Journal of Clinical and Experimental Hematopathology最新文献

CD5-positive diffuse large B cell lymphoma (CD5+ DLBCL) is a high-risk lymphoma type. Recently, the PEARL5 (a Phase II trial of DA-EPOCH and Rituximab with HD-MTX therapy for newly diagnosed DLBCL with CD5 expression) study demonstrated the efficacy of the DA-EPOCH-R (cyclophosphamide, etoposide, doxorubicin, vincristine, prednisone, and rituximab)/HD-MTX (high-dose methotrexate) regimen for CD5+ DLBCL. In this report, we revealed the impact of the DA-EPOCH-R/HD-MTX regimen on the clinical course of CD5+ DLBCL in the real-world. We retrospectively compared CD5+ and CD5- DLBCL patients diagnosed from January 2017 to December 2020 and analyzed their clinicopathological characteristics, treatment, and prognosis. There was no difference in age, sex, clinical stage, and cell of origin; however, the CD5-positive group had higher lactate dehydrogenase levels and a worse performance status than the CD5-negative group (p=0.00121 and p=0.0378, respectively). International prognostic index (IPI) was worse in the CD5-positive group than in the CD5-negative group (p=0.0498), but NCCN-IPI (National Comprehensive Cancer Network-IPI) was no different between the two groups. The CD5-positive group was more frequently treated with the DA-EPOCH-R/HD-MTX regimen than the CD5-negative group (p =0.001857). Complete remission rate and 1-year overall survival did not differ between the CD5-positive and -negative groups (90.0% vs 81.4%, p=0.853; 81.8% vs 76.9%, p=0.433). We conclude that the DA-EPOCH-R/HD-MTX regimen is effective for CD5+ DLBCL in this single institute analysis.

Outcomes of patients with histologic transformation (HT) of follicular lymphoma (FL) have been believed to be poor. The most common histologic subtype of transformation from FL is diffuse large B-cell lymphoma (DLBCL), which accounts for 90% of the cases, and the remaining 10% of the cases include classic Hodgkin lymphoma, high-grade B-cell lymphoma, plasmablastic lymphoma, B-acute lymphoblastic leukemia/lymphoma, histiocytic/dendritic cell sarcoma, and anaplastic large cell lymphoma-like lymphoma. Because the histologic criteria for the diagnosis of DLBCL transformed from FL are unclear, convenient histopathological criteria for HT are required. One of the proposed criteria of HT from our institute is the presence of diffuse architecture with a proportion of large lymphoma cells of ≥20%, and for challenging cases, Ki-67 index ≥50% is used as a reference. Patients with HT to non-DLBCL have poorer outcomes than those with HT to DLBCL; thus, rapid and accurate histologic diagnosis is desired. In this review, we discussed the recent literatures describing the histopathologic variety and proposal of definition of HT.

TAFRO syndrome is a rare systemic inflammatory disease characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. We encountered a case of calreticulin mutation-positive essential thrombocythemia (ET) with TAFRO syndrome-like features, followed by a rapid fatal course. The patient had been on anagrelide therapy for approximately three years for management of ET; however, she suddenly stopped going for follow-up and discontinued the medicine for a year. She presented with fever and hypotension, suggestive of septic shock, and was transferred to our hospital. The platelet count at the time of admission to another hospital was 50 × 10⁴ / μL; however, it decreased to 25 × 10⁴ / μL upon transfer to our hospital and further decreased to 5 × 10⁴ / μL on the day of her death. In addition, the patient showed remarkable systemic edema and progression of organomegaly. Her condition suddenly worsened and led to her death on the 7th day of hospitalization. Postmortem, serum and pleural effusion interleukin (IL)-6 and vascular endothelial growth factor (VEGF) levels were significantly increased. Consequently, a diagnosis of TAFRO syndrome, since she met the diagnostic criteria for clinical findings and had high cytokine concentrations. Dysregulation of cytokine networks has also been reported in ET. Therefore, concurrent ET and TAFRO syndrome may have further triggered cytokine storms and contributed to the aggravation of the disease on development of TAFRO syndrome. To the best of our knowledge, this is the first report of complications seen in a patient with TAFRO syndrome due to ET.

Epstein Barr Virus (EBV) has been recognized for its ability to transform B lymphocytes and for its association with different types of cancers including Hodgkin lymphoma. In addition, EBV may also modulate the microenvironment of HL. In this study, we aimed to investigate the prevalence of EBV among HL cases in Ethiopia and to assess the tissue cellular composition of EBV-related and EBV-unrelated cases. We constructed a tissue microarray (TMA) of 126 consecutive cases of classical HL (CHL) and nodular lymphocyte predominant HL (NLPHL) from a tertiary cancer centre, Tikur Anbessa Hospital, Addis Ababa, Ethiopia, and evaluated a panel of immunohistochemical markers. The quantification of immune cells was performed using HALO 2.3, a platform for image analysis from Indica Lab Inc. A total of 77/126 (61.1%) of HL cases expressed LMP1/EBER. Infiltration of CD8+, T-bet+ and FoxP3+ cells was higher in the microenvironment of EBV-related CHL, with P values of <0.001, <0.001 and <0.016, respectively. In contrast, the expression of PD1 was higher in the microenvironment of EBV-unrelated CHL cases (P < 0.001). Unlike in Western countries, the majority of HL cases in Ethiopia were associated with EBV. As FoxP3+ and PD1-expressing cells are thought to participate in down regulation of the immune response by different mechanisms, this finding highlights the previously unrecognized possibility that distinct immunosuppressive mechanisms may be ongoing within EBV positive and negative HL types. This may have important prognostic and therapeutic implications.

Subacute myelopathy is a rare but serious complication of methotrexate (MTX) that may cause paraplegia. Although its underlying mechanisms have not been fully elucidated, homocysteine is thought to play a role in the pathogenesis of this adverse effect. Herein, we report the case of a 34-years old female patient with diffuse large B-cell lymphoma who developed progressive paraplegia accompanied by dysfunctional bladder and bowel movements after treatment with a modified CODOX-M/IVAC regimen, including high-dose intravenous MTX and intrathecal (IT-) MTX. Neurological symptoms gradually improved to almost normal levels within 4.5 months of onset following treatment with a combination of S-adenosylmethionine, methionine, cyanocobalamin, and folate. During chemotherapy, including high-dose MTX and IT-MTX for hematological malignancies, MTX-induced subacute neuronal damage should be carefully evaluated, and appropriate treatment should be initiated as early as possible.

Myelodysplastic syndromes (MDS) are myeloid neoplasms that are driven by genetic mutations. Generally, it is thought that a higher number of mutations is associated with worse prognosis. However, the impact of genetic mutations when they occur in the same functional class has not been well studied. Here we investigated the impact of multiple spliceosome mutations on prognosis in MDS patients, hypothesizing that multiple mutations in the same class are biologically redundant and would not affect prognosis. Departmental Next Generation Sequencing (NGS) database (>6000 cases) was queried and the data was analyzed to identify cases with spliceosome mutations (SF3B1, SRSF2, U2AF1, ZRSR2, U2AF1). Overall, 71 patients met criteria for the study. Cases with single spliceosome mutations (i.e., no other co-mutations whatsoever) were as follows: SF3B1 (38), SRSF2 (5), U2AF2 (11), and ZRSR2 (1). Cases with concurrent spliceosome mutations were as follows: SF3B1 + SRSF2 (5), SF3B1 + U2AF1 (1), SF3B1 + ZRSR2 (3), SRSF2 + U2AF1 (2), SRSF2 + ZRSR2 (1), U2AF1 + ZRSR2 (4). Four of 55 (7.3%) of patients in the single mutation group vs. 4 of 16 (25%) of patients in the concurrent mutation group progressed to acute myeloid leukemia (AML). Mean OS in the single mutation group was 103.5 months vs. 71.6 months in the multiple concurrent mutation group (χ²= 2.404; p= 0.12). Our results challenge the current dogma that increased mutation in MDS portend worse survival. We demonstrate that multiple mutations bear no impact on clinical prognosis when the additional mutations occur in same spliceosome class.

Recently, the ratio of C-reactive protein to albumin (CAR) is used as an inflammatory marker that has been demonstrated to be a simple and reliable prognostic factor in solid tumors and hematological malignancy. However, no studies of the CAR have been performed in patients with adult T-cell leukemia-lymphoma (ATL). We retrospectively analyzed the clinical features and outcomes in 68 newly diagnosed acute- and lymphoma-type ATL [(acute-(n=42) or lymphoma-type (n=26)] patients in Miyazaki Prefecture from 2013 to 2017. Furthermore, we investigated correlations between pretreatment CAR levels and clinical features. The median age was 67 years (range, 44 - 87). Patients were initially treated by either palliative therapy (n=14) or chemotherapy [n=54; CHOP therapy (n=37)/ VCAP-AMP-VECP therapy (n=17)], and showed median survival durations of 0.5 months and 7.4 months, respectively. The factors affecting OS by multivariate analysis were age, BUN, and CAR. Importantly, we revealed that the high CAR group (optimal cut-off point; 0.553) was a significant indicator of worse OS by multivariate analysis (p< 0.001, HR; 5.46). The median survival of patients with a CAR< 0.553 was 8.37 months, while patients with a CAR>0.553 had a median survival of 3.94 months. The different clinical features between high CAR and low CAR groups were hypoproteinemia and the implementation of chemotherapy. Furthermore, in the chemotherapy group, but not the palliative therapy group, CAR was a significant prognostic marker. Our study indicated that CAR may be a new simple and significant independent prognostic marker in acute- and lymphoma-type ATL patients.

Myeloid sarcoma (MS) is a condition characterized by a tumor mass of myeloid blasts in any site of the body other than the bone marrow, with or without acute myeloid leukemia. A 93-year-old man underwent laparoscopy-assisted distal gastrectomy with D1 lymphadenectomy for advanced gastric cancer. Other than metastatic foci of gastric cancer cells, some dissected lymph nodes showed destructive architecture with proliferation of small- to medium-sized atypical hematopoietic cells. Those cells were focally positive for naphthol AS-D chloroacetate esterase. Immunohistochemically, positive results were obtained for CD4, CD33, CD68 (KP1), Iba-1, lysozyme, myeloperoxidase, and PU.1, with focally positive results for CD13, CD14, CD68 (PGM1), CD163, and CD204, and negative results for AE1/AE3, CD1a, CD3, CD20, and S-100 protein. These results suggested MS with phenotypically myelomonocytic differentiation. We report a rare case of MS incidentally found in specimens resected for other purposes. Careful diagnosis and consideration of differential diagnoses including MS using an adequate panel of antibody markers for dissected lymph nodes is warranted.

Cold agglutinin disease (CAD) is a rare form of acquired autoimmune hemolytic anemia driven mainly by antibodies that activate the classical complement pathway. Several patients with CAD experience its development or exacerbation of hemolysis after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or after receiving the SARS-CoV-2 mRNA vaccine. Therefore, these patients cannot receive an additional SARS-CoV-2 mRNA vaccination and have a higher risk of severe SARS-CoV-2 infection. Sutimlimab is a monoclonal antibody that inhibits the classical complement pathway of the C1s protein and shows rapid and sustained inhibition of hemolysis in patients with CAD. However, whether sutimlimab could also inhibit hemolysis caused by SARS-CoV-2 mRNA vaccination is uncertain. Here, we present the case of a 70-year-old man with CAD who repeatedly experienced a hemolytic crisis after receiving SARS-CoV-2 mRNA vaccines. The patient eventually underwent SARS-CoV-2 mRNA vaccination safely, without hemolytic attack, under classical pathway inhibition therapy with sutimlimab. This report suggests that appropriate sutimlimab administration can suppress SARS-CoV-2 mRNA vaccination-induced CAD exacerbation, and that it could be a preventive strategy to minimize hemolytic attacks in susceptible populations.

A Japanese subgroup analysis from the Asian phase II study of darinaparsin in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) was performed to evaluate the efficacy and safety outcomes of the Japanese population. In this Asian phase II study, darinaparsin was administered to 65 patients, including 37 Japanese patients. In the Japanese population, the histopathological type of PTCL was PTCL, not otherwise specified in 26 patients (70.3%), angioimmunoblastic T-cell lymphoma in 9 patients (24.3%) and anaplastic large cell lymphoma, anaplastic lymphoma kinase (ALK) -negative in 2 patients (5.4%), and the median patient age was 70.0 (range: 43-85). 94.6% and 35.1% of the Japanese population had previously received multi-agent and single-agent regimen, respectively. The efficacy and safety were summarized and compared between the overall and Japanese populations. Based on central assessment, the overall response rate was 22.2% (8/36; 90% confidence interval [CI]: 11.6-36.5) in the Japanese population and 19.3% (11/57; 90% CI: 11.2-29.9) in the overall population. There were no essential differences in the safety profile of darinaparsin between the Japanese population and the overall population. The results of this subgroup analysis indicate that the efficacy and safety profiles of the Japanese subpopulation were broadly consistent with that of the overall population, and that darinaparsin is potentially an effective treatment with a manageable safety profile in Japanese patients with relapse or refractory PTCL.