Publications by authors named "Kazuko Ino"

29 Publications

  • Page 1 of 1

Voriconazole as a secondary prophylaxis for cryptococcal meningitis during hematopoietic stem cell transplantation.

IDCases 2021 26;25:e01241. Epub 2021 Jul 26.

Department of Hematology and Oncology, Mie University Graduate School of Medicine/Faculty of Medicine, Tsu, Japan.

Antifungal prophylaxis is crucial for successful hematopoietic stem cell transplantation (HSCT). Maintenance therapy with fluconazole (FLCZ) is generally prescribed as secondary prophylaxis in patients with human immunodeficiency virus infection and non-immunocompromised hosts. However, previous reports have revealed that FLCZ is insufficient as a secondary prophylaxis for cryptococcal infection in HSCT cases. There is no well-established evidence of effective secondary prophylaxis against cryptococcal infection in conditions of severe immunosuppression, such as in HSCT. Herein, we report a case of atypical chronic myeloid leukemia (aCML) presenting with cryptococcal meningitis. A 58-year-old man with progressive leukocytosis and headache was referred to our hospital. Bone marrow biopsy revealed aCML. Because the estimated overall survival was limited, HSCT was indicated. Furthermore, enhanced magnetic resonance imaging and lumbar puncture aided in diagnosing cryptococcal meningitis, which was treated with a combination therapy comprising liposomal amphotericin B and 5-fluorocystine for 28 days. Given the high recurrence rate of cryptococcal meningitis, voriconazole (VRCZ) dose was calculated using the trough concentration of VRCZ in the cerebrospinal fluid. Eventually, HSCT was successfully performed at an appropriate therapeutic range of VRCZ. To the best of our knowledge, there is no case report on HSCT with secondary prophylaxis against cryptococcal meningitis. Our report thus emphasizes the efficacy of VRCZ maintenance therapy as secondary prophylaxis for cryptococcal infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.idcr.2021.e01241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329504PMC
July 2021

Clinical utility of oral management in allogeneic hematopoietic stem cell transplantation recipients: microbiological evidence based on molecular analysis of oral bacteria.

Support Care Cancer 2021 Aug 10. Epub 2021 Aug 10.

Department of Hematology and Oncology, Mie University Hospital, Mie, Japan.

Purpose: This study aimed to clarify the clinical utility of oral management to prevent bloodstream infections by oral bacteria microbiologically in patients undergoing allogeneic hematopoietic stem cell transplantation (ASCT).

Methods: Ten consecutive patients with hematological malignancies undergoing ASCT were enrolled in this study. We implemented dental treatments before transplantation, if required, and carried out oral hygiene instructions and oral management every other day after transplantation. Molecular analysis of bacterial DNA for seven oral species using a polymerase chain reaction (PCR) assay was performed for oral samples and peripheral blood once a week for 3 weeks after transplantation.

Results: Periodontitis was found in all 10 patients (mild grade in 3 and middle grade in 7) for whom basic periodontal therapy was conducted. Necessary dental procedures, including tooth extraction were performed in 5 patients. After transplantation, oral mucositis occurred in 10 patients (grade 1 in 3, grade 2 in 2, and grade 3 in 5) for whom oral hygiene instruction and oral care were continued every other day. PCR-identified three to six bacterial species in oral samples from nine patients, but none in peripheral blood from any patient during the observation period.

Conclusions: Our study suggests that oral management could prevent bloodstream infections by oral bacteria in ASCT recipients despite the existence of periodontitis or oral mucositis. Its utility was confirmed by microbiological evidence based on molecular data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00520-021-06462-9DOI Listing
August 2021

Comparison of Transplantation Outcomes after Foscarnet and Ganciclovir Administration as First-Line Anti-Cytomegalovirus Preemptive Therapy.

Transplant Cell Ther 2021 04 16;27(4):342.e1-342.e10. Epub 2020 Dec 16.

Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Ganciclovir (GCV) and foscarnet (FCN) are effective anti-cytomegalovirus (CMV) preemptive therapies; however, the impact of the 2 agents on various clinical outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) remains unclear. We retrospectively analyzed data on 532 patients undergoing allogeneic HSCT from unrelated donors and administered FCN (n = 86) or GCV (n = 446) as first-line anti-CMV preemptive therapy. Overall survival, relapse, and nonrelapse mortality (NRM) did not differ between the FCN and GCV groups, whereas the GCV group had a higher risk of chronic graft-versus-host disease (cGVHD) (hazard ratio [HR], 2.38; 95% confidence interval [CI], 1.28 to 4.39; P = .006) and extensive cGVHD (HR, 3.94; 95% CI, 1.43 to 10.9; P = .008). All 13 patients with cGVHD in the FCN group survived. Switching to the other agent was done mainly due to hematologic adverse events in the GCV group and mainly due to insufficient efficacy in the FCN group. The incidence of end-organ CMV disease was similar in the 2 groups. Selection of FCN or GCV as first-line preemptive anti-CMV therapy did not affect survival, relapse, or NRM. Physicians can select either of the agents, depending on the clinical situation; however, the selection may influence the cGVHD-related clinical course in HSCT recipients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtct.2020.12.012DOI Listing
April 2021

Early central nervous system relapse of monomorphic epitheliotropic intestinal T-cell lymphoma after cord blood transplantation.

Int J Hematol 2021 Jul 1;114(1):129-135. Epub 2021 Mar 1.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare subtype of intestinal T-cell lymphoma that occurs mostly in Asia. CHOP-like therapy is usually selected, but the prognosis is very poor. This report concerns a 43-year-old woman with newly diagnosed stage IVA MEITL. The patient obtained a partial response after 4 cycles of GDP (gemcitabine, dexamethasone, cisplatin) and achieved a complete response (CR) after cord blood transplantation (CBT) conditioned with total body irradiation, cyclophosphamide, and cytarabine. Seven months after transplantation, the patient experienced cognitive impairment. Magnetic resonance imaging of the brain showed a high-intensity lesion in the right cerebral peduncle and internal capsule. A cerebrospinal fluid examination confirmed central nervous system (CNS) relapse of MEITL. After 3 cycles of MPV (methotrexate, procarbazine, vincristine) followed by whole-brain radiotherapy, her cognitive impairment improved. Due to disease progression, she died 6 months after CNS relapse. Given the CNS relapse after achieving a CR with GDP and CBT in this patient, CNS prophylaxis during first-line therapy may be beneficial in the treatment of MEITL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12185-021-03107-9DOI Listing
July 2021

[Therapy-related acute promyelocytic leukemia with complex karyotype accompanied by cryptic PML/RARA on chromosome 15 by metaphase FISH].

Rinsho Ketsueki 2020 ;61(11):1577-1583

Department of Hematology and Oncology, Mie University Graduate School of Medicine.

A 53-year-old male presented with pancytopenia for 13 months. He had a past history of follicular lymphoma and hypopharyngeal cancer, which was treated via chemotherapy and radiotherapy. Bone marrow aspiration biopsy of the patient revealed a hypocellular marrow with 32% of hypergranular blasts without Auer bodies. There were also erythroid and megakaryocytic dysplasia in the bone marrow. Although the PML/RARA transcript was detected by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR), the G-banding karyotype analysis showed a complex karyotype without t (15;17). The PML/RARA fusion signal was identified on chromosome 15 by metaphase FISH. The patient was diagnosed of therapy-related acute promyelocytic leukemia (t-APL) with cryptic PML/RARA. He successfully attained molecular complete remission with all-trans retinoic acid (ATRA) and two courses of arsenic trioxide (ATO). He was subsequently administered nivolumab without ATRA maintenance therapy because of a progressing metastasis of a hypopharyngeal cancer to the lung. The patient had a relapse of t-APL following nine courses of nivolumab, 8 months after ending consolidation therapy with ATO. Reinduction therapy with ATRA was not effective for the relapsed t-APL that was accompanied by del (5q) and monosomy 7. Little has been previously reported on t-APL with cryptic PML/RARA. Therefore, the clinical course of this patient may provide useful insights about the characteristics of t-APL with cryptic PML/RARA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11406/rinketsu.61.1577DOI Listing
February 2021

[Successful treatment with a combination of elotuzumab, lenalidomide and dexamethasone of extramedullary disease in a patient with refractory multiple myeloma].

Rinsho Ketsueki 2020 ;61(3):223-227

Department of Hematology and Oncology, Mie University Graduate School of Medicine.

A 56-year-old man diagnosed with multiple myeloma was treated with CBD (cyclophosphamide, bortezomib, and dexamethasone; DEX), which was discontinued because of bortezomib-associated adverse events. Thereafter, he was treated with Ld (lenalidomide; LEN+DEX) followed by high-dose chemotherapy with autologous stem cell rescue, resulting in a complete response. Ld as maintenance therapy was discontinued because of immune thrombocytopenia, resulting in disease progression. Although treatment was switched to Pd (pomalidomide+DEX), DLd (daratumumab+LEN+DEX), and IRd (ixazomib+LEN+DEX); the patient's M protein level continued to increase and the extramedullary disease expanded despite radiotherapy. He was treated with E-Ld (elotuzumab+LEN+DEX) after 3 cycles of short VAD (vincristine, doxorubicin, and DEX). The extramedullary disease disappeared after 8 cycles of E-Ld. To the best of our knowledge, this is the first report showing the effectiveness of E-Ld treatment for extramedullary disease of a heavily treated patient for multiple myeloma. We believe that the clinical course of this patient provides useful insights about the antimyeloma mechanism of elotuzumab.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11406/rinketsu.61.223DOI Listing
May 2020

Achievement of long-term remission of disseminated histoplasmosis in an AIDS patient.

Med Mycol Case Rep 2020 Mar 19;27:25-28. Epub 2019 Dec 19.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan.

Histoplasmosis, a fungal infection caused by , is poor prognosis once it disseminated, especially in immunocompromised patients. A 50-year-old Japanese-Brazilian male with multiple cervical lymphadenopathies was diagnosed as disseminated histoplasmosis and acquired immunodeficiency syndrome (AIDS). Anti-fungal therapy was initiated followed by anti-retroviral therapy (ART). He achieved long-term remission by treatment with voriconazole. Here we report a case of an AIDS patient with disseminated histoplasmosis who achieved long-term survival in non-endemic area.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mmcr.2019.12.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938860PMC
March 2020

[Atypical hemolytic uremic syndrome with C3 p.I1157T missense mutation successfully treated with eculizumab].

Rinsho Ketsueki 2018;59(2):178-181

Department of Hematology and Oncology, Mie University Graduate School of Medicine.

A 23-year-old man from Mie Prefecture, Japan, with past and family history of hematuria was diagnosed with influenza A and admitted to our hospital on the following day because of hemoglobinuria. He was diagnosed with thrombotic microangiopathy and was suspected of having atypical hemolytic uremic syndrome (aHUS). C3 p.I1157T missense mutation, which we had previously reported in eight aHUS patients from six families in Mie Prefecture, was identified. The laboratory findings and symptoms of our patient promptly improved after administering eculizumab. Little information is available on abnormalities of the complement system in aHUS or on mutation-specific outcomes of eculizumab therapy. Eculizumab was effective for treating our aHUS patient with C3 p.I1157T missense mutation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11406/rinketsu.59.178DOI Listing
February 2019

Clinical Utility of Wilms' Tumor 1 Monitoring in Patients with Myeloid Malignancy and Prior Allogeneic Hematopoietic Stem Cell Transplantation.

Biol Blood Marrow Transplant 2017 Oct 30;23(10):1780-1787. Epub 2017 Jun 30.

Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is 1 of the standard treatments for myeloid malignancy, relapse remains a major obstacle to cure. Early detection of relapse by monitoring of minimal residual disease (MRD) may enable us to intervene pre-emptively and potentially prevent overt relapse. Wilms' tumor 1 (WT1) is well known as a pan-leukemic marker. We retrospectively examined serially monitored WT1 levels of peripheral blood in 98 patients (84 with acute myeloid leukemia and 14 with myelodysplastic syndrome). At the time of allo-HSCT, 49 patients (50%) were in complete remission. Patients were divided into 3 groups according to WT1 levels (<50 copies/µg RNA, 50 to 500 copies/µg RNA and >500 copies/µg RNA). The cumulative incidence of relapse (CIR) and overall survival (OS) differed statistically according to the WT1 levels before allo-HSCT and at days 30 and 60 after allo-HSCT. In multivariate analysis, WT1 >500 copies/µg RNA before and at day 60 after allo-HSCT and WT1 ≥50 copies/µg RNA at day 30 were correlated with CIR. Moreover, WT1 >500 copies/µg RNA at day 60 after allo-HSCT was only correlated with worse OS. Our data suggest that serial monitoring of WT1 levels in peripheral blood may be useful for MRD monitoring and as a predictor of hematological relapse in allo-HSCT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2017.06.007DOI Listing
October 2017

Management of Pulmonary Mucormycosis Based on a Polymerase Chain Reaction (PCR) Diagnosis in Patients with Hematologic Malignancies: A Report of Four Cases.

Intern Med 2017 17;56(6):707-711. Epub 2017 Mar 17.

Department of Hematology and Oncology, Mie University Hospital, Japan.

Pulmonary mucormycosis (PM) is a life-threatening fungal infection in patients with hematologic malignancies, and early and accurate diagnostic modalities are urgently needed. We conducted a polymerase chain reaction (PCR) assay targeting these fungi in peripheral blood from four patients with hematologic malignancies who were strongly suspected of having PM. In these four patients, the Rhizopus species was identified in two patients, and the Cunninghamella and Absidia species in one each. Based on these molecular findings, all of the patients were successfully treated via targeted therapy with liposomal amphotericin B. In this report, a PCR analysis proved very useful for managing PM in patients with hematologic malignancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2169/internalmedicine.56.7647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410485PMC
May 2017

Bacteremia due to Leuconostoc pseudomesenteroides in a Patient with Acute Lymphoblastic Leukemia: Case Report and Review of the Literature.

Case Rep Hematol 2016 22;2016:7648628. Epub 2016 Aug 22.

Department of Hematology and Oncology, Mie University Hospital, Tsu, Mie 514-8507, Japan.

Leuconostoc species are vancomycin-resistant Gram-positive cocci. Infections due to Leuconostoc species have been reported in various immunocompromised patients, but little is known about such infection in patients with hematologic malignancies. We report a case of Leuconostoc infection in a 44-year-old woman with acute lymphoblastic leukemia. The patient developed a high fever despite antimicrobial therapy with doripenem after induction chemotherapy. After an isolate from blood cultures was identified as L. pseudomesenteroides, we changed the antibiotics to piperacillin-tazobactam and gentamicin, after which the patient recovered from the infection. Physicians should be aware of Leuconostoc species as causative pathogen if they encounter Gram-positive cocci bacteremia resistant to standard antibiotics such as vancomycin and teicoplanin, especially in patients with hematologic malignancies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2016/7648628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011224PMC
September 2016

Acute pulmonary edema with new giant V wave immediately after pericardiocentesis.

Int J Cardiol 2016 Jun 24;212:253-4. Epub 2016 Mar 24.

Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2016.03.158DOI Listing
June 2016

Association of Cumulative Steroid Dose with Risk of Infection after Treatment for Severe Acute Graft-versus-Host Disease.

Biol Blood Marrow Transplant 2016 06 8;22(6):1102-1107. Epub 2016 Mar 8.

Department of Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.

This study aimed to characterize the incidence and risk factors of invasive fungal disease, cytomegalovirus infection, other viral diseases, and gram-negative rod infection after glucocorticoid treatment for severe acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation and to elucidate the associations of cumulative steroid dose with the risks of individual infections. The study cohort included 91 consecutive patients who developed maximum grades III and IV acute GVHD at our center. The mean cumulative prednisolone-equivalent dose was 41 mg/kg during the first 4 weeks. The cumulative incidence rates of fungal disease, cytomegalovirus disease, other viral diseases, and gram-negative rod infection at 6 months after glucocorticoid treatment were remarkably high, at 14%, 21%, 28%, and 20%, respectively. GVHD within 26 days after transplantation and low lymphocyte count at GVHD treatment were associated with increased risks of several infections. Cumulative prednisolone-equivalent steroid doses ≥ 55 mg/kg during the first 4 weeks were associated with an increased risk of fungal disease (hazard ratio, 3.65; P = .03) and cumulative doses ≥ 23 mg/kg were associated with an increased risk of non-cytomegalovirus viral diseases (hazard ratio, 4.14; P = .02). Strategies to reduce the risk of infectious complications are needed, particularly for patients who have risk factors and those who receive high cumulative steroid doses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2016.02.020DOI Listing
June 2016

Splenectomy increases the number of circulating hematopoietic stem/progenitor cells in patients with hepatitis C virus-associated liver cirrhosis.

Hepatol Res 2014 Dec 25;44(14):E376-E385. Epub 2014 Mar 25.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan.

Aim: The spleen is not believed to contribute to hematopoiesis in healthy adults. However, several reports have demonstrated that the spleen in adults contains a large number of hematopoietic stem/progenitor cells (HSC). Although splenectomy increases platelet and leukocyte counts, the effects of splenectomy on circulating HSC have not been elucidated. In this study, we evaluated the association between the number of circulating HSC and splenectomy in patients with hepatitis C virus (HCV)-associated liver cirrhosis (LC).

Methods: In 48 patients with various stages of HCV-associated chronic liver disease and seven patients with LC who underwent splenectomy, and 10 healthy volunteers, we determined the numbers of circulating CD34 cells and colony-forming unit culture by flow cytometry and methylcellulose culture, respectively. Plasma stromal cell-derived factor-1α (SDF-1α) concentrations were measured using an enzyme-linked immunosorbent assay.

Results: The numbers of circulating CD34 cells and colony-forming unit culture decreased but the plasma SDF-1α concentration increased with the progression of liver disease. There was an inverse correlation between the number of circulating HSC and the plasma SDF-1α concentration. The numbers of circulating HSC and platelets were determined before and after splenectomy in seven patients with LC. In these patients, the numbers of circulating HSC and platelets increased significantly after splenectomy and the enhancing effect persisted for a long time.

Conclusion: Our data suggest that the spleen plays an important role in modulating HSC dynamics in patients with HCV-associated chronic liver disease. Our results also imply that splenectomy may improve liver function in patients with LC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hepr.12319DOI Listing
December 2014

Monocytes infiltrate the pancreas via the MCP-1/CCR2 pathway and differentiate into stellate cells.

PLoS One 2014 8;9(1):e84889. Epub 2014 Jan 8.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.

Recent studies have shown that monocytes possess pluripotent plasticity. We previously reported that monocytes could differentiate into hepatic stellate cells. Although stellate cells are also present in the pancreas, their origin remains unclear. An accumulation of enhanced green fluorescent protein (EGFP)(+)CD45(-) cells was observed in the pancreases and livers of chimeric mice, which were transplanted with a single hematopoietic stem cell isolated from EGFP-transgenic mice and treated with carbon tetrachloride (CCl4). Because the vast majority of EGFP(+)CD45(-) cells in the pancreas expressed stellate cell-associated antigens such as vimentin, desmin, glial fibrillary acidic protein, procollagen-I, and α-smooth muscle actin, they were characterized as pancreatic stellate cells (PaSCs). EGFP(+) PaSCs were also observed in CCl4-treated mice adoptively transferred with monocytes but not with other cell lineages isolated from EGFP-transgenic mice. The expression of monocyte chemoattractant protein-1 (MCP-1) and angiotensin II (Ang II) increased in the pancreas of CCl4-treated mice and their respective receptors, C-C chemokine receptor 2 (CCR2) and Ang II type 1 receptor (AT1R), were expressed on Ly6C(high) monocytes isolated from EGFP-transgenic mice. We examined the effect of an AT1R antagonist, irbesartan, which is also a CCR2 antagonist, on the migration of monocytes into the pancreas. Monocytes migrated toward MCP-1 but not Ang II in vitro. Irbesartan inhibited not only their in vitro chemotaxis but also in vivo migration of adoptively transferred monocytes from peripheral blood into the pancreas. Irbesartan treatment significantly reduced the numbers of EGFP(+)F4/80(+)CCR2(+) monocytic cells and EGFP(+) PaSCs in the pancreas of CCl4-treated chimeric mice receiving EGFP(+) bone marrow cells. A specific CCR2 antagonist RS504393 inhibited the occurrence of EGFP(+) PaSCs in injured mice. We propose that CCR2(+) monocytes migrate into the pancreas possibly via the MCP-1/CCR2 pathway and give rise to PaSCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0084889PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3885670PMC
September 2014

Alcoholic ketoacidosis that developed with a hypoglycemic attack after eating a high-fat meal.

Acute Med Surg 2014 Apr 16;1(2):109-114. Epub 2013 Dec 16.

Department of Emergency Medicine Matsusaka Chuo Hospital Matsusaka Mie Japan.

Case: Alcoholic ketoacidosis (AKA) usually occurs in patients with a history of prolonged alcohol abuse and recent binge drinking followed by abrupt cessation of alcohol consumption.

Outcome: A 61-year-old man was brought to our emergency department. He had a history of eating barbecued beef with beer the previous night. He had unexplained hypoglycemia with high anion gap metabolic acidosis and fatty liver, and we strongly suspected AKA. After hydration with saline solution, dextrose, and thiamine, given i.v., his metabolic acidosis rapidly improved. A history of alcohol abuse and high serum β-hydroxybutyrate concentration were subsequently confirmed, and the diagnosis of AKA was finally made.

Conclusion: Our case suggests that a high-fat meal can induce AKA without abrupt cessation of alcohol consumption and that AKA should be considered when encountering patients with unexplained high anion gap metabolic acidosis with hypoglycemia and fatty liver, even if the past history of alcohol abuse is unknown.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ams2.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997211PMC
April 2014

[Development of syndrome of inappropriate secretion of ADH and reversible posterior leukoencephalopathy during initial rituximab-CHOP therapy in a patient with diffuse large B-cell lymphoma].

Rinsho Ketsueki 2013 Mar;54(3):269-72

Department of Internal Medicine, Matsusaka Chuo General Hospital, Japan.

A 61-year-old woman presented with a right mandibular tumor and was diagnosed with DLBCL clinical stage IIIA from the biopsy results of the tumor and CT examination. An initial rituximab was administrated a week after the first CHOP treatment. During the infusion of rituximab, she exhibited disorientation, seizure, and consciousness disturbance. Hyponatremia due to SIADH and hypertension were coincidentally observed. MRI revealed T2 and FLAIR hyperintense signals involving the bilateral occipital, parietal, frontal lobes and the cerebellum that were consistent with reversible posterior leukoencephalopathy syndrome (RPLS). Her consciousness level recovered in parallel with corrections in serum sodium levels and blood pressure. Although she presented with transient cortical blindness, all neurological abnormalities disappeared 40 hours after the occurrence of seizure. She received a further 7 cycles of CHOP followed by 7 cycles of rituximab treatment with no relapse of RPLS. After irradiation for a residual abdominal tumor, she has maintained complete remission for 2 years. Although RPLS is a rare complication of rituximab-CHOP chemotherapy, it should be considered in patients with DLBCL who present with acute neurological deterioration.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2013

Manipulation of human early T lymphopoiesis by coculture on human bone marrow stromal cells: potential utility for adoptive immunotherapy.

Exp Hematol 2013 Apr 17;41(4):367-76.e1. Epub 2012 Dec 17.

Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.

T cell precursors are an attractive target for adoptive immunotherapy. We examined the regulation of human early T lymphopoiesis by human bone marrow stromal cells to explore in vitro manipulation of human T cell precursors in a human-only coculture system. The generation of CD7(+)CD56(-)cyCD3(-) proT cells from human hematopoietic progenitors on telomerized human bone marrow stromal cells was enhanced by stem cell factor, flt3 ligand, and thrombopoietin, but these stimulatory effects were suppressed by interleukin 3. Expression of Notch ligands Delta-1 and -4 on stromal cells additively promoted T cell differentiation into the CD7(+)cyCD3(+) pre-T cell stage, while cell growth was strongly inhibited. By combining these coculture systems, we found that initial coculture with telomerized stromal cells in the presence of stem cell factor, flt3 ligand, and thrombopoietin, followed by coculture on Delta-1- and -4-coexpressing stromal cells led to a higher percentage and number of pre-T cells. Adoptive immunotherapy using peripheral blood T cells transduced with a tumor antigen-specific T cell receptor (TCR) is a promising strategy but has several limitations, such as the risk of forming a chimeric TCR with the endogenous TCR. We demonstrated that incubation of TCR-transduced hematopoietic progenitors with the combination of coculture systems gave rise to CD7(+)TCR(+)CD3(+)CD1a(-) T cell precursors that rapidly proliferated and differentiated under the culture condition to induce mature T cell differentiation. These data show the regulatory mechanism of early T lymphopoiesis on human stromal cells and the potential utility of engineered human stromal cells to manipulate early T cell development for clinical application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.exphem.2012.12.001DOI Listing
April 2013

Human bone marrow stromal cells simultaneously support B and T/NK lineage development from human haematopoietic progenitors: a principal role for flt3 ligand in lymphopoiesis.

Br J Haematol 2012 Jun 30;157(6):674-86. Epub 2012 Mar 30.

Haematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.

The regulation of human early lymphopoiesis remains unclear. B- and T-lineage cells cannot develop simultaneously with conventional stromal cultures. Here we show that telomerized human bone marrow stromal cells supported simultaneous generation of CD19(+) CD34(lo/-) CD10(+) cyCD79a(+) CD20(+/-) VpreB(-) pro-B cells and CD7(+) CD34(+) CD45RA(+) CD56(-) cyCD3(-) early T/Natural Killer (NK) cell precursors from human haematopoietic progenitors, and the generation of both lymphoid precursors was promoted by flt3 ligand (flt3L). On the other hand, stem cell factor or thrombopoietin had little or no effect when used alone. However, both acted synergistically with flt3L to augment the generation of both lymphoid precursors. Characteristics of these lymphoid precursors were evaluated by gene expression profiles, rearrangements of IgH genes, or replating assays. Similar findings were observed with primary human bone marrow stromal cells. Notably, these two lymphoid-lineage precursors were generated without direct contact with stromal cells, indicating that early B and T/NK development can occur, at least in part, by stromal cell-derived humoral factors. In serum-free cultures, flt3L elicited similar effects and appeared particularly important for B cell development. The findings of this study identified the potential of human bone marrow stromal cells to support human early B and T lymphopoiesis and a principal role for flt3L during early lymphopoiesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1365-2141.2012.09109.xDOI Listing
June 2012

IKAROS isoform 6 enhances BCR-ABL1-mediated proliferation of human CD34+ hematopoietic cells on stromal cells.

Int J Oncol 2012 Jan 7;40(1):53-62. Epub 2011 Sep 7.

Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Mie 514-8507, Japan.

The BCR-ABL1 induces chronic myelogenous leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL). Recent studies revealed high ratios of loss of the IKZF1 gene which encodes IKAROS in BCR-ABL1+ ALL and lymphoblastic crisis (LBC) of CML. However, little is known about the cooperativity between the aberrant IKAROS and BCR-ABL1 in primary human hematopoietic cells. We investigated the effects of expression of BCR-ABL1 and/or IK6, a natural dominant negative isoform of IKAROS, on proliferation and differentiation of human CD34+ cord blood cells with or without human bone marrow-derived stromal cells which support early B cell differentiation. Cell proliferation was remarkably enhanced by co-expression of BCR-ABL1 and IK6, with reduced expression of glycophorin A and increased expression of CD41, especially on stromal cells, compared with expression of BCR-ABL1 alone that resulted in expansion of erythroid progenitors. Interestingly, p190BCR-ABL1 showed higher dependency on stromal cells to stimulate cell growth with IK6, than p210BCR-ABL1. Furthermore, the cooperation was found to depend on direct cell adhesive interaction of hematopoietic progenitors with stromal cells. These findings suggest that IK6 and BCR-ABL1 synergistically contribute to leukemogenesis in human bone marrow stromal microenvironment, and may provide a clue to elucidate the mechanisms of leukemogenesis of Ph+ ALL and CML-LBC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ijo.2011.1192DOI Listing
January 2012

Ly6C(+) monocytes are extrahepatic precursors of hepatic stellate cells in the injured liver of mice.

Exp Hematol 2011 Sep 14;39(9):934-46. Epub 2011 Jun 14.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Japan.

Objective: We previously reported that hepatic stellate cells (HpSCs) are of hematopoietic origin in liver injury. However, the immediate precursors of HpSCs remain unknown. This study was conducted to elucidate whether terminally differentiated blood cells can differentiate into HpSCs.

Materials And Methods: We adoptively transferred a variety of cells isolated from enhanced green fluorescent protein (EGFP)-transgenic mice into carbon tetrachloride (CCl(4))-treated nontransgenic mice twice weekly for 2 weeks. We examined the presence of EGFP(+) HpSCs in the injured liver using immunofluorescence analysis.

Results: Monocytes, neutrophils, eosinophils, B cells, or T cells from EGFP mice were transferred into CCl(4)-treated mice. Thirty percent of EGFP(+) cells in the livers of mice given Ly6C(high)c-kit(-) monocytes were negative for CD45, but were positive for glial fibrillary acidic protein, desmin, CD146, ADAMTS13, and α-smooth muscle actin, well-known markers of HpSCs. EGFP(+)CD45(-) cells were predominantly positive for glial fibrillary acidic protein. Although 48% of EGFP(+) cells were positive for procollagen type I, half of them were CD45(-). In the livers of mice given neutrophils, eosinophils, B cells, or T cells, all of the EGFP(+) cells were CD45(+). The majority of EGFP(+) cells in the nonparenchymal cell fraction purified from the livers of mice given Ly6C(high)c-kit(-) monocytes contained lipid droplets and were positive for glial fibrillary acidic protein, desmin, ADAMTS13, and procollagen type I. When Ly6C(+) monocyte-depleted peripheral blood total nucleated cells were adoptively transferred into CCl(4)-treated mice, we found no EGFP(+)CD45(-) cells in the liver.

Conclusions: These results suggest that Ly6C(+) monocytes can become HpSCs in the injured liver.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.exphem.2011.06.001DOI Listing
September 2011

[Aggressive NK-cell leukemia with sustained relapse-free survival after allogeneic peripheral blood stem cell transplantation].

Rinsho Ketsueki 2010 Apr;51(4):258-63

Department of Internal Medicine, Matsusaka Chuo General Hospital.

A 46-year-old Japanese man was admitted to our hospital because of prolonged fever. Laboratory examination demonstrated leukopenia, thrombocytopenia, marked liver dysfunction, and elevation of serum ferritin. A bone marrow examination showed several hemophagocytic macrophages, and a diagnosis of hemophagocytic syndrome was made. He was treated using HLH-94 protocol, and his clinical symptoms and laboratory data were rapidly improved. After 5 weeks, fever and liver dysfunction reappeared. A repeat bone marrow examination demonstrated that 28.4% of marrow nucleated cells were atypical lymphocytes, which were positive for CD2, CD7, CD16, CD56, and HLA-DR. Clonality of these proliferating NK cells was confirmed by an analysis of EB virus terminal repeat sequence and cytogenetic analysis, and final diagnosis of aggressive NK-cell leukemia was made. After induction chemotherapy consisting of dexamethasone, etoposide, ifosfamide, and L-asparaginase, the patient achieved partial remission. He received allogeneic peripheral blood stem cell transplantation from his one locus mismatched son, and is alive with no evidence of disease 20 months after transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
April 2010

A potential activity of valproic acid in the stimulation of interleukin-3-mediated megakaryopoiesis and erythropoiesis.

Exp Hematol 2010 Aug 8;38(8):685-95. Epub 2010 Apr 8.

Mie University Graduate School of Medicine, Japan.

Objective: Although the anticancer activities of histone deacetylase (HDAC) inhibitors have been studied, a role for HDAC in normal hematopoiesis has not been clearly defined. Previous studies have shown that the potent HDAC inhibitor FK228 stimulates interleukin (IL)-3-mediated erythropoiesis. Here, we examined whether the widely used valproic acid (VPA) affects megakaryopoiesis as well as erythropoiesis.

Materials And Methods: CD34(+) cells were incubated in serum-free or serum-containing cultures with cytokines, with or without VPA.

Results: In the serum-free cultures containing IL-3+stem cell factor (SCF), VPA significantly increased generation of CD61(+)GPA(-) megakaryocytic and a CD61(+)GPA(+) mixture of megakaryocytic and erythroid precursors from CD34(+) hematopoietic precursors at a pharmacological concentration (100 microg/mL). The increase in generation of megakaryocytic and erythroid precursors by VPA was confirmed by replating cultured cells with thrombopoietin+SCF and erythropoietin+SCF, respectively. VPA was as potent as FK228. In cultures with granulocyte-macrophage colony-stimulating factor+SCF, where CD61(-)GPA(+) erythroid precursors were mostly developed, VPA mainly enhanced the generation of CD61(-)GPA(+) erythroid precursors. In serum-containing cultures, only low numbers of CD61(+) or GPA(+) cells were developed with IL-3+SCF. Nevertheless, a substantial number of these cells were generated with VPA. Furthermore, these stimulating effects of VPA were observed by incubating CD34(+) cells from patients with myelodysplastic syndrome. Quantitative reverse transcription polymerase chain reaction showed that VPA enhanced GATA-2, but not GATA-1, messenger RNA expression with IL-3+SCF.

Conclusions: These results indicate a novel role for VPA in enhancing the potential of IL-3 to stimulate megakaryopoiesis as well as erythropoiesis and suggest a new therapeutic approach of epigenetic therapy for hematological disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.exphem.2010.03.019DOI Listing
August 2010

Breakthrough cryptococcosis in a patient with systemic lupus erythematosus (SLE) receiving micafungin.

J Infect Chemother 2008 Aug 17;14(4):311-4. Epub 2008 Aug 17.

Internal Medicine, Matsusaka Chuo General Hospital, and Department of Hematology and Oncology, Mie University Graduate School of Medicine, Matsusaka, Mie, Japan.

A 67-year-old woman with systemic lupus erythematosus (SLE) was admitted to our hospital because of lupus nephritis. Methylprednisolone minipulse therapy dramatically reduced her proteinuria; however; she then complained of general fatigue with low-grade fever. Radiological and culture studies revealed no infectious focus, but she was treated with meropenem and micafungin, considering her immunosuppressive state. Cytomegalovirus antigenemia was later determined and ganciclovir was added. She became afebrile, but complained of nausea and headache, and disorientation, without meningeal signs. Because a brain computed tomography (CT) scan showed no abnormality, we initially suspected some kind of drug interaction. Despite the discontinuation of all drugs, however, she still suffered from disturbance of consciousness. A lumbar puncture revealed yeast cells stained by India ink. A diagnosis of cryptococcal meningitis was confirmed. Though fluconazole and meropenem were administered, the patient died. Autopsy findings revealed disseminated cryptococcosis concomitant with pulmonary aspergillosis. Micafungin is a recently approved echinocandin-class antifungal agent that is now widely used in Japan because of its minimal toxicity and broadspectrum activity. However, such echinocandins have limited activity against a number of fungi. Indeed, breakthrough trichosporonosis is becoming a significant problem in patients with hematological malignancies who are receiving echinocandins. To the best of our knowledge, breakthrough cryptococcosis, as seen in our patient, has not been reported previously in patients who were receiving micafungin as an empiric antifungal therapy. This case highlights that cryptococcosis should be kept in mind as a possible breakthrough infection during the administration of echinocandins, especially in patients with cellular immunodeficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10156-008-0616-1DOI Listing
August 2008

[Acute myeloid leukemia invasion of the central nervous system, detected only along the Virchow Robin space].

Rinsho Ketsueki 2008 May;49(5):340-3

Internal Medicine, Matsusaka Chuo Hospital.

A 66year-old man with sustained fever was diagnosed as having acute myeloid leukemia with multilineage dysplasia. Induction therapy with etoposide and AraC was initiated, but was ineffective. Although fever had persisted for more than a few days, there was no evidence of any infection on radiological examination or culture studies. The patient was disorientated and demonstrated personality change. After a severe convulsive seizure, the patient died. Autopsy findings showed that the leukemic cells had permeated the Virchow Robin space, but without a mass lesion in the cerebral parenchyma. He was diagnosed as having had central nervous system leukemia (CNSL) that provoked sustained fever, consciousness disturbance and convulsive seizure. These findings suggested that the Virchow Robin space plays a particular role in the development of CNSL. Even with repeated cerebrospinal fluid examinations and radiological tests, we were unable to correctly diagnose CNSL before death, which may indicate the intractability of diagnosing CNSL spread along the Virchow Robin space. This case provides useful information about the pathophysiology and diagnosis of CNSL.
View Article and Find Full Text PDF

Download full-text PDF

Source
May 2008

[Prolonged survival in a patient with human herpesvirus-8-negative primary effusion lymphoma after combination chemotherapy with rituximab].

Gan To Kagaku Ryoho 2008 Apr;35(4):691-4

Department of Internal Medicine, Matsusaka Chuo Hospital.

Primary effusion lymphoma (PEL) is a unique clinicopathological entity usually associated with human herpesvirus-8 (HHV-8) infection. It occurs almost exclusively in human immunodeficiency virus (HIV) -infected individuals. We presented a rare case of HIV-negative PEL in an elderly HHV-8-negative patient who developed cardiac tamponade due to pericardial effusion. The patient was treated with rituximab and cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). This disease generally has a poor prognosis; however, this patient achieved complete remission and remains without signs of disease 30 months after the last treatment. Because most HIV-negative and HHV-8- negative PEL cases show pan-B-cell markers, there is considerable usage of rituximab, though its optimal usage for PEL is unclear. To the best of our knowledge, there have been five reported cases where rituximab treatment has been used against HIV-negative and HHV-8-negative PEL. The clinical courses of these cases were relatively good without specific adverse effects. HIV-negative and HHV-8-negative PEL appears to be a reasonably new clinicopathological entity. While further investigation will of course be needed, the use of rituximab is worth considering for treatment of such patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
April 2008

[Marked hyponatremia with consciousness disturbance probably caused by linezolid in a patient with acute myeloid leukemia].

Kansenshogaku Zasshi 2008 Jan;82(1):38-42

Internal Medicine, Matsusaka Chuo Hospital.

We report the case of a 75-year-old man with acute myeloid leukemia who developed hyponatremia after linezolid administration. Because induction therapy did not achieve complete remission for this man, we initiated re-induction therapy with enocitabin and daunomycin. Seven days after chemotherapy, the patient experienced a catheter-related blood stream infection (CRBSI) due to methicilin resistant staphylococcus aureus (MRSA). When treatment with albekacin and fosfomycin was in effective, linezolid was administrated intravenously and he became afebrile. On day 8 after linezolid administration, however, he reported general fatigue and slight consciousness disturbance. His serum sodium concentration was 119 mEq/L and his urinary sodium excretion rose to 143 mEq/day, although intravenous sodium intake was 98 mEq/day. Because of the sufficiency of urine volume and weight loss, we surmise that inappropriate ADH secretion (SIADH) syndrome was unlikely. We diagnosed renal salt wasting syndrome (RSWS) based on calculation of the amount of sodium intake and the amount of sodium excreted from the kidneys. After linezolid was discontinued and aggressive treatment with sodium supplement begun, his consciousness cleared as his low serum sodium level rose. This is, to the best of our knowledge, the first case reported on the development of RSWS after linezolid treatment. Although the process remains unclear, our case suggests that linezolid may induce RSWS after intensive chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11150/kansenshogakuzasshi1970.82.38DOI Listing
January 2008

[Multiple myeloma accompanying splenic amyloidosis and overwhelming pneumococcemia].

Rinsho Ketsueki 2007 Nov;48(11):1503-7

Internal Medicine, Matsusaka Chuo Hospital.

We present the case of an 84-year-old woman with multiple myeloma who developed overwhelming pneumococcemia. Significant pathologic findings of amyloidosis were confirmed in the spleen, adrenal glands, kidneys, liver and bone marrow on autopsy. In particular, the spleen was almost replaced by diffuse linear deposition of amyloid, and residual lymphoid tissue was scant. There is a well-established association between asplenia and a predisposition to fulmination, frequently with fatal bacterial infection. In this case, functional hyposplenism as a result of amyloid replacement of the spleen led to overwhelming pneumococcemia. Functional hyposplenism due to amyloidosis predisposes patients to septicemia. As bacterial infections are a common complication in patients with multiple myeloma, it is important to know whether they have accompanying splenic amyloidosis. If there are findings of hyposplenism, it may be necessary to establish strategies to prevent fatal infection. Thought needs to be given to providing detailed education, and prophylactic or stand-by antibiotics for such patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
November 2007
-->