of 17 cases (29%), with a mean percentage of positivity in the tumor cells of 26.5% and intensity of 0.8. No differences were found in the IHC results between the different specimen types (FNA versus fluid) in any group. CONCLUSIONS: TRPS-1 is a highly sensitive new diagnostic IHC marker for breast carcinoma, with a similar positivity rate in ER/PR+ and HER2+ BC compared with GATA-3 and a higher positivity rate than GATA-3 and SOX-10 in TNBC in cytology specimens. In particular, when only a few clusters of tumor cells are present on the cell block, TRPS-1 can be highly useful, because its mean percentage of positive tumor cells and intensity are higher than those of other IHC markers.

Is Adenoidectomy and/or Tonsillectomy a Risk Factor for Allergic Diseases and Asthma in Adulthood?

OBJECTIVE: To determine the relationship between adenoidectomy and/or tonsillectomy in childhood and allergic diseases in adulthood. MATERIALS AND METHODS: A survey investigating the history of adenoidectomy and/or tonsillectomy was administered to patients that were followed-up by our department between January and June 2014 with the diagnosis of asthma, allergic rhinitis, urticaria-angioedema, drug allergy, food allergy, and venom allergy; patients willing to participate were included in the study. The relationship and risk ratios were analyzed. RESULTS: Totally, 510 (female/male: 379/131) patients were included in the study: 248 with asthma, 205 with rhinitis, 82 with drug allergy, 73 with urticaria, 24 with food allergy, and 14 with venom allergy. Of these, 65 (12.7%) had undergone adenoidectomy and/or tonsillectomy. Of these 65 patients, 41 had asthma, 33 had allergic rhinitis, and 28 had other allergic diseases. No relation between the history of atopy and adenoidectomy and/or tonsillectomy (p=0.129) was detected; however, there was a positive correlation between asthma and patients aged <15 years having a history of tonsillectomy and/or adenoidectomy (p=0.020). The risk of asthma was determined to be increased by 1.96 fold among the patients, provided the patient had undergone adenoidectomy and/or tonsillectomy (confidence interval [CI]:1.14-3.36). No connection was observed between atopic and non-atopic asthmatic patients in relation to adenoidectomy and/or tonsillectomy (p=0.46). No relationship was observed between allergic rhinitis and adenoidectomy and/or tonsillectomy. CONCLUSION: Adenoidectomy and/or tonsillectomy in childhood increase the risk of asthma in adulthood, whereas it does not increase the risk of atopy. This result signifies the criticality of adenoidectomy or tonsillectomy in the pathogenesis of asthma.