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ABSTRACT: A 22-year-old male with Ph-positive chronic myelogenous leukemia (CML) was started on treatment with imatinib. After 12 months of therapy, he achieved a complete cytogenetic response (CCyR). Although the CCyR persisted in his bone marrow, he developed an isolated CML blast crisis in his central nervous system (CNS) after 29 months of therapy. He underwent allogeneic hematopoietic stem cell transplantation (HSCT) following combination therapy with dasatinib, intrathecal chemotherapy and cranial irradiation. Subsequently, 168 days after allogeneic HSCT, he was started on dasatinib maintenance therapy to prevent a CNS relapse. Thirty-eight months after allogeneic HSCT, he has sustained a complete molecular response in both bone marrow and CNS. We believe dasatinib has the potential to prevent CNS relapse if used for maintenance therapy after allogeneic HSCT.
Acta Haematologica 03/2013; 130(2):111-114. · 1.35 Impact Factor
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Mizuki Aimoto,
Takahisa Yamane,
Mitsuru Ichii,
Katsuhito Mori,
Ran Moriguchi-Aimoto,
Eri Wada-Inoue,
Hideo Koh,
Takahiko Nakane,
Yasunobu Takeoka,
Mika Akahori-Nakamae,
Saori Nishiki-Kosaka,
Yoshiki Terada,
Hirohisa Nakamae, Ki-Ryang Koh,
Takafumi Nakao,
Masahiko Ohsawa,
Kenichi Wakasa,
Eiji Ishimura,
Masaaki Inaba,
Masayuki Hino
[show abstract]
[hide abstract]
ABSTRACT: A 38-year-old man was diagnosed with acute lymphoblastic leukemia. We performed myeloablative bone marrow transplantation from an unrelated donor during the patient's first complete remission. After engraftment, he developed acute graft-versus-host disease involving the gastrointestinal tract on day 32. Steroids and mycophenolate mofetil were initiated from day 39. His symptoms improved and the dose of immunosuppressants was tapered and then discontinued on day 421. On day 491, he developed nephrotic syndrome (NS). Based on renal biopsy, membranous nephropathy was diagnosed. There were no apparent symptoms or abnormal laboratory data suggestive of chronic graft-versus-host disease (cGVHD). Steroid therapy was initiated from day 518 and proteinuria improved significantly. NS is very rare following allogeneic hematopoietic stem cell transplantation (allo-HSCT). When there is no concomitant cGVHD, as in this case, allo-HSCT-associated NS is difficult to distinguish from idiopathic NS.
[Rinshō ketsueki] The Japanese journal of clinical hematology 07/2011; 52(7):556-62.
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ABSTRACT: We describe a patient with chronic myelogenous leukemia (CML) who developed drug-induced agranulocytosis. A 75-year-old female was diagnosed with CML in December 2001. She had been receiving imatinib therapy for more than five years. In August 2007, she was hospitalized due to a severe neutropenia 10 days after colonoscopy. She was diagnosed as having agranulocytosis induced by colonoscopy premedication including scopolamine butylbromide and flumazenil. Severe neutropenia was resolved by G-CSF treatment without CML progression. Agranulocytosis in patients with CML is rare, but potentially lethal. Here, we report the clinical course in this patient.
[Rinshō ketsueki] The Japanese journal of clinical hematology 05/2011; 52(5):278-81.
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Takahiko Nakane,
Hirohisa Nakamae,
Hideo Koh,
Mika Nakamae,
Yoshiki Hayashi,
Mitsutaka Nishimoto,
Takuro Yoshimura,
Eri Inoue,
Atsushi Inoue,
Ran Aimoto,
Mizuki Aimoto,
Yoshiki Terada, Ki-Ryang Koh,
Takahisa Yamane,
Masayuki Hino
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ABSTRACT: In reduced intensity, allogeneic stem cell transplantation from unrelated donors (u-RIST), graft-versus-host disease (GVHD), graft failure, and non-relapse mortality (NRM) are persistent problems. Although anti-thymocyte globulin, alemtuzumab, and total body irradiation (TBI) have been explored as conditioning modalities for u-RIST, the necessity for T-cell depletion or TBI to prevent GVHD or facilitate engraftment in u-RIST has not been determined. We here report the use of u-RIST with bone marrow grafting, following a simple conditioning regimen of 180 mg/m(2) fludarabine and 8 mg/kg of oral or intravenous busulfan without TBI or T-cell depletion. The study population was exclusively Japanese patients with a history of prior chemotherapy. We retrospectively analyzed 31 consecutive patients (median age 53 years). Twenty-five patients (81%) were transplanted from HLA-A, -B, and -DRB1 allele-matched donors. In all patients, neutrophil engraftment was achieved. The cumulative incidence of grade II-IV acute GVHD was 42%. However, 77% of patients with acute GVHD improved with, and could be managed by, initial, systemic, high-dose steroid treatment alone. Two-year overall and event-free survival was 62 and 53%, respectively. The NRM of 10% at 2 years was relatively low. Our results suggest that u-RIST without TBI or T-cell depletion may improve the prognosis after u-RIST in certain patient populations.
International journal of hematology 03/2011; 93(4):509-16. · 1.17 Impact Factor
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Hideo Koh,
Hirohisa Nakamae,
Kiyoyuki Hagihara,
Takahiko Nakane,
Masahiro Manabe,
Yoshiki Hayashi,
Mitsutaka Nishimoto,
Yukari Umemoto,
Mika Nakamae,
Asao Hirose, [......],
Masahiro Yoshida,
Masato Bingo,
Hiroshi Okamura,
Ran Aimoto,
Mizuki Aimoto,
Yoshiki Terada, Ki-Ryang Koh,
Takahisa Yamane,
Masahiko Ohsawa,
Masayuki Hino
[show abstract]
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ABSTRACT: There has been insufficient examination of the factors affecting long-term survival of more than 5 years in patients with leukemia that is not in remission at transplantation.
We retrospectively analyzed leukemia not in remission at allogeneic hematopoietic cell transplantation (allo-HCT) performed at our institution between January 1999 and July 2009. Forty-two patients with a median age of 39 years received intensified conditioning (n = 9), standard (n = 12) or reduced-intensity conditioning (n = 21) for allo-HCT. Fourteen patients received individual chemotherapy for cytoreduction during the three weeks prior to reduced-intensity conditioning. Diagnoses comprised acute leukemia (n = 29), chronic myeloid leukemia-accelerated phase (n = 2), myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) (n = 10) and plasma cell leukemia (n = 1). In those with acute leukemia, cytogenetic abnormalities were intermediate (44%) or poor (56%). The median number of blast cells in bone marrow (BM) was 26.0% (range; 0.2-100) before the start of chemotherapy for allo-HCT. Six patients had leukemic involvement of the central nervous system. Stem cell sources were related BM (7%), related peripheral blood (31%), unrelated BM (48%) and unrelated cord blood (CB) (14%).
Engraftment was achieved in 33 (79%) of 42 patients. Median time to engraftment was 17 days (range: 9-32). At five years, the cumulative probabilities of acute graft-versus-host disease (GVHD) and chronic GVHD were 63% and 37%, respectively. With a median follow-up of 85 months for surviving patients, the five-year Kaplan-Meier estimates of leukemia-free survival rate and overall survival (OS) were 17% and 19%, respectively. At five years, the cumulative probability of non-relapse mortality was 38%. In the univariable analyses of the influence of pre-transplant variables on OS, poor-risk cytogenetics, number of BM blasts (>26%), MDS overt AML and CB as stem cell source were significantly associated with worse prognosis (p = .03, p = .01, p = .02 and p < .001, respectively). In addition, based on a landmark analysis at 6 months post-transplant, the five-year Kaplan-Meier estimates of OS in patients with and without prior history of chronic GVHD were 64% and 17% (p = .022), respectively.
Graft-versus-leukemia effects possibly mediated by chronic GVHD may have played a crucial role in long-term survival in, or cure of active leukemia.
Journal of Experimental & Clinical Cancer Research 01/2011; 30:36. · 2.15 Impact Factor
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Mizuki Aimoto,
Takahisa Yamane,
Atushi Inoue,
Dai Momose,
Ran Moriguchi-Aimoto,
Eri Wada-Inoue,
Syuuichirou Okamoto,
Hideo Koh,
Takahiko Nakane,
Yasunobu Takeoka,
Mika Akahori-Nakamae,
Saori Nishiki-Kosaka,
Yoshiki Terada,
Hirohisa Nakamae, Ki-Ryang Koh,
Takafumi Nakao,
Masahiko Ohsawa,
Masayuki Hino
[show abstract]
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ABSTRACT: A 64-year-old man was diagnosed as having acute myeloid leukemia. We performed sequential treatment with chemotherapy and reduced-intensity stem cell transplantation from an unrelated donor while the patient was in partial remission. After engraftment, he developed acute graft-versus-host disease of the gut on day 42 and steroid therapy was started. Despite transient aggravation of diarrhea, his symptoms slowly improved and the dose of steroid was tapered. On day 159, he complained of acute left lower abdominal pain. A CT scan showed perforation of the digestive tract and ileectomy was performed. At surgery, multiple ulcers of the intestine were found and one of the ulcers was perforated. Pathologically, transmural and diffuse proliferation of atypical cells in the ulcer were confirmed. Since these cells were positive for CD20 and Epstein-Barr-virus (EBV) encoded RNA, we made a diagnosis of EBV-associated post-transplant lymphoproliferative disorder (PTLD). Reduction in the dose of immunosuppressive agents and rituximab led to complete remission of PTLD. PTLD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is relatively rare, and the development of gastrointestinal perforation after allo-HSCT is very rare.
[Rinshō ketsueki] The Japanese journal of clinical hematology 12/2010; 51(12):1775-80.
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ABSTRACT: Acute leukemia (AL) is characterized by overgrowth of neoplastic hematopoietic precursor cells in the bone marrow. After successful chemotherapy in patients with AL, the growth of leukemic cell is thought to be replaced by the recovery of normal hematopoietic cells as a consequence of the activity of anti-cancer agents in eradicating all hematopoietic cells, whether or not they are leukemic cells. However, little is known about the effects of anti-cancer agents on marrow stromal cells, which play a crucial role in supporting hematopoietic cell development. In the present study, we investigated the direct activity of cytosine arabinoside (Ara-C), a key drug for treatment of AL, on human non-leukemic marrow stromal cells by analyzing the effect of Ara-C on gene expression.
Stromal cells were established from 11 patients with no neoplastic hematopoietic precursor cells in the bone marrow. The cells were treated with Ara-C for one week, co-cultured with allogeneic CD34-positive cells, and subjected to colony assay to evaluate their supportive function. A genome-wide DNA microarray analysis was performed to determine Ara-C-induced changes in gene expression in the stromal cells.
Treatment of the stromal cells with Ara-C resulted in a dose-dependent increase in their supportive function. These effects were more evident in the late phase than in the early phase of co-culture with CD34-positive cells, suggesting that Ara-C-treated stromal cells preferably support very immature cells, rather than committed progenitor cells. Furthermore, gene expression profiling with DNA microarrays revealed prominent up-regulation of growth-differentiation factor 15 (GDF15), a divergent member of the transforming growth factor beta superfamily, with concomitant down-regulation of colony-stimulating factor 1 receptor (CSF-1R), both of which are predominantly expressed on macrophages.
Our present study demonstrated that Ara-C directly enhanced the ability of stromal cells to support the development of immature hematopoietic cells, possibly by modulating the function of macrophages in the bone marrow microenvironment. This novel action of Ara-C in the marrow microenvironment may contribute to the better understanding and management of chemotherapy for AL.
Osaka city medical journal 12/2010; 56(2):11-20.
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Hideo Koh,
Hirohisa Nakamae, Ki-Ryang Koh,
Masahiko Ohsawa,
Takahiko Nakane,
Yasunobu Takeoka,
Ran Aimoto,
Mizuki Aimoto,
Eri Wada-Inoue,
Yoshiki Terada,
Takahisa Yamane,
Masayuki Hino
[show abstract]
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ABSTRACT: A 59-year-old man with lymphoma-type adult T-cell leukemia/lymphoma was admitted to hospital for treatment of a skin relapse on day 398 after allogeneic hematopoietic stem cell transplantation (allo-HSCT). To induce a graft-versus-adult T-cell leukemia/lymphoma effect, we discontinued methylprednisolone and tacrolimus. About a month after the discontinuation, he developed grade II acute graft-versus-host disease (GVHD) with a high fever. Soon after the development of GVHD, all the skin lesions regressed in size and finally vanished. However, he developed diffuse alveolar hemorrhage (DAH), which was resistant to high-dose corticosteroid therapy. He was intubated for respiratory insufficiency on day 451. Cyclophosphamide pulse therapy was administered at a dose of 1 g per day for 2 days and his oxygen saturation then improved, and ventilatory support was released on day 465. On analysis of cytokine profiles at the onset of DAH, we found elevated serum levels of T-helper 2 cytokines as well as T-helper 1 cytokines, suggesting that both T-helper 1 and T-helper 2 cytokines might play a role in the occurrence of DAH following allo-HSCT. Pulse cyclophosphamide treatment might be very effective in suppressing the exaggerated allogeneic immune response in DAH.
Acta Haematologica 10/2010; 124(3):171-5. · 1.35 Impact Factor
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Hirohisa Nakamae,
Yoshiki Terada,
Takahiko Nakane,
Hideo Koh,
Mika Nakamae,
Ran Aimoto,
Asao Hirose,
Yoshiki Hayashi,
Mitsutaka Nishimoto,
Eri Inoue,
Takuro Yoshimura,
Atsushi Inoue, Ki-Ryang Koh,
Takahisa Yamane,
Masayuki Hino
[show abstract]
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ABSTRACT: In nine patients with advanced acute or chronic leukemia, we performed allogeneic hematopoietic stem cell transplantation (HSCT) following a modified myeloablative conditioning regimen intended to optimize the intensity of conditioning. This regimen consisted of intravenous busulfan 8mg/kg, cyclophosphamide 120mg/kg and total lymphoid irradiation 7.5 Gy. The median age of the patients was 30 years (range 18-59). Stem cell sources were related bone marrow in two, related peripheral blood in one, and unrelated bone marrow in six patients. Prophylaxis against acute graft-versus-host disease (GVHD) was cyclosporine and short-term methotrexate. Acute GVHD appeared in six patients (67%), grade II in all. Extensive chronic GVHD occurred in three of seven evaluable patients. The median follow-up period after HSCT was 813 days (248- 1,702). Of nine patients, five relapsed or progressed after HSCT. However, no patient relapsed or progressed within 100 days after HSCT. During the full follow-up period, transplant-related mortality (TRM) was not observed. The two-year overall survival and event-free survival were 88.9% and 50.0%, respectively. Our results suggested that we might reduce the incidence of TRM and simultaneously control disease by using an optimized conditioning regimen for HSCT.
Gan to kagaku ryoho. Cancer & chemotherapy 09/2010; 37(9):1691-5.
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ABSTRACT: Side effects of varying severity are frequent in peripheral blood stem cell harvest (PBSCH). Life-threatening complications associated with PBSCH have also been reported. Heart rate variability (HRV), which reflects sympathovagal balance and autonomic cardiovascular control, has been a subject of intense interest in various diseases precipitating sudden death. Here, we prospectively assessed the impact of leukapheresis on HRV among autologous hematopoietic cell transplant patients and healthy donors. We found that HRV indicators, the standard deviation of normal-to-normal intervals (SDNN) value, the square root of the mean of the sum of squared differences between the adjacent normal-to-normal interval (r-MSSD) value, total frequency (TF), high frequency (HF) and low frequency (LF) powers decreased significantly to morbid levels during leukapheresis (all P < 0.01). Morbid changes in SDNN value, TF and LF powers were significantly sustained for 6-9 h after leukapheresis (all P < 0.05). Furthermore, TF and LF powers prior to leukapheresis were significantly lower in subjects with symptomatic hypotension than in the other subjects [3282 (3121-4427) vs. 6018 (4983-9816) ms(2), P = 0.03; 93 (42-144) vs. 237 (142-360) ms(2), P = 0.03, respectively]. Our results suggest that HRV analysis might be of use in evaluating and predicting the adverse effects of cardiovascular complications in PBSCH.
International journal of hematology 03/2010; 91(3):478-84. · 1.17 Impact Factor
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Yoshiki Terada,
Hirohisa Nakamae,
Ran Aimoto,
Hiroshi Kanashima,
Erina Sakamoto,
Mizuki Aimoto,
Eri Inoue,
Hideo Koh,
Takahiko Nakane,
Yasunobu Takeoka,
Masahiko Ohsawa, Ki-Ryang Koh,
Takahisa Yamane,
Yoshitaka Nakao,
Kensuke Ohta,
Atsuko Mugitani,
Hirofumi Teshima,
Masayuki Hino
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ABSTRACT: 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.
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.
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.
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.
Journal of Experimental & Clinical Cancer Research 09/2009; 28:116. · 2.15 Impact Factor
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ABSTRACT: Thyroid hormone receptors (TRs) are ligand-dependent transcription factors with a major impact on erythroid cell development. Here we investigated TR activity on red cell gene expression and identified TR target genes. The impact of the TR target gene GAR22 (growth arrest-specific 2 [GAS2]-related gene on chromosome 22) on red cell differentiation was determined.
Stem cell factor/erythropoietin (SCF/EPO)-dependent red cell progenitors were differentiated in vitro in the presence or absence of thyroid hormone. Hormone-induced changes in gene expression were measured by a genome-wide approach with DNA microarrays. Ectopic expression of the TR target gene GAR22 was used to determine its impact on red cell differentiation.
Ligand-activated TR effectively accelerated red cell progenitor differentiation in vitro concomitantly with inducing growth arrest. We demonstrate that activated TR-induced specific gene expression patterns of up- or downregulated genes, including distinct clusters associated with accelerated differentiation in response to treatment. Mining for T3-induced genes identified basic transcription element binding protein 1/Krüppel-like factor 9 (BTEB1/KLF9) and GAR22 as TR target genes. BTEB1/KLF9 is a known TR target gene while GAR22, initially identified as a putative tumor suppressor, represents a novel TR target gene. We demonstrate that ectopic GAR22 expression in red cell progenitors lengthens the cell cycle and causes growth inhibition, but leaves red cell gene expression unaffected.
This study identifies GAR22 as a novel and direct TR target gene. Our results suggest that hormone-induced GAR22 might represent an important trigger of growth inhibition induced by thyroid hormone in red cell progenitors.
Experimental hematology 06/2009; 37(5):539-548.e4. · 3.11 Impact Factor
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Takahiko Nakane,
Hirohisa Nakamae,
Takashi Muro,
Hiroyuki Yamagishi,
Yoshiki Kobayashi,
Mizuki Aimoto,
Erina Sakamoto,
Yoshiki Terada,
Mika Nakamae, Ki-Ryang Koh,
Takahisa Yamane,
Minoru Yoshiyama,
Masayuki Hino
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ABSTRACT: Recent reports have shown that cardiomyopathy caused by hemochromatosis in severe aplastic anemia is reversible after reduced-intensity allogeneic stem-cell transplantation (RIST). We comprehensively evaluated cardiac and autonomic nerve function to determine whether cardiac dysfunction due to causes other than hemochromatosis is attenuated after RIST. In five patients with cardiac dysfunction before transplant, we analyzed the changes in cardiac and autonomic nerve function after transplant, using electrocardiography (ECG), echocardiography, radionuclide angiography (RNA), serum markers, and heart rate variability (HRV), before and up to 100 days after transplant. There was no significant improvement in cardiac function in any patient and no significant alteration in ECG, echocardiogram, RNA, or serum markers. However, on time-domain analysis of HRV, the SD of normal-to-normal RR intervals (SDNN) and the coefficient of variation of the RR interval (CVRR) decreased significantly 30 and 60 days after transplant (P = 0.04 and 0.01, respectively). Similarly, on frequency-domain analysis of HRV, low and high frequency power (LF and HF) significantly and temporarily decreased (P = 0.003 and 0.03, respectively). Notably, in one patient who had acute heart failure after transplantation, the values of SDNN, CVRR, r-MSSD, LF, and HF at 30 and 60 days after transplantation were the lowest of all the patients. In conclusion, this study suggests that (a) RIST is well-tolerated in patients with cardiac dysfunction, but we cannot expect improvement in cardiac dysfunction due to causes other than hemochromatosis; and (b) monitoring HRV may be useful in predicting cardiac events after RIST.
Annals of Hematology 02/2009; 88(9):871-9. · 2.62 Impact Factor
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International journal of hematology 09/2008; 88(3):348-50. · 1.17 Impact Factor
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ABSTRACT: A 31-year-old female with acute myelocytic leukemia was admitted to our hospital in June 2004. She had complications of brain abscess at the WBC nadir after the second course of induction therapy. However,because the platelet count was low, neurosurgical procedures, including craniotomy/abscess resection, or abscess drainage, were not performed, and we could not detect bacteria or fungus as the cause of brain abscess. Combination therapy with meropenem trihydrate and fosfluconazole was effective. Thereafter, she underwent related peripheral blood stem cell transplantation, and has had no recurrence of brain abscess. Brain abscess during chemotherapy for patients with acute leukemia is commonly due to fungus,particularly Aspergillus, which has a very high fatality rate. Therefore, the treatment of brain abscess without the detection of bacteria and fungus requires combination therapy with antifungal agents and antibiotics. In this case, methionine-positron emission tomography was useful for the evaluation of therapeutic effectiveness for brain abscess.
Gan to kagaku ryoho. Cancer & chemotherapy 06/2007; 34(5):789-92.
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Yasunobu Takeoka,
Mika Nakamae,
Hirohisa Nakamae,
Kiyoyuki Hagihara,
Erina Sakamoto,
Takahiko Nakane,
Hideo Koh, Ki-Ryang Koh,
Kensuke Ohta,
Takahisa Yamane,
Masayuki Hino
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ABSTRACT: There have been many reports of patients with ampulla cardiomyopathy described as takotsubo-shaped cardiomyopathy in the cardiovascular field. This unique cardiomyopathy is characterized by transient apical ballooning and hypokinesis of the left ventricle. We describe 2 cases of ampulla cardiomyopathy associated with hemophagocytic lymphohistiocytosis (HLH). In both of the patients, ventricular dysfunction suddenly occurred during the active phase of HLH. In each case, the findings on ECG, echocardiogram and left ventriculogram were compatible with ampulla cardiomyopathy. To our knowledge, this communication is the first to report cases of ampulla cardiomyopathy associated with HLH. Our cases suggest that HLH hypercytokinemia may have a role in causing ampulla cardiomyopathy.
Acta Haematologica 02/2007; 117(4):205-10. · 1.35 Impact Factor
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Hideo Koh,
Takahisa Yamane,
Takahiko Nakane,
Yasunobu Takeoka,
Erina Sakamoto,
Hiroshi Kanashima,
Mika Nakamae,
Hirohisa Nakamae, Ki-Ryang Koh,
Kunizo Mochizuki,
Noriko Hayashi,
Masayuki Hino
[show abstract]
[hide abstract]
ABSTRACT: 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.
[Rinshō ketsueki] The Japanese journal of clinical hematology 01/2007; 47(12):1539-43.
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Asao Hirose,
Takahisa Yamane,
Yasuhiro Nakajima,
Masahiro Manabe,
Hiroshi Kanashima,
Kiyoyuki Hagihara,
Erina Sakamoto,
Mika Nakamae,
Yoshiki Terada,
Saori Kosaka,
Yasutaka Aoyama,
Chikahiko Sakamoto,
Takeo Kumura, Ki-Ryang Koh,
Manabu Hirai,
Kensuke Ohta,
Yoshitaka Nakao,
Atsuko Mugitani,
Hirohumi Teshima,
Masayuki Hino
[show abstract]
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ABSTRACT: 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 (p<0.05, 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 (p<0.05, 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.
Gan to kagaku ryoho. Cancer & chemotherapy 12/2005; 32(13):2059-64.
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Ryo Matsumoto,
Takashi Omura,
Minoru Yoshiyama,
Tetsuya Hayashi,
Sakiko Inamoto, Ki-Ryang Koh,
Kensuke Ohta,
Yasukatsu Izumi,
Yasuhiro Nakamura,
Kaname Akioka,
Yasushi Kitaura,
Kazuhide Takeuchi,
Junichi Yoshikawa
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ABSTRACT: Vascular endothelial growth factor (VEGF) plays an important role in inducing angiogenesis. Mesenchymal stem cells (MSCs) may have potential for differentiation to several types of cells, including myocytes. We hypothesized that transplantation of VEGF-expressing MSCs could effectively treat acute myocardial infarction (MI) by providing enhanced cardioprotection, followed by angiogenic effects in salvaging ischemic myocardium.
The human VEGF165 gene was transfected to cultured MSCs of Lewis rats using an adenoviral vector. Six million VEGF-transfected and LacZ-transfected MSCs (VEGF group), LacZ-transfected MSCs (control group), or serum-free medium only (medium group) were injected into syngeneic rat hearts 1 hour after left coronary artery occlusion. At 1 week after MI, MSCs were detected by X-gal staining in infarcted region. High expression of VEGF was immunostained in the VEGF group. At 28 days after MI, infarct size, left ventricular dimensions, ejection fraction, E wave/A wave ratio and capillary density of the infarcted region were most improved in the VEGF group, compared with the medium group. Immunohistochemically, alpha-smooth muscle actin-positive cells were most increased in the VEGF group.
This combined strategy of cell transplantation with gene therapy could be a useful therapy for the treatment of acute MI.
Arteriosclerosis Thrombosis and Vascular Biology 07/2005; 25(6):1168-73. · 6.37 Impact Factor
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ABSTRACT: Immunomodulatory derivative (IMiD) CC-4047, a new analog of thalidomide, directly inhibits growth of B-cell malignancies in vivo and in vitro and exhibits stronger antiangiogenic activity than thalidomide. However, there is little information on whether CC-4047 affects normal hematopoiesis. Here we investigated the effect of CC-4047 on lineage commitment and differentiation of hematopoietic stem cells. We found that CC-4047 effectively inhibits erythroid cell colony formation from CD34+ cells and increases the frequency of myeloid colonies. We also demonstrate that development of both erythropoietin-independent and erythropoietin-dependent red cell progenitors was strongly inhibited by CC-4047, while terminal red cell differentiation was unaffected. DNA microarray analysis revealed that red cell transcription factors, including GATA-1, GATA-2, erythroid Kruppel-like factor (EKLF), and growth factor independence-1B (Gfi-1b), were down-regulated in CC-4047-treated CD34+ cells, while myeloid transcription factors such as CCAAT/enhancer binding protein-alpha (C/EBPalpha), C/EBPdelta, and C/EBPepsilon were induced. Analysis of cytokine secretion indicated that CC-4047 induced secretion of cytokines that enhance myelopoiesis and inhibit erythropoiesis. In conclusion, these data indicate that CC-4047 might directly influence lineage commitment of hematopoietic cells by increasing the propensity of stem and/or progenitor cells to undergo myeloid cell development and concomitantly inhibiting red cell development. Therefore, CC-4047 provides a valuable tool to study the mechanisms underlying lineage commitment.
Blood 06/2005; 105(10):3833-40. · 9.90 Impact Factor
