Hirofumi Teshima

Risk of non-Hodgkin's lymphoma in patients with hepatitis C virus infection

Hepatitis C virus (HCV) has been suggested to play an etiological role in the development of B‐cell non‐Hodgkins lymphoma (NHL) in Italy. However, another study in Scotland questioned increased risk of development of NHL in patients with chronic HCV infection. A total of 2,162 patients admitted to 3 hospitals in Osaka, where the incidence of HCV‐related hepatitis is highest in Japan, during the period from 1957 to 1997 were followed up from the date of diagnosis of chronic HCV‐related hepatitis until 30 October 1997. Overall, 12,404.5 person‐years of observation were accrued with a follow‐up period ranging from 0.25 to 40.4 (average 5.74) years. NHL of the B‐cell type developed in 4 patients. The interval between onset of chronic HCV and NHL ranged from 6 to 36 (median 13) years. Expected number of cases of NHL in the sex‐, age‐ and calender year‐matched general population was 1.90, which gave a relative risk (RR) of 2.10 (95% confidence interval 0.57–5.38; p = 0.247). Taking the much higher RR for hepatocellular carcinoma among patients with HCV infection into account, chronic HCV infection was considered to be moderately associated with increased risk of NHL. Int. J. Cancer 80:237–239, 1999.

Tc-99m MIBI localization in bone marrow: a marker of bone marrow malignancy.

To determine the potential of Tc-99m MIBI for detecting bone marrow malignancy, MIBI imaging of the femur was evaluated. There was no detectable MIBI activity in 125 of 141 (89%) control patients. Clearly demonstrated focal or tubular MIBI activity indicating intramedullary accumulation was demonstrated in 44 of 45 (98%) patients with proven marrow malignancy: 9 patients with multiple myeloma, 10 patients with malignant lymphoma, 11 patients with acute leukemia, 1 patient with chronic leukemia, and 14 patients with skeletal metastases. No abnormal MIBI activity was observed in the femur in 19 of 22 (86%) patients who had no evidence of malignant involvement in the femoral marrow, in 3 patients with solitary plasmacytomas of the spine, sternum or iliac bone, or in 16 patients with malignant lymphoma. In 12 of 24 patients with acute leukemia in complete remission, no abnormal MIBI accumulation was shown in the femur, but in 12 patients, abnormal accumulation indicating residual leukemic activity was demonstrated. MIBI imaging correlated extremely well with MRI studies; 26 of 28 patients with focal or tubular increased MIBI activity in the femur showed decreased signal on T1-weighted images and a high signal on short inversion recovery images, and 11 patients with no abnormal activity showed a high signal on T1 images. MIBI imaging of the femoral bone marrow may be a new modality for detecting marrow malignancy.

Extramedullary plasmacytoma of the dura mimicking meningioma

In December 2005, a 59-year-old man presented at ourNeurosurgery Department with a 2-month history ofamnesia and gait disturbance. A solid mass lesion wasdetected in the right temporal region on magnetic reso-nance imaging (MRI), presumed to be a meningioma(Fig. 1). He underwent surgery via a right temporal frontalcraniotomy and partial resection of the mass. Biopsy of themass demonstrated a densely cellular tumor composed ofplasma cells, positive for IgG and kappa light chain(Fig. 2), and negative for lambda chain, CD56 and cyclinD1. These findings were consistent with intracranialplasmacytoma.No additional sites of plasmacytoma were identified oneither computed tomography or bone scintigraphy, and bonemarrow plasmacytosis was absent (1.8% plasma cells,morphologically normal), and bone marrow cells showed anormal karyotype. Serum immunoglobulin levels werealmost normal (IgG 1,374 mg/dL, IgA 443 mg/dL, IgM54 mg/dL, IgE 81 IU/mL, IgD 7.6 mg/dL), and postopera-tive serum protein immunoelectrophoresis showed a smallM-component only (IgG-j). Urine Bence-Jones protein wasnot detected. Other organopathies, such as nephropathy,hypercalcemia and bone region, were absent. Thus, a diag-nosis of extramedullary plasmacytoma was made accordingto the classification of the International Myeloma WorkingGroup (IMWG) [1]. He underwent external beam radio-therapy to the brain at a dosage of 50 Gy, which resulted inthe disappearance of the remaining tumor region.In January 2007, he developed hoarseness and thoracicpain. Since CT scans demonstrated new masses at other sites(rib and vertebral bones), he was diagnosed with diseaseprogression. Laboratory findings showed an increased totalserum protein of 8.6 g/dL, IgG 3,629 mg/dL, and serumprotein immunoelectrophoresis revealed an evidentM-component of IgG-j. Bone marrow examination showedno evidence of plasmacytosis (2.4% plasma cells, withoutatypia) and chromosomal analysis revealed a normalkaryotype. Thereafter, he received several courses of che-motherapy with vincristine, doxorubicin and dexametha-sone. Despite treatment, regrowth of the mass was observed.He refused further therapy and was discharged from ourhospital.Patients with a solitary dural plasmacytoma have beenreported with a female predominance of 84% and a meanage of 50.2 years. Clinically, combination therapy includ-ing surgical resection followed by at least 50 Gy radio-therapy is recommended, and long-term survival has beenobserved. On the other hand, patients with myelomatousmeningeal involvement have shown an extremely poorprognosis despite intensified treatment, including intrathe-cal and/or systemic chemotherapy and cranial radiotherapy[2]. Our patient showed a recurrence almost 1 year after theinitial diagnosis. We consider that postoperative radio-therapy was delayed by about 2 months because of inten-sive care, which might have caused the early recurrence.

BK virus-associated nephropathy in an HIV-positive patient with gingival plasmablastic lymphoma

BK virus (BKV) nephropathy is common after renal transplantation, but less well characterized in patients with human immunodeficiency virus (HIV). Here, we report a rare case of BKV nephropathy in a patient with acquired immunodeficiency syndrome (AIDS)-related plasmablastic lymphoma (PBL). A 32-year-old man was admitted to our hospital with a complaint of gingival swelling in the right lower jaw of 3-month duration in February 2006. He had been diagnosed with an AIDS-related cytomegalovirus (CMV) enteropathy, in January 2006, when his CD4-positive lymphocyte count was 40/lL and HIV RNA viral load was 84000 copies/mL. He had no prior history of homosexuality or drug abuse. Treatment with ganciclovir and highly active antiretroviral therapy (HAART) was begun 1 month before admission to our hospital. On examination, there was a small left anterior cervical adenopathy, but no other lymph node was palpable. Intraorally, a painful outgrowth from the gingiva was present in the right mandibular molar area (Fig. 1). Laboratory values available on admission included a white blood cell count of 2130/lL (76% polymorphonuclear leukocytes, 18% lymphocytes, 5% eosinophils), a hemoglobin concentration of 8.6 g/dL, and platelet count of 367000/lL. Lactate dehydrogenase was 428 IU/L, blood urea nitrogen was 8.8 mg/dL and serum creatinine was 0.78 mg/dL. Urine dipstick indicated neither proteinuria nor glycosuria, and specific gravity was 1.010. The CD4 count was 3/lL, and HIV viral load was 4400 copies/mL. Biopsy sample from the right mandible region showed monomorphic dense proliferation of lymphoid cells with large, central or eccentrically placed nuclei, prominent nucleoli and abundant mitotic figures (Fig. 2). Immunohistochemical stains revealed that the large atypical lymphocytes were positive for CD79a, kappa light chain and CD38, and weakly positive for CD20 and Epstein–Barr virus (EBV) latent membrane protein (LMP). Results were negative for CD3, CD10, lambda light chain and CD138. The proliferation rate, as assessed by Ki-67/MIB-1 staining, was over 90%. EBV was identified by in situ hybridization, but no evidence of human herpes virus-8 (HHV-8) was detected. A diagnosis of PBL was made based on the diagnostic criteria of WHO. Computed tomography (CT) scans of the neck revealed an infiltrative mass in the right mandible with swelling of the soft tissue, and a lymph node (23 9 15 mm) in the left neck. Additional imaging of the chest, abdomen, and pelvis, and bone marrow aspiration were negative for lymphoma. Clinically, he had stage 2 disease. Chemotherapy was begun with cyclophosphamide, doxorubicin, vincristine and prednisolone. After three cycles of chemotherapy, he underwent external beam radiotherapy to the neck at a dosage of 30 Gy, which resulted in the disappearance of the remaining tumor lesion; however, he developed severe cytopenia and kidney dysfunction that serum creatinine progressed from 0.9 to 5.5 mg/dL over a 3-month period. Antiretroviral drugs and ganciclovir were suspected as the etiology, but a trial to M. Manabe (&) Y. Yoshii S. Mukai E. Sakamoto H. Kanashima H. Teshima Department of Hematology, Osaka City General Hospital, 2-13-22 Miyakojimahondori, Miyakojima-Ku, Osaka 534-0021, Japan e-mail: m1153564@med.osaka-cu.ac.jp

Induction of autologous graft-versus-host disease after autologous peripheral blood stem cell transplantation

BACKGROUND Autologous graft-versus-host disease has been reported after the administration of cyclosporine in patients who have received autologous bone marrow transplantation. OBJECTIVE The purpose of this study was to determine whether autologous graft-versus-host disease could be induced in recipients of autologous peripheral blood stem cell transplantation and whether tacrolimus induced the disease instead of cyclosporine. METHODS Twelve patients with acute leukemia and 5 patients with malignant lymphoma received either cyclosporine (1 mg/kg/day) or tacrolimus (0. 05 mg/kg/day) orally after autologous bone marrow or peripheral blood stem cell transplantation. RESULTS Autologous graft-versus-host disease of the skin, confirmed by histopathologic criteria, occurred in 40% of the patients at 8 to 25 days after transplantation and lasted 3 to 15 days. The frequency of autologous graft-versus-host disease was approximately the same (40%) irrespective of the source of the graft (bone marrow cells or peripheral blood stem cells) and the drug used for induction (cyclosporine or tacrolimus). CONCLUSIONS This pilot study suggests that autologous graft-versus-host disease can be induced in recipients of autologous peripheral blood stem cell transplantation by cyclosporine or tacrolimus.

VNCOP-B plus rituximab therapy in elderly patients with aggressive B-cell non-Hodgkin lymphoma: a multicenter experience.

CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) plus rituximab is a standard chemotherapy used to treat patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL). However, among elderly patients, this regimen has not been completely satisfactory in its efficacy and safety. We report our clinical experience in 8 collaborative institutions to determine if the VNCOP-B (etoposide, mitoxantrone, cyclophosphamide, vincristine, prednisolone, and bleomycin) combination therapy plus rituximab was effective and safe to treat elderly patients with aggressive B-NHL. Between September 2004 and December 2007, 23 previously untreated patients, median age 73 years, 50.0% classified as high-intermediate/high-risk on the standard International Prognostic Index (IPI) entered this trial. Complete remission rate was 90.5%, with a 100% overall response rate (RR) at the end of induction therapy; overall survival (OS) rate at 3 years was 76.4% (median follow-up 744 days), with an 82.6% 3-year progression-free survival (PFS) rate (median follow-up 744 days). The most common grade 3/4 toxicities were hematologic, including neutropenia in 75.0% of the patients despite prophylactic administration of granulocyte colony-stimulating factor (G-CSF), febrile neutropenia in 30.0%, respectively. There was no treatment-related mortality (TRM). Rituximab not only combined with chemotherapy but also given sequentially improved survival. R-VNCOP-B could be another option for elderly patients who are not considered to tolerate in receiving R-CHOP.

Simple diagnosis of graft-versus-host disease

BACKGROUND Among patients undergoing allogeneic bone marrow transplantation, we previously detected an increase of CD8+S6F1+ and CD8+CD57- cells with the onset of acute graft-versus-host disease. OBJECTIVE This study was an attempt to develop a simple laboratory test for graft-versus-host disease. METHODS We analyzed the percentage of the two lymphocyte subsets in the peripheral blood mononuclear cells of healthy volunteers, patients with posttransfusion graft-versus-host disease, and recipients of allogeneic bone marrow transplants. RESULTS Two patients with posttransfusion graft-versus-host disease showed a high percentage of both subsets. When the graft-versus-host disease pattern was defined as 45% or more CD8+S6F1+ cells and 35% or more CD8+CD57- cells, it was found in none of 17 recipients without acute graft-versus-host disease, 9 of 16 recipients with grade I disease, and 8 of 9 recipients with grade II or worse disease had this pattern. CONCLUSIONS Our test may be useful for the laboratory diagnosis of acute graft-versus-host disease.

A Rare t(9;22;16)(q34;q11;q24) Translocation in Chronic Myeloid Leukemia for Which Imatinib Mesylate Was Effective: A Case Report

The t(9;22)(q34;q11) translocation is found in about 90% of chronic myeloid leukemia (CML) patients. About 5–10% of CML patients have complex variant translocations involving a third chromosome in addition to chromosomes 9 and 22. Herein, we describe a CML-chronic phase male with a complex translocation involving chromosome 16, t(9;22;16)(q34;q11;q24). First, he was treated with interferon-alpha and intermittent hydroxyurea, but only a partial cytogenetic response was attained. Subsequently, the patient was treated with imatinib mesylate because of an additional chromosome abnormality, trisomy 8. A major molecular response was obtained after one years imatinib therapy, and the follow-up chromosomal analysis performed 4 years and 3 months after the initiation of imatinib therapy displayed a normal karyotype of 46,XY.

Transient efficacy of cord blood transplantation in acute myeloid leukemia with t(16;21)(p11;q22)

A 58-year-old woman presented with a 2-week history of coughing and purpura in October 2006. A physical exam only found purpura and anemic conjunctiva. Her laboratory values on admission included a white blood cell count of 10340/mL (73% blasts), a hemoglobin concentration of 8.5 g/dL, a platelet count of 4000/mL and a lactate dehydrogenase level of 676 IU/L. Her bone marrow aspirate revealed 78% blasts, some of which displayed hemophagocytosis and intracytoplasmic vacuolation or both (Fig. 1). Cytochemically, the blasts were positive for myeloperoxidase. In surface marker analysis, the blasts displayed CD13, CD33, CD41, CD34 and CD56 expression but were negative for HLA-DR. A chromosomal study of her bone marrow cells revealed her karyotype to be 46XX,t(16;21)(p11.2;q22)[19]/46XX[1]. A diagnosis of acute myeloid leukemia (AML) with maturation was made. The patient received induction chemotherapy involving 100 mg/m cytosine arabinoside (Ara-C) on days 1 to 7 and 12 mg/m idarubicin on days 1 to 3 but remission was not achieved. Therefore, re-induction with 7 mg/m mitoxantrone on days 1 to 3 and 200 mg/m Ara-C on days 1 to 5 was attempted twice, eventually achieving complete hematological remission with no detectable chromosomal abnormalities. She then underwent an unrelated cord blood transplantation with a serologically 2 loci mismatched graft in March 2007. Due to her age, reduced-intensity conditioning consisting of 25 mg/m fludarabine per day for 5 days, 80 mg/m melphalan per day, and total body irradiation (4 Gy in two doses) was employed as a preparative regimen to avoid transplant-related mortality. Her posttransplantation course was relatively uneventful except for grade II acute graft versus host disease (GvHD) of the gut, which was resolved with the addition of steroids. By day +100, she had achieved full donor chimerism in her bone marrow and no chronic GvHD was seen. In January 2009 she was found to have a decreased hemoglobin level and she subsequently suffered a hematological relapse. Owing to her poor performance status she was administered only palliative chemotherapy consisting of Ara-C 100 mg/m alone on days 1 to 7 and died from pneumonia 31 months after the initial diagnosis. To date, about 60 cases of AML harboring t(16;21)(p11;q22) have been reported, and interestingly, according to the review by Kim et al., most of the t(16;21)(p11;q22)-AML cases involved Asians, especially from Korea and Japan. It was reported that this type of AML displays characteristics including hemophagocytosis and vacuolation of leukemic cells as well as a poor prognosis. Imashuku et al. suggested that its characteristic bone marrow morphology could be used to aid the prompt identification of patients with high risk t(16;21)(p11;q22)-AML requiring a hematopoietic stem cell transplantation (HSCT) in the early stages of treatment. Concerning HSCT, to the best of our knowledge, around 15 patients with t(16;21)(p11;q22)-AML have undergone an allogenic HSCT. However, only a few long-term survivors were reported to be among these HSCT recipients as the others suffered relapses. Although we used cord blood as a stem cell source so that we could perform allogenic HSCT promptly, unfortunately her AML relapsed. However, complete remission was maintained for 22 months after the transplantation. As the prognosis of t(16;21)(p11;q22)-AML is extremely poor, this type of AML should be treated early using a powerful modality such as HSCT during the first remission. Although the significance of an association between the genesis of t(16;21)(p11;q22) and regional differences in the incidence of this disease have not been clarified, we suggest that hematologists in Asia, the area where t(16;21)(p11;q22)-AML occurs most frequently, should be aware of the diagnostic and clinical features of this type of AML in order to improve the prognosis of patients with this translocation. Asia–Pacific Journal of Clinical Oncology 2011; 7: 315–316 doi:10.1111/j.1743-7563.2011.01427.x