Optimal index for detecting splenic involvement on 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging in diffuse large B-cell lymphoma.

Accurate clinical staging is important in diffuse large B-cell lymphoma (DLBCL) to adapt to optimal therapy. Splenic involvement of DLBCL has been recently more detectable with the advancement of a diagnostic scan by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT). Our clinical question is whether splenic involvement was adequately diagnosed by FDG-PET/CT imaging. This retrospective study aimed to determine the optimal index for evaluating splenic involvement in patients with DLBCL. Patients with newly diagnosed DLBCL who were examined with FDG-PET/CT at diagnosis and the end of induction chemotherapy (EOI) was enrolled. The splenic involvement with the splenic FDG uptake value higher than that of the liver at diagnosis or with the decrease of splenic uptake at EOI by visual evaluation was evaluated as positive. The calculative evaluation of splenic involvement, based on the data of standardized uptake value (SUV) of the spleen, used maximum SUV (SUVmax), mean SUV (SUVmean), spleen total lesion glycolysis (spleen TLG), and spleen length. A change in each index following induction chemotherapy was expressed as an index. Receiver operating characteristic analysis was used to set the cutoff value for each index. This study included 52 patients. Spleen TLG (0.904) showed the best accuracy, followed by SUVmax (0.885) and SUVmean (0.885), among the 5 indexes for splenic involvement at diagnosis. Splenic involvement was predicted with a higher accuracy level (0.923) when selecting the cases with values higher than the cutoff level on both spleen TLG and SUVmax. The decision at EOI was more suitable by selecting both positive cases of ∆ TLG and ∆ SUVmax. Obtaining both the positive spleen TLG and SUVmax is recommended at diagnosis to predict splenic involvement. The assessment by ∆ spleen TLG and ∆ SUVmax seems to be optimal.

Irreversible Intrathecal Chemotherapy-induced Myelopathy in a Patient with Diffuse Large B-cell Lymphoma.

Intrathecal chemotherapy is often administered for prophylaxis and treatment of central nervous system involvement in hematological malignancies. However, it may rarely cause neurotoxicity as a side effect. We herein report a 74-year-old woman with diffuse large B-cell lymphoma including a spinal lesion. She received systemic and intrathecal chemotherapy. After five doses of intrathecal chemotherapy, she developed intrathecal chemotherapy-induced myelopathy. Intrathecal treatment was discontinued, and she was administered vitamin B12 and folic acid, along with steroid pulses. However, her symptoms did not improve. Intrathecal chemotherapy-induced myelopathy is rare, but may be irreversible; therefore, clinicians should be aware of this potential complication.

RUNX1 rearrangement in mature B-cell acute lymphoblastic leukemia with non-L3 morphology.

Mature B-cell acute lymphoblastic leukemia (ALL) is defined by the expression of light chain-restricted surface immunoglobulin (sIg) and usually has features of the leukemic phase of Burkitt lymphoma including FAB-L3 morphology and MYC rearrangement. Recently, another distinct entity in childhood mature B-cell ALL has been characterized as non-L3 morphology and KMT2A rearrangement. Here we report an unusual case of mature B-cell ALL that presented with RUNX1 rearrangement. A 65-year-old male was admitted to our department for thorough examination of leukocytosis and thrombocytopenia. The patient's bone marrow was hypercellular and infiltrated with 97.8% myeloperoxidase-negative, medium-to-large-sized blasts without cytoplasmic vacuoles. Immunophenotypes were characterized by the presence of light chain-restricted sIg and the lack of immature markers, indicating a diagnosis of mature B-cell ALL with L2 morphology: sIg-κ+, CD19+, CD20+, CD22+, CD79a+, TdT-, and CD34-. G-banding combined with spectral karyotyping showed the following complex karyotype: 45,X,der(Y;10)(p10;q10),del(13)(q?),inv(21)(p13q22.1). Fluorescence in situ hybridization revealed separated signals of RUNX1 at 21q22.1, whereas rearrangements of MYC and KMT2A were not found. To our knowledge, inv(21)(p13q22.1) involving RUNX1 is a novel cytogenetic aberration and this is the first case of mature B-cell ALL that presented with RUNX1 rearrangement. Thus, RUNX1 may be implicated in the pathogenesis of mature B-cell ALL showing non-L3 morphology without MYC rearrangement.

Early diagnosis of sinusoidal obstruction syndrome after hematopoietic stem cell transplantation, with modified diagnostic criteria including refractory thrombocytopenia.

Sinusoidal obstruction syndrome (SOS) is a fatal complication of hematopoietic stem cell transplantation (HSCT). Early diagnosis for SOS can improve clinical outcomes significantly. Here, we performed a retrospective study to investigate the Cairo diagnostic criteria, in which SOS was defined as the development of two or more in seven events, including transfusion-refractory thrombocytopenia. Among 154 cases of allogeneic HSCT, 10 cases of SOS using the European Society for Blood and Marrow Transplantation criteria (EBMT16) as the reference standard were identified. The original Cairo criteria could diagnose SOS 5 days earlier than any other established criteria, with some false-positive results (sensitivity = 100.0%; specificity = 72.2%). When the cutoff was set to three events for the Cairo criteria, the diagnosis of SOS could be made 3 days earlier than that using the EBMT16 criteria, with comparable precision (specificity = 86.1%). The accuracy of the Cairo criteria improved further when the cutoff point was set to four (specificity = 93.8%). The fulfillment of the Cairo criteria was associated with high mortality. Based on our results, the Cairo criteria were also considered clinically useful, especially at three or four cutoff points. Further studies are required to validate and refine the criteria.

Global longitudinal strain is superior to ejection fraction for long-term follow-up after allogeneic hematopoietic stem cell transplantation.

Global longitudinal strain (GLS), a new cardiac parameter measured by the speckle-tracking method, is reportedly more sensitive than ejection fraction (EF) in detecting slight cardiac dysfunction in heart failure patients. We validated the utility of GLS in allogeneic hematopoietic stem cell transplantation (HSCT) patients during a long-term follow-up. Medical records of patients who underwent allogeneic HSCT between 2013 and 2020 were reviewed retrospectively. We evaluated the last echocardiography performed before transplantation and those performed annually during the 5 years after transplantation. We also investigated newly diagnosed cardiac events, which developed after HSCT. Among 85 patients, 22 used cardioprotective drugs. The median follow-up duration in surviving patients was 54.1 months (range, 2.9-92.6 months). GLS significantly decreased year by year, and patients taking cardioprotective agents tended to have a better GLS at 5 years than at 3 years, while EF did not change. Fifteen patients developed newly diagnosed cardiac events. Multivariate analysis revealed that low GLS and high serum ferritin levels at baseline were independently associated with the development of cardiac events. Therefore, we need a continuous follow-up of cardiac function by GLS and prescription of cardioprotective drugs might be considered for HSCT patients with low GLS. Further research is warranted.

A Third Dose COVID-19 Vaccination in Allogeneic Hematopoietic Stem Cell Transplantation Patients.

We previously reported that a second dose of BNT162b2 was safe and effective for allogeneic hematopoietic stem cell transplantation (HSCT) patients. Here, we investigated the safety and efficacy of a third dose of COVID-19 mRNA vaccine in allogeneic HSCT patients. Antibody titers against the S1 spike protein were measured using the QuaResearch COVID-19 Human IgM IgG ELISA kit. The previous study included 25 allogeneic HSCT patients who received two doses of BNT162b2. Following the exclusion of three patients because of the development of COVID-19 (n = 2) and loss to follow-up (n = 1), the study evaluated 22 allogeneic HSCT patients who received a third dose of COVID-19 mRNA vaccine (BNT162b2 [n = 15] and mRNA-1273 [n = 7]). Median age at the time of the first vaccination was 56 (range, 23-71) years. Five patients were receiving immunosuppressants at the third vaccination, namely calcineurin inhibitors (CI) alone (n = 1), steroids alone (n = 2), or CI combined with steroids (n = 2). Twenty-one patients (95%) seroconverted after the third dose. None of our patients had serious adverse events, new-onset graft-versus-host disease (GVHD), or GVHD exacerbation after vaccination. A third dose of the BNT162b2 and mRNA-1273 COVID-19 vaccines was safe and effective for allogeneic HSCT patients.

Treatment of sick sinus syndrome in a patient with cardiac lymphoma via chemotherapy without pacemaker implantation: A case report.

Successful treatment of the acute phase of bradycardia in patients with cardiac lymphoma via medical therapy alone has not been reported. This case report describes the successful treatment of sick sinus syndrome in an 84-year-old man with cardiac lymphoma via chemotherapy without pacemaker implantation.

The Safety and Immunogenicity of the BNT162b2 mRNA COVID-19 Vaccine in Japanese Patients after Allogeneic Stem Cell Transplantation.

Patients who have undergone hematopoietic stem cell transplantation (HSCT) for hematological disease experience high mortality when infected by coronavirus disease 2019 (COVID-19). However, the safety and efficacy of the COVID-19 vaccine in HSCT patients remain to be investigated. We prospectively evaluated the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine (Pfizer BioNTech) in 25 Japanese allogeneic HSCT patients in comparison with 19 healthy volunteers. While anti-S1 antibody titers in almost all healthy volunteers after the second dose were higher than the cut-off value reported previously, levels in HSCT patients after the second dose were diverse. Nineteen patients (76%) had seroconversion of anti-S1 IgG. The median optical density of antibody levels in HSCT patients with low IgG levels (<600 mg/dL), steroid treatment, or low lymphocytes (<1000/µL) was significantly lower than that in the other HSCT patients. There were no serious adverse events (>Grade 3) and no new development or exacerbation of graft-versus-host disease after vaccination. We concluded that the BNT162b2 mRNA vaccine is safe and effective in Japanese allogeneic HSCT patients.

Limited increase in antibody titers following mRNA SARS-CoV-2 vaccination for more than 3 years after final dose of anti-CD20 antibody.

We investigated the efficacy of BNT162b2 mRNA COVID-19 vaccine in patients with B-cell malignancies treated with anti-CD20 antibody. Although T-cell-mediated immune responses were detected even in patients receiving R-CHOP treatment, the S1 antibody titer following BNT162b2 vaccination remained only marginally increased for more than 3 years after the final dose of anti-CD20 antibody. We found no relationship between the percent of B-cells and S1 antibody titer. The duration of this suppression was much longer than we anticipated. Further protection and treatment strategies against COVID-19 for these patients are warranted.