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An ultrahigh-performance magnetically shielded room was completed as a part of a biomagnetic measuring system using superconducting quantum interference device. From the difference between environmental magnetic noise and a signal, necessary shielding factor was decided to be 1/100000 at low frequencies and 1/1000 at high frequencies. The soccer ball shaped room consists of four layers of permalloy and a layer of aluminum, and provides a space 4 meters in diameter in which magnetic fields are very weak. An independent base was built and the room was fixed rigidly to it. Because permalloy is very sensitive to shocks, the materials for the room were cut in the factory, carried with care, and assembled with screws on site. Xenon lamps supply light via optical fibers and the room is ventilated by way of many small holes in the floor. The door is equipped with the air pressure system.

Background: CD36 is a glycoprotein expressed on platelets and monocytes of the blood. There are two types of CD36 deficiency, type I and type II. Individuals with type I-deficiency do not express CD36 in any cell type and can produce the CD36 antibody, which causes pathological conditions, such as fetal/neonatal alloimmune thrombocytopenia (FNAIT) and platelet transfusion refractory (PTR), through antigenic exposure via transfusion or pregnancy., Case Presentation: We experienced a case of Philadelphia-positive acute lymphoblastic leukaemia with PTR. In addition to the CD36 antibody, multiple-specificity HLA antibodies were present in the patient's plasma, requiring transfusion of HLA-compatible and CD36-negative platelets (PC-HLA). Since the number of donors was limited, it was necessary to set-up a blood transfusion schedule so that hyper-fractionated cyclophosphamide, vincristine and doxorubicin therapy (hyper-CVAD) and ponatinib combination chemotherapy could be safely administered to achieve molecular remission. Rituximab administration resulted in reduced levels of both CD36 antibody and HLA antibody. Given the expression of CD36 on haematopoietic stem cells and the limited availability of CD36-negative PC-HLA, haematopoietic stem cell transplantation (HSCT) was not considered to be an option., Conclusion: If CD36-negative, allogeneic haematopoietic stem cell donors are unable to be found, the indications for HSCT in patients with type I CD36-deficiency should be carefully weighed. In the present case, molecular remission has been able to be maintained to the present day after completion of a two-year maintenance regimen., (© 2021 International Society of Blood Transfusion.)

A novel induction therapy, including intensive L-asparaginase, was designed in 2007 for patients aged <45 years with Philadelphia-negative acute lymphoblastic leukemia (ALL). We analyzed seven de novo cases and one case of recurrence who received this treatment. The median age was 21 years (range: 16-35 years). Four patients had T-ALL and the others had B-ALL. All the patients achieved complete remission and proceeded to cord blood transplantation. In the median 72-month follow-up, there were no cases of observed mortality or recurrence. Our results indicate scope for further development of both induction therapy and postremission therapy.

Aim: The aim of this study was to evaluate the usefulness of the trial umbilical cord blood sampling bag for unrelated cord blood transplantation., Material and Methods: Data were obtained from 100 vaginal deliveries. In 50 cases, umbilical cord blood (UCB) was taken with the traditional Kawasumi type UCB sampling bag. In another 50 cases, UCB were taken with trial UCB sampling bag offered by NIPRO Co. We compared the sampling volume between the two groups. Furthermore, 10 cases in each group were matched by sampling volume; we examined the quality of UCB on the number and concentration of nucleated cells, mononuclear cells, CD34+ cells and colony-forming unit granulocyte macrophage and the numbers tested positive for bacteria., Results: Whereas there were no significant differences in gestational weeks at sampling, the ratio of primipara women to multipara women, maternal age, and neonatal weight between the two groups, the sampling UCB volumes with the trial sampling bag were significantly higher than those with traditional sampling bags (P < 0.05). In addition, this phenomenon was more significant in the latter part of the study period (P < 0.05). On the other hand, there were no significant differences in the quality of UCB between the two groups., Conclusion: Once clinicians have become accustomed to the trial UBC sampling bag, this method might be a useful method for collecting UCB for unrelated cord blood transplantation., (© 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.)

The majority of cord blood transplantations (CBTs) have human leukocyte antigen (HLA) disparities. We investigated the impact that patients' pretransplantation anti-HLA antibodies have on the outcome of CBTs. Testing for anti-HLA antibody and its specificity was performed retrospectively at the Japanese Red Cross Tokyo Blood Center with sensitive solid-phase antibody detection assays. Among 386 CBTs, which were first myeloablative stem cell transplantations for malignancies and used a single unit of cord blood, 89 tested positive. Among the antibody-positive group, the cord blood did not have the corresponding HLA type for the antibody in 69 cases (ab-positive), while 20 cases had specificity against the cord blood HLA (positive-vs-CB). Cumulative incidence of neutrophil recovery 60 days after transplantation was 83% (95% confidence interval [CI], 79%-87%) for the antibody-negative group (ab-negative), 73% (95% CI, 61%-82%) for ab-positive, but only 32% (95% CI, 13%-53%) for the positive-vs-CB (P < .0001, Gray test). With multivariate analysis, the ab-positive showed significantly lower neutrophil recovery than the ab-negative (relative risk [RR] = 0.69, 95% CI, 0.49-0.96, p = .027). The positive-vs-CB had significantly lower neutrophil recovery (RR = 0.23, 95% CI, 0.09-0.56, P = .001) and platelet recovery (RR = 0.31, 95% CI, 0.12-0.81, P = .017) than the ab-negative. Patients' pretransplantation anti-HLA antibodies should be tested and considered in the selection of cord blood.

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.

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., (Copyright (c) 2005 S. Karger AG, Basel.)

Unrelated cord blood transplantation (CBT) has now become more common, but as yet there have been only a few reports on its outcome compared with bone marrow transplantation (BMT), especially for adults. We studied the clinical outcomes of 113 adult patients with hematologic malignancies who received unrelated BM transplants (n = 45) or unrelated CB transplants (n = 68). We analyzed the hematopoietic recovery, rates of graft-versus-host disease (GVHD), risks of transplantation-related mortality (TRM) and relapse, and disease-free survival (DFS) using Cox proportional hazards models. The time from donor search to transplantation was significantly shorter among CB transplant recipients (median, 2 months) than BM transplant recipients (median, 11 months; P < .01). Multivariate analysis demonstrated slow neutrophil (P < .01) and platelet (P < .01) recoveries in CBT patients compared with BMT patients. Despite rapid tapering of immunosuppressants after transplantation and infrequent use of steroids to treat severe acute GVHD, there were no GVHD-related deaths among CB transplant recipients compared with 10 deaths of 24 among BM transplant recipients. Unrelated CBT showed better TRM and DFS results compared with BMT (P = .02 and P < .01, respectively), despite the higher human leukocyte antigen mismatching rate and lower number of infused cells. These data strongly suggest that CBT could be safely and effectively used for adult patients with hematologic malignancies.

We carried out a survey on platelet transfusions performed in nine general hospitals. We evaluated 303 adults who received a total of 24455 units over 1864 platelet transfusions. The underlying diseases were hematologic disorders with chemotherapy (59.7%), hematologic disorders without chemotherapy (15.5%), hematopoietic stem cell transplantation (18.5%), and others (2.0%). The patient platelet count before transfusion (platelet trigger value) was measured in only 77.1%. The platelet trigger value differed greatly between the hospitals, with an average of 2.2 x 10(4)/microl, a minimum of 1.3 x 10(4)/microl, and maximum of 3.2 x 10(4)/microl. Only 55.3% of the platelet transfusions carried out complied with the Platelet Transfusion Guideline published by the Ministry of Health, Labour and Welfare. The hospitals surveyed could be divided into those who gave mainly around 10 units and those who gave over 10 units. The total dose of platelets transfused was more in the hospitals that used mainly 15 or more unit-PCs than in the hospitals that used mainly 10 unit-PCs. These results indicate that platelet transfusion may be greatly reduced by complying with the 2 x 10(4)/microl of platelet transfusion threshold and by selecting less than 10 units of PC per transfusion.

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 2x dilution method originally developed in the New York Blood Center showed earlier myeloid engraftment,1 although follow-up clinical studies have not performed., Study Design and Methods: To clarify the influence of the removal of DMSO by this method on the speed of engraftment in unrelated cord blood transplantation, 46 adult patients with cord blood units processed by the Tokyo Cord Blood Bank from September 1998 to March 31, 2002 were studied. Twenty-four patients received 2.6 +/- 0.71 x 10(7) nucleated cells per kg without washing (nonwashed group), while 22 patients were received 2.7 +/- 0.52 x 10(7) nucleated cells per kg after 2x dilution washing (washed group)., Results: The cumulative incidence of engraftment was not significantly different between the two groups. Median neutrophil recovery (>/=5 x 10(9)/L) in the nonwashed and washed groups was 26 and 25 days, respectively, and the median platelet recovery (>/=20 x 10(9)/L) in patients with myeloid engraftment was 44 and 40 days, respectively (NS). On the other hand, the doses of CFCs and CD34+ cells showed the influence on myeloid and platelet recovery., Conclusion: A 2x dilution after thawing cord blood did not result in the improvement of myeloid engraftment speed.

Between January 1993 and June 1994, the JMDP facilitated marrow donations from unrelated donors for 171 patients with malignant and non-malignant disorders. The median age of the patients was 21 years. All patients received marrow from phenotypically HLA -A, -B, -DR identical donors. About half of the patients wrer treated with total body irradiation (TBI)-containing regimens and about 80% of the patients received short-courses methotrexate and cyclosporine for graft-versus-host disease (GVHD) prophylaxis. Eight out of 171 patients, (4.7%) had graft failure and 63 out of 144 patients (44%), who survived for more than 30 days posttransplant, developed grade II to IV acute GVHD. The incidence of chronic GVHD was 47% (extensive form; 27%); most of them were progressive/quiscent type. The incidence of moderate to severe acute GVHD was higher than that observed in sibling transplants. On the other hand, the incidence of chronic GVHD was similar to that observed in sibling transplants. Overall survival at 1.5 years posttransplant was about 50% with no significant differences between diseases. The age correlated significantly with the survival in standard risk leukemia but not in high-risk leukemia. Despite the risk of graft failure and acute GVHD, this preliminary analysis demonstrates that transplantation of marrow from unrelated donors can be an effective treatment for certain hematologic disorders.

Plasma concentration of cytosine arabinoside (Ara-C) was determined in elderly patients with myelodysplastic syndromes or acute myelocytic leukemia who were treated with subcutaneous injection of Ara-C (Ara-C s.c.; 10 mg/m2/12 hr, 14-21 days), continuous drip infusion of Ara-C (Ara-C d.i.v.; 20 mg/m2/day, 24 hr 14 days) and/or oral administration of cytarabine ocfosfate (SPAC) (SPAC p.o.; 100 mg-300 mg/body/day, 14 days) by radioimmunoassay. In the Ara-C s.c. patients, the peak plasma level (Cmax) of Ara-C was 103 ng/ml and the time to reach Cmax was 15 min. The elimination half-like (t1/2) was 25 min and no accumulation was detected after 14 days of consecutive Ara-C s.c. administrations. In the SPAC p.o. patients, Cmax of Ara-C was 3-8 ng/ml and it took 3-5 days to reach Cmax. The plasma concentration level of Ara-C remains almost at the Cmax level during the SPAC p.o. administration and it remained higher than 0.32 ng/ml for as long as 15 days after the end of administration. In a Ara-C d.i.v. patient, plasma level of Ara-C was detected 4-7 ng/ml during the administration (day 7 through day 14). In all patients bone marrow suppression was observed after chemotherapy regardless of regimen, and there was no significant difference between nadir peripheral cell blood counts of Ara-C s.c. patients and SPAC p.o. patients.

Four patients with fresh Hodgkin's disease were treated with MOPP/ABV hybrid regimen using nitrogen mustard-N-oxide hydrochloride (NH2-O). All patients responded well to this therapy and achieved complete remission. Toxicity was minimum except for an older patient. He was 70 years old and developed arrhythmia after MOPP therapy but recovered without any treatment. The continuation of therapy was possible by dose reduction in this case. We conclude MOPP/ABV regimen using NH2-O is valuable for the treatment of Hodgkin's disease.

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. Furthermore, the survival rate of the KM2210-treated mice was significantly higher than that of the cyclosporine-treated (2 mg/kg/day, p.o.) mice, and no adverse effect of KM2210 on hematopoietic recovery was found. These results strongly suggest possible clinical benefits of KM2210 as a new immunosuppressive agent for the prevention and treatment of graft-versus-host disease and other allospecific immune reactions.

Human interferon-alpha (IFN-alpha) has been shown to be effective in the treatment of Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) in the benign stable phase. The present study indicates that IFN-alpha may have a suppressive effect on Ph1-positive clones not only in the early stable phase but also in the accelerated phase with additional chromosomal abnormalities in some patients. In this study, in addition to 5 benign-phase patients, 3 patients with CML in the accelerated phase who had additional chromosomal abnormalities were treated with IFN-alpha. The presence of the Ph1-positive clone was estimated by chromosomal analysis and by Southern analysis at the DNA level using a 3' breakpoint cluster region (bcr) probe. Hematological remission and the suppression of proliferation of Ph1-positive clone to various extents were achieved by IFN-alpha treatment in 2 benign-phase patients and 3 patients with additional chromosomal abnormalities. Interestingly, in one of the latter three patients, Ph1-positive clones with or without additional chromosomal abnormalities were completely suppressed judging from chromosomal analysis and from the disappearance of bcr gene rearrangements.

Human granulocyte colony-stimulating factor (G-CSF) specifically stimulates granulocyte production and enhances functions of mature granulocytes. It also proliferates myeloid leukemic cells. The molecule was purified and molecularly cloned in 1986. In this study, 51 patients received single daily injections with recombinant human (rh) G-CSF (2-20 micrograms/kg) after bone marrow transplantation were compared with control 36 patients. Blood neurophilic recovery was accelerated remarkably by rhG-CSF administration without any adverse effects including delay in reticulocyte and platelet recoveries. Furthermore, the duration for the management in laminar airflow room and febrile days greater than or equal to 38 degrees C were shortened in rhGS-CSF treated group. In 6 patients with myeloid leukemia in relapse, we also tested the effects of the rhG-CSF-combined conditioning regimen. In all the patients tested, the leukemic cells responded to rhG-CSF. Clinically no relapse was observed and 3 patients are well on day 224-357 for the time being. These findings indicate that rhG-CSF is very useful in bone marrow transplantation.

A new non-T cell, non-B cell lymphoma cell line, designated IN-1, was established from the ascitic fluid of a patient with non-Hodgkin lymphoma. The IN -1 cells did not show any T cell and B cell immunophenotypes. There were rearrangements of T cell receptor beta- and gamma-chain gene, but no rearrangement of T cell receptor delta-chain gene and immunoglobulin JH gene. Electron microscopically, the cell had numerous pseudopods, mitochondria, vesicles, a conspicuous nucleolus, and scattered heterochromatin at the periphery of the nucleus. They reacted with only OKT9 monoclonal antibody. Molecular analysis revealed that cellular DNA from the IN-1 cells did not hybridize with Bam HI W fragment of EB virus DNA. Cytogenetic analysis showed that the chromosome number of the IN-1 was in the range of 61 -63 whose karyotype analysis demonstrated multiple numerical and structural chromosome changes. The IN-1 cells were resistant to etoposide in comparison with an IC50 of K562 (human chronic myelogenous leukemia). Interestingly, this IN-1 cell possessed 85 KD protein, but not P-glycoprotein, both of which are considered to be multidrug resistance-related proteins.

Myeloperoxidases were purified from leukemic myeloblasts (Mbl-MPO) and from normal neutrophilic granulocytes (Gra-MPO) and were compared with each other biochemically. Gel filtration studies showed that the molecular weights (Mr) of Mbl-MPO and Gra-MPO were about 70,000 and 130,000, respectively, so that the former is almost one-half the molecular size of the latter. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis with 2-mercaptoethanol, both MPOs split into two major subunits, heavy and light peptide chains. However, each of these chains of Mbl-MPO seemed to be smaller than that of Gra-MPO, Mr 58,000 versus Mr 62,000 for the heavy chain and Mr 12,000 versus Mr 15,000 for the light chain. On the other hand, another band of Mr 34,000 also appeared in Mbl-MPO under nonreducing conditions and in both MPOs after being boiled. The size of this band was not different in the two MPOs, but the ratio of this band to the others was much higher in Mbl-MPO. The activity of Mbl-MPO could be demonstrated in the heavy chain of Mr 58,000, using a blotting method, and was found to be less heat stable than that of Gra-MPO. These findings indicate that Mbl-MPO may represent an incomplete, unstable half-enzyme form of Gra-MPO.

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.

Posttransplant hematologic recovery was compared between 9 autologous and 11 allogeneic marrow transplant patients who received similar marrow-lethal chemoradiotherapies before transplantation. Although the autotransplant patients were infused with much lower marrow doses compared with the allotransplant patients, they showed adequate hematologic recovery with acceptable risk. Regardless of marrow doses, delayed platelet recovery and failure of platelet recovery were observed in 7 patients. All of these patients experienced early transplantation-related complications before engraftment. Despite the limited number of patients, a number of myeloid progenitor cells (CFUC) infused correlated significantly with the period for recovery of polymorphonuclear cells in autologous marrow recipients while there was no significant correlation found between marrow dose and hematologic recovery in both groups of patients. Furthermore, autotransplant patients showed a characteristic recovery pattern of peripheral blood lymphocytes in an early posttransplant period, whic was not observed in allotransplant patients.

Expression of IgD was studied immunopathologically on 50 cases of B cell lymphomas (B MLs), together with various B cell markers including IgM, kappa and lambda 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. lambda 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.