Hideki Kodo

Transient hematopoietic stem cell rescue using umbilical cord blood for a lethally irradiated nuclear accident victim.

We performed stem cell rescue and allogeneic skin transplantation on a lethally neutron-irradiated nuclear accident victim. HLA-DRB1 mismatched unrelated umbilical cord blood cells (2.08 × 107/kg recipient body weight) were transplanted to an 8–10 Gy equivalent neutron-irradiated patient because of a lack of a suitable bone marrow or peripheral blood donor. Pre-transplant conditioning consisted of anti-thymocyte γ-globulin alone, and GVHD prophylaxis was a combination of cyclosporine (CYA) and methylprednisolone (mPSL). Granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO), and thrombopoietin (TPO) were concurrently administered after transplantation. The absolute neutrophil count reached 0.5 × 109/l on day 15, the reticulocyte count rose above 1% on day 23, and the platelet count was over 50 × 109/l on day 27, respectively. Cytogenetic studies of blood and marrow showed donor/recipient mixed chimerism. Rapid autologous hematopoietic recovery was recognized after withdrawal of CYA and mPSL. Repeated pathological examinations of the skin revealed no evidence of acute GVHD. Eighty-two days after the irradiation, skin transplantation was performed to treat radiation burns. Almost 90% of the transplanted skin engrafted. Immunological examination after autologous hematopoietic recovery revealed an almost normal T cell count. However, immune functions were severely impaired. The patient died from infectious complication 210 days after the accident.Bone Marrow Transplantation (2002) 29, 197–204. doi:10.1038/sj.bmt.1703356

Wash-out of DMSO does not improve the speed of engraftment of cord blood transplantation: follow-up of 46 adult patients with units shipped from a single cord blood bank.

BACKGROUND:  Prolonged periods of marrow hypoplasia have been a problem in cord blood transplantation. DMSO is thought to produce osmotic shock to the progenitors when the thawed cells are infused into the patients. To solve this problem, a 2× dilution method originally developed in the New York Blood Center showed earlier myeloid engraftment, 1 although follow‐up clinical studies have not performed.

Suppression of mixed lymphocyte reaction by cells of human first trimester pregnancy endometrium

In order to identify an immunological role for decidual tissue in pregnancy we have prepared single cell suspensions from the tissues of normal pregnant women and examined the effects of these cells on one-way mixed-lymphocyte reactions (MLR). The separated cells were heterogeneous, containing classical decidual cells, glandular epithelial cells, granular endometrial cells, macrophages and small lymphoid cells. [3H]Thymidine incorporation at day 6 of the MLR was suppressed by addition of the cells at the initiation of the cultures and the degree of suppression was inversely correlated to the gestational age of the decidual tissue, apparently through inhibition of the antigen recognition phase of the MLR. These findings support the view that the cells of the human first trimester pregnancy endometrium may play an important role in protecting the feto-placental unit from rejection, at least in the early phase of pregnancy.

Allogeneic cord blood transplantation for adult acute lymphoblastic leukemia: retrospective survey involving 256 patients in Japan

We investigated the efficacy of cord blood transplantation (CBT) for adult acute lymphoblastic leukemia (ALL) by reviewing medical records of 256 patients reported to the Japan Cord Blood Bank Network between June 1997 and August 2006. Cumulative incidence of neutrophil engraftment at day 100 was 78%. Infused CD34-positive cell dose (>1 × 105 cells/kg) was associated with successful neutrophil engraftment. Cumulative incidence of grade II–IV acute graft-versus-host disease (GVHD) at day 100 was 37%. A 2-year disease-free and overall survival (OS) rates were 36% and 42%, respectively. Multivariate analysis showed that age (51 or older vs younger than 50) (hazard ratio 1.9, 95% confidence interval (CI), 1.3–2.8, P=0.001), disease status (non-remission vs remission) (hazard ratio 2.2, 95% CI, 1.5–3.2, P<0.0001), grade III–IV acute GVHD (hazard ratio 2.0, 95% CI, 1.2–3.2, P=0.006) and absence of chronic GVHD (hazard ratio 2.4, 95% CI, 1.1–5.1, P=0.02) were negatively associated with OS. CBT is effective for some patients with advanced ALL. It is worth considering for further evaluation.

Donor cell-derived acute monoblastic leukemia involving MLL gene translocation in an adult patient who received umbilical cord blood transplantation.

Donor cell-derived acute monoblastic leukemia involving MLL gene translocation in an adult patient who received umbilical cord blood transplantation

A Case of Pure Red Cell Aplasia Complicated with Diffuse Large B Cell Lymphoma, T-Cell-Rich/Histiocyte-Rich Variant: Effectiveness of Rituximab and Implications for a Common Immunopathogenic Role of B Lymphocytes

Diffuse large B cell lymphoma, T-cell-rich/histiocyte-rich variant (DLBL-TH), is characterized by the presence of neoplastic B cells set in a background containing numerous non-neoplastic T lymphocytes and histiocytes. We report here the case of a patient with DLBL-TH who developed overt pure red cell aplasia (PRCA) following chemotherapy and autologous peripheral blood stem cell transplantation. Posttransplantation bone marrow biopsies revealed the absence of erythroid precursors associated with lymphoid aggregates composed of B cells mixed with numerous T cells and histiocytes. Administration of rituximab has led to complete recovery of erythropoiesis, which was associated not only with B cell depletion but also with a marked reduction in bone marrow T cells and histiocytes. These observations strongly suggest the particular pathogenetic role of the patient’s B cells in inducing PRCA and recruiting T cells and histiocytes in situ.

Induction of remission of relapsed acute myeloid leukemia after unrelated donor cord blood transplantation by concomitant low-dose cytarabine and calcitriol in adults

Abstract:  Low‐dose cytarabine and calcitriol (LDCA + VD3) combination therapy was performed in two adult patients with acute myeloid leukemia (AML) that relapsed within 1 yr after unrelated donor cord blood transplantation (URD CBT) performed in a relapse or non‐remission stage. Concomitant aclarubicin was also administered in one patient. Remission because of recovery of donor cord blood hematopoiesis was obtained in both patients. The treatment was low intensive, and neither adverse effects in terms of digestive symptoms nor hypercalcemia was observed. Activity of daily life was maintained. The patients were followed as outpatients after remission, and the remission duration was approximately 6 months in both patients. Although LDCA + VD3 therapy is minimally intensive chemotherapy, it may prolong the survival time of patients with relapsed AML after URD CBT.

Postoperative erythrodermia (POED), a type of graft-versus-host reaction (GVHR)?

Postoperative erythrodermia (POED) is a rare disease appearing several days after surgery for which blood transfusion has been required, characterized by erythrodermia, fever, pancytopenia, hepatic insufficiency or diarrhea. Most affected patients die within four weeks. The etiology remains unknown, but some assume it to be a type of graft-versus-host reaction (GVHR) caused by transfused lymphocytes. In this study, skin biopsies taken from 9 POED patients were examined to clarify whether POED is a type of GVHR. In seven samples, changes compatible with GVHR, such as lymphocyte infiltration in the basal layer and occasional eosinophilic or vacuolar degeneration of the epidermal cells, with occasional satellitosis, were noted. Immunopathologically, infiltrating lymphocytes mostly expressed suppressor/cytotoxic T cell markers like those in GVHR. Meanwhile, immunostaining with anti-HLA-A type specific antibodies failed to differentiate infiltrating lymphocytes from host cells. Thus, the present morphologic and in vivo marker study suggested POED to be a type of GVHR, while in vivo HLA-A typing showed two contradictory possibilities: first, that POED is a GVHR in which major histocompatibility antigen-matched donor lymphocytes attack host cells, and secondly that POED is not a GVHR, the infiltrating lymphocytes being of host origin.

EXPRESSION OF IgD ON B CELL MALIGNANCY|An Immunopathological Study of 50 Cases

Expression of IgD was studied immunopathologically on 50 cases of B cell lymphomas (B MLs), together with various B cell markers including IgM, ϰ and Λ chains, B1, B2, (OK)B2, (OB)B7, (OK)T10, NUB1, Leu 1, Leu 14, and PCA. IgD was demonstrated on 19 cases heavily and on 8 weakly. It associated well with expression of two antigens, B2 (C3d receptor molecule) and Leu1 (pan‐T antigen), besides IgM, while, B2 was closely related in expression on B MLs to (OK)B2, (OK)B7, and NUB1. Λ chain was dominant on IgD heavily‐stained cases. Histopathologically, IgD positive MLs were distributed in various types. All of diffuse intermediate type were shown to be IgD positive (4/4, 3 heavily). As cases of this type were shown to express most of other B cell antigens present on non‐tumorous primary follicle B cells or mantle zone B cells, this type of MLs is speculated to be a neoplastic counterpart of such non‐tumorous B cells. Eight out of 18 cases of diffuse large cell type were IgD heavily positive, suggesting some unusual mechanisms in IgD expression on these neoplastic large cells, as non‐tumorous B cells lose most of their surface IgD soon after blastoid transformation. Other types of MLs were discussed with special emphasis on expression of IgD. ACTA PATHOL. JPN. 36: 1429‐1440, 1986.

The alloantigen-specific immunosuppressive activity of estradiol-chlorambucil conjugate (KM2210) and its beneficial effect on allogeneic bone marrow transplantation in mice

KM2210, a conjugate of estradiol and chlorambucil (CBL), which was originally developed as an anti-breast cancer agent, inhibits proliferative response of human mononuclear cells to alloantigens in mixed lymphocyte culture in a dose-dependent manner, but has no effect on their response to phytohemagglutinin. Neither estradiol benzoate nor CBL alone showed these unique actions. The suppressive effect of KM2210 on MLC was abrogated by adding of anti-transforming growth factor-beta (TGF-beta) antibody to the culture, but was not affected by the addition of interleukin-2, suggesting that KM2210, unlike CBL, displays its actions via TGF-beta. In experimental allogeneic bone marrow transplantation using mice, daily oral administration of KM2210 (2 mg/kg/day) for 30 days posttransplant significantly inhibited the alloantigen-specific immune reactions.