Current Status of Flow Cytometric Immunophenotyping of Hematolymphoid Neoplasms in Korea

Background@#Flow cytometric immunophenotyping of hematolymphoid neoplasms (FCIHLN) is essential for diagnosis, classification, and minimal residual disease (MRD) monitoring. FCI-HLN is typically performed using in-house protocols, raising the need for standardization. Therefore, we surveyed the current status of FCI-HLN in Korea to obtain fundamental data for quality improvement and standardization. @*Methods@#Eight university hospitals actively conducting FCI-HLN participated in our survey.We analyzed responses to a questionnaire that included inquiries regarding test items, reagent antibodies (RAs), fluorophores, sample amounts (SAs), reagent antibody amounts (RAAs), acquisition cell number (ACN), isotype control (IC) usage, positiveegative criteria, and reporting. @*Results@#Most hospitals used acute HLN, chronic HLN, plasma cell neoplasm (PCN), and MRD panels. The numbers of RAs were heterogeneous, with a maximum of 32, 26, 12, 14, and 10 antibodies used for acute HLN, chronic HLN, PCN, ALL-MRD, and multiple myeloma-MRD, respectively. The number of fluorophores ranged from 4 to 10. RAs, SAs, RAAs, and ACN were diverse. Most hospitals used a positive criterion of 20%, whereas one used 10% for acute and chronic HLN panels. Five hospitals used ICs for the negative criterion. Positiveegative assignments, percentages, and general opinions were commonly reported. In MRD reporting, the limit of detection and lower limit of quantification were included. @*Conclusions@#This is the first comprehensive study on the current status of FCI-HLN in Korea, confirming the high heterogeneity and complexity of FCI-HLN practices. Standardization of FCI-HLN is urgently needed. The findings provide a reference for establishing standard FCI-HLN guidelines.

Advantage of achieving deep response following frontline daratumumab-VTd compared to VRd in transplant-eligible multiple myeloma: multicenter study

Background@#The goal of induction therapy for multiple myeloma (MM) is to achieve adequate disease control. Current guidelines favor triplet (bortezomib-lenalidomide-dexamethasone;VRd) or quadruplet regimens (daratumumab, bortezomib-thalidomide-dexamethasone;D-VTd). In the absence of a direct comparison between two treatment regimens, we conducted this study to compare the outcomes and safety of VRd and D-VTd. @*Methods@#Newly diagnosed MM patients aged ＞18 years who underwent induction therapy followed by autologous stem cell transplantation (ASCT) between November 2020 and December 2021 were identified. Finally, patients with VRd (N=37) and those with D-VTd (N=43) were enrolled. @*Results@#After induction, 10.8% of the VRd group showed stringent complete remission (sCR), 21.6% showed complete response (CR), 35.1% showed very good partial response (VGPR), and 32.4% showed partial response (PR). Of the D-VTd group, 9.3% showed sCR, 34.9% CR, 48.8% VGPR, and 4.2% PR (VGPR or better: 67.6% in VRd vs. 93% in D-VTd, P =0.004). After ASCT, 68.6% of the VRd group showed CR or sCR, while 90.5% of the D-VTd group showed CR or sCR (P=0.016). VRd was associated with an increased incidence of skin rash (P=0.044). Other than rashes, there were no significant differences in terms of adverse events between the two groups. @*Conclusion@#Our study supports the use of a front-line quadruplet induction regimen containing a CD38 monoclonal antibody for transplant-eligible patients with newly diagnosed MM.

Clinical, Laboratory, and Bone Marrow Findings of 31 Patients With Waldenström Macroglobulinemia

BACKGROUND@#Waldenström macroglobulinemia (WM) is a subset of lymphoplasmacytic lymphoma (LPL) with bone marrow (BM) involvement and an IgM monoclonal gammopathy of any level. We aimed to identify the clinical, laboratory, and BM findings of patients with WM and to evaluate the usefulness of CD154 for the diagnosis and prognosis of WM.@*METHODS@#We reviewed the medical records and BM studies and/or flow cytometric immunotyping of 31 patients with untreated WM. Semiquantitative immunohistochemistry (CD20, CD138, tryptase, and CD154) of BM was performed.@*RESULTS@#Only six patients presented with symptoms of hyperviscosity syndrome. Eleven patients had solid cancer and/or another hematologic malignancy. Mast cells (MC) increased in all samples, with some in close contact with tumor cells. Tryptase-positive MC (17.1/ high-power fields [HPF], 1.2–72.0/HPF) and CD154-positive MC (8.6/HPF, 0.1–31.1/HPF) were observed. The high CD154-positive MC (≥8.6/HPF) group showed a lower overall five-year survival rate than the low CD154-positive MC (<8.6/HPF) group (71.9% vs. 100.0%; P=0.012). Flow cytometric immunophenotyping of BM aspirates showed increased B lymphocytes and plasma cells with a normal phenotype (CD138⁺/CD38⁺/CD19⁺/CD45⁺/CD56⁻).@*CONCLUSIONS@#Approximately one third of WM patients showed other malignancies and all patients had increased MC. Immunohistochemistry and flow cytometric immunophenotyping are useful for diagnosing WM, and increased CD154-positive MC can indicate poor prognosis.

Two Rare Cases of Therapy-Related Acute Lymphoblastic Leukemia in Patients With Plasma Cell Myeloma

No abstract available.

Ceftizoxime-induced immune hemolytic anemia associated with multi-organ failure / 영남의대학술지

Drug-induced immune hemolytic anemia (DIIHA) is a rare side effect of drugs. DIIHA may cause a systemic inflammatory response that results in acute multi-organ failure and death. Ceftizoxime belongs to the class of third generation cephalosporins, which are the most common drugs associated with DIIHA. Herein, we present a case of a 66-year-old man who developed fatal DIIHA after receiving a second dose of ceftizoxime. He was admitted to receive photodynamic therapy. He had a history of a single parenteral dose of ceftizoxime 3 months prior to admission. On the day of the procedure — shortly after the infusion of ceftizoxime — the patient's mental status was altered. The blood test results revealed hemolysis. Oliguric acute kidney injury developed, and continuous renal replacement therapy had to be applied. On the suspicion of DIIHA, the patient underwent plasmapheresis. Diagnosis was confirmed by a detection of drug-dependent antibody with immune complex formation. Although his hemolysis improved, his liver failure did not improve. He was eventually discharged to palliative care, and subsequently died.

Ceftizoxime-induced immune hemolytic anemia associated with multi-organ failure / 영남의대학술지

Drug-induced immune hemolytic anemia (DIIHA) is a rare side effect of drugs. DIIHA may cause a systemic inflammatory response that results in acute multi-organ failure and death. Ceftizoxime belongs to the class of third generation cephalosporins, which are the most common drugs associated with DIIHA. Herein, we present a case of a 66-year-old man who developed fatal DIIHA after receiving a second dose of ceftizoxime. He was admitted to receive photodynamic therapy. He had a history of a single parenteral dose of ceftizoxime 3 months prior to admission. On the day of the procedure — shortly after the infusion of ceftizoxime — the patient's mental status was altered. The blood test results revealed hemolysis. Oliguric acute kidney injury developed, and continuous renal replacement therapy had to be applied. On the suspicion of DIIHA, the patient underwent plasmapheresis. Diagnosis was confirmed by a detection of drug-dependent antibody with immune complex formation. Although his hemolysis improved, his liver failure did not improve. He was eventually discharged to palliative care, and subsequently died.

A Case of Pneumonia Caused by Pneumocystis jirovecii Resistant to Trimethoprim/Sulfamethoxazole in the Absence of Previous Drug Exposure

Pneumocystis jirovecii pneumonia is a common opportunistic infection seen in patients with human immunodeficiency virus (HIV) infection. Dihydropteroate synthase (DHPS) is a target of sulfa drugs, and mutations in DHPS gene are associated with failure in treatment and prophylaxis of P. jirovecii infections in HIV-infected patients. Here, we report a case of a patient with P. jirovecii infection, harboring DHPS gene mutations, who had not been previously treated with trimethoprim/sulfamethoxazole (TMP/SMX). A 50-yr-old man was admitted to the hospital with symptoms such as fever, cough, sputum, and sore throat. Chest computed tomography scanning revealed diffuse ground glass opacity in both the lungs, and the patient was diagnosed as having HIV infection with a CD4+ T cell count of 22/µL. Immunohistochemical test results were positive for P. jirovecii. He was treated with TMP/SMX; however, his symptoms and laboratory findings did not improve. The treatment was changed to clindamycin and primaquine, and his symptoms improved after 3 days. Molecular testing of the sample for the detection of DHPS gene mutations and the typing of mitochondrial large subunit rRNA (mtlsurRNA) revealed DHPS gene mutations at codon 55 and 57, respectively, and the case had type 3 mtlsurRNA. This case study illustrates that DHPS mutation test results can be positive even in patients without previous exposure to TMP/SMX.

Performance Evaluation of Two Automated Quantitative Fecal Occult Blood Tests

BACKGROUND: The performance of the fecal occult blood test (FOBT) has recently improved with the use of quantitative immunochemical assays. We evaluated the two latest immunochemical FOBTs: OC-Sensor PLEDIA (Eiken Chemical, Japan) and NS-Prime (Alfresa Pharma, Japan). METHODS: The precision was evaluated by using the quality control materials at two levels and carry-over rates were measured at high and low concentrations of the sample, prepared from the calibrators. Linearity was measured by using five concentrations of human hemoglobin (0-1,000 ng/mL), prepared from erythrocyte lysates. Correlation between the two systems was analyzed by testing approximately 50 selected stool specimens per day and comparing the results obtained with those of the currently used analyzer, OC-Sensor DIANA (Eiken Chemical), for 10 consecutive working days. RESULTS: The variation for repeatability, between-run, between-day, and intermediate precision at both levels was 0.99 for both systems. In total, 499 stool specimens were analyzed, of which 127 (25.5%), 130 (26.1%), and 129 (25.9%) specimens tested positive by DIANA, PLEDIA, and NS-Prime, respectively. The agreement between PLEDIA and NS-Prime was 98.4%. Quantification by PLEDIA was linear to that by NS-Prime (y=1.0372x+17.744; r²=0.9064). CONCLUSIONS: The analytical performances of PLEDIA and NS-Prime warrant their use as diagnostic tests. They showed excellent categorical agreement; however, the quantitative value obtained by NS-Prime was lower than that obtained by PLEDIA.

Multiple Myeloma in a Patient with Acromegaly

Acromegaly is a slowly progressing condition resulting from excess growth hormone (GH), generally caused by a GH-secreting pituitary adenoma. Cancer is the third most common cause of mortality in patients with acromegaly, and insulin-like growth factor 1 (IGF-1) is known to influence tumor formation by increasing cell proliferation and inhibiting apoptosis. Multiple myeloma (MM) is a plasma cell neoplasm, and previous studies have suggested the possible role of IGF-1 in its development of MM. However, no cases of acromegaly accompanied with MM have been reported in Asia to date. We here report the case of a 58-year-old woman with acromegaly accompanied with MM who presented with longstanding acromegalic manifestations resulting from a GH-secreting pituitary adenoma and also exhibited anemia, a reversed albumin/globulin ratio, and plasmacytosis on bone marrow examination. Because IGF-1 has been suggested to play an important role in the development and progression of MM, the patient promptly underwent surgical removal of the pituitary adenoma via a transsphenoidal approach. Since there is currently no consensus on therapeutic guidelines and suggested prognosis for MM with acromegaly, long-term follow-up of such cases is needed.

Biological Meaning of the Histo-Blood Group Antigens Composed of Sugar Chains / 대한수혈학회지

All living creatures on this planet, from bacteria to human, produce sugar chains (glycans). This means that sugar chains are essential for living a life. Abundant, diverse, and highly regulated repertoire of glycans are synthesized by glycosylation process in cells. Located in proteins (N-glycans and O-glycans) and lipids (glycosphingolipids), glycans participate in many vital biological processes including molecular recognition, cell adhesion, molecular trafficking and clearance, receptor activation, and signal transduction. Histo-blood group antigens that are composed of sugar chains are expressed under the control of the Secretor, Lewis and ABO glycosyltransferases. They play important roles in microbial infections and cancers. Many of sugar chains associated with histo-blood group antigens are exploited as receptors for microorganisms. Aberrant glycosylation of proteins and lipids occurs commonly during malignant transformation and leads to the expression of tumor-associated glycans. In this review, over the scope of transfusion medicine, we discussed deep down the biologic meaning of sugar chains, through exploring how the sugar chains are synthesized, structured, and functioning.