Successful Treatment of Steroid-Refractory Immune Thrombocytopenia in a Patient Developing Multiple Myeloma While on Immune Checkpoint Inhibitor Therapy for Lung Cancer: A Case Report.

Immune checkpoint inhibitor-related thrombocytopenia (irTCP) is a relatively rare immune-related adverse event (irAE); however, overall survival may worsen when it occurs. Prolonged use of high-dose steroids can diminish the effectiveness of immune checkpoint inhibitor (ICI) therapy on the primary disease because of T lymphocyte suppression, thus early tapering is necessary. We experienced a rare case of a 79-year-old male who concurrently developed irTCP and multiple myeloma (MM) during treatment with ICIs for lung adenocarcinoma. The patient exhibited severe thrombocytopenia and elevated serum IgA levels. Based on various tests, we diagnosed MM and irTCP. Despite administering the standard bortezomib plus dexamethasone (Bd therapy) treatment for MM, there was no response and the irTCP was steroid-resistant. Consequently, we administered a regimen including daratumumab (DPd therapy) for steroid-resistant irTCP and refractory MM, which resulted in a response. As a result, we were able to avoid prolonged use of high-dose steroids and the patient is stable without exacerbation of lung adenocarcinoma for 1 year and 5 months after the onset of MM. To our knowledge, there are no cases of MM developing during ICI treatment and this is the first case report in which daratumumab was effective for the treatment of irTCP.

Accuracy of Seismic Response Evaluation of Two-Dimensional Analysis Model with Rigid Joints for RC Frame Buildings.

Three- or two-dimensional (2D) numerical models are used for the evaluation of the seismic performance of reinforced concrete (RC) buildings. This study examines a 2D numerical model for a specimen used in a full-scale four-story RC shaking-table test and evaluates the accuracy of the seismic response of the 2D numerical model, which is composed of a square fiber section model for the columns, a T-shape fiber section model for the beam and slab, and a rigid joint model for the beam-column joint. A parametric analysis of the effective slab width is performed to analyze its effects on the modal shape and natural period. The results suggest that the primary natural period of the considered model is almost identical to that associated with the experimental results. The applicability of the 2D numerical model for estimating the seismic response of the structure is established. By comparing the results of the seismic analysis and the experiment in the 50% amplitude of the JMA-Kobe wave, which corresponds to slightly exceeding VII on the modified Mercalli intensity scale, the root-mean-square percentage error of the 2D numerical model is 1.03% for the floor acceleration and 4.7% for the inter-story drift. Thus, the analytical model used in this study has sufficient accuracy in evaluating the seismic performance of buildings constructed in regions with a maximum seismic intensity of VII.

A case of Philadelphia chromosome-positive acute lymphocytic leukaemia with type I CD36 deficiency.

BACKGROUND: CD36 is a glycoprotein expressed on platelets and monocytes of the blood. There are two types of CD36 deficiency, type I and type II. Individuals with type I-deficiency do not express CD36 in any cell type and can produce the CD36 antibody, which causes pathological conditions, such as fetal/neonatal alloimmune thrombocytopenia (FNAIT) and platelet transfusion refractory (PTR), through antigenic exposure via transfusion or pregnancy. CASE PRESENTATION: We experienced a case of Philadelphia-positive acute lymphoblastic leukaemia with PTR. In addition to the CD36 antibody, multiple-specificity HLA antibodies were present in the patient's plasma, requiring transfusion of HLA-compatible and CD36-negative platelets (PC-HLA). Since the number of donors was limited, it was necessary to set-up a blood transfusion schedule so that hyper-fractionated cyclophosphamide, vincristine and doxorubicin therapy (hyper-CVAD) and ponatinib combination chemotherapy could be safely administered to achieve molecular remission. Rituximab administration resulted in reduced levels of both CD36 antibody and HLA antibody. Given the expression of CD36 on haematopoietic stem cells and the limited availability of CD36-negative PC-HLA, haematopoietic stem cell transplantation (HSCT) was not considered to be an option. CONCLUSION: If CD36-negative, allogeneic haematopoietic stem cell donors are unable to be found, the indications for HSCT in patients with type I CD36-deficiency should be carefully weighed. In the present case, molecular remission has been able to be maintained to the present day after completion of a two-year maintenance regimen.

Successful Treatment of Adolescents and Young Adults with Philadelphia-Negative Acute Lymphoblastic Leukemia by Novel L-Asparaginase-Intensified Induction Therapy and Cord Blood Transplantation: A Single-Center Decade Report.

A novel induction therapy, including intensive L-asparaginase, was designed in 2007 for patients aged <45 years with Philadelphia-negative acute lymphoblastic leukemia (ALL). We analyzed seven de novo cases and one case of recurrence who received this treatment. The median age was 21 years (range: 16-35 years). Four patients had T-ALL and the others had B-ALL. All the patients achieved complete remission and proceeded to cord blood transplantation. In the median 72-month follow-up, there were no cases of observed mortality or recurrence. Our results indicate scope for further development of both induction therapy and postremission therapy.

Induction of remission of relapsed acute myeloid leukemia after unrelated donor cord blood transplantation by concomitant low-dose cytarabine and calcitriol in adults.

Low-dose cytarabine and calcitriol (LDCA + VD3) combination therapy was performed in two adult patients with acute myeloid leukemia (AML) that relapsed within 1 yr after unrelated donor cord blood transplantation (URD CBT) performed in a relapse or non-remission stage. Concomitant aclarubicin was also administered in one patient. Remission because of recovery of donor cord blood hematopoiesis was obtained in both patients. The treatment was low intensive, and neither adverse effects in terms of digestive symptoms nor hypercalcemia was observed. Activity of daily life was maintained. The patients were followed as outpatients after remission, and the remission duration was approximately 6 months in both patients. Although LDCA + VD3 therapy is minimally intensive chemotherapy, it may prolong the survival time of patients with relapsed AML after URD CBT.

Phase I/II study of the rituximab-EPOCT regimen in combination with granulocyte colony-stimulating factor in patients with relapsed or refractory follicular lymphoma including evaluation of its cardiotoxicity using B-type natriuretic peptide and troponin T levels.

PURPOSE: Standard treatment for relapsed or refractory follicular lymphoma has not been established. Doxorubicin is often given during the initial treatment. The dosage or drugs chosen for salvage therapy are limited by doxorubicin-induced cardiomyopathy. EXPERIMENTAL DESIGN: The R-EPOCT (rituximab with etoposide, vincristine, pirarubicine, cyclophosphamide, and prednisone) regimen, in which less cardiotoxic pirarubicine is used instead of doxorubicin, with granulocyte colony-stimulating factor (G-CSF) was administered to 20 patients with relapsed or refractory follicular lymphoma. The safety (especially cardiotoxicity) and efficacy of this regimen were studied. As markers of cardiotoxicity, serum troponin T and plasma B-type natriuretic peptide (BNP) levels were measured. RESULTS: Adverse reactions occurred in 14 of the 20 patients and mainly consisted of grade 3/4 hematologic toxicity. In the evaluation of cardiotoxicity, the BNP level was slightly elevated before the treatment in two patients and the BNP level did not significantly increase after R-EPOCT treatment. The troponin T level was undetectable before and after the treatment in all patients. The response rate was 100%, with complete remission in 16 patients (80%). G-CSF administration increased both Fc gamma receptor type I expression on neutrophils and antibody-dependent cellular cytotoxicity activity. There were no significant differences in the levels of Fc gamma receptor type I expression nor antibody-dependent cellular cytotoxicity activity after three or five cycles of the treatment. CONCLUSION: We conclude that the combination of R-EPOCT and G-CSF is well tolerated. This regimen was not cardiotoxic. We are planning a randomized trial to compare the efficacy between R-EPOCT and a combination of R-EPOCT with G-CSF.