[Transformation of follicular lymphoma to classical Hodgkin lymphoma during observation].

A 44-year-old female was diagnosed with follicular lymphoma (FL), grade 3A stage III, by right cervical lymph node biopsy at the age of 43 years. The patient chose to not receive the treatment despite the high tumor burden. The patient came back after 18 months with respiratory distress and had systemic infiltration and pleural effusion. Positron emission tomography (PET)/computed tomography (CT) showed fluorine-18 deoxyglucose accumulation with maximum standardized uptake value ranging from 10 to 18 in bone marrow, liver, spleen, lung, and systemic lymph nodes (cervical, supraclavicular, infraclavicular, axillary, mediastinal, hilar, para-aortic, iliac, and inguinal). Left inguinal lymph node biopsy revealed mixed cellularity classical Hodgkin lymphoma (CHL), which was thought to be an FL transformation or a composite condition. The patient was treated with A + AVD and achieved lymph node shrinkage as well as improvement of tumor fever and pleural effusion. Interim PET/CT showed improvement in most parts after two courses; however, it revealed some new or progressive lesions in the bone marrow and left cervical lymph nodes. Left cervical lymph node biopsy revealed nodular sclerosis CHL. The patient was treated with ESHAP, which resulted in stable disease; following this, the patient was treated with nivolumab, which was highly effective. FL transformation to CHL is rare, and this is the first report of such transformation without treatment.

[The efficacy of alemtuzumab for pure red cell aplasia associated with autoimmune polyendocrine syndrome type 1].

We present a case of a 41-year-old woman who was diagnosed with autoimmune polyendocrine syndrome type 1 (APS-1) at the age of 2. She developed severe anemia and was diagnosed with pure red cell aplasia (PRCA) and T-cell large granular lymphocyte leukemia at the age of 34. The pathogenesis of APS-1 is based on the presence of an inactive mutation in the autoimmune regulator gene on thymic medullary epithelial cells. It is thought that the autoimmune T cells generated by impaired negative selection in the thymus induce PRCA. The patient was treated with immunosuppressive therapy (ciclosporin, antithymocyte globulin, prednisolone, and cyclophosphamide) for a long time by her previous doctor. After a long period of remission and exacerbation, she became dependent on blood transfusion approximately at the age of 40 and was transferred to our hospital. At our hospital, alemtuzumab treatment resulted in the disappearance of large granular lymphocytes and improvement of anemia. We report this case as a valuable demonstration of the efficacy of alemtuzumab for treating PRCA associated with APS-1.

Romiplostim is effective for eltrombopag-refractory aplastic anemia: results of a retrospective study.

Eltrombopag (EPAG) and romiplostim (ROM), thrombopoietin receptor-agonists with demonstrated efficacy against aplastic anemia (AA) in prospective controlled studies, were authorized in Japan for use in adults with aplastic anemia in 2017 and 2019, respectively. So far, no data are available on the potential contribution of switching from ROM to EPAG or vice versa in terms of efficacy or tolerance. Efficacies and tolerance profiles of ten patients, who failed to respond to the maximum dose of EPAG and then switched to ROM, were evaluated. All ten patients received a maximum dose of ROM (20 µg/kg/week). At a median follow-up of twelve months, seven of ten patients (70%) had achieved either neutrophil, erythroid, or platelet response, including one complete response. No patients showed platelet count fluctuations that were reported during ROM treatment for immune thrombocytopenia. In univariate analysis of the relationship between efficacy and demographics, the response had a correlation with neither factors. None of the patients stopped the ROM treatment because of adverse events. Although a larger number of patients and a longer follow-up period are needed to confirm our findings, our results show the efficacy of ROM in patients with EPAG-refractory AA.

Disappearance of monosomy 7 in a patient with aplastic anemia after eltrombopag treatment.

We present the case of a patient with aplastic anemia (AA) who was treated with eltrombopag. To the best of our knowledge, this is the first report of the disappearance of monosomy 7 after eltrombopag treatment. The patient was a 77-year-old woman with intraoral hematoma and purpura who was diagnosed with very severe AA with a normal karyotype. After combination therapy with rabbit antithymocyte globulin, cyclosporin, and granulocyte-colony-stimulating factor (G-CSF), pancytopenia transiently improved. When pancytopenia worsened again, the patient was administered darbepoetin alfa for renal anemia and danazol. Bone marrow examination showed 2.5% blasts with the karyotype 45,XX,-7[17]/46,XX[3], and 87.0% of marrow cells had monosomy 7, as determined by 7q31 interphase fluorescence in situ hybridization (FISH) analysis. Pancytopenia was considered owing to the evolution of myelodysplastic syndrome, and we stopped G-CSF and darbepoetin treatment. As she refused treatment with a hypomethylating agent, considering her age, eltrombopag was started against refractory pancytopenia after obtaining informed consent. She showed an improvement in pancytopenia and became transfusion independent. After 1 year of eltrombopag treatment, bone marrow examination revealed 0.7% blasts with the karyotype 46,XX[20] and without monosomy 7 clone by FISH analysis. After a further 1 year of eltrombopag treatment with dose tapering, she has achieved a complete response. This case suggested that eltrombopag treatment is not necessarily contraindicated in patients with monosomy 7.

Generation of HIV-Resistant Macrophages from IPSCs by Using Transcriptional Gene Silencing and Promoter-Targeted RNA.

Highly active antiretroviral therapy (HAART) has markedly prolonged the prognosis of HIV-1 patients. However, lifelong dependency on HAART is a continuing challenge, and an effective therapeutic is much desired. Recently, introduction of short hairpin RNA (shRNA) targeting the HIV-1 promoter was found to suppress HIV-1 replication via transcriptional gene silencing (TGS). The technology is expected to be applied with hemato-lymphopoietic cell transplantation of HIV patients to suppress HIV transcription in transplanted hemato-lymphopoietic cells. Combination of the TGS technology with new cell transplantation strategy with induced pluripotent stem cell (iPSC)-derived hemato-lymphopoietic cells might contribute to new gene therapy in the HIV field. In this study, we evaluated iPSC-derived macrophage functions and feasibility of TGS technology in macrophages. Human iPSCs were transduced with shRNAs targeting the HIV-1 promoter region (shPromA) by using a lentiviral vector. The shPromA-transfected iPSCs were successfully differentiated into functional macrophages, and they exhibited strong protection against HIV-1 replication with alteration in the histone structure of the HIV-1 promoter region to induce heterochromatin formation. These results indicated that iPS-derived macrophage is a useful tool to investigate HIV infection and protection, and that the TGS technology targeting the HIV promoter is a potential candidate of new gene therapy.

[Successful treatment of large granular lymphocytic leukemia accompanied by refractory anemia with alemtuzumab].

A 39-year-old man with anemia presented at our hospital in November 2011. Peripheral blood analysis revealed lymphocytosis with a large granular lymphocyte (LGL) count of 2,272/µl, with CD3+, CD4-, CD8+, CD56-, TCR-αß+; Southern blotting analysis revealed clonal TCR Cß 1 gene rearrangement, leading to the diagnosis of T-LGL leukemia. In June 2012, the patient was administered with cyclophosphamide as an initial treatment because he developed transfusion-dependent anemia. His anemia improved, and the treatment was discontinued in March 2013. However, anemia recurred in March 2014. The administration of cyclophosphamide was resumed; however, it was subsequently replaced with cyclosporine because of the risk of secondary cancer due to the long-term use of cyclophosphamide. However, his anemia did not improve. Further, the patient was administered with prednisone, methotrexate, and pentostatin; however, the transfusion-dependent state persisted with the cumulative transfusion of 186 RBC units until March 2016. After CD52 expression on the surface of LGL cells was confirmed, treatment with alemtuzumab, which is a monoclonal antibody against CD52, was initiated in April 2016 and the dose was gradually increased from 3 mg to 30 mg thrice per week. The patient's anemia began to improve 1 week after initiating alemtuzumab treatment, and he became transfusion-independent in the second week. Although alemtuzumab treatment was discontinued at the fifth week on the basis of a positive test result for CMV antigenemia, the result consequently became negative after ganciclovir treatment. To date, the patient's hemoglobin level has been maintained at approximately 12 g/dl without any treatment. Herein we reported the case of a patient having LGL leukemia with refractory anemia that was successfully treated using alemtuzumab.

Efficacy of pomalidomide in a multiple myeloma patient requiring hemodialysis.

A 67-year-old male patient developed multiple myeloma with acute renal failure caused by myeloma kidney. Although a very good partial response was achieved with bortezomib with dexamethasone (BD) therapy under temporary dialysis, relapse occurred 3 years later. Thalidomide was added to the BD therapy but was discontinued because of drug-induced eczema. Subsequently, bone lesions and chromosomal abnormalities appeared. Because renal failure progressed with increased serum free light chain levels, maintenance hemodialysis was introduced. Administration of lenalidomide showed no effect due to intolerance. BD therapy was re-started, but diffuse ground-glass opacity with pleural effusion was observed in both lungs, leading to the discontinuation of this treatment. Subsequently, pomalidomide with low-dose dexamethasone (PD) therapy was begun under hemodialysis. Seven cycles of PD therapy maintained disease stability. However, a dosage adjustment was needed because of pancytopenia. Maintaining the therapeutic effect apparently required a pomalidomide dose of 4 mg/day in this case. These findings suggest that pomalidomide is useful in relapsed or refractory advanced myeloma, with careful dose reductions and supportive care, even for patients with renal failure requiring hemodialysis.