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Shin Mineishi

Publications and source records attributed to Shin Mineishi.

At least 19 recordsLinked to original sources
PubMed2005

An irradiation-free nonmyeloablative bone marrow transplantation model: importance of the balance between donor T-cell number and the intensity of conditioning.

BACKGROUND: Animal allogeneic bone marrow transplantation (BMT) models with nonmyeloablative conditioning regimens have so far required irradiation or antibodies in addition to immunosuppressive drugs for engraftment. Moreover, although it is known that the balance between donor T-cell number and the dose of immunosuppressive drugs would be critical for engraftment, it has not been experimentally clarified in a nonmyeloablative regimen. METHODS: We used C57BL/6 mice as donors and DBA/2 mice as recipients with a nonmyeloablative regimen including fludarabine (Flu) and cyclophosphamide (CPA) without irradiation or antibodies. To determine the adequate doses, we injected recipients with various doses of Flu and CPA, and 2x10 bone marrow cells (BMC) and 5x10 splenocytes (SC). Furthermore, using T-cell-depleted BMC and enriched T cells, we investigated the balance between donor T-cell number and the dose of Flu. RESULTS: Doses of Flu at 150 mg/kg/dayx6 and CPA at 150 mg/kg/dayx2 were most appropriate for engraftment with low mortality. All mice appropriately pretreated and transplanted with both BMC and SC exhibited complete donor chimeras. Donor cell engraftment was not enhanced by any increase of BMC transplanted, and dose escalation of donor T cells but not BMC led to the reduction of Flu dose required for engraftment of donor cells. CONCLUSIONS: We have established a murine nonmyeloablative BMT model in a fully MHC-mismatched combination for donor cell engraftment with complete donor chimerism. Simultaneously, we have quantitatively demonstrated that the balance between donor T-cell number and the dose of immunosuppressive drugs is critical for stable engraftment.

Animals↗
PubMed2004

Graft-versus-host disease in mini-transplant.

Mini-transplant has been used popularly in recent years. The intensity of conditioning regimens is less in mini-transplant, thus the anti-tumor effect is mainly carried by an immunological reaction, called graft-versus-leukemia (GVL)/graft-versus-tumor (GVT) effect. Thus, graft-versus-host disease (GVHD) in mini-transplant has drawn much attention as a surrogate marker for GVL/GVT effect. However, as the regimen-related toxicity is less in mini-transplant, it is also true that GVHD is the single most worrisome adverse event after mini-transplant. As opposed to early predictions, the incidence and severity of GVHD after mini-transplant does not seem to be much different from the one after conventional stem cell transplant (CST). In addition, researchers find that host antigen presenting cells (APC) may play an important role in the development of GVHD, and thus the existence of donor-host chimerism may be critical. As a result, the theory regarding GVHD after mini-transplant is getting more confusing. A comprehensive understanding of GVHD after mini-transplant is necessary.

Graft vs Host Disease↗
PubMed2004

Philadelphia chromosome-positive acute lymphoblastic leukemia rescued with a second allogeneic stem cell transplantation from a haploidentical mother after relapse following cord blood transplantation.

A 32-year-old female patient who had Philadelphia chromosome-positive acute lymphoblastic leukemia underwent cord blood transplantation while in her second remission. However, she had a hematological and central nervous system relapse 3 months later. After reinduction with imatinib mesylate, unmanipulated peripheral blood stem cell transplantation was performed from the patient's haploidentical mother with a reduced-intensity conditioning regimen. Rabbit antithymocyte globulin, tacrolimus, and methylprednisolone were used for prophylaxis of graft-versus-host disease. Engraftment of neutrophils was observed on day 12, and complete donor chimerism was obtained by day 24. The posttransplantation course was uneventful. Although the patient had a relapse 10 months later, this case demonstrated that transplantation from a haploidentical donor is clearly a feasible alternative for patients who desperately need rescue transplantation.

Adult↗
PubMed2003

Antithymocyte globulin affects the occurrence of acute and chronic graft-versus-host disease after a reduced-intensity conditioning regimen by modulating mixed chimerism induction and immune reconstitution.

BACKGROUND: There have been no detailed analyses of the induction of donor cell-type chimerism, the onset and incidence of acute and chronic graft-versus-host disease (GVHD), and the immune recovery kinetics after reduced-intensity stem cell transplantation (RIST). METHODS: To address these, with particular emphasis on the impact of the use of antithymocyte globulin (ATG) in RIST, we compared 39 consecutively registered patients who underwent RIST from an HLA-matched related donor and 33 patients who underwent conventional marrow-ablative transplantation. RESULTS: The incidences of grades II to IV acute and chronic GVHD tended to be less in RIST with ATG than in either RIST without ATG or conventional marrow-ablative transplantation. In a multivariate analysis, the predictive factors for acute and chronic GVHD included, respectively, ATG and grades II to IV acute GVHD. In a chimerism analysis, the achievement of complete donor chimera in T-cell lineage was delayed in RIST without ATG compared with RIST with ATG (P=0.038), which might explain the observed delayed onset of acute GVHD in RIST with ATG compared with the other two regimens. The ratio of type 1 and 2 dendritic cells did not affect the development of GVHD, whereas the number of naive CD4+ T cells did. No difference was observed in the incidence of clinically definitive infection, including cytomegalovirus, among the three cohorts, regardless of the use of ATG. CONCLUSIONS: We suggest that the conditioning regimen and immunosuppressive strategy after RIST should be carefully balanced against the risk of GVHD and of relapse of the basic disorder caused by the lack of a graft-versus-leukemia benefit.

Acute Disease↗
PubMed2003

Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991-2000).

The reported outcome of hematopoietic stem cell transplantation (HSCT) from HLA-mismatched family members has been inconsistent. The object of this study was to evaluate the true impact of HLA-mismatch by using recent data from a homogenous population, excluding HSCT procedures that used graft manipulations, and by considering genotypic matching. Clinical data of 2947 patients who underwent allogeneic HSCT for leukemia or myelodysplastic syndrome were extracted from the database of the Japan Society for Hematopoietic Cell Transplantation. The main outcome measures were survival and the incidence of graft-versus-host disease (GVHD). The presence of serologic HLA-mismatch, higher age, and high-risk disease were identified as independent risk factors for both shorter survival and the development of grade III to IV acute GVHD. The impact of HLA-mismatch on survival was more relevant in standard-risk patients. These findings persisted when we used genotypic HLA matching. Survival after one-locus-mismatched HSCT was equivalent to that after HLA-matched unrelated HSCT. We concluded that when a one-locus-mismatched family donor is available for high-risk patients, immediate HSCT using this donor is warranted. In standard-risk patients, however, survival after one-locus-mismatched HSCT is significantly shorter than that after HLA-matched HSCT, and the indications for HSCT should be considered carefully.

Acute Disease↗
PubMed2003

[Mini-transplantation].

Explore the source record for details and available documents.

Hematopoietic Stem Cell Transplantation↗
PubMed2003

Feasibility of acute physiology and chronic health evaluation (APACHE) II and III score-based screening in patients receiving allogeneic hematopoietic stem-cell transplantation.

Patients who require management in the intensive care unit (ICU) for complications after allogeneic hematopoietic stem-cell transplantation (HSCT) generally have a poor outcome. We retrospectively studied whether the risk-prediction stratification systems commonly used for patients admitted to the ICU, that is, the Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE III systems, could be useful for identifying patients who should receive intensive care earlier. We reviewed the medical records of 210 patients who underwent allogeneic HSCT and found that 18 (8.6%) had been admitted to the ICU for acute respiratory failure (n=9), acute renal failure (n=7), and septic shock (n=2). The median APACHE II and III scores were, respectively, 16 (10-27) and 55 (22-87) at the onset of complications and 26 (15-43) and 101 (65-157) upon admission to the ICU. Thus, both the APACHE II and APACHE III scores at ICU admission were higher than those at the onset of complications (P <0.0001). Seventeen patients (94%) subsequently died, with a median ICU stay of 7.5 days (1-51 days), as a result of multiorgan failure (n=14), respiratory failure (n=2), and septic shock (n=1). The APACHE II and III scores of the sole surviving patient were, respectively, 21 and 71 at the onset and 24 and 86 upon transfer to the ICU. Thus, the APACHE scores in this study were lower than those reported for other surgical or medical patients treated in the ICU, despite their uniform poor prognosis. Although nine patients had developed grade III to IV acute graft-versus-host disease, which is the most common cause of morbidity and mortality after allogeneic HSCT, this was not fully evaluated in the current scoring systems. Application of these systems to HSCT will require adequate modification, with particular attention to organ dysfunction secondary to graft-versus-host disease.

APACHE↗
PubMed2003

Impact of graft-versus-host disease in reduced-intensity stem cell transplantation (RIST) for patients with haematological malignancies.

To clarify the impact of graft-versus-host disease (GVHD) on the outcome of reduced-intensity stem cell transplantation (RIST), 40 patients who received RIST were compared with those who received conventional stem cell transplantation (CST). RIST regimens consisted of either cladribine (0.11 mg/kg/d x 6, n = 13) or fludarabine (30 mg/m(2)/d x 6, n = 27) with busulphan (BU, 4 mg/kg/d orally x 2), with or without antithymocyte globulin (ATG). CST regimens were either cyclophosphamide/total body irradiation (CY/TBI, n = 23), BU/CY (n = 19) or others (n = 6). The RIST group contained more patients who were at high risk of transplant-related mortality, including older patients, while the two groups contained the same percentages of patients at high risk of relapse. There were no differences between these groups in the incidences of acute (grade II-IV, 31.6% RIST vs 33.3% CST, P = 0.6742) and chronic GVHD (56.2%vs 64.1%, P = 0.8512), relapse rate (15.0%vs 18.8%, P = 0.6642), or overall (69.3%vs 65.6%, P = 0.4817) and progression-free survival (64.7%vs 63.8%, P = 0.6920) at d 500. Multivariate analysis of progression-free survival identified only grade III-IV acute GVHD and relapse risk dose as adverse risk factors. Although GVHD is a major threat in RIST, appropriate induction of GVHD may be associated with anti-tumour activity in RIST comparable to that of CST.

Acute Disease↗
PubMed2003

TRALI after the infusion of marrow cells in a patient with acute lymphoblastic leukemia.

BACKGROUND: TRALI is one of the most serious, life-threatening complications after blood transfusion. Antibodies against neutrophils or HLA molecules from the donor are thought to be the primary causative agents. Rarely, antibodies in the recipient may react with transfused neutrophils and initiate the same events, which raises the possibility that TRALI may also occur in an allogeneic PBPC transplantation setting. CASE REPORT: A 30-year-old Japanese man with acute lymphoblastic leukemia developed TRALI immediately after the infusion of marrow cells from an unrelated donor. The infusion was suspended, and he gradually improved after receiving steroids and oxygen support. The next day, the remaining cells, which were separated to MNCs, were infused with no reactions. He then recovered over 5 days without the use of mechanical ventilation. RESULTS: Laboratory evaluation disclosed the presence of antibodies to neutrophils in his sera sampled after transplantation, but not in the donor's marrow graft. Hence, antibodies to neutrophils in the recipient may have reacted with neutrophils in the graft and contributed to the development of TRALI. CONCLUSION: This is the first reported case of TRALI after allogeneic BMT. TRALI should be recognized as a rare but serious complication in allogeneic hematopoietic stem cell transplantation.

Acute Disease↗
PubMed2003

[Immunobiology of mini-transplant].

Mini-transplant has become much more popular since mid-90's worldwide. Mini-transplant has not only provided opportunity for cure to many patients who otherwise could not undergo allogeneic stem cell transplant, but also has lead to many new findings which may answer some questions related to scientific basis of allogeneic stem cell transplantation. Mini-transplant has shown that engraftment of donor stem cells can be achieved without complete ablation of host bone marrow. Role of post-transplant immunosuppression has also been clarified through the experience of mini-transplant. In this review, we discuss the mechanism and basics under the theory of mini-transplant.

Animals↗
PubMed2003

[Mini-transplant from a matched unrelated donor].

It is also important to establish a method to use alternative donors in mini-transplant settings. However, there are some problems, such as difficulty in performing donor-lymphocyte infusion(DLI) from an unrelated donor. In most countries including Japan, bone marrow is mostly used as a source of stem cells in unrelated transplant. This may cause another problem in engraftment. In addition, graft rejection and GVHD may also be a problem because of the difference in minor antigens. Despite these problems, early experience including our own has shown that mini-transplant from an unrelated donor is a feasible procedure and further development is expected.

Graft Rejection↗
PubMed2003

[Future directions of mini-transplant].

Mini-transplant has developed very rapidly in a shot period of time. In order to solve some basic questions, prospective studies such as comparison of mini-transplant and conventional, non-transplant treatment in elderly, as well as comparison of mini-transplant with conventional transplant in younger population are necessary in the near future. In addition, studies to figure out the most suitable conditioning regimen for each disease are also needed. Together with the development into new directions such as treatment of benign diseases or utilization of other stem cell sources such as cord blood or mismatched related donors, mini-transplant will become more useful tool for physicians and patients in the future.

Clinical Trials, Phase III as Topic↗
PubMed2002

Limited efficacy of lamivudine against hepatitis B virus infection in allogeneic hematopoietic stem cell transplant recipients.

BACKGROUND: Reactivation of chronic hepatitis B virus (HBV) infection is a major complication when HBV carriers receive immunosuppressive therapy. Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) carry the highest risk of fatal HBV disease (up to 12%). METHODS: In an attempt to identify a suitable procedure for the prevention and management of HBV reactivation, the administration of lamivudine over the course was tested in two patients. RESULTS: Generally, the patients transplant courses were successfully managed despite their difficult clinical situations: a high HBV load before transplant in one patient and intense steroid therapy for complicated acute graft-versus-host disease (GVHD) in the other patient. However, one patient showed a reactivation of HBV after discontinuing lamivudine and the other showed persistently high DNA polymerase activity despite prolonged administration of lamivudine. CONCLUSIONS: We concluded that lamivudine could have a place in the management of patients who suffer from chronic HBV infection and who are undergoing allogeneic HSCT. However, the efficacy of lamivudine seemed to be limited compared with other settings, including solid organ transplantation and autologous HSCT.

Adult↗
PubMed2002

Response-oriented preemptive therapy against cytomegalovirus disease with low-dose ganciclovir: a prospective evaluation.

BACKGROUND: Preemptive therapy against cytomegalovirus (CMV) disease has succeeded in reducing the incidence of CMV disease, but the toxicity of ganciclovir remains problematic. METHODS: We prospectively evaluated the efficacy and toxicity of a preemptive protocol with ganciclovir at a reduced initial dose in 40 patients who achieved engraftment after allogeneic hematopoietic stem cell transplantation. RESULTS: Twenty-three (58%) patients had high-risk features, including transplant from an HLA-mismatched or unrelated donor, or associated acute graft-versus-host disease. CMV antigenemia assay was performed weekly, and ganciclovir was started in a risk-adapted manner, in which the initial dose of ganciclovir was fixed at 5 mg/kg/d and then adjusted based on the results of a weekly CMV antigenemia assay. In this protocol, 23 (58%) patients demonstrated positive antigenemia, and 19 (48%) received a preemptive administration of ganciclovir. Only one patient had CMV disease in the gastrointestinal system, which was successfully treated with a regular therapeutic dose of ganciclovir. Consequently, the total dose of ganciclovir was significantly less than that in a previous protocol using the conventional double dose (5 mg/kg twice daily) of ganciclovir (134 mg/kg vs. 190 mg/kg on average, P=0.046). There were no significant toxicities attributed to ganciclovir, except for neutropenia <0.5 x 109/L, which developed in three patients for 3, 4, and 14 days, respectively, with granulocyte colony-stimulating factor support. CONCLUSION: Preemptive therapy with a low initial dose of ganciclovir appeared to be effective even in high-risk patients. Further randomized controlled trial is warranted.

Adult↗
PubMed2002

Sustained molecular remission in a patient with CML in blastic crisis receiving dose-reduced hematopoietic stem-cell transplantation followed by early withdrawal of cyclosporine and prophylactic use of interferon-alpha.

A 54-year-old man with chronic myelocytic leukemia in blastic phase received reduced-intensity transplantation (RIST) from an HLA-identical unrelated donor. The preparative regimen consisted of busulfan, fludarabine, and anti-thymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis was cyclosporine alone. Because he had a high risk of relapse, we discontinued cyclosporine on day 37, but he did not develop any signs of acute GVHD. To induce GVHD and augment a graft-versus-leukemia effect, we initiated interferon-alpha therapy on day 80 to a maximum dosage of three million units five times a week. He achieved molecular remission on day 94 followed by the development of extensive chronic GVHD the severity of which paralleled to the dose of interferon-alpha GVHD gradually subsided after discontinuation of interferon-alpha and the patient remains in molecular remission 18 months after transplantation. This case suggests that early withdrawal of cyclosporine and the prophylactic use of interferon-alpha are promising in RIST for high-risk leukemia.

Blast Crisis↗
PubMed2002

Impact of stem cell source and conditioning regimen on erythrocyte recovery kinetics after allogeneic haematopoietic stem cell transplantation from an ABO-incompatible donor.

We evaluated erythrocyte recovery in 121 allogeneic haematopoietic stem cell transplantation (HSCT) recipients. There were 35 major and minor ABO-incompatible transplants, respectively, including 10 bi-directionally ABO-incompatible transplants. The use of peripheral blood stem cells facilitated erythrocyte recovery, regardless of the presence or absence of major ABO-incompatibility, and was associated with a frequent detection of anti-host isohaemagglutin early after minor ABO-incompatible transplantation, which was not associated with clinically relevant haemolysis. The use of a reduced-intensity regimen combining a purine analogue and busulphan did not delay erythrocyte recovery after major ABO-incompatible transplantation, suggesting this regimen had a strong activity against host plasma cell.

ABO Blood-Group System↗