Mineo Kurokawa’s research while affiliated with The University of Tokyo and other places

Erdheim-Chester disease (ECD) is a rare histiocytic disorder that poses significant diagnostic challenges owing to its non-specific symptoms. We herein report the case of a 71-year-old woman with exertional dyspnea and bilateral edema who was initially suspected to have heart failure based on cardiomegaly and pericardial effusion. Pericardiocentesis with a cell block analysis revealed histiocytes that were positive for CD68 and negative for CD1a, thus increasing the likelihood of ECD. The bone biopsy results were consistent, thus leading to a diagnosis of ECD. This case highlights the diagnostic utility of a pericardial fluid cell block analysis, which offers a minimally invasive method to identify ECD in patients with significant pericardial effusion.

Introduction Drug‐induced thrombocytopenia (DITP) can be caused by many kinds of drugs. Its treatment generally involves discontinuation of the responsible drug. Case Presentation A 70‐year‐old man received a subcutaneous injection of long‐acting (24‐week) leuprorelin depot as androgen deprivation therapy for prostate cancer. Four days after the injection, he presented with gingival bleeding and his platelet count was remarkably decreased (< 1000/μL). There was no sign of malignancy but the presence of megakaryocytes on bone‐marrow examinations. Considering immune and/or DITP, he started immunoglobulin and steroid therapy while stopping all suspected medications. However, even a month later, his platelet count did not recover with the need for frequent platelet transfusions. Therefore, he eventually underwent surgical resection of the leuprorelin injection site. After the surgery, his platelet count drastically recovered and platelet transfusion became unnecessary. Conclusion We report a case of leuprorelin‐induced thrombocytopenia that was successfully treated with surgical resection of the injection site.

Although genetic abnormalities are increasingly crucial for diagnosing and classifying haematopoietic diseases, dysplasia remains crucial for distinguishing myelodysplastic neoplasms (MDS) from aplastic anaemia (AA). Erythroid dysplasia may be observed in AA, complicating the differentiation between these conditions. In a previous study using the data from the Japan Idiopathic Myelodysplastic Syndrome Study Group's registry, we found that erythroid dysplasia does not affect the prognosis of AA. This current study was designed to compare the prognosis of patients with lower risk hypoplastic MDS (LR‐hMDS), as determined by our review, and patients with severe AA (SAA), all enrolled concurrently, to validate our diagnostic approach. Stringent criteria were used to rule out MDS, considering bone marrow cellularity and megakaryocyte counts, with a confirmed AA diagnosis only following a reduced megakaryocyte count. The study comprised 39 severe cases extracted from a cohort of 100 AA patients previously reported and 41 patients with LR‐hMDS. Significant differences in overall and leukaemia‐free survival were observed between the two groups (p < 0.0001). Even among patients undergoing immunosuppressive therapy, a marked prognostic distinction became evident after 5 years, although their response to the therapy did not differ significantly. Therefore, the megakaryocyte count is pivotal in differentiating MDS from AA.

Introduction: Fibrillary glomerulonephritis (FGN) is a rare form of immune complex-mediated primary glomerular disease frequently coexisting with malignancies or autoimmune diseases. The kidney prognosis is extremely poor, with approximately 50% of patients progressing to end-stage kidney disease within two to four years after diagnosis. However, no established treatment currently exists. Case Presentation: Here we describe a rare case of FGN diagnosed in a patient progressing from monoclonal gammopathy to multiple myeloma. The histopathological findings of the kidney biopsy were consistent with classical FGN and revealed no evidence of myeloma cast nephropathy. Albumin-dominant, Bence Jones protein-negative proteinuria further supported this diagnosis. The patient was successfully treated with anti-myeloma chemotherapies including autologous stem cell transplant, resulting in significant improvement in kidney function. Conclusion: Based on our experience, secondary FGN associated with plasma cell neoplasms may represent a rare entity that responds favorably to anti-myeloma therapies. Initial investigations to rule out coexistent plasma cell neoplasms are crucial for the optimal management of FGN patients.

Fluid retention presenting as effusions in body cavities is sometimes encountered following allogeneic stem cell transplantation (allo-HSCT). It is unclear whether cavity effusions at independent sites may serve as cumulative correlates of fluid overload and whether a higher number of effusion sites are associated with a worse prognosis. Here, we comprehensively reviewed pleural, peritoneal, and pericardial effusions in 178 first allo-HSCT recipients retrospectively. A total of 123 (69.1%) patients developed effusions in any cavity. New pleural, peritoneal, and pericardial effusions were found after allo-HSCT in 106, 88, and 53 patients, at a median of 38.0 (range, 2–2950), 22.5 (range, 2–1324), and 40 (range, 2–945) days, respectively. The cumulative incidence at day 100 was 41.0%, 40.4%, and 20.8%, respectively. Of the 92 patients who presented with effusions by day 100, 28 patients presented with effusion in a single cavity, 39 in two cavities, and 25 in all three cavities. The 2-year overall survival rates of patients with effusions in zero, one, two, and three cavities by day 100 were 86.1%, 60.0%, 59.6%, and 18.8%, respectively, showing an additive adverse association with outcome. Prospective studies to further characterize fluid dynamics following allo-HSCT are warranted.

The incidence of leukemic conversion during the clinical course of paroxysmal nocturnal hemoglobinuria (PNH) has been reported to be 0.6–2.9%. Such an association is logically linked to the progression of PNH to acute leukemia, especially the M6 subtype of acute myeloid leukemia (AML-M6). In many of these cases (11/26, 42%), leukemic conversion from PNH is associated with development of AML-M6. A literature review including our cases showed that this leukemic conversion from PNH has two distinct development patterns. In type 1, leukemic clones were derived from non-PNH clones in most cases, and the PNH phenotype of erythrocytes disappeared with progression. In one of our cases, however, the patient was diagnosed with concomitant PNH and AML-M6, and leukemic cells were observed alongside CD55-negative and CD59-negative PNH clones. In Type 2 cases such as this one, conversion of PNH is characterized by the coexistence of leukemic cells with PNH clones. Flow cytometry revealed that CD34-positive blast cells were deficient in CD55 and CD59. In Type 2, PNH clones do progress into malignancies, albeit rarely, demonstrating a distinct second development pattern of leukemic conversion from PNH.

Type I cryoglobulinemia is typically associated with hematological malignancies such as B-cell lymphomas and plasma cell neoplasms. Its treatment basically targets underlying hematological malignancies, and the prognosis remains unsatisfactory. Despite several reports of type I cryoglobulinemia treated with bortezomib-based regimens, little is available on the treatment of bortezomib-resistant cases. We report a case of severe type I cryoglobulinemia associated with plasma cell neoplasm, refractory to bortezomib and daratumumab, which was successfully managed with a combination of carfilzomib, cyclophosphamide, and dexamethasone (KCd therapy). No sign of relapse has been seen for more than 3 years with maintenance therapy with ongoing carfilzomib. This case highlights the potential efficacy of carfilzomib-based regimens in bortezomib-resistant type I cryoglobulinemia, offering a promising option for cases refractory to conventional treatments.

CD19 chimeric antigen receptor (CAR) T-cell therapy is associated with potentially life-threatening immunological toxicities. We herein report an 81-year-old woman who experienced multiple perforations in the small intestine 8 days after tisagenlecleucel infusion for relapsed and refractory follicular lymphoma with no gastrointestinal involvement. A pathological examination of the resected small intestine revealed multiple ulcers that formed after resection but without lymphoma involvement. Based on these findings, tocilizumab used for cytokine release syndrome was considered to be associated with these lesions. This case illustrates a previously undescribed but serious sequela of CAR T-cell therapy, calling for relevant personnel to be vigilant about gastrointestinal symptoms.

Background Pleural effusion and ascites developing after allogeneic hematopoietic stem cell transplantation (allo‐SCT) are generally associated with inferior overall survival (OS); however, the prognostic value of pretransplant effusion on transplant outcomes remained unclear. Methods We retrospectively evaluated minimal pleural effusion and ascites detected by computed tomography in 248 consecutive adult patients who underwent their first allo‐SCT from January 2007 to December 2022. Results Forty‐eight patients demonstrated minimal pleural effusion or ascites within 100 days before transplantation (Effusion group) and the other 200 had no effusion (No effusion group). Serum albumin level was significantly lower in the Effusion group than in the No effusion group (median 3.8 vs. 3.4 g/dL, p < 0.001). Performance status (PS) was significantly inferior and refined disease risk index tended to be higher in the Effusion group. The 2‐year OS rate after transplantation was significantly worse in the Effusion group (57.1% vs. 36.7%, p < 0.001). The Effusion group had a significantly lower cumulative incidence of neutrophil and platelet engraftment and higher hepatic veno‐occlusive disease. Moreover, a tendency toward higher cumulative incidence of relapse and non‐relapse mortality was shown in the Effusion group. In multivariate analysis, the Effusion group had a significantly inferior OS with a hazard ratio of 1.848 (95% confidence interval 1.231–2.774), even after adjustment for disease risk, serum albumin level, PS, and Hematopoietic Cell Transplant‐Comorbidity Index points. Conclusion Reflecting high disease activity and impaired general condition, pretransplant effusion can be a complementary indicator for poor prognosis in allo‐SCT.

Methotrexate-associated lymphoproliferative disorder (MTX-LPD) constitutes a subset of lymphoid proliferations and lymphomas that are associated with immune deficiency and dysregulation. The clinical management of MTX-LPDs is contingent on their histopathological subtypes. Polatuzumab vedotin is a novel therapeutic approach that is particularly beneficial for selecting patients with previously untreated diffuse large B-cell lymphoma (DLBCL); however, DLBCL-type MTX-LPD is still treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) because of the exclusion of MTX-LPD from clinical trials. We recently encountered a case of DLBCL-type MTX-LPD with parathyroid hormone-related protein-C (PTHrP)-mediated hypercalcemia that was managed with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP). We herein report our experience to encourage hematologists to explore the safe and effective use of Pola-R-CHP under such conditions.