Tadaaki Inano

Introduction: Splenomegaly is frequently encountered in patients with myeloproliferative neoplasms. Splenomegaly is associated with an increased incidence of engraftment failure during allogeneic hematopoietic stem cell transplantation (allo-HSCT), and some centers perform prior low-dose splenic irradiation (LDSI) which has been reported to be both safe and effective. However, we report conflicting results by presenting three allo-HSCT patients undergoing LDSI that subsequently developed sinusoidal obstruction syndrome (SOS). Case Presentation: The underlying diseases of the presented cases were atypical chronic myeloid leukemia, secondary myelofibrosis following essential thrombocythemia, and acute myeloid leukemia transforming from myeloproliferative neoplasm, unclassifiable. Endothelial Activation and Stress Index (EASIX) scores of the 3 patients were 0.40, 3.82, and 4.40, respectively. Conclusion: SOS is a potentially fatal complication of allo-HSCT, and the mortality rates of severe cases are reported to be above 80%. LDSI has not been recognized as a risk factor of SOS to date. Alternative management methods of splenomegaly during allo-HSCT such as ruxolitinib administration may be safer compared to LDSI.

Summary: Risk‐adapted therapy is recommended to prevent major clinical complications, such as thrombo‐haemorrhagic events, in patients with essential thrombocythaemia (ET). In this study, we analysed the association between non‐driver gene mutations and thrombo‐haemorrhagic events in 579 patients with ET. ASXL1 and TP53 mutations were frequently identified in patients with ET complicated by thrombosis (22.7% and 23.1%, respectively), and the DNMT3A mutation was frequently identified in patients who experienced haemorrhage (15.2%). Multivariate analyses of thrombosis‐free survival (TFS) revealed that ASXL1 and TP53 mutations are associated with thrombosis (hazard ratio [HR] = 3.140 and 3.752 respectively). Patients harbouring the ASXL1 or TP53 mutation had significantly worse TFS rates than those without mutation (p = 0.002 and p < 0.001 respectively). Furthermore, JAK2V617F‐mutated patients with accompanying ASXL1 mutations showed significantly shorter TFS compared with those without ASXL1 mutations (p = 0.003). Multivariate analyses of haemorrhage‐free survival (HFS) revealed that the DNMT3A mutation (HR = 2.784) is associated with haemorrhage. DNMT3A‐mutated patients showed significantly shorter HFS than those without the mutation (p = 0.026). Non‐driver gene mutations should be considered in treatment strategies and may provide important information for personalised treatment approaches.

Since MPL mutation is a rare driver gene mutation found in a small number of essential thrombocythemia (ET) patients, the clinical characteristics of patients with MPL mutations and their association with thrombotic events have not yet been elucidated in Japan. We enrolled 579 Japanese ET patients based on the diagnostic criteria of the WHO classification 2017 and compared clinical characteristics of MPL-mutated patients (n = 22; 3.8%) to JAK2V617F-mutated (n = 299; 51.6%), CALR-mutated (n = 144; 24.9%), and triple-negative (TN) (n = 114; 19.7%) patients. Thrombosis during follow up was observed in 4 out of 22 (18.2%) in the MPL-mutated group, which was the highest among all driver gene mutation groups (JAK2V617F-mutated, 8.7%; CALR-mutated, 3.5%; TN,1.8%). The MPL- and JAK2V617F-mutated groups had worse thrombosis-free survival (TFS) than the CALR-mutated (p = 0.043) and TN groups (p = 0.006). Univariable analysis revealed that a history of thrombosis was a possible risk factor for thrombosis among MPL-mutated patients (hazard ratio: 9.572, p = 0.032). MPL-mutated ET patients should require more intensive management to prevent recurrence of thrombosis.

Paroxysmal cold hemoglobinuria (PCH) is an extremely rare subtype of autoimmune hemolytic anemia (AIHA) in adults. PCH is caused by the biphasic Donath–Landsteiner (DL) antibody which fixes complement to red blood cells at low temperatures and dissociates at warmer temperatures, leading to complement‐mediated intravascular hemolysis. Autoimmune hematological disorders including AIHA and immune thrombocytopenia have been reported to develop following the mRNA COVID‐19 vaccination. However, PCH developing subsequent to mRNA vaccination has never been reported. We report a 59‐year‐old male who developed PCH approximately a month after his second mRNA COVID‐19 vaccination.

TAFRO syndrome is a relatively new disease entity first reported in 2010. We report a case of TAFRO syndrome accommodated by abnormal exacerbation of moderately differentiated gastric adenocarcinoma. The pathophysiology of TAFRO syndrome is largely unknown, but because the disease often responds to immunosuppressive therapy and also because T follicular helper (Tfh) cells are reported to be drastically decreased in TAFRO syndrome, involvement of a dysregulated immune system can be speculated. Growing evidence points toward a pivotal role of Tfh cells in tumor immunity through supporting ectopic lymphoid structures, which are recruitment sites for cells directly engaging in antitumor activity such as CD8⁺ T cells, NK cells, and macrophages. In fact, Tfh cells are reported to positively correlate with longer survival in human colorectal and breast cancer. Combined with our observations of hyperprogressive gastric cancer in the presented patient, an impaired tumor immunity is strongly indicated in TAFRO syndrome.