Thrombocytopenia and Anemia with Anti-c-Mpl antibodies Effectively Treated with Cyclosporine in a Patient with Rheumatoid Arthritis and Chronic Renal Failure.

A 61-year-old woman with rheumatoid arthritis who was undergoing hemodialysis for end-stage renal failure was transferred to our hospital due to severe thrombocytopenia and anemia. A bone marrow biopsy showed the complete absence of megakaryocytes and erythroblasts. Cyclosporine treatment resulted in the improvement of her megakaryocyte and erythroblast levels, and a decrease in her serum level of anti-c-Mpl (thrombopoietin receptor) antibodies. After this initial improvement, her anemia progressively worsened, despite the continuous administration of immunosuppressive therapy with cyclosporine. Her platelet and leukocyte counts remained stable. This is the first report of a probable case of anti-c-Mpl antibody-associated pure red cell aplasia and acquired amegakaryocytic thrombocytopenic purpura.

[Successful treatment with dose-adjusted EPOCH-R for triple-hit lymphoma having BCL2, BCL6 and MYC translocations].

Double- and triple-hit lymphomas (DHL/THL), high-grade B-cell lymphomas with an extremely poor prognosis, are defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint. The successful use of dose-adjusted (DA) EPOCH-R in patients with MYC-positive lymphoma and Burkitt lymphoma (BL) was recently reported. A 74-year-old man with acute renal dysfunction and hyperkalemia was transferred to our emergency center by ambulance. PET-CT revealed a left renal hilar mass enveloping the abdominal para-aortic domain and bladder and hydronephrosis. High (18)F-FDG uptake revealed lymph node, peritoneum, and multiple bone metastases. Analysis of the bone marrow aspirate revealed abnormal lymphoid cells with deeply basophilic cytoplasm and numerous vacuoles resembling Burkitt cells. Chromosomal analysis revealed a complex chromosomal karyotype, including t(14;18)(q32;q21), and FISH analysis confirmed split BCL2, BCL6, and MYC signals. Bone marrow biopsy revealed diffusely infiltrating large abnormal lymphoid cells with a CD10⁺, CD20⁺, BCL2⁺, BCL6⁺, c-MYC⁺ and MUM1(-) immunophenotype. B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and BL, was diagnosed. The patient achieved a partial response after eight courses of DA-EPOCH-R chemotherapy. Our experience suggests that DA-EPOCH-R may be an effective treatment for DHL/THL.

Identification of anti-thrombopoietin receptor antibody in prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation treated successfully with eltrombopag.

A 55-year-old female with stage IVA follicular lymphoma in third complete remission underwent allogeneic peripheral blood stem cell transplantation. Neutrophil engraftment was achieved on day +18; however, platelet counts remained below 10 × 10(3)/µL, necessitating transfusions twice a week for more than 3 months. Bone marrow showed a decreased number of megakaryocytes with hypolobulated nuclei. No graft versus host disease, viral infection, or disease relapse was observed. Furthermore, severe thrombocytopenia below 5.0 × 10(3)/µL refractory to transfusion appeared on day +240 after influenza virus infection. Treatments with intravenous immunoglobulin, romiplostim, and rituximab were administered without any recovery. Subsequently, eltrombopag was initiated on day +443, after which platelet counts rose gradually and continued to rise above 20 × 10(3)/µL after 10 weeks of administration. The serum thrombopoietin (TPO) level was markedly elevated, and anti-TPO receptor (TPOR) antibody was detected in the patient's serum. Anti-TPOR antibody may play an important role in some cases of prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation with unknown etiology, and eltrombopag could be a novel therapeutic option for such cases.

[Langerhans cell sarcoma developing acute myeloid leukemia after achieving complete response by THP-COP].

An 86-year-old man presented with enlarged left submandibular, left inguinal, and superficial femoral lymph nodes. He was diagnosed with Langerhans cell sarcoma (LCS) on the basis of the histopathological findings of the left inguinal lymph node biopsy. In addition, laboratory examinations revealed normocytic normochromic anemia, and bone marrow aspiration and biopsy led to a diagnosis of idiopathic cytopenia of undetermined significance (ICUS). Because of the patient's age, he was administered a regimen of cyclophosphamide, pirarubicin, vincristine, and prednisolone (THP-COP), and achieved a partial response after six courses. However, he developed acute myeloid leukemia (AML) 11 months after completion of the THP-COP therapy, and received only supportive care until his death. LCS is an extremely rare and aggressive dendritic cell neoplasm. To the best of our knowledge, only 67 cases have been reported in the literature. There are case reports describing the concurrence of hematological malignancies. Herein, we report the first documented development of LCS in a patient with ICUS who progressed to AML, and summarize the published data on the epidemiology of and therapeutic options for LCS.

Anti-erythropoietin receptor antibody-associated pure red cell aplasia accompanied by Coombs-negative autoimmune hemolytic anemia in a patient with T cell/histiocyte-rich large B cell lymphoma.

A 79-year-old female diagnosed with T cell/histiocyte-rich large B cell lymphoma in complete remission after six cycles of rituximab-combined chemotherapy developed severe anemia, reticulocytopenia, and bone marrow erythroid hypoplasia. She was diagnosed with pure red cell aplasia (PRCA) accompanied by Coombs-negative autoimmune hemolytic anemia evidenced by a lack of glycophorin-A-positive cells in the bone marrow, haptoglobin under the detection level, and a high titer of RBC-bound IgG. Anti-erythropoietin receptor (EPOR) antibody was detected in the serum, and oligoclonal α/ß and γ/δ T cells were also detected in her peripheral blood by Southern blotting analysis. Parvovirus B19 DNA was not detected by PCR. Although the treatment with rituximab had limited efficacy (specifically, only for hemolysis), subsequent cyclosporine therapy led to prompt recovery of erythropoiesis with the disappearance of anti-EPOR antibody and oligoclonal T cells. This is the first case report of anti-EPOR antibody-associated PRCA in a patient with malignant lymphoma treated successfully with cyclosporine.