[Good's syndrome developing hemophagocytic lymphohistiocytosis following thymectomy].

This report presents the case of a 68-year-old female patient previously diagnosed with thymoma by her local doctor. She was referred to our hospital for surgery, and the thymoma was removed and diagnosed as a World Health Organization (WHO) classification type AB thymoma. After surgery, she experienced general malaise, a loss of appetite, and weight loss, so she visited our hospital in May 2019. A blood test showed hypogammaglobulinemia and low B lymphocytes. A bone marrow examination revealed no morphological abnormalities. Flow cytometric analysis indicated a marked decrease in both the B cell-related surface markers CD19 and CD20 and the T cell-related surface marker CD4, and the CD4/CD8 ratio was also low. She was diagnosed with Good's syndrome, and immunoglobulin replacement therapy was administered. She subsequently developed hemophagocytic lymphohistiocytosis (HLH) due to infection and was treated according to the HLH2004 protocol, but she finally succumbed to multiple organ damage as a result of sepsis. Given that Good's syndrome is associated with both humoral and cellular immune dysfunctions, affected patients tend to develop severe infections and have a poor prognosis. In such cases, early detection, regular immunoglobulin replacement therapy, and infection prevention therapies are important.

[Significance of upper and lower gastrointestinal endoscopy for screening small intestinal lesions in non-Hodgkin's lymphoma].

The gastrointestinal tract is a common site for the occurrence of non-Hodgkin's lymphoma (NHL). NHL with gastrointestinal lesions may lead to clinically relevant intestinal complications such as obstruction, perforation, and exsanguination during the course of the disease. Consequently, patients with NHL are often examined by means of upper and lower gastrointestinal endoscopy at the initial visit. There are no clear guidelines regarding which patients should undergo capsule endoscopy (CE) and balloon enteroscopy for detecting small intestinal lesions. We retrospectively examined the feasibility of detecting small intestinal lesions in NHL using upper and lower gastrointestinal endoscopy. Between January 2007 and October 2015, 198 patients with primary NHL were admitted to our hospital. We collected data from 51 patients with NHL with gastrointestinal lesions diagnosed through upper and lower gastrointestinal endoscopy, CE, or double balloon enteroscopy (DBE). We chosed these cases that gastrointestinal lesions was doubted by an examination for image. Nineteen of these patients presented with lymphoma at the duodenal bulb/descending part when examined by upper gastrointestinal endoscopy and at the distal ileum when examined by lower gastrointestinal endoscopy. Ectopic jejunoileal lymphoma was simultaneously detected in 13 of the 19 patients (68.4%) through the use of CE or DBE. Conversely, of the 32 patients who did not exhibit lesions at the duodenal bulb/descending part or at the distal ileum, 6 patients (18.8%) presented with small intestinal lesions, indicating a smaller percentage compared to the patients with ectopic jejunoileal lymphoma. Based on these findings, a proactive search for small intestinal lesions using CE or DBE is recommended in patients with NHL presenting with lymphoma at the duodenal bulb/descending part or at the distal ileum, as examined using both upper and lower gastrointestinal endoscopy during the initial visit.

Spontaneous regression of methotrexate-related diffuse large B-cell lymphoma following bladder lesion resection.

A 71-year-old woman who had been treated with methotrexate (MTX) and prednisolone for rheumatoid arthritis since 2010 presented with hematuria. Cystitis was diagnosed. Chest and abdominal CT images revealed a bladder tumor, with lung and bilateral adrenal metastases. Transurethral resection of the bladder tumor (TUR-BT) confirmed these findings in September 2014. Histological findings of the bladder included large atypical lymphoid cells indicating diffuse large B-cell lymphoma. After TUR-BT, CT imaging showed that the tumor had shrunk. Still, MTX was continued. She was diagnosed with MTX-related lymphoproliferative disorders in November 2014 and MTX was discontinued. Fluorodeoxyglucose-positron emission tomography on March 2015 showed a complete response.

Thrombotic microangiopathy due to malignant hypertension complicated with late-onset bleeding after renal biopsy.

A 47-year-old man presented at a local ophthalmological hospital with blurred vision. He had been diagnosed with hypertensive retinopathy and renal failure and was referred to our hospital for treatment. A renal biopsy was done to evaluate pathology of high proteinuria, hematuria, and rapidly progressive glomerulonephritis. Blood pressure remained high despite antihypertensive therapy; anemia and thrombocytopenia gradually progressed. Thrombotic microangiopathy (TMA) was suspected based on red blood cell fragmentation due to hemolytic anemia, thrombocytopenia, and renal failure. However, plasma exchange resolved neither thrombocytopenia nor renal failure, and anemia gradually progressed. Backache suddenly developed 13 days later, and CT findings indicated a retroperitoneal hematoma secondary to bleeding from the kidney. Selective renal artery embolization via angiography stopped the bleeding, but the patient went into hemorrhagic shock. Pathological findings on renal biopsy were identical to those in malignant hypertension, namely an edematous membrane lining, thickened arterioles, and stenosis. We diagnosed thrombotic microangiopathy due to malignant hypertension, without decrease in activities of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif) or its antibodies. Renal failure did not improve, and continuous hemodiafiltration was needed. This procedure stabilized blood pressure and improved the TMA.

[Effective BiRd Therapy after the Addition of Clarithromycin for Lenalidomide and Dexamethasone Resistant Multiple Myeloma Ineligible for Stem Cell Transplantation].

BiRd combination therapy, which comprises clarithromycin(CAM: Biaxin®), lenalidomide(LEN: Revlimid®), and dexamethasone( DEX), is a highly effective treatment for newly diagnosed symptomatic multiple myeloma(MM). However, its efficacy against recurrent myeloma refractory to LEN and DEX combination therapy(Rd therapy)remains unclear. In this study, we retrospectively analyzed the data of 7 patients(4 men and 3 women, median age of 76 years)with MM, who had clarithromycin added to their Rd regimen. In all patients, the starting dose of clarithromycin was 400 mg daily and the median number of prior therapies was 3(range, 1-4). Patients received a median of 9 cycles of Rd(range, 6-27 cycles)for a median duration of 8 months. Then, patients received a median of 14 cycles of BiRd(range 2-36 cycles). One patient showed partial response(PR), which was the best response, while the others showed stable disease(SD). Our results demonstrated that the addition of clarithromycin to Rd could overcome resistance to Rd and lead to durable responses, without exacerbating hematological or non-hematological toxicities. Thus, BiRd therapy may represent a therapeutic option for symptomatic MM resist- ant to Rd therapy.

[Cardiac Diffuse Large B-Cell Lymphoma Presenting with Acute Heart Failure Due to Cardiac Tamponade].

A 75-year-old man was admitted to our hospital in May 2016 with progressive shortness of breath. We considered him to be experiencing acute heart failure caused by atrial fibrillation. Contrast-enhanced computed tomography showed a hypodense mass involving the right atrium and left ventricle, pericardial effusion, and lymphadenopathy of the groin. Histological finding from the groin and pericardial effusion analysis showed diffuse large B-cell lymphoma(DLBCL). We thus diagnosed this patient with cardiac tamponade owing to the involvement of the heart by DLBCL. Treatment was initiated with tetrahy- dropyranyldoxorubicin/cyclophosphamide/vincristine/prednisolone(THP-COP)therapy(50% dose)and continuous pericardial drainage. We carefully added rituximab 4 days after monitoring his symptoms and vital signs. There were a few adverse effects, and after treatment, the mass and pericardial effusion disappeared. Subsequently, 8 courses of THP-COP therapy accompanied by rituximab(R-THP-COP)(full dose)were administered, resulting in a complete response.

[Efficacy of levocarnitine for tyrosine kinase inhibitor-induced painful muscle cramps in patients with chronic myelogenous leukemia].

Muscle cramps are side effects commonly associated with tyrosine kinase inhibitor (TKI) treatment. Patients suffering from muscle cramps are treated with various medications such as calcium, magnesium and vitamin supplements, but these therapies are often ineffective. We report two patients with chronic myelogenous leukemia who developed muscle cramps caused by TKI. These patients were treated successfully with levocarnitine. Both of our cases revealed the beneficial effects of levocarnitine treatment on TKI-induced muscle cramps.

[Zoledronic Acid Administration is Effective for Hematopoiesis Management in a Patient with Primary Myelofibrosis].

An 80-year-old man received a diagnosis of anemia and a decreased platelet count from his physician in 2008, and was referred to our department where primary myelofibrosis was diagnosed.The patient was classified into the lower risk group according to the International Prognostic Scoring System(IPSS), and was followed up without treatment.In June 2010, pancytopenia progressed, and the patient was reclassified into the higher risk group.Blood count did not increase with metenolone treatment, but increased with zoledronic acid(ZA)that he started receiving from January 2012. After ZA treatment, circulating levels of vascular endothelial growth factor(VEGF)and transforming growth factor-b(TGF-b)decreased, and bone marrow biopsy showed an absence of reticular fibers and collagen fibers.In the present case, we observed that the blood count increased because of ZA-induced improvements in myelofibrosis.

[RS3PE syndrome associated with senile Epstein-Barr virus-positive diffuse large B cell lymphoma of a patient with colon cancer].

A 75-year-old woman consulted her doctor in January 2014 because of pain in the dorsum of the hands, elbows, shoulders, and knees, bilaterally, and was diagnosed as having remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. Although the joint pain improved with low-dose prednisolone administration, she was referred to our department in April of 2014 because she had become aware of swelling of the right cervical lymph node. Biopsy of the lymph node demonstrated that she had Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly, and colonoscopy revealed early colon cancer. Also, both the lymphoma and colon cancer stained positive for vascular endothelial growth factor (VEGF). Complete remission was achieved after two courses of R-CHOP, and RS3PE syndrome did not relapse. This case suggested the involvement of VEGF produced by EBV-positive DLBCL in the pathogenesis of RS3PE syndrome.

[The efficacy of early use of recombinant soluble thrombomodulin for disseminated intravascular coagulation complicated with hematologic malignancies].

We retrospectively investigated treatment outcomes with soluble recombinant thrombomodulin (rTM) for disseminated intravascular coagulation (DIC) associated with hematological malignancies (acute leukemia and malignant lymphoma) at our hospital. After rTM administration, DIC scores improved in 29 of 39 cases with hematological malignancies (74.36%). Although one case with recurrent and refractory APL died due to cerebral bleeding during rTM administration, no bleeding-associated adverse events were observed in the other 38 cases. DIC improvement was augmented in cases with acute leukemia when rTM was introduced in the pre-DIC state. CRP decreased in 26 of 36 cases with hematological malignancies (72.22%) after rTM introduction, and CRP decreased particularly significantly in cases with malignant lymphoma, suggesting rTM to exert anti-inflammatory activity. Taken together, these observations indicate that rTM, which rarely causes bleeding-associated adverse events, is an excellent agent in terms of both efficacy and safety for treating DIC associated with hematological malignancies, and the potential anti-inflammatory activity of this agent was also suggested.

[A Newly Diagnosed Case of Multiple Myeloma in Which Lenalidomide Was Continued after Surgery for a Pancreatic Neuroendocrine Tumor That Developed during Lenalidomide Maintenance Therapy].

A 75-year-old woman was diagnosed with symptomatic IgG-l multiple myeloma (good-prognosis group) in December 2010. A stringent complete response (sCR) was achieved by using induction therapy with bortezomib (BOR, Velcade®)+ dexamethasone (DEX)(VD) and consolidation therapy with BOR+lenalidomide (LEN, Revlimid®)+DEX(VRD). Although maintenance therapy with Revlimid®+DEX(Rd) was initiated, a pancreatic neuroendocrine tumor was detected in April 2013. Therefore, LEN was discontinued and distal pancreatectomy was performed in September 2013. Because discontinuation of LEN was followed by exacerbation of myeloma, LEN was resumed with the consent of the patient; however, she became resistant to the treatment. The course of this case suggests that some patients must continue to receive LEN even if a sCR is achieved.

[Successful Hematopoietic Cell Transplantation Following Azacitidine Treatment in an Acute Myeloid Leukemia Patient with t(3;3)(q21;q26.2) Translocation and Marked Thrombocythemia].

A 39-year-old man visited our department complaining of general malaise and appetite loss. He presented with anemia and marked thrombocythemia; his plasma transforming growth factor (TGF)-b concentration was markedly increased and his thrombopoietin (TPO)concentration was decreased. Since the patient's disease had progressed to acute myeloid leukemia (AML) with an increase in the peripheral blast count, he was diagnosed with AML along with t(3;3) (q21;q26.2) through a bone marrow aspiration sample. Remission induction therapy was performed using idarubicin/cytarabine. The patient achieved complete remission. His platelet count returned to the normal range, plasma TGF-b concentration decreased, and serum TPO concentration increased. The patient was treated with azacitidine as post-remission therapy for bone marrow transplantation, following which he underwent allogeneic hematopoietic cell transplantation.

[A Case of Acute Lymphoblastic Leukemia with Adult-Onset Still's Disease-Like Erythema].

A 62-year-old woman developed B lymphoblastic leukemia (B-ALL) in April 2010, and achieved complete remission after hyper-CVAD/high-dose-MA therapy combined with rituximab. ALL recurred in December 2011, and remission was again achieved with the Japan Adult Leukemia Study Group (JALSG) ALL202 protocol combined with rituximab. Owing to a fever and rash that persisted from July 2012, the patient was examined again. On examination, redness was observed in the pharynx, and poorly defined oval erythemas were seen on the cheeks, posterior region of the neck, and upper arms. Blood test results showed high levels of ferritin, tumor necrosis factor (TNF)-α, an d C-reactive protein (CRP), and mild hepatosplenomegaly was identified on abdominal computed tomography (CT), indicative of an adult-onset Still's disease-like condition. Prednisolone therapy was initiated in August 2012, and remission was achieved. A second recurrence of ALL developed in September 2012, and although remission was again achieved using the JALSG ALL202 protocol, a third recurrence of ALL occurred in April 2013, and the patient could not be saved. In this case, adult-onset Still's disease-like erythema developed during the remission phase of ALL.

[A case of primary testicular diffuse large B-cell lymphoma with a p53 gene point mutation].

A 52-year-old man with bilateral swelling in the scrotum was referred to the department of urology in our hospital in January 2013. Pathological examination of the scrotum revealed diffuse large B-cell lymphoma(DLBCL). Immunohistochemical staining revealed p53 overexpression, and polymerase chain reaction-single strand conformation polymorphism(PCRSSCP) revealed a point mutation in exon 7 of the p53 gene. Rituximab plus cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone(R-CHOP)therapy and intrathecal prophylaxis were initiated. After three courses of R-CHOP therapy, high-dose cytarabine was administered, followed by peripheral blood stem cell harvesting. Busulfan, etoposide, and Ara-C(BEA)therapy was then administered, followed by autologous peripheral blood stem cell transplantation(auto- PBSCT). Primary testicular lymphoma(PTL)is a rare, clinically aggressive form of extranodal lymphoma, and there is a high incidence rate of relapse in the central nervous system(CNS). The vast majority of cases are histologically DLBCL. The p53 mutation is an independent marker of poor prognosis in patients with DLBCL treated with R-CHOP therapy. Our patient has been disease free for 17 months after auto-PBSCT with high-dose chemotherapy, which results in a greater level of penetration into the CNS.

[Subcutaneous myeloid sarcoma in a patient with essential thrombocythemia that transformed into acute myeloid leukemia].

Since November 2008, an 80-year-old man had been administered hydroxyurea and aspirin for the treatment of essential thrombocythemia (ET). In January 2012, his white blood cell count was markedly elevated, and he was treated with busulfan and cytarabine. In October 2012, he was hospitalized because of fever and general malaise, and a central venous port was placed in the right anterior chest owing to difficulty obtaining peripheral vascular access. Approximately 2 weeks after port placement, a subcutaneous mass was observed near the port. The patient died in November 2012 owing to exacerbation of the original disease. Autopsy revealed transformation to acute myeloid leukemia( AML; M2 subtype) and myeloid sarcoma (MS) in lymph nodes and the right anterior chest. The incidence of transformation of ET to AML is low, and MS as a comorbidity is rare. However, the risk of MS complications should be considered in patients with hematological malignancies due to recent increases in the use of central venous ports in such cases.

[Polycythemia vera developed after a major molecular response to imatinib mesylate treatment in a patient with chronic myelogenous leukemia].

A 68-year-old man complained of dizziness and was referred to our hospital by his primary physician for evaluation of an elevated leukocyte count. In April 2002, soon after the chronic phase of chronic myeloid leukemia had been diagnosed, he was treated with imatinib. In March 2010, imatinib treatment was completed and the BCR/ABL fusion gene had become undetectable by real time quantitative PCR. Subsequently, leukocyte counts and the hematocrit gradually rose. In August 2012, a bone marrow aspirate showed hypercellular marrow with marked erythroid hyperplasia and the presence of the JAK2 gene V617F mutation. He was diagnosed with polycythemia vera. Phlebotomy and chemotherapy were started in addition to imatinib administration. Shortly thereafter complete blood counts returned to normal levels.

[Successful treatment with combination of plasma exchange and chemotherapy for CD5-positive primary hepatosplenic diffuse large B-cell lymphoma complicated with acute liver injury].

Primary hepatosplenic CD5-positive diffuse large B cell lymphoma (CD5⁺ DLBCL) has recently been characterized as showing hepatosplenomegaly without lymphadenopathy, a portal and intrasinusoidal pattern of infiltration in the liver, and bone marrow invasion by lymphoma cells, without intravascular involvement. A 45-year-old man presented with fever and malaise in June 2013. Computed tomography showed hepatosplenomegaly and multiple liver tumors without lymphadenopathy. An ultrasonography-guided needle biopsy of the liver mass revealed portal and intrasinusoidal infiltration of CD5⁺CD20⁺ lymphoma cells and large numbers of destroyed hepatocytes. These findings were diagnostic of primary hepatosplenic CD5⁺ DLBCL. Upon admission, lymphoma cells also appeared in the peripheral blood and serum hepatocyte growth factor (HGF) was markedly elevated. A bone marrow biopsy revealed extensive invasion by lymphoma cells. Seven days after admission, his laboratory data showed elevated aminotransferase and serum creatinine levels. Therefore, dose-reduced CH(O)P, with rituximab (R-CHOP) therapy, plasma exchange, and continuous hemodiafiltration, was initiated. The patient achieved complete remission after 4 courses of R-CHOP therapy. HGF is useful for predicting acute liver damage. If the HGF level is high, remission induction therapy, with plasma exchange, is necessary at an early stage.

Successful treatment of an essential thrombocythemia patient complicated by Sweet's syndrome with combination of chemotherapy and lenalidomide.

A 79-year-old man had been followed up since July 2003 based on a diagnosis of essential thrombocythemia (ET). The patient visited our hospital after developing a high fever and rash in August 2010, and Sweet's syndrome was diagnosed based on skin biopsy results. The bone marrow aspirate showed features like those of myelodysplastic/myeloproliferative neoplasm (MDS/MPN, unclassifiable). Administration of metenolone and azacitidine was initiated in March and May 2011, respectively, but the rash associated with Sweet's syndrome showed exacerbation. Ranimustine was therefore administered starting in July 2011 to control the blood cell count, but the rash associated with Sweet's syndrome persisted. Combination therapy with lenalidomide was initiated in September 2012, and resulted in control of the blood cell count and marked improvement of Sweet's syndrome.

[Three cases of lenalidomide-resistant IgA myeloma for which a response was regained after the addition of clarithromycin].

BiRd combination therapy, which comprises clarithromycin (CAM: Biaxin®), lenalidomide (LEN: Revlimid®), and dexamethasone ( DEX), is a highly effective treatment for newly diagnosed symptomatic myeloma. However, its efficacy against recurrent myeloma refractory to combination therapy with LEN and DEX(Rd therapy) remains unclear. Here, we report on BiRd therapy administered to three patients with IgA myeloma exacerbated during Rd therapy and for whom transplantation was not indicated, by adding CAM to the Rd regimen. Because the IgA levels increased again after Rd therapy in all patients, treatment was switched to BiRd therapy. In all cases, the IgA levels decreased after switching to BiRd therapy, with no exacerbation or hematological or non-hematological toxicity observed. Thus, BiRd therapy may represent a therapeutic option for symptomatic myeloma resistant to Rd therapy.

[Combined modality therapy for a patient with primary adrenal lymphoma].

A 71-year-old man with malaise, anorexia, and weight loss was referred to our hospital from a clinic. Abdominal computed tomography(CT)revealed bilateral adrenal masses. An ultrasound-guided percutaneous needle biopsy of the adrenal grand indicated diffuse large B-cell lymphoma. A rapid adrenocorticotropic hormone(ACTH)test revealed primary adrenal failure. Rituximab-cyclophosphamide/doxorubicin/vincristine/prednisolone(common name, R-CHOP)therapy accompanied by intrathecal treatment was initiated along with steroid replacement therapy. After the fourth courses, a CT scan showed a reduction of the adrenal masses, and there was no[18F]-fluorodeoxyglucose(FDG)uptake in the adrenal masses. The patient has remained in metabolic complete remission. Subsequently, both adrenal lymphomas were irradiated. The patient has been disease-free for 6 months after the diagnosis of primary adrenal lymphoma. The combined modality of chemoradiation therapy plus intrathecal treatment could be effective for primary adrenal lymphoma with a poor prognosis.