E34 CORRESPONDENCE 1-4, thalidomide 100 mg p.o. daily days1-21, doxorubicin 10 mg/m 2 daily on days 1-4, cyclophosphamide 400 mg/m 2 daily on days 1-4, and etoposide 40 mg/m 2 daily on days 1-4).A 74-year-old male was admitted to the UAMS inpatient service with complaints of generalized malaise and fatigue, and decreased urine output. Complete blood count revealed severe anemia with a hemoglobin level of 7.7 g/dL, and a creatinine level of 4.7 mg/dL, with a Glomerular Filtration Rate of 12.2 mL/min/1.73 m 2 . Peripheral smear showed circulating plasma cells, Figure 1A. This was further confirmed by flow-cytometry (54% circulating plasma cells in peripheral blood).Additional work up revealed markedly elevated lambda light chains of 1800 mg/dL. Bone marrow (BM) biopsy revealed 90% plasma cells positive for CD138, Figure 1B,C. Flourescence in situ hybridization was positive for translocation t(11:14) (95%) and a deletion 17p in 25%. His immunoglobulins, including IgG, IgA and IgM were all suppressed, and immunofixation in the serum and urine was positive for lambda light chains. The patient presented with 8 g proteinuria, which was predominantly due to increased urinary light chain excretion (Urine M-protein = 7.4 g/dL), suggestive for light chain cast nephropathy as a cause of the patient's renal compromise. The patient's albumin at presentation was
Introduction. We previously reported that PD-1 and PD-L1 were increased in patients with Ph(-) myeloproliferative neoplasm (MPN) ( Wang et al., Leuk Res 2019). The PD-1 inhibitor therapy or immune checkpoint inhibitor therapy (ICI) trial in MPN by Hobbs et al. reported a negative result (Blood, 2020 (supplement )). Resistance to ICI therapy has been reported to be related to myeloid-derived suppressor cells (MDSCs) in melanoma and breast carcinoma. We also previously reported that MDSCs were increased in patients with Ph(-) MPN (Wang et al., Leu Res 2016). Regulation of immune suppression by MDSCs has been reported to be related to PD-1and PD-L1 expression on the MDSC. Therefore, the current study measured PD-1 and PD-L1 expression in MDSCs in patients with Ph(-) MPN. Materials and Methods. Twenty-six patients, including 11 essential thrombocythemias (ETs), six polycythemia vera (PV), and nine myelofibrosis (six primary MF, one post-ET-MF, two post-PVMF) were compared with ten normal volunteer controls. MDSCs were measured as follows: the pelleted PBMNCs were used for Magnetic-assisted cell separation (MACS, Miltenyi Biotech, Inc.). PBMNCs are sequentially selected for HLA-DR - cells, from which we further selected for CD14 + and CD14 - cells using Miltenyic magnetic microbeads kits, respectively, according to the manufacturer's protocol. The resulting HLA-DR -CD14 + and HLA-DR -CD14 - cells were stored at -80°C until use. Flow cytometric assay:HLA-DR -CD14 + and HLA-DR -CD14 - cells were stained with both anti-human CD274 (PD-L1) FITC and human CD279 (PD-1) PE (BD Biosceinces, Inc.), together with anti-human CD14 APC or anti-human CD33 APC (BD Biosceinces, Inc.), respectively. Flow cytometric assessment was done using the BD Accuri C6 flow cytometer. While HLA-DR -CD14 +Monocytic MDCS cells were gated and assayed for surface expression of PD-1 (CD274) and PDL-1 (CD279), G-MDSC (granulocytic MDSC), and M-NDSC (Monocytic MDSC) were assayed as HLA-DR -CD14 - , CD33 + and HLA-DR -CD14 +, respectively. These MDSCs were then assayed for surface expression of PD-1 (CD274) and PDL-1 (CD279). The flow data were analyzed using FlowJo V8 (Flowjo, LLC), and the mean fluorescent intensity (MFI) was calculated. Results. PD-L1 on the m-MDSCs was significantly elevated in patients with MPN (grouping patients with ET, PV, and MF) and MF than controls. PD-1 on the M-MDSCs was not different between ET, PV, MF, or MPN compared with normal controls. Compared to controls, PD-L1 on the G-MDSC was significantly elevated in patients when ET, PV, and MF were grouped as MPN. PD-1 on the G-MDSC were not different between ET, PV, MF, or MPN and controls. Conclusion. Ph(-) MPN was found to have significantly elevated PD-L1 on the M-MDSCs and G-MDSCs, but PD-1 levels were not significantly elevated. Further studies to employ drugs, such as a combination of IMiDs (e.g., lenalidomide) and anti-MDSC drugs in combination with ICI in vitro and clinical trials, may be warranted. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
Patient: Male, 27-year-old Final Diagnosis: Immune thrombocytopenic purpura (ITP) Symptoms: Bleeding • purpura Medication: Azathioprine • eltrombopag • fostamatinib • intravenous immunoglobulin • IVIG • prednisone • rituximab • steroids Clinical Procedure: EGD • PET-CT • plasmapheresis • splenectomy Specialty: Gastroenterology and Hepatology • Hematology • General and Internal Medicine Objective: Unusual clinical course Background: Immune thrombocytopenic purpura (ITP) is primarily caused by antibody-mediated destruction of platelets. Alterations in immune homeostasis can induce loss of peripheral tolerance and promote the development of self-reactive antibodies. Primary ITP is the diagnosis of exclusion made after the extensive work-up rules out other possible causes of thrombocytopenia. The association between the ITP and other autoimmune disorders is well-established. In recent years, increasing attention has been directed toward the association between celiac disease (CD) and ITP. Case Report: A 27-year-old man with a history of primary ITP presented with an occasional nosebleed, 1 episode of rectal bleeding, and easy bruising. The patient was later found to have high titers of TTG-IGA and endomysial IGA levels consistent with CD. Our patient not only failed to improve with the gluten-free diet, but also failed multiple lines of treatment including steroids, IVIG, rituximab, eltrombopag, and even a non-traditional treatment for ITP (azathioprine and plasma exchange). The patient’s CD-related antibody titers remained elevated. Conclusions: It is possible that in certain cases the alteration of immune response caused by CD with a concurrent elevation of CD-related antibodies can make ITP refractory to all medical management. Whether or not this refractoriness to treatment is related to the persistently elevated antibody titers of CD or unknown genetic relationship between ITP and CD remains not entirely clear and warrants further molecular, immunologic, and genetic analysis.
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