Hiroshi Kanashima

Impact of relative dose intensity (RDI) in CHOP combined with rituximab (R-CHOP) on survival in diffuse large B-cell lymphoma

BackgroundRecently, maintaining higher relative dose intensity (RDI) of chemotherapeutic drugs has become a widespread practice in an attempt to achieve better outcomes in the treatment of aggressive lymphoma. The addition of rituximab to chemotherapy regimens has significantly improved outcome in diffuse large B-cell lymphoma (DLBL). However, it is unknown if higher RDI in chemotherapy when combined with rituximab leads to a better outcome in aggressive B-cell lymphoma.MethodsWe retrospectively evaluated the impact of the RDI of initial chemotherapy (consisting of cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) on outcome in 100 newly diagnosed DLBL patients.ResultsA multivariate Cox regression model showed that RDI trended towards a significant association with mortality [hazard ratio per 0.1 of RDI = 0.8; 95% confidence interval 0.6–1.0; P = 0.08]. Additionally, on multivariate logistic analysis, advanced age was a significant factor for reduced RDI.ConclusionOur data suggest that in DLBL patients, mortality was affected by RDI of R-CHOP as the initial treatment, and the retention of a high RDI could therefore be crucial.

Prognostic value of serum surfactant protein D level prior to transplant for the development of bronchiolitis obliterans syndrome and idiopathic pneumonia syndrome following allogeneic hematopoietic stem cell transplantation.

Bronchiolitis obliterans syndrome (BOS) and idiopathic pneumonia syndrome (IPS) cause high mortality and impaired survival after allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Early recognition of patients at high risk of developing BOS/IPS may lead to improving the outcome of allo-HSCT. We retrospectively analyzed serum surfactant protein A, D (SP-A, -D) and Kerbs von Lungren 6 Ag (KL-6) levels before allo-HSCT in 56 patients who survived more than 90 days after allo-HSCT and compared values of these serum markers and other transplant factors in BOS/IPS patients with those in non-BOS/IPS patients. Five patients developed BOS and two developed IPS at a median interval of 303 and 117 days (range, 100–452 and 95–153) from transplantation. As a result of univariate analysis, pretransplant serum SP-D levels but not SP-A, KL-6 in BOS/IPS patients were significantly lower than those in non-BOS/IPS patients (P=0.03). In multivariate analysis, the patients with lower pretransplant serum SP-D level had a trend toward frequent development of BOS/IPS (P=0.08). Constitutive serum SP-D level before allo-HSCT may be a useful, noninvasive predictor for the development of BOS/IPS.

Analysis of elderly patients with diffuse large B-cell lymphoma: aggressive therapy is a reasonable approach for ‘unfit’ patients classified by comprehensive geriatric assessment

The treatment strategy for diffuse large B‐cell lymphoma (DLBCL) in elderly patients is problematic. Although several researchers have reported the effectiveness of comprehensive geriatric assessment (CGA) and the futility of curative treatment in ‘unfit’ patients with DLBCL, these propositions are not firmly established.

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

Imatinib non-responsive chronic eosinophilic leukemia with ETV6–PDGFRA fusion gene

DISCLAIMER: The ideas and opinions expressed in the journal’s Just Accepted articles do not necessarily reflect those of Informa Healthcare (the Publisher), the Editors or the journal. The Publisher does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of the material contained in these articles. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosages, the method and duration of administration, and contraindications. It is the responsibility of the treating physician or other health care professional, relying on his or her independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Just Accepted articles have undergone full scientific review but none of the additional editorial preparation, such as copyediting, typesetting, and proofreading, as have articles published in the traditional manner. There may, therefore, be errors in Just Accepted articles that will be corrected in the final print and final online version of the article. Any use of the Just Accepted articles is subject to the express understanding that the papers have not yet gone through the full quality control process prior to publication. Just Accepted by Leukemia & Lymphoma

Morganella morganii Pericarditis in a Patient with Multiple Myeloma

Purulent pericarditis caused by Morganella morganii is extremely rare. We report herein a case of a 61-year-old man who presented with chest pain and dyspnea fourteen days after chemotherapy for multiple myeloma. Echocardiogram and computed tomography revealed a massive pericardial effusion and associated cardiac tamponade. Pericardiocentesis was performed. Pericardial fluid was found to be purulent, and Morganella morganii was isolated from the fluid. The patient was successfully treated with antibiotic therapy and surgical drainage of the fluid. Morganella morganii should be considered a possible pathogen when immunocompromised patients develop purulent pericarditis.

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