[Veno-venous extracorporeal membrane oxygenation for capillary leak syndrome during induction chemotherapy in acute myeloid leukemia].

A 44-year-old woman was diagnosed with acute myeloid leukemia (RUNX1::RUNX1T1 translocation) and received induction chemotherapy with idarubicin hydrochloride and cytosine arabinoside. The pneumonia that had been present since admission worsened, and a drug-induced skin rash appeared. On day 17, she presented with respiratory failure and shock, complicated by hemoconcentration and hypoalbuminemia. This was considered capillary leak syndrome due to pneumonia and drug allergy, so she was started on pulse steroid therapy and IVIG, and was intubated on the same day. On day 18, venovenous-extracorporeal membrane oxygenation (VV-ECMO) was started due to worsening blood gas parameters despite ventilatory management. Bronchoalveolar lavage fluid was serous, and both blood and sputum cultures yielded negative. The patient was weaned from VV-ECMO on day 26 as the pneumonia improved with recovery of hematopoiesis. She was disoriented, and a CT scan on day 28 revealed cerebral hemorrhage. Her strength recovered with rehabilitation. After induction chemotherapy, RUNX1::RUNX1T1 mRNA was not detected in bone marrow. The patient received consolidation chemotherapy, and has maintained complete remission. Severe respiratory failure during induction chemotherapy for acute leukemia can be fatal, but VV-ECMO may be lifesaving.

Aortitis after switching short-acting granulocyte colony-stimulating factors in a lymphoma patient with HLA-B52.

Aortitis is a rare adverse event of granulocyte colony-stimulating factor (G-CSF) treatment. Several previous studies have described recurrent aortitis caused by re-administration of the same G-CSF. However, no previous studies have examined the safety of switching between short-acting G-CSFs in patients who develop aortitis. We report the case of a 55-year-old man with refractory diffuse large B-cell lymphoma, who developed G-CSF-associated aortitis. The aortitis was triggered by filgrastim and recurred after treatment with lenograstim. The patient possessed human leukocyte antigen B52, which has been implicated in Takayasu arteritis. In addition, a drug-induced lymphocyte stimulation test for lenograstim performed upon detection of recurrent G-CSF-associated aortitis produced a positive result. Our case suggests that switching from one short-acting G-CSF to another does not prevent recurrence of G-CSF-associated aortitis. Although the etiology of G-CSF-associated aortitis has not been fully elucidated, our case also suggests that some patients may be genetically predisposed to aortitis.

Comparison of platelet transfusion effectiveness between Helicobacter pylori-positive and -negative immune thrombocytopenia.

Immune thrombocytopenia (ITP) is characterized by early platelet destruction and impaired platelet production. Helicobacter pylori (H. pylori) infection seems to contribute to the pathogenesis in certain ITP patients in Japan. We compared the effectiveness of platelet transfusion in severe ITP in the presence or absence of H. pylori. The median corrected count increment (CCI) at 24 h after platelet transfusion (CCI-24) of the H. pylori-positive ITP patients was higher than that of the H. pylori-negative ITP patients (6463 vs. 754, p < 0.001), and the CCI-1 was also in the same direction but not significant (23 351 vs. 11 578). Multiple regression analyses showed that H. pylori infection was independently associated with CCI-24. Our study suggests that platelet transfusion may be more effective in H. pylori-positive ITP patients.

Predictive Model for Occurrence of Febrile Neutropenia after Chemotherapy in Patients with Diffuse Large B-Cell Lymphoma: A Multicenter, Retrospective, Observational Study.

Febrile neutropenia (FN) is a major concern in patients undergoing chemotherapy for diffuse large B-cell lymphoma (DLBCL); however, the overall risk of FN is difficult to assess. This study aimed to develop a model for predicting the occurrence of FN in patients with DLBCL. In this multicenter, retrospective, observational analysis, a multivariate logistic regression model was used to analyze the association between FN incidence and pretreatment clinical factors. We included adult inpatients and outpatients (aged ≥ 18 years) diagnosed with DLBCL who were treated with chemotherapy. The study examined 246 patients. Considering FN occurring during the first cycle of chemotherapy as the primary outcome, a predictive model with a total score of 5 points was constructed as follows: 1 point each for a positive hepatitis panel, extranodal involvement, and a high level of soluble interleukin-2 receptor and 2 points for lymphopenia. The area under the receiver operating characteristic curve of this model was 0.844 (95% confidence interval: 0.777-0.911). Our predictive model can assess the risk of FN before patients with DLBCL start chemotherapy, leading to better outcomes.

Comparison of two apheresis systems for granulocyte collection without hydroxyethyl starch.

BACKGROUND AND OBJECTIVES: Granulocyte transfusion (GTX) is a treatment option for severe infections in patients with neutropenia. In previous studies, hydroxyethyl starch (HES) was used to enhance red blood cell sedimentation for granulocyte collection (GC). However, there are safety concerns about HES, and HES is not readily available in some countries. Therefore, we compared the granulocyte counts and GC efficiency achieved by two apheresis systems without HES. MATERIALS AND METHODS: All consecutive GC procedures performed between July 2011 and March 2018 at our hospital were analysed. COBE Spectra was used until 5 February 2016, and Spectra Optia was used afterwards. HES was not used. RESULTS: Twenty-six GC procedures were performed, including 18 performed using COBE Spectra and 8 using Spectra Optia. When Spectra Optia was used, >1 × 1010 neutrophils were collected from seven of the eight (88%) procedures. Although there was no significant difference in the granulocyte yield between COBE Spectra-based and Spectra Optia-based GC procedures, the collection efficiency of Spectra Optia was significantly higher than that of COBE Spectra (p = 0.021). Furthermore, the granulocyte yields of Spectra Optia-based GC tended to be more strongly correlated with the peripheral blood neutrophil count on the day of apheresis than those of COBE Spectra-based GC. CONCLUSION: Our results suggest that Spectra Optia achieves greater GC efficiency than COBE Spectra, even without HES. GTX may be a therapeutic option for severe neutropenia, even in places where HES is not available.

[Guillain-Barré syndrome associated with Epstein-Barr virus and cytomegalovirus reactivation during treatment for chronic graft-versus-host disease after allogeneic bone marrow transplantation].

Guillain-Barré syndrome (GBS) is a rare neurological complication of allogeneic hematopoietic stem cell transplantation (HSCT). The pathogenesis of post-HSCT GBS is unclear. Here, we report a case of GBS coincident with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivation that occurred after HSCT in a patient with myelodysplastic syndrome. A 61-year-old man was admitted to our hospital because of gait disturbance due to lower limb muscle weakness, which arose during treatment for chronic graft-versus-host disease (GVHD) five months after allogeneic HSCT. He was diagnosed with GBS based on his clinical course, cerebrospinal fluid analysis, and a nerve conduction study. At that time, he exhibited EBV and CMV reactivation. GBS improved after intravenous injection of immunoglobulins. Our case suggests that reactivation of EBV and CMV during treatment for chronic GVHD may induce GBS, and that rapidly progressive muscular weakness coincident with EBV or CMV reactivation can be a diagnostic sign of GBS after allogeneic HSCT.

Clinical Characteristics and Diagnostic Prediction of Severe Fever with Thrombocytopenia Syndrome and Rickettsiosis in the Co-Endemic Wakayama Prefecture, Japan.

Background and Objectives: The Wakayama prefecture is endemic for two types of tick-borne rickettsioses: Japanese spotted fever (JFS) and scrub typhus (ST). Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne hemorrhagic viral disease with a high mortality rate and is often difficult to differentiate from such rickettsioses. SFTS cases have recently increased in Wakayama prefecture. For early diagnosis, this study aimed to evaluate the clinical characterization of such tick-borne infections in the co-endemic area. Materials and Methods: The study included 64 febrile patients diagnosed with tick-borne infection in Wakayama prefecture between January 2013 and May 2022. Medical records of 19 patients with SFTS and 45 with rickettsiosis (JSF, n = 26; ST, n = 19) were retrospectively examined. The receiver operating curve (ROC) and area under the curve (AUC) were calculated to evaluate potential factors for differentiating SFTS from rickettsiosis. Results: Adults aged ≥70 years were most vulnerable to tick-borne infections (median, 75.5 years; interquartile range, 68.5-84 years). SFTS and rickettsiosis occurred mostly between summer and autumn. However, no significant between-group differences were found in age, sex, and comorbidities; 17 (89%) patients with SFTS, but none of those with rickettsiosis, experienced gastrointestinal symptoms such as vomiting, abdominal pain, and diarrhea. Meanwhile, 43 (96%) patients with rickettsiosis, but none of those with SFTS, developed a skin rash. The AUCs of white blood cells (0.97) and C-reactive protein (CRP) levels (0.98) were very high. Furthermore, the differential diagnosis of SFTS was significantly associated with the presence of gastrointestinal symptoms (AUC 0.95), the absence of a skin rash (AUC 0.98), leukopenia <3.7 × 109/L (AUC 0.95), and low CRP levels < 1.66 mg/dL (AUC 0.98) (p < 0.001 for each factor). Conclusions: Clinical characteristics and standard laboratory parameters can verify the early diagnosis of SFTS in areas where tick-borne infections are endemic.

Detection of the JAK2 V617F Mutation in Urinary Cell-free DNA in Patients with Myeloproliferative Neoplasms.

Objective Testing for the Janus activating kinase 2 (JAK2) V617F mutation is important for diagnosing and treating myeloproliferative neoplasms (MPNs). Recently, urine cell-free DNA (ucfDNA) was reported to be useful for detecting tumor-specific gene mutations in several solid tumors. However, its utility in detecting such mutations in hematological malignancies has not yet been assessed. In this study, we assessed whether or not the JAK2 V617F mutation could be detected in ucfDNA and whether or not its positivity rate in ucfDNA was associated with the JAK2 V617F allele ratio of peripheral blood cells in patients with MPN. Methods The JAK2 V617F allele ratio of genomic DNA from peripheral blood cells was determined using quantitative polymerase chain reaction (qPCR) or droplet digital PCR (ddPCR). ucfDNA was subjected to ddPCR. The correlation between the JAK2 V617F mutation positivity rates of blood-derived DNA and those of ucfDNA was assessed. Materials Twelve patients with polycythemia vera and 12 patients with essential thrombocythemia were enrolled. Ethylenediaminetetraacetic acid-treated peripheral blood (100 mL) and 15-30 mL of fresh urine were used. Results The JAK2 V617F mutation was detected in the ucfDNA from all 20 JAK2 V617F mutation-positive patients. In addition, the JAK2 V617F mutation positivity rate of ucfDNA was correlated with the JAK2 V617Fｓ allele ratio of blood-derived DNA, including in both estimated glomerular filtration rate (eGFR) groups (patients with an eGFR ≥50 or <50 mL/min/1.73 m2). Conclusion Our results indicate that ucfDNA is a valuable tool for diagnosing and monitoring MPN. Given these findings, other disease-specific gene mutations in hematological malignancies may also be detectable in ucfDNA.

Comparison of the outcomes of patients with primary central nervous system lymphoma between the neurosurgery and hematology/oncology departments based on the relative dose intensity of methotrexate.

Primary central nervous system lymphoma (PCNSL) is an extranodal type of lymphoma, which is treated with methotrexate (MTX)-based induction therapy. Although PCNSL is a hematological malignancy, patients with PCNSL may be treated at neurosurgery or hematology/oncology departments; however, the outcomes of PCNSL treatment have not been compared between these two departments. The present study compared the outcomes of 26 patients with newly diagnosed PCNSL that were treated at the Department of Neurological Surgery or Department of Hematology/Oncology (Wakayama Medical University Hospital, Wakayama, Japan) between January 2011 and December 2021. The relative dose intensity (RDI) and relative treatment intensity of MTX were assessed as indicators of the intensity of chemotherapy. The median RDI of MTX was 67 and 93% in the neurosurgery and hematology/oncology groups, respectively (P<0.001). The proportion of patients that achieved a complete response after high-dose MTX-based therapy was significantly higher in the hematology/oncology group than in the neurosurgery group (P=0.038). The estimated 2-year overall survival was 72 and 100% in the neurosurgery and hematology/oncology groups, respectively (P=0.046). As with the difference in the outcomes observed between pediatrics and hematology departments for adolescents with acute lymphoblastic leukemia, the outcomes of patients with PCNSL may differ between neurosurgery and hematology/oncology departments.

Administration of combined venetoclax and azacitidine in a patient with acute myeloid leukemia and multiple comorbidities undergoing dialysis: A case report.

Patients with acute myeloid leukemia (AML) who have comorbidities have limited treatment options, thereby resulting in poor prognosis. Venetoclax, a specific B-cell lymphoma-2 inhibitor, has recently been approved for AML in combination with hypomethylating agents; however, only one report has described its use in patients undergoing dialysis. Herein, we report the effectiveness of combined venetoclax and azacitidine in a 73-year-old man with AML undergoing dialysis and who was ineligible for standard therapies. The safety of venetoclax and azacitidine in patients undergoing dialysis has been reported, and their combination may be a feasible option for patients with AML undergoing dialysis.

Severe systemic inflammation mimicking TAFRO syndrome following COVID-19.

TAFRO syndrome is a rare systemic inflammatory disease. Its pathogenesis mainly involves excessive cytokine secretion and autoimmune dysfunction. Although its etiology is unclear, some viral infections have been reported to cause it. Here, we report a case of severe systemic inflammation mimicking TAFRO syndrome that arose after COVID-19. A 61-years-old woman suffered from a continuous fever, ascites, and edema after contracting COVID-19. She developed progressive thrombocytopenia, renal failure, and elevated C-reactive protein levels. She was tentatively diagnosed with multisystem inflammatory syndrome in adults (MIS-A) and received steroid pulse therapy. However, she exhibited worsening fluid retention and progressive renal failure, which are not typical of MIS-A. A bone marrow examination showed reticulin myelofibrosis and an increased number of megakaryocytes. Although a definitive diagnosis of TAFRO syndrome was not made according to current diagnostic criteria, we determined that her symptoms were clinically consistent with those of TAFRO syndrome. Combination therapy, including steroid pulse therapy, plasma exchange, rituximab, and cyclosporine, improved her symptoms. There are pathological similarities between hyperinflammation that arises after COVID-19 and TAFRO syndrome in terms of the associated cytokine storms. COVID-19 may have triggered the development of systemic inflammation mimicking TAFRO syndrome in this case.

Rituximab Monotherapy for Grade 2-3 Lymphomatoid Granulomatosis with Central Nervous System Involvement in a Patient Receiving Methotrexate for Rheumatoid Arthritis.

Lymphomatoid granulomatosis (LYG) is a rare lymphoproliferative disorder (LPD). The optimal management strategy of methotrexate (MTX) related-LPD with central nervous system (CNS) involvement and histological features of LYG remains unclear. We herein report a case of grade 2-3 LYG in a rheumatoid arthritis patient, in which an intracranial mass accompanied by hemorrhaging and pulmonary and skin lesions developed. The patient received successful rituximab monotherapy. The tumor cells in the skin and brain showed monoclonal and oligoclonal proliferation, respectively. Our case suggests that rituximab monotherapy may be effective against MTX-LPD with CNS involvement, especially in cases with LYG histology.

An evaluation based on relative treatment intensity in older patients treated with reduced-dose R-THP-COP therapy for diffuse large B-cell lymphoma: A multicenter retrospective cohort study.

INTRODUCTION: The number of older patients with diffuse large B-cell lymphoma (DLBCL) is increasing. Although the standard treatment for newly diagnosed younger patients with DLBCL has been established, no consensus has been reached regarding the optimal chemotherapy intensity and regimen for older patients with DLBCL. In addition, no method for evaluating treatment intensity in retrospective studies when different numbers of chemotherapy courses are administered has been elucidated. MATERIALS AND METHODS: A multicenter retrospective analysis was conducted to evaluate the outcomes of a reduced-dose R-THP-COP regimen, which included 30 mg/m2 of pirarubicin, in 54 patients with DLBCL who were aged ≥75. To assess treatment intensity, we defined the relative treatment intensity (RTI) as the number of courses administered multiplied by the relative dose intensity (RDI). RESULTS: The estimated four-year overall survival rates (OS) of the patients aged 75-80 and ≥ 80 were 55.1% and 60.6%, respectively. There was no significant difference in four-year OS between these age groups. In our cohort, there was no significant difference in the estimated four-year OS between the patients who received reduced-dose R-THP-COP at an RDI of ≥61% and those that received it at an RDI of <61% (P = 0.35). On the other hand, the patients who received reduced-dose R-THP-COP at an RTI of ≥2.7 exhibited a significantly higher estimated four-year OS than those treated at an RTI of <2.7 (68.5% vs. 28.7%; P < 0.001). Multivariate analysis revealed that the RTI was a significant independent predictor of OS. The cumulative incidence of treatment-related mortality (TRM) at one year was 4.2% and 3.4% in the 75-80 and ≥ 80 age groups, respectively. The cumulative incidence of TRM was significantly worse among the patients with Charlson Comorbidity Index (CCI) scores of ≥2 than among those with CCI scores of 0 or 1. DISCUSSION: Our study suggests that the reduced-dose R-THP-COP regimen is a suitable treatment option for older patients with DLBCL, especially those with CCI scores of <2. Our study also showed that the RTI may be a valuable tool for assessing treatment intensity in retrospective studies involving older patients.

Acute-type acquired hemophilia A after COVID-19 mRNA vaccine administration: A new disease entity?

Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder. Various autoimmune diseases, including AHA, have been reported to occur after the administration of mRNA COVID-19 vaccines. However, the characteristics of these AHA cases remain unclear. We report a case in which AHA arose in a young patient after the administration of an mRNA COVID-19 vaccine, but improved rapidly. The patient's factor VIII (FVIII) inhibitor titer spontaneously decreased to less than half of that seen at diagnosis. One week after the initial immunosuppressive therapy, the FVIII inhibitor had disappeared. Our case suggests that AHA that arises in young patients after COVID-19 vaccination may resolve spontaneously, and the levels of FVIII inhibitors may decrease more rapidly in such cases than in idiopathic AHA. Unlike for immune thrombocytopenic purpura (ITP), no acute type of AHA has been recognized. This case suggests that just as there is an acute type of ITP that develops in children/after vaccination, there may be an acute type of AHA that arises in young patients that receive mRNA COVID-19 vaccines.

Sudden Cardiac Death in a Patient with Thrombotic Thrombocytopenic Purpura: A Case Report.

A 49-year-old female was admitted to our hospital with malaise and gross hematuria. As ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13) activity was absent and the ADAMTS13 inhibitor was detected, she was diagnosed with acquired thrombotic thrombocytopenic purpura (TTP). In addition to plasma exchange and corticosteroid therapy, she received rituximab therapy for inhibitor boosting but died suddenly of a cardiac arrest on day 9. The postmortem revealed microvascular platelet thrombi in multiple organs. In this case, the deterioration of the patient's clinical status was considered to have been caused by inhibitor boosting-induced systemic microvascular occlusion. In particular, her sudden death may have been due to cardiovascular microthrombosis. Since inhibitor boosting can cause TTP patients to deteriorate rapidly, it is crucial to manage TTP patients who undergo inhibitor boosting appropriately. The monitoring of cardiac complications in TTP patients may also be essential, especially in the acute phase.

Use of thromboelastography before the administration of hemostatic agents to safely taper recombinant activated factor VII in acquired hemophilia A: a report of three cases.

BACKGROUND: Acquired hemophilia A (AHA) is a rare autoimmune disease characterized by bleeding events. Recombinant activated factor VII (rFVIIa) is a first-line bypassing agent, which is effective against clinically significant bleeding. However, there is no standard way of tapering and discontinuing rFVIIa, mainly because there is no established method for monitoring rFVIIa therapy for AHA. CASE PRESENTATION: Here, we report three AHA cases, in which we adjusted the rFVIIa dosing interval based on the results of thromboelastography (TEG) performed just before the administration of the next dose of rFVIIa. The dosing interval of rFVIIa was prolonged based on the reaction rate time (R) according to TEG, which is correlated with coagulation factor activity. The R-value reference range reported by the manufacturer of the TEG system was used as a threshold for making decisions. In these three cases, there was no rebleeding, and the patients' ability to perform activities of daily living did not decline. CONCLUSION: Our cases suggest that conducting TEG-based monitoring just before the administration of the next dose of rFVIIa may be useful for guiding increases in the rFVIIa dosing interval without causing rebleeding events. Further investigations are warranted to examine how TEG could be used to determine the most appropriate rFVIIa dosing interval, e.g., through regular TEG-based monitoring, and the optimal TEG-derived threshold for indicating changes to the rFVIIa dosing interval.

Severe aplastic anemia after COVID-19 mRNA vaccination: Causality or coincidence?

The development of various autoimmune diseases has been reported after COVID-19 infections or vaccinations. However, no method for assessing the relationships between vaccines and the development of autoimmune diseases has been established. Aplastic anemia (AA) is an immune-mediated bone marrow failure syndrome. We report a case of severe AA that arose after the administration of a COVID-19 vaccine (the Pfizer-BioNTech mRNA vaccine), which was treated with allogeneic hematopoietic stem cell transplantation (HSCT). In this patient, antibodies against the SARS-CoV-2 spike protein were detected both before and after the HSCT. After the patient's hematopoietic stem cells were replaced through HSCT, his AA improved despite the presence of anti-SARS-CoV-2 antibodies. In this case, antibodies derived from the COVID-19 vaccine may not have been directly involved in the development of AA. This case suggests that the measurement of vaccine antibody titers before and after allogeneic HSCT may provide clues to the pathogenesis of vaccine-related autoimmune diseases. Although causality was not proven in this case, further evaluations are warranted to assess the associations between vaccines and AA.