In vivo T-cell depletion with alemtuzumab in allogeneic hematopoietic stem cell transplantation: Combined results of two studies on aplastic anemia and HLA-mismatched haploidentical transplantation.

We evaluated the efficacy of in vivo T-cell depletion with alemtuzumab in two prospective studies according to the International Conference on Harmonisation (ICH)-Good Clinical Practice (ICH-GCP) guidelines; one was for patients with aplastic anemia (AA study) and the other was for patients who were undergoing hematopoietic stem cell transplantation (HSCT) from a 2- or 3-antigen-mismatched haploidentical donor (MM study). The final dose of alemtuzumab in these studies was 0.16 mg/kg/day for 6 days.

Diagnosis and evaluation of intestinal graft-versus-host disease after allogeneic hematopoietic stem cell transplantation following reduced-intensity and myeloablative conditioning regimens.

Colonoscopic evaluation of mucosal tissues after allogeneic hematopoietic stem cell transplantation (HSCT) is very useful in evaluating pathogenesis and diagnosis of intestinal graft-versus-host disease (GVHD). However, information on the timing and sites of biopsies and the immunohistological evaluation of mucosal tissues for diagnosing intestinal GVHD, especially following reduced-intensity (RIC) regimens, remains very limited. A total of 33 patients with histologically proven GVHD after allogeneic HSCT with RIC (n = 23) and myeloablative conditioning (MAC, n = 10) regimens were enrolled in the present study.

Comparison of outcomes after allogeneic hematopoietic stem cell transplantation in patients with follicular lymphoma, diffuse large B-cell lymphoma associated with follicular lymphoma, or de novo diffuse large B-cell lymphoma.

The outcome after allogeneic hematopoietic stem cell transplantation (allo-HCT) for diffuse large B-cell lymphoma (DLBCL) associated with follicular lymphoma (FL), which includes DLBCL with pre- or co-existing FL, remains controversial, and few previous reports have compared the outcomes after allo-HCT for FL, DLBCL associated with FL, and de novo DLBCL. We retrospectively analyzed 97 consecutive patients with FL (n = 46), DLBCL associated with FL (n = 22), or de novo DLBCL (n = 29) who received allo-HCT at our institute between 2000 and 2010. With a median follow-up of 53 months, the 5-year overall survival (OS) and progression-free survival (PFS) were, respectively, 77% and 70% for FL, 62% and 57% for DLBCL associated with FL, and 26% and 23% for de novo DLBCL.

Real-time in vivo cellular imaging of graft-versus-host disease and its reaction to immunomodulatory reagents.

Visualizing the in vivo dynamics of individual donor cells after allogeneic hematopoietic stem cell transplantation (HSCT) will enable deeper understanding of the process of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL). In this study, using non-invasive in vivo fluorescence imaging of the ear pinna, we successfully visualized green fluorescent protein (GFP) donor cells at the single cell level in the skin. This imaging model enabled visualization of the movement of GFP cells into blood vessels in real time after allogeneic HSCT.

Phase 1 trial of Wilms tumor 1 (WT1) peptide vaccine and gemcitabine combination therapy in patients with advanced pancreatic or biliary tract cancer.

An open-labeled, dose-escalation phase 1 trial of Wilms tumor 1 (WT1) vaccine and gemcitabine (GEM) combination therapy for patients with advanced pancreatic cancer or biliary tract cancer was performed. The primary end point was evaluation of toxicity, safety, and optimal immunologic dose of vaccine. Human leukocyte antigen (HLA)-A 0201, HLA-A 0206, and/or HLA-A 2402-positive patients with inoperable advanced pancreatic or biliary tract cancer who had not previously been treated with GEM were eligible for this study.

A Markov decision analysis of allogeneic hematopoietic cell transplantation versus chemotherapy in patients with acute myeloid leukemia in first remission.

Various prospective trials have been performed to assess the roles of allogeneic hematopoietic cell transplantation (allo-HCT) and chemotherapy in patients with acute myeloid leukemia (AML) in first complete remission (CR1). However, the results have not always been consistent, and there has been a limited evaluation of quality of life (QOL) in these postremission strategies. We performed a Markov decision analysis that enabled us to compare survival outcomes with a QOL evaluation using a database of 2029 adult AML patients who achieved CR1.

Cost and effectiveness of reduced-intensity and conventional allogeneic hematopoietic stem cell transplantation for acute myelogenous leukemia and myelodysplastic syndrome.

Goals Of Work: Allogeneic stem cell transplantation with a reduced-intensity regimen (RIST) has been evaluated mostly in terms of its clinical benefit, and the pharmacoeconomic aspects of this procedure remain unclear. We compared the cost and effectiveness of RIST with those of stem cell transplantation using a conventional myeloablative regimen (CST).

Patients And Methods: Fifty consecutive patients who underwent transplantation for myeloid malignancy were included.

Feasibility of reduced-intensity cord blood transplantation as salvage therapy for graft failure: results of a nationwide survey of adult patients.

To evaluate whether rescue with cord blood transplantation (CBT) could improve the poor survival after graft failure (GF), we surveyed the data of 80 adult patients (median age, 51 years) who received CBT within 3 months of GF (primary 64, secondary 16), with fludarabine-based reduced-intensity regimens with or without melphalan, busulfan, cyclophosphamide, and/or 2-4 Gy total-body irradiation (TBI). A median number of 2.4 × 10(7)/kg total nucleated cells (TNC) were infused, and among the 61 evaluable patients who survived for more than 28 days, 45 (74%) engrafted.

Hematopoietic stem cell transplantation for therapy-related myelodysplastic syndrome and acute leukemia: a single-center analysis of 47 patients.

The prognosis of therapy-related myelodysplastic syndrome and acute leukemia (t-MDS/AL) remains poor. We retrospectively analyzed the data of 47 patients (31 AL and 16 MDS) who were treated at our institute. Thirty-three patients received disease-adapted chemotherapy, with a response rate of 73%, while 14 received no interventions due to an indolent course, such as MDS.

Comparison of allogeneic hematopoietic cell transplantation and chemotherapy in elderly patients with non-M3 acute myelogenous leukemia in first complete remission.

The benefits of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with acute myelogenous leukemia (AML) in first complete remission (CR1) have mostly been evaluated in younger patients. Although favorable outcomes of allo-HCT over chemotherapy have been reported with the use of reduced-intensity conditioning (RIC) regimens in elderly patients with AML in CR1, information is still limited, especially on the effects of cytogenetic risks and donor sources. We collected data from AML patients aged 50 to 70 years who achieved CR1, and compared the outcome in 152 patients who underwent allo-HCT in CR1 (HCT group) to that in 884 patients who were treated with chemotherapy (CTx group).

Prognostic factors and outcomes of adult patients with acute myeloid leukemia after first relapse.

Background: Patients with acute myeloid leukemia who are treated with conventional chemotherapy still have a substantial risk of relapse; the prognostic factors and optimal treatments after relapse have not been fully established. We, therefore, retrospectively analyzed data from patients with acute myeloid leukemia who had achieved first complete remission to assess their prognosis after first relapse.

Design And Methods: Clinical data were collected from 70 institutions across the country on adult patients who were diagnosed with acute myeloid leukemia and who had achieved a first complete remission after one or two courses of induction chemotherapy.

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

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.

Identification of molecular markers for pre-engraftment immune reactions after cord blood transplantation by SELDI-TOF MS.

Cord blood transplantation (CBT) is frequently associated with pre-engraftment immune reaction (PIR), which is characterized by high-grade fever that peaks around day 9 of transplantation. PIR mimics hyperacute GVHD or engraftment syndrome; however, it is considered to be of different etiology as it occurs before engraftment. Proteomic patterns have been studied in the fields of transplantation, but no specific marker has been identified.

Outcome of 93 patients with relapse or progression following allogeneic hematopoietic cell transplantation.

Relapse/progression after allogeneic hematopoietic cell transplantation (allo-HCT) remains the major cause of treatment failure. In this study, the subsequent clinical outcome was overviewed in 292 patients with leukemia/myelodysplastic syndrome who received allo-HCT. Among them, 93 (32%) showed relapse/progression.

Regular dose of gemcitabine induces an increase in CD14+ monocytes and CD11c+ dendritic cells in patients with advanced pancreatic cancer.

Objective: Chemotherapy and immunotherapy often seem to contradict each other. However, recent reports suggested that the anticancer effects in some chemotherapeutic agents were concerned with immune response. This study was designed to evaluate the immunological reaction by gemcitabine for future clinical trial of combination therapy with gemcitabine and cancer vaccines.

Intensive glucose control after allogeneic hematopoietic stem cell transplantation: a retrospective matched-cohort study.

Some studies have shown that intensive glucose control (IGC) improves outcome in the intensive care unit setting. However, it is the benefit of IGC in hematopoietic SCT (HSCT) that is not well defined. Between June 2006 and May 2007, IGC was maintained prospectively after allogeneic HSCT and clinical outcomes were compared with a cohort matched for conditioning regimen, source of stem cells, age and relation to donor.

Busulfex (i.v. BU) and CY regimen before SCT: Japanese-targeted phase II pharmacokinetics combined study.

To evaluate the toxicity and efficacy of an i.v. preparation of BU (12.

Impact of T cell chimerism on clinical outcome in 117 patients who underwent allogeneic stem cell transplantation with a busulfan-containing reduced-intensity conditioning regimen.

Within the concept of reduced-intensity stem cell transplantation (RIST) there is a wide range of different regimens used, and little information is available on the clinical impact of chimerism status in patients conditioned with a busulfan-containing regimen. Therefore, we retrospectively reviewed lineage-specific chimerism and the subsequent clinical outcome in 117 patients (median age, 55 years; range: 29-68) who underwent busulfan-containing RIST. The conditioning regimen consisted of busulfan (oral 8 mg/kg or i.

Reduced-intensity unrelated donor bone marrow transplantation for hematologic malignancies.

To review a current experience of unrelated bone marrow transplantation (BMT) with reduced-intensity conditioning (RIC) regimens, we conducted a nationwide survey with 77 patients (age, 25-68 years). The backbone RIC regimen was a combination of fludarabine or cladribine, busulfan or melphalan and total body irradiation at 2-4 Gy. Five patients died early, but 71 (92%) achieved initial neutrophil recovery.

Insufficient ex vivo expansion of Valpha24(+) natural killer T cells in malignant lymphoma patients related to the suppressed expression of CD1d molecules on CD14(+) cells.

Background: Valpha24(+) natural killer T (NKT) cell is a human counterpart of mice Valpha14(+) NKT cell that has a regulatory role for innate and acquired potential antitumor activity. The efficient expansion of NKT cells is an obstacle to the clinical application of Valpha24(+) NKT cells for immunotherapy.

Methods: We used mononuclear cells (MNC) obtained from the peripheral blood (PB) of normal healthy donor (HD) and malignant lymphoma (ML) patients before and after granulocyte colony-stimulating factor (G-CSF) treatment.