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Biomedical subjects

Y Takaue

Publications and source records attributed to Y Takaue.

At least 19 recordsLinked to original sources
PubMed2004

Allogeneic peripheral blood stem cell transplantation from two- or three-loci-mismatched related donors in adult Japanese patients with high-risk hematologic malignancies.

With the increasing frequency of haploidentical transplantation, it is becoming more important to establish the degree of HLA mismatch that can be accepted. We retrospectively analyzed clinical data of 50 adult Japanese patients with high-risk hematologic malignancies who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from two- or three-loci-mismatched related donors with HLA class I and II gene disparities in the graft-versus-host direction. They were treated at 20 transplant centers between 1996 and 2002. In all, 18 patients received unmanipulated PBSC, while 32 received purified CD34+ blood cells. Conventional (n=31) or reduced-intensity (n=19) conditioning regimens were used. Of the 39 patients (78%) who survived for > or =28 days after transplant, 37 (95%) achieved neutrophil engraftment, while graft failure and rejection occurred in two of 39 (5%) and three of 37 (8%) patients, respectively. Stepwise Cox regression analysis revealed a significantly lower incidence of grades II-IV acute GVHD in patients receiving purified CD34+ cells (hazard ratio 0.32; 95% CI 0.12-0.84; P=0.022). By 1 year post transplant, 28 patients (56%) had died of transplant-related problems, including infectious complications (30%). Although the number of patients is small, our data suggest that transplant-related problems, particularly infectious complications, are major obstacles to the success of this therapy.

Adolescent↗
PubMed2004

Clinical significance of cytomegalovirus (CMV) antigenemia in the prediction and diagnosis of CMV gastrointestinal disease after allogeneic hematopoietic stem cell transplantation.

To evaluate the clinical significance of a cytomegalovirus (CMV) antigenemia assay in the prediction and diagnosis of CMV gastrointestinal (CMV-GI) disease after hematopoietic stem cell transplantation (HSCT), 19 allogeneic HSCT recipients developing CMV-GI disease were retrospectively reviewed. All patients were monitored by a CMV antigenemia assay, at least once weekly after engraftment. The median onset of CMV-GI disease occurred 31 days post transplant (range: 19-62). Only four of 19 patients (21%) developed a positive CMV antigenemia test before developing CMV-GI diseases. Although all 19 patients subsequently developed positive CMV antigenemia tests during their clinical courses, the values remained at a low-level in nine (47%) patients. Among the 14 patients in whom results of real-time polymerase chain reaction (PCR) were available, seven (50%) yielded positive results of real-time PCR before developing CMV-GI disease. In contrast to the values of CMV antigenemia, all 14 patients exclusively yielded high viral loads (median: 2.8 x 10(4) copies/ml plasma). We conclude that CMV antigenemia testing has limited value in prediction or early diagnosis of CMV-GI disease, and that real-time PCR could have a more diagnostic significance.

Adult↗
PubMed2004

Feasibility of reduced intensity hematopoietic stem cell transplantation from an HLA-matched unrelated donor.

To evaluate the feasibility of reduced intensity stem cell transplantation (RIST) with bone marrow from a matched unrelated donor (MUD), we retrospectively investigated 20 patients with hematological disorders who received RIST in the Tokyo SCT consortium from January 2000 to October 2002. The preparative regimens were fludarabine-based (150-180 mg/m(2), n=18) or cladribine-based (0.77 mg/kg, n=2). To enhance engraftment, antithymocyte globulin (ATG) and 4 or 8 Gy total body irradiation (TBI) were added to these regimens in nine and 11 patients, respectively. GVHD prophylaxis was cyclosporine with or without methotrexate. In all, 19 achieved primary engraftment. Three developed graft failure (one primary, two secondary), and five died of treatment-related mortality within 100 days of transplant. Seven of the 19 patients who achieved initial engraftment developed grade II-IV acute GVHD, and seven of 13 patients who survived >100 days developed chronic GVHD. At a median follow-up of 5.5 months, estimated 1-year overall survival was 35%. Compared with a TBI-containing regimen, an ATG-containing regimen was associated with a high risk of graft failure (30 vs 0%, P=0.0737). This study supports the feasibility of RIST from MUD; however, procedure-related toxicities remain significant in its application to patients.

Adult↗
PubMed2003

Successful treatment of meningoencephalitis caused by methicillin-resistant Staphylococcus aureus with intrathecal vancomycin in an allogeneic peripheral blood stem cell transplant recipient.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common infectious pathogen during stem cell trans-plantation. We report a case of meningoencephalitis with multiple abscess formation caused by MRSA, which occurred in a 4-year-old boy soon after allogeneic peripheral blood stem cell transplantation. We successfully cured the infection with a combination of intravenous and intrathecal vancomycin.

Anti-Bacterial Agents↗
PubMed2003

High complete response rate after allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning regimens in advanced malignant lymphoma.

The possible advantage of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a graft-versus-lymphoma effect. We explored the feasibility and efficacy of allo-HSCT with reduced-intensity (RI) regimens in advanced malignant lymphoma (ML). A total of 20 patients with indolent (n=9) or aggressive lymphoma (n=11) received allo-HSCT with an RI regimen (RIST). The preparative regimen consisted of a combination of purine analog and alkylating agent with or without antithymocyte globulin. A total of 11 patients had chemorefractory disease, seven had chemosensitive relapsed disease and two had residual disease. All of the patients received G-CSF-mobilized blood stem cells from HLA-matched siblings. Of the 20 patients, 19 achieved engraftment with acceptable regimen-related toxicities. Seven patients developed grade II-IV acute GVHD and 15 developed chronic GVHD. Of the 15 patients with evaluable disease, 12 achieved a complete response. One died of invasive fusariosis, four subsequently died of GVHD complicated with fungal infection and one died of progressive disease. With a median follow-up of 358 days, the Kaplan-Meier estimates for 1-year overall and progression-free survival were both 70%. The high response rate with low relapse observed in this study suggests that RIST may be an effective alternative curative treatment for patients with advanced ML.

Adult↗
PubMed2003

Induction of graft-versus-autoimmune (GVA) disease effect against refractory psoriasis by complete donor-type chimerism and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

A 67-year-old man with AML, who had a 21-year history of psoriasis without remission, received a reduced-intensity transplantation from an HLA-identical sibling. The preparative regimen consisted of busulfan and fludarabine. Graft-versus-host-disease (GVHD) prophylaxis was cyclosporine and methotrexate. Psoriasis was completely resolved on day 18. The subsequent clinical course was uneventful until day 42, when psoriasis recurred at the same sites as before RIST. Peripheral blood examined on day 63 showed mixed chimerism with 54% recipient type. Cyclosporine was rapidly tapered off over the next 2 weeks. On day 90, 100% donor-type chimerism was confirmed. Subsequently, psoriasis improved simultaneously with the occurrence of mucositis and rash as a manifestation of GVHD. Scattered erythematous patches of psoriasis disappeared again by day 105. We initiated 0.5 mg/kg prednisolone on day 119, and resumed cyclosporine on day 133. At 7 months after RIST, he still suffers from chronic GVHD, but his psoriasis remains in remission for the first time in 21 years. The anti-psoriasis effect of the conditioning is mild and transient, while the graft-versus-autoimmunity effect, related to the induction of complete donor-type chimerism and GVHD, is more profound and persisting. A graft-versus-autoimmunity effect lies in the delicate balance between alloimmunity and immunosuppressant used for GVHD prophylaxis/treatment.

Aged↗
PubMed2003

Immune reconstitution following reduced-intensity transplantation with cladribine, busulfan, and antithymocyte globulin: serial comparison with conventional myeloablative transplantation.

The primary object of the conditioning regimen for allogeneic reduced-intensity stem cell transplantation (RIST) is immunosuppression to achieve stable engraftment of donor cells, rather than bone marrow ablation. Therefore, immune reconstitution after RIST might be different from that after conventional stem cell transplantation (CST). In this study, 22 patients underwent RIST and 28 underwent CST. The RIST regimen consisted of cladribine (2-CdA; 0.11 mg/kg/day for 6 days), BU (4 mg/kg/day for 2 days), and rabbit anti-thymocyte globulin (ATG; 2.5 mg/kg/day for 2-4 days). The CST group received either the BU (4 mg/kg/day x 4 days)/CY (60 mg/kg/day x 2 days) (n=13) or CY (60 mg/kg/day x 2 days)/TBI (4 Gy/day x 3 days) regimen (n=15). All patients underwent transplantation with G-CSF-mobilized blood stem cells. Engraftment speed after RIST was fast and seven of 22 patients did not require platelet transfusion. We noted that the numbers of CD4+, CD4+CD45RA+, and CD4+CD45RO+ T cells after transplant in the RIST group were significantly lower than those in the CST group (P=0.0001 for both the comparisons). However, the reconstitution of CD20+ B cells was faster in the RIST group (P=0.0001). The response of T cells to PHA stimulation was lower in the RIST group (P=0.0001 on day 30 and P=0.02 on day 90). Nevertheless, there were no significant differences in the incidence of bacterial, fungal, or viral infections between the two groups. We concluded that our RIST regimen might delay laboratory-evaluated T-cell immune reconstitution compared to CST; however, the observed setbacks did not directly translate into clinically significant increases in infectious episodes.

Adolescent↗
PubMed2003

Late hemorrhagic cystitis after reduced-intensity hematopoietic stem cell transplantation (RIST).

We reviewed medical records of 256 patients to investigate the frequency and characteristics of hemorrhagic cystitis (HC) associated with reduced-intensity stem cell transplantation (RIST) as opposed to conventional stem cell transplantation (CST); 137 patients underwent CST and 119 RIST. Diagnosis of HC was made based on two or more episodes of sterile, macroscopic hematuria with normal coagulation profiles, without any evidence of renal stones or genitourinary malignancy. Actuarial frequency of HC development in RIST group was 7.6% (9/119), which gave a cumulative annual incidence of 11.7%. In CST group, 13 of 137 patients (9.5%) developed HC, giving an estimated annual incidence of 9.7%. The probability of developing HC was similar between the two groups (P=0.77). The viral etiologies of HC, adenovirus (n=12) and BK virus (n=2), were documented in eight patients after RIST and in six after CST. HC was milder and of a shorter duration, with less blood transfusion requirements, in RIST group than in CST group. A multivariate analysis revealed that HC was associated with antiadenovirus antibody positivity in the recipients, total dose of busulfan, and chronic GVHD. Although HC following RIST is less severe than that following CST, it is still a significant problem.

Adenoviridae↗
PubMed2002

Primary cutaneous aspergillosis caused by Aspergillus ustus following reduced-intensity stem cell transplantation.

A 19-year-old woman with myelodysplastic syndrome underwent reduced-intensity stem cell transplantation [RIST: (cladribine 0.11 mg/kg for 6 days, busulfan 4 mg/kg for 2 days, and rabbit antithymocyte globulin)] from her one HLA-mismatched mother. Prophylaxis against graft-versus-host disease (GVHD) was performed with cyclosporine A (CSA) alone. Severe acute GVHD in the skin, gut, and liver developed concurrently with stable engraftment, and methylprednisolone was administered (1-2 mg/kg per day, then pulse therapy with 1 g/day for 3 days) until day 40 of transplant, when a necrotic lesion of 10 mm in diameter appeared on the right cheek. The initial skin biopsy of the affected area showed a nonspecific inflammatory change. Routine X-ray and computed tomography examinations of the sinuses, chest, and abdomen disclosed no particular abnormalities. Despite intensive antibiotic therapy, the lesion rapidly extended to form an ulcer. A second biopsy specimen obtained from the lesion showed massive septa hyphae, suggesting mold infection. Although we immediately started amphotericin B, she died of multiorgan failure on day 68. Postmortem DNA sequence analysis of the specimen using the polymerase chain reaction identified Aspergillus ustus. Although this is an extremely rare complication after transplantation, this case highlights that we should pay more attention to primary cutaneous aspergillosis in severely immunosuppressed patients.

Adult↗
PubMed2002

Suspected delayed immune recovery against cytomegalovirus after reduced-intensity stem cell transplantation using anti-thymocyte globulin.

A reduced-intensity hematopoietic stem cell transplantation (RIST) regimen was developed to induce immunosuppression to facilitate the engraftment of donor cells. However, there have been concerns that the incidence of opportunistic infection may increase after this procedure. To address this problem, we retrospectively analyzed the medical records of 24 RIST recipients who were treated over a recent 16-month period for comparison with 31 recipients of conventional allogeneic transplantation (CST). The RIST regimen consisted of cladribine (0.66 mg/kg), busulfan (8 mg/kg), and rabbit anti-thymocyte globulin (ATG; 5-10 mg/kg). All of the patients received allogeneic peripheral blood stem cells from an HLA-identical or one-locus mismatched related donor. Although the incidence of positive CMV antigenemia was comparable between the two groups (58% vs 68%), RIST patients developed positive antigenemia significantly sooner than did CST patients (P = 0.01) and showed higher initial and maximum antigenemia values (P = 0.026 and P = 0.003, respectively). These findings may suggest that immune recovery against CMV was delayed after our RIST procedure, but this did not directly translate into an increase in clinically significant CMV disease. Early therapeutic intervention with ganciclovir might play a role in preventing the progression of early CMV infection to CMV disease.

Adolescent↗
PubMed2002

Successful allogeneic blood stem cell transplantation for aplastic anemia in a patient with renal insufficiency requiring dialysis.

A 27-year-old man with aplastic anemia and renal insufficiency requiring dialysis underwent allogeneic PBSCT. The preparative regimen consisted of melphalan, ATG and TLI. GVHD prophylaxis consisted of cyclosporine and prednisolone. He was dialyzed prior to administration of melphalan and at 24 and 72 h after it. Otherwise, the dialysis schedule was unchanged, at three times a week. Engraftment was rapid. Regimen-related toxicity was minimal. Pharmacokinetic parameters of melphalan were not significantly altered with its plasma half-life 1.5 h. Patients with renal failure can receive allogeneic HSCT, and a combination of melphalan, ATG and TLI may serve as an alternative to CY and ATG.

Adult↗
PubMed2001

Early onset Pneumocystis carinii pneumonia after allogeneic peripheral blood stem cell transplantation.

Pneumocystis carinii (P. carinii) is one of the major opportunistic pathogens responsible for hematopoietic stem cell transplantation (HSCT)-related pneumonias. Although trimethoprim-sulfamethoxazol (TMP/SMX) prophylaxis has been shown to prevent almost all P. carinii infections, 1%-2% of patients may still experience this complication. P. carinii pneumonia (PCP) is usually a late complication in patients receiving TMP/SMX prophylaxis, with most cases occurring later than 2 months post-transplant. We report a patient who developed early onset PCP after allogeneic peripheral blood stem cell transplantation (PBSCT) from an HLA-identical sibling donor. On day 12, the patient complained of dyspnea and cough. A chest X ray showed infiltrates in right upper lobe with bilateral pleural effusion. By the findings of Grocott stain on bronchoalveolar lavage fluid obtained on day 14, he was diagnosed as having PCP. Intravenous TMP/SMX failed to improve the lesion. This is the earliest onset PCP in the literature after HSCT despite the prophylactic administration of TMP/SMX before transplant.

Antibiotic Prophylaxis↗
PubMed2001

Successful application of nonmyeloablative transplantation for paroxysmal nocturnal hemoglobinuria.

OBJECTIVE: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder that manifests as hemolytic anemia, venous thrombosis, and deficient hematopoiesis. Although allogeneic hematopoietic stem cell transplantation is considered the only curative therapeutic measure, transplant-related mortality is not negligible. Several studies supported the use of nonmyeloablative stem cell transplantation (NST) for patients of advanced age or with organ dysfunction. Hence, we used NST in a PNH patient who suffered from acute renal failure due to repeated episodes of hemolysis. MATERIALS AND METHODS: We performed NST using a conditioning regimen consisting of cladribine 0.11 mg/kg x 6, busulfan 4 mg/kg x 2, and rabbit anti-thymocyte globulin 2.5 mg/kg x 2. He received peripheral blood stem cells from his human leukocyte antigen-matched brother. Prophylaxis against graft-vs-host disease was performed with cyclosporine A alone. Chimerism of peripheral blood mononuclear cells was evaluated serially using short tandem repeat analysis and flow cytometry. RESULTS: No meaningful regimen-related toxicities were documented. Donor chimerism of 90 to 100% was achieved on day 14 and thereafter. The patient is doing well, without any recurrence of hemolysis 6 months after transplant. Follow-up chimerism studies confirmed stable and functioning donor-type hematopoiesis. CONCLUSIONS: NST may become a safe and curative approach in patients with PNH. Further studies are needed to establish the role of NST for treatment of PNH.

Antilymphocyte Serum↗
PubMed2001

Pre-emptive therapy against cytomegalovirus (CMV) disease guided by CMV antigenemia assay after allogeneic hematopoietic stem cell transplantation: a single-center experience in Japan.

From April 1998 to March 2000, a cytomegalovirus (CMV) antigenemia-guided pre-emptive approach for CMV disease was evaluated in 77 adult patients who received allogeneic hematopoietic stem cell transplantation at the National Cancer Center Hospital. A CMV antigenemia assay was performed at least once a week after engraftment. High-level antigenemia was defined as a positive result with 10 or more positive cells per 50 000 cells and low-level antigenemia was defined as less than 10 positive cells. Among the 74 patients with initial engraftment, 51 developed positive antigenemia. Transplantation from alternative donors and the development of grade II-IV GVHD were independent risk factors for positive antigenemia. Ganciclovir was administered as pre-emptive therapy in 39 patients in a risk-adapted manner. None of the nine low-risk patients with low-level antigenemia as their initial positive result developed high-level antigenemia even though ganciclovir was withheld. Only one patient developed early CMV disease (hepatitis) during the study period. CMV antigenemia resolved in all but two cases, in whom ganciclovir was replaced with foscarnet. In eight patients, however, the neutrophil count decreased to 0.5 x 10(9)/l or less after starting ganciclovir, including three with documented infections and two with subsequent secondary graft failure. The total amount of ganciclovir and possibly the duration of high-dose ganciclovir might affect the incidence of neutropenia. We concluded that antigenemia-guided pre-emptive therapy with a decreased dose of ganciclovir and response-oriented dose adjustment might be appropriate to decrease the toxicity of ganciclovir without increasing the risk of CMV disease.

Adolescent↗
PubMed2001

Long-term low-dose acyclovir against varicella-zoster virus reactivation after allogeneic hematopoietic stem cell transplantation.

To evaluate the efficacy of long-term administration of acyclovir as prophylaxis against varicella-zoster virus (VZV) reactivation, we analyzed the medical records of 86 consecutive adult patients who obtained engraftment after allogeneic hematopoietic stem cell transplantation from January 1996 to March 2000. We started long-term low-dose (400 mg/day) oral administration of acyclovir in June 1999, and this was continued until the end of immunosuppressive therapy after transplantation. There was no breakthrough reactivation of VZV in patients receiving acyclovir. Five patients who were receiving cyclosporine or prednisolone developed VZV reactivation after discontinuing acyclovir. With this prophylaxis, the cumulative incidence of VZV reactivation at 1 year after transplantation decreased from 33% to 10% (P = 0.025). On multivariate analysis, the use of long-term acyclovir was identified as a significant independent parameter for the development of VZV reactivation. These findings suggest the efficacy of long-term prophylaxis with low-dose acyclovir. Resumption of acyclovir upon restarting immunosuppressive therapy might be important for the further prevention of VZV reactivation. The benefit of long-term low-dose acyclovir should be confirmed prospectively.

Acyclovir↗