Takahiro Fukuda

Human herpesvirus-6 encephalitis in hematopoietic SCT recipients in Japan: a retrospective multicenter study.

Human herpesvirus-6 encephalitis in hematopoietic SCT recipients in Japan: a retrospective multicenter study

Long-term outcomes of autologous PBSCT for peripheral T-cell lymphoma: retrospective analysis of the experience of the Fukuoka BMT group

Peripheral T-cell lymphoma (PTCL) is generally characterized by poor prognosis after conventional chemotherapy compared with aggressive B-cell lymphoma. To elucidate the role of high-dose chemotherapy (HDCT) with auto-SCT, we retrospectively analyzed the outcomes of 39 patients with PTCL who received HDCT and auto-SCT between 1990 and 2005. Eleven patients were histologically typed as angioimmunoblastic, nine as anaplastic large-cell lymphoma, seven as natural killer/T-cell lymphoma and twelve as PTCL unspecified. Clinical conditions at transplantation were complete response (CR) in 27 patients and non-CR in 12 patients. Thirty-two patients received a pre-transplant conditioning regimen (MCEC) comprising ranimustine, carboplatin, etoposide and CY, and seven did other TBI-based regimens. Rapid engraftment was obtained in all cases, and transplant-related death was not seen. An estimated 5-year OS was 62.1% with a median follow-up of 78 months. The 5-year OS was significantly higher in patients transplanted during complete response than in those during other disease status (71.4% vs 27.3%, P=0.046). HDCT supported by auto-SCT may therefore be effective as consolidation in CR for PTCL treatment.

Proliferative involvement of ENX-1, a putative human polycomb group gene, in haematopoietic cells.

Homeobox genes have important roles in haematopoiesis and are regulated in an activated state by the trithorax group (trxG) of genes. In a repressed state, they are regulated by the Polycomb group (PcG) of genes. ENX‐1, a putative human PcG gene product, interacts with the proto‐oncogene product Vav. We report an investigation of the role of ENX‐1 in human haematopoiesis. CD34+ cells mobilized to peripheral blood strongly expressed ENX‐1. When stimulated to proliferate, both T and B lymphocytes rapidly up‐regulated ENX‐1. ENX‐1 was expressed in all cell lines of the various lineages examined. When HL‐60 cells were differentiated to mature granulocytes with all‐trans retinoic acid, ENX‐1 was down‐regulated. Moreover, ENX‐1 antisense oligodeoxynucleotide suppressed DNA synthesis in HL‐60 cells. Our data indicate that ENX‐1 is involved in the proliferation of both normal and malignant haematopoietic cells.

Infectious complications in chronic graft-versus-host disease: a retrospective study of 145 recipients of allogeneic hematopoietic stem cell transplantation with reduced- and conventional-intensity conditioning regimens

Abstract: To assess infectious complications associated with chronic graft‐versus‐host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) with reduced‐ and conventional‐intensity conditioning regimens (RIC, n=91; CIC, n=54, respectively), we retrospectively analyzed data from 145 consecutive patients with cGVHD after allogeneic HSCT from a human leukocyte antigen‐matched related or unrelated donor. In the present retrospective analysis, 57% (83/145) of patients with cGVHD developed infections, with a mortality rate of 27% (22/83). The incidences of bacteremia (n=28), central venous catheter‐related infections (n=11), bacterial pneumonia (n=4), invasive aspergillosis (n=7), and adenoviral hemorrhagic cystitis (n=8) were significantly higher in patients with prednisolone dose ≥1 mg/kg at the time of diagnosis of cGVHD. The present results suggest that infections associated with cGVHD, especially after high‐dose prednisolone, are predictive of poor outcome regardless of whether the patient received RIC or CIC.

Platelet factor 4 release from the platelets stored in platelet concentrates

Many consider that granular components of platelets should remain intact during storage of platelet concentrates (PCs) in order to participate in hemostasis when infused. The present investigations were done to determine factors affecting the release of an alpha‐granular component, platelet factor 4 (PF‐4), from platelets stored as PCs. Sedimentation of the pelleted platelet button and stronger flat‐bed agitation induced a significant PF‐4 release. After 1 day of storage at 22 degrees C, the percent PF‐4 release correlated roughly with a pH fall in PCs (r = 0.520, y = 0.014 + 7.204). Rates of pH fall were roughly proportional to the platelet count. In addition, there was a positive relationship between PF‐4 release and the platelet count per unit volume (r = 0.615, y = 0.045 + 1.327). The results indicated that one of the critical factors which determines the amount of PF‐4 release during storage is concentrated pH. Lowering the platelet count per unit volume in PCs is better for the maintenance of granular components in platelets during storage because of the intact platelet metabolism.

Rituximab does not compromise the mobilization and engraftment of autologous peripheral blood stem cells in diffuse-large B-cell lymphoma

To investigate effects of the preautografting administration of rituximab on the mobilization and engraftment of peripheral blood stem cells (PBSC), we retrospectively analyzed the outcomes of 43 newly diagnosed diffuse-large B-cell lymphoma patients who received CHOP chemotherapy with or without rituximab as a first-line treatment before autologous PBSC transplantation (PBSCT). There was no difference in the number of CD34+ cells among PBSC between the non-rituximab and the rituximab groups. Although B-cells were completely depleted from PBSC in the rituximab group, we found no difference in the expression of CXCR-4, VLA-4 and c-Kit on PBSC, indicating that rituximab did not affect the expression of these adhesion molecules, which might be involved in the mechanism of mobilization. There was no significant difference in the recovery of neutrophils and platelets, transplant-related toxicity and post-transplant complications between the two groups. Despite the short follow-up, there was no significant difference in progression-free survival between the two groups. These results indicated no adverse effect of rituximab on the mobilization and engraftment of PBSC. Larger studies are required to determine the impact of rituximab on the mobilization and function of PBSC as well as whether a survival advantage exists in patients who undergo auto-PBSCT with rituximab.

Predominance of myeloid antigens in CD34‐positive peripheral blood stem cells over those in bone marrow after administration of granulocyte colony‐stimulating factor

Abstract: We analyzed the surface phenotype of CD34‐positive (CD34+) cells in peripheral blood (PB) during the period of hematopoietic recovery following myelosuppressive chemotherapy. A significantly higher proportion of PB CD34+ cells coexpressed the CD13 and CD33 myeloid antigens (80.8%, 78.1%, respectively) than did BM CD34*** cells (45.8%, 37.8%, respectively) (both p < 0.01). In particular, the CD13 positivity of PB CD34+ cells harvested with granulocyte colony‐stimulating factor (G‐CSF) was significantly higher than that of those without G‐CSF. Most of the PB CD34+ cells possessed the HLA‐DR antigen, and less than 10% of the CD34+ cells coexpressed a mature cell antigen, such as CD14, GPA or Plt‐1. The administration of G‐CSF enhanced the appearance of significantly larger amounts of CD13+ 34+ and CD33+ 34+ cells (both p<0.01). This G‐CSF mobilization also resulted in an increased number of CD 13‐34+ and CD33‐34+ cells and all types of colony‐forming cells. On the other hand, macrophage colony‐stimulating factor administration exerted little influence on the mobilization of PB CD34+ cells. Thus, G‐CSF seemed to induce not only an expansion of circulating hematopoietic stem cells but also the myeloid differentiation of stem cells.

Mismatched unrelated cord blood transplantation in a patient with T-cell prolymphocytic leukemia

Mismatched unrelated cord blood transplantation in a patient with T-cell prolymphocytic leukemia

CD7-positive acute myeloid leukemia : further evidence of cellular immaturity

SummaryAmong 63 cases of acute myeloid leukemia (AML), 14 were found to express the CD7 antigen, a cell surface marker usually found at an early stage during T lineage differentiation. The CD7-positive AML cases consisted of 5 cases of M1, 3 cases of M2, 3 cases of M4, 1 case of M5, 1 case of M6 and 1 case of M7. Among these 63 cases, the proportion of blast cells expressing the CD34 antigen was examined. The proportion of CD34-stained cells among the CD7-positive AML cases, although varying, was significantly larger than that among the CD7-negative AML cases (P<0.05). As the CD34 antigen was expressed on hematopoietic progenitor cells and was considered to reflect an early hematopoietic stage, the high proportion of cells expressing CD34 among the CD7-positive AML cases may support the notion that CD7-positive AML cells are immature.

Autoimmune thrombocytopenia with clonal expansion of CD8-positive T cells after autologous peripheral blood stem cell transplantation for diffuse large B-cell lymphoma.

Autoimmune thrombocytopenia with clonal expansion of CD8-positive T cells after autologous peripheral blood stem cell transplantation for diffuse large B-cell lymphoma