bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current Activities of AsiaCORD: Fast Searching System of the Qualified Cord Blod Units for Asian Patients.
Authors: Takahashi Tsuneo A. , Lin Kai Hsin , Han Hoon , van Binh Tran , Binh Nguyen Tan , Han Zhongchao , Liu Kai Yan , Issaragrisil Surapol , Kodo Hideki , Asano Shigetaka , Lu Dao Pei 
Published: April 2020

Abstract
The necessities of cord blood transplantation and banking are increasing rapidly in Asian countries as well as others around the world. In China nearly 20,000 units are cryopreserved and more than 100 patients have received transplants using these units. In Japan, more than 17,000 units are cryopreserved and archived in Japan Cord Blood Bank Network and 1,700 patients have received transplants using these units. Adoption of this new medical technology is particularly rapid in Asia because of smaller family size, which makes it difficult to find matched bone marrow donors for patients and treat them by bone marrow transplantation. To facilitate cord blood searching and develop cord blood transplantation, the network of cord blood banks in Asia, AsiaCORD, was founded in November 2000 in Bangkok, Thailand.
The members of AsiaCORD are the leading public cord banks in Asia; Bangkok (Thailand), Beijing(China), Ho Chi Minh City (Viet Nam), Seoul (Korea), Taipei (Taiwan), Tianjin (China) and Tokyo (Japan). AsiaCORD has established a statute and standards for cord blood banking that is based on the International Standards of FACT/NETCORD while also reflecting each country’s standards, ethics, historical background and epidemiology. The banks have been inspected by inspectors composed with multi centers of AsiaCORD based on the standards. An electronic search system (http://asiacord.org) has been developed and transplantation were performed through the system. A more advanced interactive web site for transplant physicians to directly search AsiaCORD inventory for their patients is under preparation.
AsiaCORD is open to membership applications from additional cord blood banks in Asia who are able to comply with the standards and share their goal to supply cord blood units of only the highest quality to patients in Asia and also those living in all over the world.
The AsiaCORD Inventory and Use (August2004)
CB BANK Inventory Transplanted Children Adults Beijing 5800 70 44 26 Tianjin 5400 15 10 5 Seoul 32000 84 80 4 Taipei 6700 9 9 0 Ho Chi Minh 1076 7 7 0 Bangkok 315 1 1 0 Tokyo 5563 277 105 172 Total 56854 463 256 207
Quality Control of Cell Processing and Cord Blood Storage Using HALO To Measure Proliferative Potential of Stem and Progenitor Cells.
Authors: Rich Ivan N. , Hall Karren , Bartelmez Stephen H. 
Published: April 2020

Abstract
Prior to the introduction of flow cytometry to detect and measure CD34+ cells in the early 1980s, quality control of stem cell transplants was performed using the granulocyte-macrophage colony-forming assay (GM-CFC). The major disadvantages of this growth potential assay are that progenitor and not stem cells are detected and the assay takes too long to perform. Yet, measurement of the growth potential of proliferating cell populations in vitro is the only technique that guarantees the presence of stem cells after cell processing and may predict engraftment and reconstitution. There are no assays presently that exhibit these characteristics in real-time. However, it is now possible to measure the proliferative potential of stem and progenitor cells after cell processing and/or storage in half the time required by the classical colony-forming assay (CFA). Originally developed for hemotoxicity testing for all stages of drug development, HALO (Hematopoietic/Hemotoxicity Assays via Luminescence Output) can be used as an in-line stem cell processing quality control procedure as well as a method to ensure the growth potential of processed and stored umbilical cord blood. HALO sensitively measures small numbers of proliferating cells and because cell differentiation is not detected, manual enumeration of colonies is not required. The assay is based on the CFA procedure. However, as cells proliferate in response to growth factors, there is a proportional increase in the intracellular ATP concentration. The assay is performed in a 96-well plate and release of intracellular ATP drives a luciferin/luciferase reaction to produce bioluminescence in the form of light measured in a plate luminometer. The kinetics of most hematopoietic proliferating populations, including mature stem cells, allows results to be obtained after 6–7 days in culture. Measurement of luminescence for all 96 well cultures takes about 5 minutes. An ATP standard dose response performed prior to sample measurement not only provides quality control of the reagents used, but intra- and interlaboratory comparison of results. Due to the rapid and easy set-up procedure with high-throughput capability, the proliferative capacity of several stem and progenitor cell populations from either single or large numbers of samples from bone marrow, peripheral blood or cord blood can be analyzed simultaneously. Rapid assay turnaround and multiparameter capability should therefore allow an increased safety factor for patients undergoing stem cell transplantation. Additional studies are underway to further validate this approach.
Analysis of Chimerism Induction Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) with a Reduced-Intensity Regimen.
Authors: Kojima Rie , Heike Yuji , Narumi Jun , Yamagata Shizuka , Chizuka Aki , Nosaka Kisato , Kami Masahiro , Mori Shin-ichiro , Tanosaki Ryuji , Tobinai Kensei , Takaue Yoichi 
Published: April 2020

Abstract
&lt;Background&gt; Although the analysis of chimerism induction has become an important diagnostic tool for providing better clinical management of patients undergoing allogeneic HSCT, the techniques have not been fully standardized. Moreover, it is currently unknown whether the onset of graft-versus-host disease (GVHD) is related to the status of mixed chimerism (MC) or complete donor-type chimerism (CDC).
&lt;Methods&gt; First, to validate our chimerism analysis system, we performed experiments with artificially mixed cell samples from healthy volunteers to examine the reliability of short tandem repeat (STR) determination by quantitative polymerase chain reaction (PCR). We confirmed a linear correlation between the proportion of mixed cells and the calculated ratio, with a correlation coefficient of 0.99, which enables the detection of target cells at 3% (median standard deviation, 1.6%). Next, using this validated system, we prospectively evaluated the kinetics of chimerism in CD3+, CD19+, and peripheral blood mononuclear cells (PBMC), for correlation with the occurrence of GVHD in 19 patients with various hematological diseases (median age, 53y) who had received allogeneic HSCT from an HLA-identical sibling donor between July 2003 and February 2004. The preparative regimen was fludarabine/busulfan (BU) (n=12) or cladribine/BU (n=7). GVHD prophylaxis consisted of cyclosporin alone (n=8), cyclosporin plus short-term methotrexate (n=7), or tacrolimus (n=4). Chimerism analysis was repeated weekly after transplantation.
&lt;Results&gt; We evaluated 405 consecutive blood samples from these 19 recipients, 12 of whom developed acute GVHD. Six of these 12 patients showed MC, i.e. 91% (83–94%; MC) donor cells in the CD3+ fraction at the onset of GVHD, but all except one subsequently achieved CDC within a median of 15 (7–33) days without additional DLI. The remaining patient showed persistent MC and relapsed 158 days after transplantation.
&lt;Conclusion&gt; We found that the presence of MC in the CD3+ fraction is rather common at the onset of acute GVHD, but GVHD subsequently eradicates residual host hematopoietic cells. Alternatively, GVHD is part of a clinical manifestation of an immune reaction that is related to the induction of CDC.
Rapid Ex Vivo Expansion of CMV Specific CTL Suitable for Clinical Immunotherapy Using CpG-DNA Matured PBMC Infected with Recombinant MVA.
Authors: Diamond Don J. , Wang Zhongde , Lacey Simon F. , La Rosa Corinna 
Published: April 2020

Abstract
Adoptive transfer of ex vivo expanded CMV-specific T cells is an effective approach, and an attractive alternative to using anti-virals to manage CMV infection for HSCT recipients. We recently published a robust approach to expanding CMV-specific CTL based on infection of autologous EBV-LCL with the attenuated poxvirus, Modified Vaccinia Ankara (MVA), expressing CMV pp65, pp150, and IE1 proteins. This approach causes vigorous, up to 500fold expansions in as little as 12–14 days of memory CD8+ T cells specific for these immunodominant antigens. In order to improve the specificity of the expanded T cells, a method was sought to derive effective antigen presenting cells (APC) that avoided the use of EBV-LCL. Of equal importance is to develop an expansion approach that avoids the need to involve virally infected APC in developing a clinical product. Our preliminary observation is that rMVA can infect PBMC in vitro, causing high levels of expression of recombinant CMV antigens. To be permissible for high level expression from rMVA, fresh PBMC were treated with different combinations of single-stranded CpG-containing phosphorothioate backbone oligonucleotides (ODN). A three-day incubation with a combination of two ODN (ODN # 2006 and 2216) which are known to stimulate both plasmacytoid dendritic and B-cells were found to reproducibly generate a highly rMVA infectable population of PBMC. In all five healthy CMV-positive donors tested, CpG ODN treated autologous PBMC, infected with recombinant rMVA, elicited a 20-fold average expansion of CMV-specific CD8+ T cells, in 10 days. Several different rMVA expressing CMV genes were evaluated, including a novel vector expressing the UL44 gene product, an immunodominant target of the host cellular immune response. The expanded T cell populations showed minimal alloreactivity, and exhibited high levels of CMV-specific MHC Class I tetramer binding, epitope-specific cytokine production, and cytotoxic activity. The availability of a source of autologous professional APC that can be used after only 3 days of priming, enhances the attractiveness of using rMVA for adoptive immunotherapy for HSCT recipients or donor vaccination.
Comparison of Lung Function after Nonmyeloablative Versus Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Chien Jason W. , Maris Michael B. , Parimon Tanyalak , Sandmaier Brenda M. , Maloney David G. , Storb Rainer F. , Clark Joan G. 
Published: April 2020

Abstract
Lung function decline is a well-recognized occurrence after myeloablative hematopoietic stem cell transplantation (HCT) that has not been studied after nonmyeloablative conditioning regimens. We examined the lung function of patients before and after receiving nonmyeloablative and myeloablative preparative regimens. Before HCT, nonmyeloablative patients had lower baseline values of percent of predicted FEV1 (pFEV1) and FVC (pFVC), reflecting their greater ages and often, poorer, medical conditions. However, nonmyeloablative patients experienced a slower overall rate of pFEV1 decline after HCT (4% ± 17 versus 12.7% ± 32 per year, P = 0.001), with patients &gt;50 years of age having the lowest risk for rapid pFEV1 decline in a multivariable model. Rapid pFEV1 decline was associated with both total body irradiation (TBI) and non-TBI based myeloablative regimens. These findings were evident even one year or more after HCT. Myeloablative patients had a higher risk for death based upon pretransplant pFEV1 (HR 7.2 versus 3.9), with a 2-year survival rate of 0% among myeloablative patients with a pretransplant pFEV1 &lt;60% (30% among nonmyeloablative patients). These results suggested that despite having worse lung function, patients receiving the nonmyeloablative regimen might experience less pulmonary toxicity and had a lower risk of mortality associated with abnormal pretransplant lung function.
Comparison of Gel Versus Capillary Electrophoresis for Chimerism Monitoring by PCR Amplification of Microsatellite Markers after Allogeneic Hematopoietic Cell Transplantation.
Authors: Zeiser Robert , Spyridonidis Alexandros , Waesch Ralph , Bertz Hartmut , Finke Jurgen 
Published: April 2020

Abstract
Hematopoietic chimerism has been demonstrated to be relevant for donor cell engraftment and detection of minimal residual disease after allogeneic hematopoietic cell transplantation (aHCT). In the light of increasing numbers of aHCT as a treatment modality, rapid, reliable and cost effective chimerism monitoring techniques acquire novel relevance. We evaluated the informativeness of five microsatellite markers in 376 donor/recipient pairs and compared the ability of polyacrylamide gel electrophoresis (GE) and capillary electrophoresis (CE) to detect mixed chimerism (MC) after aHCT. The sensitivity for GE and CE with respect to different markers was determined by limiting dilution assays with MC samples containing defined amounts of cells or DNA. Furthermore, CE was applied in 37 retrospectively selected patients with a MC detected by GE, having undergone aHCT for different hematological diseases and initially achieving a complete donor chimerism. The sensitivity and accuracy quantified by limiting dilution was higher CE as compared to GE with all microsatellites. Potential pitfalls with the combined application of CE was preferential amplification, leading to the misdiagnosis of CC in the presence of MC and the occurrence of stutter peaks in the representative area. In case of preferential amplification with the initially applied marker D1S80, evaluation with a second microsatellite was beneficial. Investigation of the selected pts samples demonstrated that detection of an increasing MC was earlier with CE as compared to GE. The detected recipient genotype by CE examination, despite a negative GE result, ranged from 0.7% to 7.1%.
We conclude that chimerism assessment with our five microsatellites identified informative alleles in 99% of all donor/recipient pairs. CE displayed a higher sensitivity and accuracy when compared to GE and additionally allowed for detection of an increasing MC suggestive for relapse. Prospective clinical investigation with CE for the predictive value of an increasing MC for graft failure or relapse is necessary.
Informativeness of the institutional microsatellite marker panel
No of pairs/ markers D1S80 THO1 D14S120 YNZ22 SE33 Numbers indicate patients were the marker was informative (ratio in %). rel: related donor; unrel: unrelated donor; n.t.: not tested; non inf.: non-informative. 165 rel/211 unrel 87 (53%)/145 (69%) n.t. n.t. n.t. n.t. 78 rel/66 unrel non inf. 22 (22%)/20 (30%) n.t. n.t. n.t. 56 rel/46 unrel non inf. non inf. 18 (32%)/16 (35%) n.t. n.t. 38 rel/20unrel non inf. non inf. non inf. 17 (45%)/15 (75%) n.t. 21 rel/5 unrel non inf. non inf. non inf. non inf. 19 (90%)/4 (80%) rel vs unrel 163/165 (98%) vs 210/211 (99%)
Safety and Potential Efficacy of Low Dose Methotrexate for Treatment of Chronic Graft-Versus-Host Disease.
Authors: Flowers Mary E.D. , Giaccone Luisa , Funke Vaneuza , Carpenter Paul A. , Moravec Carina , Hooper Heather , Storb Rainer F. , Martin Paul J. 
Published: April 2020

Abstract
Low dose methotrexate (MTX) is widely used for treatment of autoimmune diseases because of its anti-inflammatory activity. Encouraged by this practice, we have administered low dose MTX for treatment of refractory chronic GVHD, with the goal of reducing the amount of prednisone needed to control the disease. Fourteen patients with refractory chronic GVHD were treated with MTX at a dose of 7.5 mg/m2 per week for 3–50 weeks. All patients had involvement of the oral cavity and 11 of the 14 (78%) had skin involvement, often with scleroderma or fasciitis. The median duration of chronic GVHD at the start of MTX therapy was 38 (range 1–135) months. In this retrospective review, we found no grade 3–4 toxicities, and none of the patients required blood transfusion or treatment with hematopoietic growth factors. In 10 patients (71%), chronic GVHD could be adequately controlled with prednisone at doses below 1 mg/kg every other day without the addition of other immunosuppressive agents. Four patients decreased the amount of concomitant immunosuppressive treatment, 5 continued with the same regimen, 4 required an increase in immunosuppressive treatment, and one decided to discontinue all treatment. Improvement or resolution was observed most frequently in the gastrointestinal tract (80%) and skin (50%). From this preliminary analysis, MTX appears to be a well tolerated, inexpensive and possibly steroid-sparing immunosuppressive agent that is worthy of further evaluation in prospective trials for treatment of chronic GVHD.
High Incidence of Extramedullary Relapses Following Allogeneic Bone Marrow Transplant (Allo-BMT) in Adults with Acute Lymphoblastic Leukemia.
Authors: Absi Ahmed , Bolwell Brian J. , Sobecks Ronald , Pohlman Brad , Andresen Steve , Rybicki Lisa , Kalaycio Matt 
Published: April 2020

Abstract
Allo-BMT represents a curative therapy for certain patients with ALL. Unfortunately, leukemia relapse still represents a major problem following allo-BMT. Studying the pattern of relapses following allo-BMT may shed some light into the exact mechanisms of such relapses and suggest better ways to prevent them. Extramedullary relapses have been reported following allo-BMT for ALL. We investigated the pattern of ALL relapses in 57 patients after allo-BMT. All donors were HLA matched serologically at HLA A, B, and DR. All patients were treated with high-dose busulfan (16 mg/kg) combined with cyclophosphamide (120 mg/kg) with or without etoposide (50 mg/kg) and all received GVHD prophylaxis, excluding T-cell depletion. We identified 57 patients with ALL treated with BMT between 1987 and 2001. 45 patients (78.9%) had a matched related donor (MRD) and the rest had matched unrelated donors (MUD). 22 patients (39%) relapsed, 8 patients had an isolated extramedullary (IEM) relapse and 14 patients had bone marrow relapse (BM-R) with or without an isolated extramedullary relapse. The median time to relapse for the IEM relapses was 432 days with a range of 139–1422. This was significantly longer than the median time to relapse with BM (median 192 days and range 40–498) P=0.016. The following table shows the characteristics of both groups:
Number Ph + B-cell ALL CR-1 Extensive GVHD BM-R 22 3 (14%) 7 (32%) 5 (23%) 4 (18%) IEM-R 8 3 (37%) 5 (62%) 2 (25%) 2 (25%)
IEM relapses occurred in different organs including mastoid sinus, mediastinum, pericardium, nasopharyngeal lymphoid tissue, bone, CNS, and breast. Hematopoietic chimerism was determined utilizing the polymerase chain reaction (PCR) amplification of Short Tandem Repeat (STR) loci on DNA extracted from peripheral blood leukocytes compared with Pre-Transplant STR loci of donors and recipients. At the time of relapse all the patients with IEM relapses had 100% donor chimerism. Treatment plans for those IEM relapses included donor lymphocytes infusion (DLI), local radiation therapy, reinduction chemotherapy, imatinib for Ph+ patients, and one patient had an additional Allo-BMT. Only one patient in the IEM relapse group eventually had a relapse in the bone marrow, only 2 patients (25%) were alive more than 2 years following relapse and 3 patients died due to transplant complications.
We concluded from our review that IEM relapse following Allo-BMT for ALL is not an uncommon occurrence. These relapses may have a wide-range of clinical presentations depending on the organ affected which makes the diagnosis of this type of relapse challenging. These relapses have, usually, a late occurrence compared to BM-R, and their pathogenesis is poorly understood. Full donor chimerism does not exclude the possibility of IEM relapse.
Role of Chemotherapy before Allogeneic Stem Cell Transplantation (ALLO-SCT) from an HLA-Identical Sibling Donor for Myelodysplastic Syndrome (MDS).
Authors: Nakai Kunihisa , Kanda Yoshinobu , Fukuhara Shirou , Sakamaki Hisashi , Okamoto Shinichiro , Kodera Yoshihisa , Tanosaki Ryuji , Takahashi Satoshi , Matsushima Takafumi , Atsuta Yoshiko , Hamajima Nobuyuki , Kasai Masaharu , Kato Shunichi 
Published: April 2020

Abstract
The role of chemotherapy before allo-SCT remains unclear. We analyzed the data of 283 patients (median age 41 years, range 16–65 years) who underwent allo-SCT from an HLA-identical sibling donor for MDS that were reported to the Japan Society for Hematopoietic Cell Transplantation. One hundred eighty-eight patients had received chemotherapy before allo-SCT (Chemo group), whereas 95 had not (NoChemo group). The Chemo group included significantly higher proportion of patients with advanced disease and poor karyotype than the NoChemo group, (p&lt;0.0001 and p=0.004, respectively). Overall survival (OS) at 5 and 10 years was 48.8% and 42.5%, respectively. Multivariate analyses identified karyotype, FAB classification, and the history of chemotherapy before allo-SCT as significant predictors for OS. The cumulative incidence (CI) of grade II–IV and III–IV acute GVHD among those who achieved engraftment was 33% and 10%, respectively. Chronic GVHD developed in 110 (53%) among 209 patients who survived more than 100 days. The CI of relapse in those who developed grade II–IV acute GVHD and those who did not was 39.6% and 19.5%, respectively (p=0.086). The CI of relapse in those who developed chronic GVHD and those who did not was 22.0% and 20.8%, respectively (p=0.82). Then, we analyzed only 139 patients with RAEBt or leukemic transformation (LT). Twenty-eight patients belong to the NoChemo group and 111 patients belong to the Chemo group. The proportion of patients with a poor karyotype was equivalent between the two groups (p=0.44). The duration from diagnosis to allo-SCT was shorter in the NoChemo group, with marginal significance (161 days vs. 248 days in median, p=0.07). The OS curves of the NoChemo group and CR patients in the Chemo group were superimposed (57% vs. 54%, p=0.81). The CI of relapse was 26.2% in the NoChemo group and 27.6% in CR patients in the Chemo group (p=0.83). Non-relapse mortality was also similar between the two groups (18.8% vs. 17.8%, p=0.86). In conclusion, this study confirmed that allo-SCT from an HLA-identical sibling donor offers the potential for long-term survival in patients with MDS. It seems that allo-SCT may be beneficial as primary treatment for patients with a low blast cell count or those with an advanced MDS but with an indolent course. GVHD did not appear to have a clear beneficial effect on the CI of relapse.