Faculty Bibliography

Background: Numerous predictors of poor outcome in COVID-19 patients have been identified, including alterations in the composition of leukocytes in the peripheral blood. There nonetheless remains a need to improve predictions of patient outcomes following hospitalization in order to appropriately triage patients. We addressed this question by evaluating hematologic parameters and peripheral blood smear morphology in patients who either died or recovered following hospitalization.
Design(s): The study groups included 48 patients who died following admission ("cases") and 48 age-matched controls who recovered ("controls"). Laboratory values were collected for PCR-positive COVID-19 hospitalized patients at two time points: T1- the time of admission, and T2 - the time of discharge/death. Peripheral blood smears from two-time points for patients who died were analyzed independently by 4 pathologists.
Result(s): Study patient demographic details are shown in Table 1. Anemia and thrombocytopenia were present at the time of admission in both groups, and there was a significant decline in hemoglobin and RBC count between T1 and T2; PLT counts decreased, but not in a statistically significant manner (Table 2). WBC and absolute neutrophils increased following admission specifically in patients who died of disease (Table 2). No statistically significant differences were observed in all other hematologic parameters evaluated. Blood from patients who died showed pseudo Pelger-Huet changes 60.41% (n=29), toxic granulations 8.3% (n=4), atypical lymphocytes 91% (n=44), and giant platelets 94% (n=45) with immature myeloid forms increasing at T2. In contrast to patients who recovered , patients who died showed increased D-dimer values at admission; D-dimer values did not correlate with the presence of thrombocytopenia.
Conclusion(s): Hospitalized COVID-19 patients who died showed: 1) elevated D-dimer levels at admission; and 2) increasing WBC and neutrophil counts during their hospitalization. While several morphologic changes were observed in the blood in those who subsequently died, the changes observed were not specific to COVID-19; however, the presence of immature myeloid precursors in hospitalized patients was associated with subsequent neutrophilia and death. This finding suggests that in addition to closely monitoring the two laboratory parameters describe above, special care should be taken to asses blood films for the presence of immature myeloid precursors. Additional studies will be required to validate these findings in a larger group of hospitalized patients (Figure Presented)

INTRODUCTION/UNASSIGNED:: Survival in multiple myeloma (MM) has improved due to the ongoing revolution of therapeutic approaches. Nevertheless, many patients relapse, and additional novel approaches are required to prolong remissions and prevent disease progression. AREAS COVERED/UNASSIGNED:Considering the success of monoclonal antibodies (mAbs) against CD38 and SLAMF7 in relapsed/refractory MM (R/R MM), additional antigens expressed on malignant plasma cells are being investigated as treatment targets. Among these, many trials are focusing on B cell maturation antigen (BCMA), using either antibody-drug conjugates (ADCs), bispecific T cell engagers (TCE), or chimeric antigen receptor T cells (CAR-T). Other potential targets include the myeloma markers CD138, GPRC5D, FcRH5, the plasma cell differentiating factors APRIL, TACI and BAFF, and the immune checkpoint proteins CD47 and TIGIT. Additionally, novel immunomodulatory Cereblon E3 Ligase Modulators (CELMoDs) offer the potential to overcome resistance to conventional immunomodulatory agents. Based upon PubMed and abstract searches primarily from the past 4 years, here we review the data supporting novel immunotherapies for R/R MM. EXPERT OPINION/UNASSIGNED:: Overcoming disease resistance remains a challenge in R/R MM. Novel therapeutic approaches targeting MM antigens and/or enhancing immune cell function offer the potential to prolong survival and are actively being investigated in clinical trials.

UNLABELLED:= 42), OR = 0.9 (0.3-2.2). In this largest cohort to date of patients with multiple myeloma and COVID-19, we found the case fatality rate to be 29% among hospitalized patients and that race/ethnicity was the most significant risk factor for adverse outcome. SIGNIFICANCE:.

OBJECTIVES/OBJECTIVE:Crystal-storing histiocytosis (CSH) is rare in plasma cell dyscrasias, with only 3 cases reported in the setting of amyloid. No cases of crystal-negative histiocytosis coincident with multiple myeloma and amyloidosis have been reported previously. METHODS:A 58-year-old woman presented with pain due to destructive bone lesions and was found to have plasma cell myeloma (PCM) and marrow amyloid deposition associated with crystal-negative histiocytosis. Differential diagnoses included Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai Dorfman disease. BRAF mutations were negative, and there was no evidence of paraprotein crystals, arguing against typical CSH. RESULTS:The patient was treated with bortezomib, cyclophosphamide, and dexamethasone, and she subsequently underwent autologous stem cell transplant and ixazomib maintenance. She achieved complete remission with improvement of her symptoms and preserved remission after following up at 60 months. CONCLUSIONS:We describe a case of crystal-negative histiocytosis associated with PCM. CSH is a rare disorder associated with paraprotein-producing conditions in which immunoglobulins aggregate as intracellular crystals in the lysosomes of organ-specific phagocytic macrophages. Light chain tropism in PCM can also lead to the development of amyloid deposition in organs and, in rare cases, is associated with light chain aggregation as intracellular crystals in macrophages.