Efficacy and Safety of the Modified EPOCH Regimen (Etoposide, Vincristine, Doxorubicin, Carboplatin, and Prednisolone) for Adult T-cell Leukemia/Lymphoma: A Multicenter Retrospective Study.

BACKGROUND: We retrospectively analyzed patients with untreated aggressive adult T-cell leukemia/lymphoma who received the modified EPOCH (mEPOCH) regimen. PATIENTS AND METHODS: Patients received up to 6 mEPOCH cycles. Etoposide (50 mg/m2/day), doxorubicin (10 mg/m2/day), and vincristine (0.4 mg/m2/day) were each given as a continuous 96-hour infusion on days 1 to 4. Prednisolone (40 mg/m2/day) was given intravenously or orally on days 1 to 4 and then tapered and stopped on day 7, and carboplatin (dose calculated for each patient individually using Calvert's formula according to a target under the curve of 3 mg/mL/min) was given as a 2-hour intravenous infusion on day 6. RESULTS: In 103 patients, overall response rate and complete response rate were 58% and 25%, respectively. With a median follow-up of 8.9 months, the median survival time was 9.8 months (95% confidence interval, 7.2-13.9 months). The median progression-free survival (PFS) was 4.2 months (95% confidence interval, 3.4-5.7 months). Patients who completed ≥ 4 cycles experienced significantly better overall survival and PFS compared with those who completed < 4 cycles. Twenty-eight patients underwent allogeneic hematopoietic stem cell transplantation after mEPOCH and demonstrated significantly prolonged overall survival and PFS compared with those who did not undergo transplantation. CONCLUSION: The mEPOCH regimen is effective with tolerable adverse effects and may be an alternative treatment option for adult T-cell leukemia/lymphoma.

Upshaw-Schulman syndrome diagnosed during pregnancy complicated by reversible cerebral vasoconstriction syndrome.

Upshaw-Schulman syndrome (USS) is an inherited type of thrombotic thrombocytopenic purpura (TTP) that is extremely rare, but often diagnosed during pregnancy. Reversible cerebral vasoconstriction syndrome (RCVS) is the transient stenosis of several cerebral arteries that is frequently diagnosed post-partum. We describe a 28-year-old woman with USS complicated by RCVS after delivery that was treated by plasma exchange with a good outcome. She was referred to our hospital with thunderclap headache, anemia and thrombocytopenia that occurred immediately postpartum. She was diagnosed with TTP and multiple cerebral infarctions. Plasma exchange promptly improved her symptoms on hospital day 3. Moreover, multiple stenoses of cerebral arteries indicating RCVS were resolved. Since her sister also had an episode of thrombocytopenia during pregnancy, inherited TTP was suspected and genetic analyses confirmed USS. Pregnancy is a risk for not only TTP, but also RCVS. Endothelial damage might be an underlining cause and vasospasm after delivery is a trigger of RCVS. Plasma exchange was effective against both TTP and RCVS.

Methotrexate-associated lymphoproliferative disorders with angioimmunoblastic T-cell lymphoma-like features accompanied by gamma-heavy chain disease in a patient with rheumatoid arthritis.

Although gamma heavy chain disease (γ-HCD) lesions occasionally morphologically resemble angioimmunoblastic T-cell lymphoma (AITL), no association has been described in detail due to the rarity of the disease. In this report, we present a rare manifestation of methotrexate (MTX)-associated lymphoproliferative disorders (LPDs) with AITL-like features accompanied by γ-HCD in a 75-year-old man with rheumatoid arthritis (RA). A biopsy specimen was evaluated using immunohistochemistry, clonal analyses of immunoglobulin VH and T-cell receptor γ gene rearrangements by polymerase chain reaction, and Sanger sequencing for confirmation of the structure of deleted γ-HCD clones. The histological features characterized by proliferation of CD4- and PD-1-positive medium-sized T cells and arborizing high endothelial venules together with numbers of small lymphocytes, eosinophils, plasma cells, and histiocytes in the background mimicked those of AITL, but did not completely fulfill the diagnostic criteria. Clonal analysis demonstrated that the specimen contained multiple LPDs of both B-cell and T-cell lineages. Sequence analysis confirmed the co-existence of a clone responsible for production of the abnormal heavy chain. This report provides new insights into the pathology of γ-HCD. Multiple host-derived factors (e.g., RA and/or use of MTX) may be responsible for the occurrence of LPDs of multiple lineages within a single lymph node.

Fatal Disseminated Tuberculosis during Treatment with Ruxolitinib Plus Prednisolone in a Patient with Primary Myelofibrosis: A Case Report and Review of the Literature.

A 73-year-old man with primary myelofibrosis (PMF) was being treated with hydroxyurea, which was changed to ruxolitinib treatment because of worsening constitutional symptoms. Although ruxolitinib rapidly induced relief, he developed a high-grade fever. A comprehensive fever work-up found no apparent cause of the fever, except for PMF. Therefore, we increased the dose of ruxolitinib and added prednisolone, which was gradually withdrawn with resolution of the fever. However, the patient subsequently developed disseminated tuberculosis and died eight months after initiation of ruxolitinib. Our case highlights the importance of assessing and monitoring the immune status of patients receiving ruxolitinib.

Spontaneous splenic rupture in a patient with light-chain deposition disease undergoing autologous peripheral blood stem cell transplantation.

Light-chain deposition disease (LCDD) is a rare plasma cell neoplasm that secretes an abnormal immunoglobulin light chain, which is deposited in tissues, leading to organ dysfunction. Spontaneous splenic rupture is a rare and life-threatening complication of treatment with granulocyte colony-stimulating factor (G-CSF). Herein, we describe spontaneous splenic rupture after the administration of lenograstim to a patient with LCDD undergoing autologous stem cell transplantation (ASCT). The patient was successfully treated by transcatheter embolization of the splenic artery, and long-term stringent complete remission was attained. Plasma cell neoplasms, including multiple myeloma with amyloidosis, are among the most commonly reported conditions associated with spontaneous splenic rupture in patients undergoing ASCT. This finding suggests that, in addition to the effect of G-CSF on the spleen, a combination of factors, including tissue vulnerability induced by the infiltration of abnormal immunoglobulins, may be involved in the pathogenesis of spontaneous splenic rupture. Notably, splenomegaly is not always evident in these patients. Surgical treatment may not be an option, because of severe myelosuppression, and thus less invasive treatment using transcatheter embolization may be feasible.

Intravascular Large B-Cell Lymphoma Complicated by Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis that was Successfully Treated with Rituximab-Containing Chemotherapy.

A 64-year-old woman had suffered from painful livedo reticularis for 2 years and was referred to us due to fever, anasarca and paresthesia of the lower limbs. Serum proteinase-3-anti-neutrophil cytoplasmic antibody (ANCA) was positive. Abnormal lymphocytes were found in the cerebrospinal fluid and bone marrow. Skin biopsy revealed large atypical lymphoid cells with CD20 positivity lodged in the small vessels and neutrophilic infiltration into the arterial vascular wall with fibrinoid degeneration. A diagnosis of intravascular large B-cell lymphoma complicated by ANCA-associated vasculitis was made, and rituximab-containing chemotherapy followed by prednisolone was quite effective for both lymphoma and ANCA-associated vasculitis.

Pituitary and adrenal involvement in diffuse large B-cell lymphoma, with recovery of their function after chemotherapy.

BACKGROUND: Diffuse large B-cell lymphoma sometimes involves the endocrine organs, but involvement of both the pituitary and adrenal glands is extremely rare. Involvement of these structures can lead to hypopituitarism and adrenal insufficiency, and subsequent recovery of their function is rarely seen. The present report describes an extremely rare case of pituitary and adrenal diffuse large B-cell lymphoma presenting with hypopituitarism and adrenal insufficiency with subsequent recovery of pituitary and adrenal function after successful treatment of the lymphoma. CASE PRESENTATION: A 63-year-old Japanese man was referred to our hospital due to miosis, ptosis, hypohidrosis of his left face, polydipsia and polyuria. 18F-fluorodeoxy glucose positron emission tomography / computed tomography revealed hotspots in the pituitary gland, bilateral adrenal glands and the apex of his left lung. Surgical biopsy from the pituitary lesion confirmed the diagnosis of diffuse large B-cell lymphoma, with lymphoma cells replacing normal pituitary tissue. Endocrine function tests revealed adrenal insufficiency and panhypopituitarism, including a possible affection of the posterior pituitary. Hormone replacement therapy with desmopressin and hydrocortisone was started. Chemotherapy consisted of six courses of R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisolone) and two courses of high-dose methotrexate followed by autologous hematopoietic stem cell transplantation. Subsequently, his pituitary and bilateral adrenal lesions resolved, and serial endocrine function tests showed gradual improvement in pituitary and adrenal function. CONCLUSIONS: The present report describes an extremely rare case of diffuse large B-cell lymphoma with involvement of both the pituitary and bilateral adrenal glands. R-CHOP and high-dose methotrexate therapy followed by autologous hematopoietic stem cell transplantation was quite effective, and panhypopituitarism and adrenal insufficiency improved to almost normal values after successful treatment of the lymphoma with chemotherapy.

[Analyses of plasma thrombopoietin levels in patients with thrombocytopenia].

We measured plasma levels of thrombopoietin (TPO) in several patients with thrombocytopenia. Similar to previous reports, TPO levels in aplastic anemia (N=9) were markedly higher than those in idiopathic thrombocytopenic purpura (N=10): 16.19+/-9.07 fmol/ml and 1.21+/-1.06 fmol/ml, respectively. In patients with secondary failure of platelet recovery (N=7) as well as primary failure after hematopoietic stem cell transplantation, TPO levels were very high, reflecting impaired platelet production due to GVHD, drug treatments, and infection. When using new drugs such as TPO-receptor agonists, measurement of TPO levels might be important to differentiate the mechanism of thrombocytopenia.