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A 73-year-old female with malaise, anorexia, and hydrodipsia was referred to our department. Peripheral blood tests revealed leukocytosis with 51% blast cells exhibiting flower-shaped nuclei. Flow-cytometry to detect tumor cells in peripheral blood indicated CD3+, CD4+, CD8-, and CD25- expression, but those in the lymph nodes expressed CD25+. Southern blots revealed clonal HTLV-1 provirus in the tumor cells, consistent with adult T-cell leukemia-lymphoma. Cytotoxic chemotherapy was ineffective, but eight cycles of mogamulizumab induced complete remission (CR). A relapse lesion appeared on the right breast but disappeared spontaneously. The patient has currently maintained CR for over five years.

Background 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. Patients and methods We conducted a retrospective analysis using a database. Patients with DLBCL were eligible if ≧ 60 yr old. CGA stratification was performed using medical records. Results One hundred and 35 patients were identified. Anthracycline-based chemotherapy with curative intent was performed in 115 (85%) patients. According to CGA, 82 (61%) patients were classified as ‘fit’. Their 1-yr overall survival (OS) was significantly better than that of ‘unfit’ patients [91.3% vs. 53.8%, P

Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma, and it is characterized by diffuse cerebral infiltration of malignant lymphoma cells without evidence of a mass lesion. Herein, we report a patient with systemic peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) who had central nervous system involvement mimicking LC. A 72-year-old immunocompetent male presented with rapidly progressive dementia. Fluor-deoxy-glucose (FDG) -positron emission tomography revealed increased FDG uptake in the bone and skin. Histopathological examination of the skin lesion revealed PTCL-NOS infiltration. A FLAIR MRI scan of the brain revealed diffuse hyperintense lesions in the cerebral white matter of both hemispheres. These lesions were not enhanced with gadolinium, and there was no perceptible mass effect. We performed a brain biopsy, and the histology results were consistent with PTCL-NOS. The patient was treated with corticosteroid and chemotherapy; however the disease progressed, and he died 4 months after the diagnosis. This was a rare case of systemic lymphoma accompanied with central nervous system involvement mimicking LC.

Double-hit lymphomas are rare tumors that are defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint, mainly a t(14; 18)(q32;q21)involving BCL2. We report a case of a 38-yearold woman with a 2-month history of abdominaldistention. 18F-FDG PET showed multiple positive systemic lymph nodes, positive peritoneum, and multiple positive intra-abdominal masses. Histopathology results of the cervical lymph node were compatible with double-hit follicular lymphoma(Grade 3A)because fluorescence in situ hybridization(FISH)demonstrated both MYC rearrangement and BCL2 gene fusion. She was initially started on R-CHOP(rituximab and doxorubicin, vincristine, cyclophosphamide, and prednisolone), but after one course the regimen was changed to dose-adjusted EPOCH-R(rituximab and doxorubicin, etoposide, vincristine, cyclophosphamide, and prednisolone). However, she showed no response to this chemotherapy regimen or haploidentical stem cell transplantation. The treatment strategy included salvage chemothera- py. An autologous and/or allogeneic hematopoietic transplantation is important for non-responders to DA-EPOCH-R.

A 77-year-old-man was diagnosed with follicular lymphoma (FL), grade 3A. After six courses of R-THP-COP (rituximab, pirarubicin, cyclophosphamide, vincristine and prednisolone) therapy, he achieved complete remission (CR). He achieved a second CR after radiotherapy, a third CR after six courses of bendamustine /rituximab (BR) therapy, and a fourth CR after six courses of BR therapy. However 2 months after the last chemotherapy, his tumor progressed rapidly and he died. Autopsy results showed medium and large lymphoid cells with pleomorphic, irregular nuclei and prominent nucleoli infiltrated in multiple lymph nodes, the liver, the lung, and the spleen. The lymphoid cells were positive for CD3, CD8, granzymeB, TIA-1 and negative for CD4, CD20, CD79a, CD10, and CD56. Autopsy diagnosis was peripheral T-cell lymphoma, not otherwise specified. Occurrence of lymphoma in T-cell lineage should be considered, if the course of low-grade B-cell lymphomas, such as FL rapidly progresses.

We report the case of a 17-year-old man with precursor B-lymphoblastic lymphoma involving an intracardiac mass and myocardial infiltration. Intensified chemotherapy followed by autologous peripheral blood stem cell transplantation resulted in long-term complete remission for over 5 years. As the most frequent sites of B-lymphoblastic lymphoma involvement are the skin, soft tissue, bone, and lymph nodes, reports of cases harboring cardiac involvement are relatively few. This is a rare case of B-lymphoblastic lymphoma displaying cardiac involvement, in which cardiac infiltration was one of the initial manifestations.

Cutaneous extramedullary hematopoiesis has been reported in a small number of patients with myelofibrosis. A 79-year-old male with JAK2V617F-positive myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS-MPN-U), presented with multiple skin lesions. The skin lesions were papulonodular, reddish brown, and elastic hard on palpation. Based on a lesion biopsy, cutaneous extramedullary hematopoiesis associated with MDS/MPN-U was diagnosed. He died four months later due to exacerbation of MDS/MPN-U. Cutaneous invasion might be associated with progressive disease and a poor prognosis for MDS/MPN-U, as it is for myelofibrosis.

Patients with hyperleucocytic leukemia (WBC count10×10(4) mL) are at high risk of early mortality owing to pulmonary or cerebral leukostasis. Several researchers have reported the efficacy of immediate leukapheresis. Here, we report of a patient with chronic myelogenous leukemia in blast crisis and with pulmonary failure due to leukostasis who recovered after a combination therapy of leukapheresis and imatinib treatment.

A 77-year-old man was diagnosed with cold agglutinin disease in 2004. He had been treated with prednisolone with stabilization of hemoglobin in the 6- to 8-g/dl range. However, his hemolytic anemia worsened, and computed tomography showed systemic lymphadenopathy in May 2012. A pathological diagnosis of small lymphocytic lymphoma was made based on an inguinal lymph node biopsy. Treatment was started with rituximab. However, there was no response to 6 doses of rituximab monotherapy. He next received 6 courses of bendamustine in combination with rituximab. This resulted in stabilization of hemoglobin and independence from transfusion support. To the best of our knowledge, this is only the second case report describing bendamustine plus rituximab treatment for non-Hodgkin lymphoma complicated by cold agglutinin disease. Our results in this case suggest bendamustine to potentially be a useful therapeutic option in patients with cold agglutinin disease.

A 73-year-old woman was diagnosed with myelodysplastic syndrome(MDS). After 11 courses of treatment with azacitidine( AZA), her hemoglobin level and platelet count improved significantly, and she became transfusion independent. Therefore, treatment was discontinued and follow-ups were maintained. Three months later, her platelet count reduced again; we therefore treated her again with AZA. However, MDS transformed to acute myeloid leukemia in the 14th course, and she died 19 months after the initial diagnosis. AZA is an important drug for treating MDS, but premature withdrawal of treatment might cause rapid disease progression. In case treatment is discontinued, the patient needs to be carefully observed.

Purulent pericarditis caused byMorganella morganiiis 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, andMorganella morganiiwas isolated from the fluid. The patient was successfully treated with antibiotic therapy and surgical drainage of the fluid.Morganella morganiishould be considered a possible pathogen when immunocompromised patients develop purulent pericarditis.

We investigated 8 cases of non-Hodgkin lymphoma(NHL)in human immunodeficiency virus(HIV)seropositive individuals who were diagnosed and treated at Osaka City General Hospital between April 2002 and October 2012. All patients were men, and the average age at the onset of NHL was 46 years(range: 30-61). Histological types were as follows: diffuse large B cell lymphoma in 4 patients, plasmablastic lymphoma in 2 patients, primary effusion lymphoma in 1 patient, and Burkitt lymphoma in 1 patient. In 3 cases, HIV infection was identified before the onset of NHL. Highly active anti-retroviral therapy (HAART)was initiated in 6 cases, and in 4 of these, we administered antineoplastic chemotherapy. Three patients who did not receive antineoplastic chemotherapy died within 1 month of diagnosis. Although 1 of the patients who received chemotherapy achieved complete remission, this patient died of BK virus nephritis. The remaining 3 patients achieved complete remission and are currently alive after 6 to 9 months. We believe that the combination of antineoplastic chemotherapy with HAART will lead to prognostic improvement in HIV-seropositive patients with NHL.

The patient, a 44-year-old male, subjectively noticed edema in his lower legs in March, 2010. By June 2010, he could not walk, and was admitted to this hospital. Since multiple neuropathy, increased serum vascular endothelial growth factor-3, M-proteinemia, edema, pericardial effusions, papilledema, increased platelet count and skin lesions were detected in the complete examination, he was diagnosed with polyneuropathy, organomegaly, endocrinopathy, M-proteinemia and skin changes (POEMS) syndrome. Treatment with steroid and furosemide was initiated in September 2010. This markedly improved edema and brought about mild recovery of proximal lower-limb muscle strength. The patient, however, suffered prolonged difficulty in walking because his distal lower-limb muscle strength was not improved. In October 2010, he received treatment with high-dose cyclophosphamide, followed by peripheral blood stem cell sampling with granulocyte-colony stimulating factor. In November 2010, he underwent treatment with high-dose melphalan, followed by autologous peripheral blood stem cell transplantation. Recovery to neutrophils greater than 500 was achieved at 13 days after transplantation. He could walk without assistance in February 2011. M-protein was not identified by immunofixation electrophoresis in August 2011. Autologous peripheral blood stem cell transplantation is regarded as a useful treatment for POEMS syndrome.

Eltrombopag, an oral thrombopoietin receptor agonist, is a novel drug that can be used in cases with previously-treated primary immune thrombocytopenia (ITP). In this study, we retrospectively analyzed 22 Japanese ITP patients treated in four hospitals. A responder was defined as a patient achieving a platelet count between 50,000/μl and 400,000/μl, at 75% or more of on-treatment assessments. Excluding 2 patients whose treatments were interrupted at their request, 13 of 20 patients (65%) were responders. Ten of the 13 responders had been taking more than 5 mg of a steroid preparation in the form of prednisolone or its equivalent. In 7 of these patients, the steroid dose could be tapered to 5 mg or less. Disappearance or amelioration of hemorrhagic symptoms was observed in 11 of 19 patients who had these symptoms prior to treatment (9 of 10 responders, 2 of 7 non-responders), and the improvement rate was greater in responders (p=0.018). No factors were identified as being related to efficacy. Reported adverse effects were fever (1), malaise (3), headache (2), and muscle pain (1). One severe adverse event, cerebral thromboembolism, was reported in 1 patient. Although eltrombopag is a useful therapeutic agent for refractory ITP, it is necessary to evaluate its position in the overall treatment strategy for ITP after assessing long-term complications as well as therapeutic effects.

We report the case of a 66-year-old man with primary diffuse large B-cell lymphoma of the prostate presenting with urinary retention and dyschezia as first manifestation. Although a colostomy was needed due to rectal obstruction, rituximab-combined chemotherapy resulted in complete remission. He underwent stoma closure safely and has remained in complete remission for over 3years. Primary prostatic lymphoma is extremely rare, presenting as 0.1% of newly diagnosed lymphomas, but rituximab-containing chemotherapy seems to be as effective as for nodal lymphoma.

A 61-year-old man was referred to our hospital for leukocytosis and thrombocytopenia. Bone marrow examination showed hypercellular bone marrow accompanied by dysplasia, and the karyotype of his bone marrow cells was 46,XY, der(5;12)(q10;q10), +mar,inc[3]/46,XY[12]. A diagnosis of myelodysplastic syndrome, unclassifiable, was made. Analysis of major BCR/ABL1 chimeric RNA by real-time polymerase chain reaction method was positive, and then Ph chromosome was observed afterward. His Ph chromosome was seen in der(5;12)-negative cells analyzed by FISH, which suggested the late-appearing Ph chromosome evolved into another clone. Despite treatment containing imatinib, hydroxyurea, and cytosine arabinoside, he died due to respiratory dysfunction 5 months after the initial diagnosis. The autopsy revealed massive pulmonary infiltration by Ph-negative cells, suggesting MDS-derived clones. It has been reported that the late appearance of Ph chromosome associates with leukemic progression. Although the incidence of late-appearing Ph chromosome is estimated to be relatively low, further accumulation of cases is necessary for the evaluation of its impact on prognosis and disease progression.

We present three long-term survivors treated with high-dose melphalan with autologous peripheral blood stem cell transplantation(auto PBSCT)for primary AL amyloidosis. Because melphalan toxicity is dose-related, patient age and the extent of organ involvement are very important factors for the success of high-dose melphalan treatment with PBSCT. The patients were therefore given high-dose melphalan using the risk-adapted approach to melphalan dosing. They received 3 courses of a vincristine, doxorubicin and dexamethasone(VAD)regimen, along with high-dose melphalan(100-200mg/m2)with auto PBSCT. There were no serious complications or transplantation-related mortalities. Patients survived for an average of 68 months(22-100 months)in partial response. A risk-adapted approach to melphalan dosing with PBSCT is an effective treatment in patients with primary AL amyloidosis.

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 year's 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.

Background Recently, 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. Methods We 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. Results A 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. Conclusion Our 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.

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.

An 18-year-old female with myelodysplastic syndrome underwent an allogeneic cord blood transplantation in May 2005. The conditioning regimen consisted of total body irradiation, cytarabine and cyclophosphamide. The day of the cord stem cell transfusion was counted as Day 0. For acute GVHD prophylaxis, cyclosporine A (CsA) and methotrexate were used. Engraftment was achieved on Day 30, acute GVHD grade II developed on Day 45 and treatment with methylprednisolone for acute GVHD was started. On Day 68 the patient had generalized seizures accompanied by loss of consciousness, hypertension and left hemiparesis, and was intubated. A cranial CT scan showed a mass effect on the right basal ganglia, and high signal intensities on the T2-weighted and FLAIR images of a MR examination were detected in the bilateral basal ganglia and posterior lobes, the findings of which were compatible with a brain tumor or infectious disease. Since an increased level of apparent diffusion coefficient (ADC) values on the bilateral basal ganglia was noted, we suspected that vasogenic edema had caused the mass effect. She went into remission immediately after CsA treatment was discontinued. Therefore, this case was diagnosed as atypical reversible posterior leukoencephalopathy syndrome (RPLS) associated with CsA. CsA-induced encephalopathy presenting a mass effect in clinical imaging findings is very rare, and an ADC map may be useful for the diagnosis of RPLS.

Introduction: The treatment strategy for diffuse large B-cell lymphoma (DLBCL) in elderly patients is problematic. Recently, the Comprehensive Geriatric Assessment (CGA) has been proposed as an objective tool to identify those who can safely tolerate curative treatment. Although several researchers have reported the effectiveness of CGA in patients with aggressive B-cell non-Hodgkin lymphoma and revealed that intensive treatment cannot improve the outcomes of patients identified by CGA as unfit, compared with palliative treatment, the effectiveness of CGA and the effects of treatment are not firmly established. In the present study of elderly patients, we evaluated clinical outcomes and the prognostic value of clinical and biological parameters, including CGA stratification and treatment. Methods: We conducted a retrospective analysis using a database at our hospital. Patients were eligible if aged 60 years or older and diagnosed with DLBCL between November 1, 2000 and August 31, 2013. CGA stratification was performed using medical records, including assessment of the following four parameters: 1) age >= 80 years; 2) ADL including bathing, dressing, toileting, transferring, feeding, and continence; 3) comorbidity score according to the Cumulative Illness Rating Score for Geriatrics (CIRS-G) and evaluated for all organs/systems as follows: no problem – 1, mild problem – 2, moderate disabilities or morbidities (requiring treatment) – 3, severe and significant chronic disabilities – 4, and extremely severe disabilities – 5 ; and 4) geriatric syndrome, defined as the occurrence of dementia, delirium, depression, incontinence, falls, osteoporosis, neglect and abuse, or failure to thrive. Patients were classified as "fit" if they were aged We classified treatment as CHOP+-R, THP-COP+-R (THP-COP: pirarubicin 30 mg/m2, cyclophosphamide 500 mg/m2 and vincristine 1 mg/m2 on day 1 and predonisolone 30 mg/day on days 1–5), surgery alone, and palliative therapy (radiation, low-dose chemotherapy, rituximab alone, and corticosteroids). We compared overall survival (OS), progression free survival (PFS), complete response rate (CRR) and overall response rate (ORR) with each CGA stratification and treatment. Results: 87 patients were identified, with a median age of 72 years (range 60–84), 59% >= 70 years, and 16% >= 80 years; 53% male; 67% Stage III/IV; 62% IPI high–int/high, 20% loss of ADL and 13% geriatric syndrome. 70% were CGA fit and 30% unfit. 39% were treated with CHOP+-R, 53% THP-COP+-R, 2% surgery alone, 6% palliative therapy and 84% received rituximab. Median observation time was 859 days (range 40–4955). Univariate analysis showed the parameters negatively affecting OS were: loss of ADL (p At five years, the outcomes of the patients treated with CHOP+-R and THP-COP+-R were similar in terms of OS (85.0% vs 77.2%; p=0.95), see figure 1, PFS (56.4% vs 66.9%; p=0.96), CRR and ORR. The patients treated aggressively (CHOP or THP-COP +- R) had significantly better OS, PFS, CRR and ORR compared with those receiving palliation. We also observed better outcomes in terms of OS (p Conclusions: In this study, we observed similar outcomes regarding OS and PFS between two aggressive treatments (CHOP or THP-COP +- R). The patients treated aggressively had significantly better outcomes compared to those receiving palliation, irrespective of CGA stratification. Intensive treatment should be considered even for unfit patients. Disclosures No relevant conflicts of interest to declare.

To evaluate the results of high-dose chemotherapy (HDT) and autologous hematopoietic stem cell transplantation (ASCT) in patients with diffuse B-cell aggressive non-Hodgkin's lymphoma(NHL). Between 1991 and 2004, 25 patients who did not achieve complete remission and 26 in complete remission from conventional chemotherapy received HDC-ASCT. Of 25 patients with refractory NHL,14 were chemotherapy-sensitive before HDT-ASCT and 11 were chemotherapy-resistant. CR was achieved after HDC-ASCT in 50% of 14 chemotherapy sensitive patients and in none of 11 chemotherapy-resistant patients. The 5-year probability of event-free survival for chemotherapy-sensitive and chemotherapy-resistant patients was 51.3% and 20.8%, respectively (p0.05, log-rank test). Moreover, the 5-year probability of event-free survival for patients in the low-risk group with International Prognostic Index (IPI) and in the high-risk group with IPI was 75.0% and 16.3%, respectively (p0.05, log-rank test). HDT-ASCT should be considered for patients with refractory aggressive NHL who are chemotherapy-sensitive rather than chemotherapy-resistant. Twenty-six patients in complete remission received consolidation therapy with HDT-ASCT. The 5-year probability of disease-free survival for patients in the low-risk group and in the high-risk group was 68.8% and 60.0%,respectively (p = 0.9 6). HDT-ASCT should be considered for patients at high risk who achieve complete remission after induction treatment. In future, HDT-ASCT combined with rituximab as induction therapy or as consolidation therapy is needed for patients with aggressive NHL in the high-risk group.

The Astrim is a noninvasive hemoglobin monitoring device that uses near‐infrared radiation. We studied the usefulness of this device for patients with hematological disorders. We measured hemoglobin levels 309 times in 140 subjects, using an automated hematology analyzer (K‐4500) and the Astrim. The coefficient of correlation between Hb levels with the K‐4500 (K‐Hb) and the Astrim (A‐Hb) was r=0.591 (P

The E-cadherins are a family of cell-cell adhesion molecules. These molecules exhibit Ca2+ dependent cell adhesion and are expressed on epithelial cells. E-cadherin levels in serum are known to be significantly elevated in patients with epithelial carcinomas. We determined serum E-cadherin levels in 30 patients with non-Hodgkin's lymphoma (NHL) using an enzyme immunoassay and then investigated whether E-cadherin is expressed on lymphoma cells in lymph nodes of three cases selected to analyze from 15 cases of serum E-cadherin levels over mean + 2SD with monoclonal antibody immunohistochemistry. Results indicated that E-cadherin antigen is expressed on the lymphoma cells in these three patients with NHL, and that soluble E-cadherin might be released into blood from lymphoma cells. Expression of E-cadherin may contribute to the morphological appearance of some malignant lymphoma, although no conclusion can be drawn based on such small number of patients analyzed.

E-cadherin is a transmembrane glycoprotein that mediates Ca2+-dependent intracellular adhesion in normal epithelial cells. E-cadherin levels in serum are known to be significantly elevated in patients with epithelial carcinomas. However, the role of E-cadherin in haematopoietic cells is less clear. In this study, serum E-cadherin levels were therefore determined in patients with acute or chronic leukaemia, malignant lymphoma or myelodysplastic syndromes. Significant elevation of serum E-cadherin levels was detected in patients with haematological malignancies, and between types of acute leukaemias or subtypes of myelodysplastic syndromes, stages of malignant lymphoma, and phases of chronic leukaemia, respectively, compared with those in healthy adult volunteers. These findings suggest that E-cadherin might be expressed in malignant haematopoietic cells and might be useful as a diagnostic indicator in haematological malignancies.

The urinary trypsin inhibitor (UTI) levels in the urine of patients with various haematological malignancies were determined, using automated latex agglutination immunoturbidimetry. The mean UTI levels in urine in acute non-lymphocytic leukaemia, myelodysplastic syndrome, non-Hodgkin's lymphoma, and multiple myeloma groups were significantly elevated, compared with the normal control group. It was found that the UTI level in urine changed from an elevated value to a normal value with haematological improvement by chemotherapy in a patient with myelodysplastic syndrome included in a previous study. These results suggest tha

Interleukin-18 (IL-18) bioactivity in sera and IL-18 mRNA expression in leukaemia cells of three patients with adult T-cell leukaemia (ATL), acute mixed lineage leukaemia (AMLL) and acute lymphocytic leukaemia (ALL) accompanied with high serum IL-18 levels have been analysed. There was little serum IL-18 bioactivity in the three patients with ATL, AMLL and ALL, while IL-18 mRNA expression was detected in leukaemia cells of all three patients.

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.

Background. Recently several retrospective studies showed that relative dose intensity (RDI) in combination chemotherapy including CHOP significantly influences survival in aggressive lymphoma. Based on these data, maintaining high RDI in chemotherapy by, for example, prophylactic granulocyte colony-stimulating factor (G-CSF) administration has been attempted to obtain better outcome. Moreover, rituximab, a chimeric monoclonal anti CD20 antibody combined with CHOP chemotherapy (R-CHOP) has significantly ameliorated the outcome in patients with diffuse large B-cell lymphoma (DLBL). However, it is unclear if higher RDI even in combination with rituximab will improve outcome in B cell type aggressive lymphoma. Hence, in the current study, we retrospectively analyzed the impact of RDI in R-CHOP as an initial treatment on survival of patients with DLBL. Furthermore, we determined the factors influencing RDI. Patients and Methods. We studied 100 previously untreated DLBL patients who underwent more than 3 courses of R-CHOP chemotherapies at 5 institutions from December 2003 to February 2008. The median age of the patients was 60 years old (range 19–79). The median number of R-CHOP course was 6 (range, 3–8). In the current study, the RDI was calculated by averaging the delivered RDIs of cyclophosphamide (CY) and adriamycin (ADR) for all chemotherapy courses. Results. The median average RDI of CY and ADR (CY/ADR-RDI) in all patients was 87.9%. Twenty three of 100 patients were treated with RDI less than 75 %. With a median follow-up of 21.2 months, the probability of 4-year overall survival (OS) was significantly higher in patients with higher RDI (>=75%) than that in patients with lower RDI (=51 ) [odds ratio (OR) = 0.2; 95% CI 0.1–0.7; P = 0.01] and high/high-intermediate IPI (OR = 0.3; 95% CI 0.1–1.0; P = 0.04) were significant factors for reduced RDI, whereas prophylactic G-CSF (OR = 3.2; 95% CI 1.1–9.3; P = 0.04) was found to be a significant factor for increased RDI. Conclusion. In newly diagnosed DLBL patients, the current results demonstrated that high RDI in CHOP even when combined with rituximab was significantly associated with better survival and higher RDI could be effectively maintained by G-CSF.

Introduction: The achievement of a clinical response to the first induction chemotherapy has been considered for predicting survival in patients (pts) with aggressive non-Hodgkin lymphoma (NHL). Reduced dose intensity of chemotherapy has been likely to compromise long-term outcome of the patients with aggressive NHL treated with a standard chemotherapy of cyclophosphamide (CY), doxorubicin (ADR), vincristine and prednisone (CHOP). In particular, recent studies have revealed the relevance of relative dose intensity (RDI) to clinical outcomes, with reduced RDI leading to a poor survival, as well as the impact of RDI Methods: Data were retrospectively collected on 100 pts with DLCL who had been initially treated with more than 3 courses of CHOP (n=70) or CHOP plus rituximab (CHOP-R, n=30) at our institution between 1995 and 2006. We evaluated whether RDI might affect clinical outcomes, including complete response (CR) and event free survival (EFS). The average RDI derived from CY and ADR (referred to as RDI-CY/ADR) was determined for each patient, with classified into 2 populations according to the differences from the value of 85%, including RDI-CY/ADR Results: The median age of the study population was 54 years (range, 17 to 76), with 36 pts older than 60 years (yrs) of age. According to International Prognostic Index (IPI) score, pts were classified into 2 groups of low/ low-intermediate (n=46) and high/ high-intermediate (n=54). The overall CR rate reached 62%, and the probability of overall survival (OS) or EFS at 5 years estimated 77% or 43%, respectively with a median follow-up of 13.3 months. Multivariate analysis identified RDI-CY/ADR Conclusion: These data thus suggested the impact of RDI-CY/ADR

Thrombotic microangiopathy (TMA) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a serious complication with a high mortality. Acute GVHD (aGVHD) is one of risk factors for TMA and often overlaps it. In particular, gastrointestinal endothelium is a common target of aGVHD and TMA, which makes clinical diagnosis of TMA difficult, leading to delay early and appropriate treatment for it. In this study, to gain more insight into differences between TMA and aGVHD, comprehensive immunological analysis was performed. Methods: We determined kinetics of peripheral T cell subsets (CD4, CD8, Th1, Th2, γδ-T, NKT) and dendritic cell (DC) subsets (CD11c+DC and CD123+DC), serum 17 different cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, TNF-α, IFN-γ, G-CSF, GM-CSF, MIP-1β, MCP-1), and C-reactive protein (CRP) at the onsets of aGVHD or TMA in 25 patients undergoing allo-HSCT. T cell subsets including CD4 (CD3+CD4+CD8−), CD8 (CD3+CD4−CD8+), Th1 (CD4+CXCR3+CCR4−), Th2 (CD4+CXCR3−CCR4+), γδ-T (CD3+TCR-Vδ2+), and NKT (CD3+CD161+) and DC subsets were determined with a flow cytometer. TMA was diagnosed, following Iacopino’s criteria (Iacopino et al, Bone Marrow Tranplant. 24: 47, 1999). Data of aGVHD or TMA were compared with those of control without either aGVHD nor TMA between on 30 days and 60 days after allo-HSCT. Results: There was a significant decrease in the percentage of Th1 cells in CD4+T cells in TMA (9.1%, n=10), compared to in aGVHD (24.9%, n=9, p=0.003) or in control (21.6%, n=12, p=0.009). In contrast, the percentage of Th2 cells in CD4+T cells was higher in TMA (20.2%) than in aGVHD (9.3%, p Conclusion: Preferential Th2 and CD4 polarizations were observed at the onset of TMA. Thus, simultaneous monitoring of Th1, Th2, CD4 and CD8 was suggested to become a useful immunological parameter for differentiating TMA from aGVHD after allo-HSCT.

Optimal conditioning for unrelated allogeneic reduced intensity stem cell transplant (u-RIST) has not been sufficiently established yet. Most reported conditioning regimens for u-RIST include anti-thymocyte globulin (ATG), low dose total body irradiation (TBI) or Campath-1H. However, even low dose TBI can evoke additional toxic effects, and ATG or Campath-1H can over-suppress graft versus lymphoma or leukemia effects or immune reconstitution which causes opportunistic infections. Whether or not TBI, ATG or Campath-1H is indeed needed for engraftment in u-RIST, has been not yet determined.Å@The magnitude of immunnosuppression and the intensity of conditioning to facilitate engraftment are definitely different in each patient. Here we report fludarabine-based conditioning without TBI, ATG and Campath-1H for u-RIST in patients who received prior chemotherapy. In this study, we enrolled 14 patients (22 to 69 years old) with hematologic diseases who received unrelated bone marrow transplantation from September 2002 to April 2006 at our institution. These patients included 5 with acute myeloid leukemia, 4 with acute lymphoblastic leukemia, 1 with myelodysplastic syndrome, 2 with non-Hodgkin’s lymphoma, 2 with adult T-cell leukemia (ATL), and one patient with plasma cell leukemia. Ten (71%) patients were at the advanced stages of their disease. All patients received at least one course of prior chemotherapy. The median course of prior chemotherapy was 5 (1–12). The reduced-intensity conditioning for 12 patients excluding ATL consisted of fludarabine 150mg/m2 and busulfan 8 mg/m2. Whereas, the reduced-intensity conditioning for 2 patients with ATL included busulfex 8 mg/m2 instead of busulfan. As a prophylaxis for acute graft-versus-host disease (aGVHD), 12 patients received both cyclosporine A and short-term methotrexate; 3 received CyA alone because of apparent residual or active disease. In all patients, neutrophil and platelet engraftment were achieved rapidly. The median time of engraftment in neutrophil and platelet was 16.5 days (11–26) and 23.5 days (15–38), respectively. In 10 (71%) of 14 patients, complete chimerism was achieved within 60 days of transplant. Regimen related toxicity in this conditioning was minimal and grade IV of non-hematological regimen related toxicity did not appear. Grade III stomatitis and liver dysfunction occurred in 3 patients and one patient, respectively. Four out of 5 patients with grade II–IV received HLA genotype 1-locus mismatched transplants. In 5 patients with grade II–IV, acute GVHD was manageable only with additional steroids treatments except one patient with grade IV acute GVHD causing early death. In this study, day100-transplant related mortality (TRM), 1 year-TRM, event free survival, and overall survival were 7%, 24%, 70%, and 53 %, respectively. These results show that non-TBI, non-ATG containing fludarabine based-regimen for u-RIST may be less toxic and feasible at least for patients who received prior chemotherapy.

Non-infectious pulmonary complications which occur beyond 3 months of allogeneic hematopoietic stem cell transplantation (allo-HSCT) have become recognized as a critical problem. Above all, bronchiolitis obliterans (BO) and idiopathic pneumonia syndrome (IPS) are difficult to be cured and cause high mortality. Therefore, early identification of patients with higher risk for BO/IPS may lead to improving outcome of allo-HSCT. Surfactant protein D (SP-D) is one of collectins mainly synthesized by alveolar type II cells. The best known function is to prevent the collapse of alveoli by decreasing surface tension at alveolar air-lipid interface, and SP-D plays an important roles as a mediator in innate immunity in the lung. In clinical practice, high serum SP-D level is used as a marker lung diseases. Recently, low production of SP-D in the alveoli has been considered as an important pathgenesis of adult respiratory distress. We analyzed serum SP-D levels before allo-HSCT of 42 patients who received allo-HSCT in our institution between November 2001 and February 2006 and survived more than 90 days after transplant. In all patients, 5 patients had BO and 3 had IPS at a median interval of 303 and 117 days of transplantation (range; 100–452 and 95–153 days). As a result of univariate analysis, BO/IPS patients had lower serum SP-D levels prior allo-HSCT and extensive type of cGVHD except lung compared with no BO/IPS patients (p=0.06 and 0.07). KL-6 had also mildly associated with BO/IPS. On the other hand, we couldn’t find the association in sex, age, donor source, conditioning regimen, disease status, aGVHD, and FEV1.0/FVC and SP-A prior HSCT. We could not clarify the precise mechanism of the association between Decreased serum levels of SP-D and the development of BO and IPS following allo-HSCT. However, we speculate that low production of SP-D in the alveoli, which causes innate immune compromise, might contribute to extreme pulmonary alloreaction.