bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Kinetics of Etoposide (VP-16) Peripheral Blood Progenitor Cell (PBPC) Mobilization.
Authors: Bolwell Brian J. , Kuczkowski Elizabeth , Rybicki Lisa , Pohlman Brad , Andresen Steven , Sobecks Ronald , Baker Janet , Cherni Kelly , Bernhard Laura , Vellani Alison , Berry Nicole , Sungren Shawnda , Foster Leslie , Kalaycio Matt 
Published: April 2020

Abstract
The kinetics of G-CSF PBPC mobilization are well described. CD34+cells in peripheral blood rise four days after G-CSF administration, and decline after the eighth day. VP-16 is increasingly used with G-CSF as a mobilizing regimen; however, the kinetics of mobilization are sparsely described. We retrospectively reviewed 275 patients (pts) with NHL or HD who received VP-16 plus G-CSF as a primary PBPC mobilizing regimen. 214 (78%) had NHL; 31% received prior radiation therapy; 63% were male; 85% had responsive disease. Pts received VP-16 (2 gm/m2) followed by daily G-CSF (10 mcg/kg). All pts experienced a significant WBC nadir. Pts began pheresis when their WBC recovered to 5,000. Pts were pheresed for at least 2 days or until 7.0 x 106 CD34+ cells/kg were collected; pheresis continued until a minimum of 2.0 x 106 CD34+ cells were collected. WBC nadir occurred day +6 after VP-16 and WBC recovery to 5,000 occurred day +13 (median) after VP-16. Pts were pheresed for a median of 3 days which yielded a median of 9.7 x 106 CD34+ cells/kg (range, 2.0–100.1 x 106). 72% of pts began collection on day +12, day +13, or day +14. The average CD34+ cell collection was maximal on the first 3 days of pheresis, but reasonable yields continued to be obtained for approximately 10 days of pheresis, as shown below:
Figure Figure
81% collected ≥ 5 x 106 CD34+ cells/kg, and 72% collected ≥ 7 x 106 CD34+ cells/kg. The platelet count on the first day of pheresis correlated with the ability to collect 5 and 7 x 106 CD34+ cells/kg (p&lt;0.001). 50 of 275 (18%) pts did not begin pheresis until day +15 or longer after VP-16 administration. The variables that correlated with these problematic pts was the platelet count at day 1 of pheresis and refractory disease at the time of mobilization; of 24 pts with refractory disease, 11 (46%) had poor WBC recovery after VP-16 and initiated mobilization on a median of day +16 (p&lt;0.001). We conclude that VP-16 + G-CSF is a very effective mobilizing regimen. The majority of pts mobilize large numbers of CD34+ cells requiring only 3 days of leukopheresis for excellent yields. Unlike the kinetics of G-CSF for PBPC mobilization in which yields of CD34+ cells are optimal for only 3–4 days, CD34+ cell collection continues for approximately 10 days from the initiation of pheresis. A minority of pts have poor WBC recovery after VP-16 administration, and these pts tend to be those with refractory disease.
Association of Circulating CD34+ Cell Count with Liver Conditions.
Authors: Masuya Masahiro , Katayama Naoyuki , Ohishi Kohshi , Shiraki Katsuya , Uemoto Shinji , Nobori Tsutomu , Shiku Hiroshi 
Published: April 2020

Abstract
Hematopoietic stem and progenitor cells, which express CD34 antigen, circulate at a very low frequency in peripheral blood in steady state. CD34+ cells are highly mobilized after myeloablative chemotherapy or the administration of various cytokines such as granulocyte colony-stimulating factor and thrombopoietin (TPO). As TPO is mainly produced by the liver, liver conditions may be associated with hematopoiesis, especially thrombopoiesis. In fact, thrombocytopenia is common in patients with chronic liver diseases. To clarify the association of CD34+ cell mobilization with liver conditions, we examined the number of circulating CD34+ cells in 88 patients with various stages of hepatitis C virus-associated chronic liver diseases; 5 healthy carriers, 43 patients with chronic hepatitis (CH), 19 patients with liver cirrhosis (LC), and 21 patients with LC and hepatocellular carcinoma (HCC). Moreover, to assess the basal number of circulating CD34+ cells, 16 healthy controls were included. The evaluation of CD34+ cells has been carried out by flow cytometry, by applying conventional protocols. The number of circulating CD34+ cells was significantly diminished with progression of liver disease: healthy controls, 3.78 ± 3.93 cells/μL; healthy carrier, 1.89 ± 0.94 cells/μL; CH, 1.49 ± 1.41 cells/μL; LC, 0.66 ± 0.83 cells/μL; and LC with HCC, 0.58 ± 0.19 cells/μL. Next, we analyzed platelet count and number of circulating CD34+ cells before and after living donor liver transplantation (LDLT) in 12 patients who underwent LDLT for LC and/or HCC. A 4-fold increase in platelet level (from 68 x 109/L to 234 x 109/L) and a 5-fold increase in number of circulating CD34+ cells (from 0.78 cells/μL to 3.52 cells/μL) were observed after LDLT. These results suggest that not only thrombopoiesis but also mobilization of CD34+ cells from bone marrow into PB depends on liver conditions.
Bayesian Multilevel Evaluation of Stem Cell Cryopreservation at the First National Umbilical Cord Blood Bank from the Public Health Sector in Mexico.
Authors: Calderon-Garciduenas Eva D. , Sanchez-Guerrero Sergio A. , Fernandez-Torres Javier , Millan-Rocha Miriam , Marin-Lopez Antonio , Valiente-Banuet Leopoldo , Perez-Huizar Monica 
Published: April 2020

Abstract
Introduction. The umbilical cord stem cell bank was created in Mexico City in june 2003 due to the need to have access to pluripotential stem cells to cover the hematological and immunological pediatric needs. We have so far 300 units of umbilical stem cells available to the medical community. The bank has been designed with a completely automatic process and the standards are based in NETCORD-FAHCT outlines.
Objective. In the present study we made a balance of the evaluation of umbilical cord stem cell process including the maternal setting, the standarization of the methodology to obtain the stem cells, compared to other institutions around the world.
Material and methods. Bayesian analysis allow us to evaluate our procedures at the different levels. Bayesian networks are directed acyclic graphs (DAGs) where the nodes are random variables and certain independence assumptions hold.
Results. In table 1 we show the results of the first 300 units process with the automatic process. The arcs in a bayesian network specify the independence assumptions that must hold between the random variables and the global dependence of the total factors. Figure 1.
Conclusion. Through the bayesian analysis, we found a direct influence of the collected volume, the time between the collection and the procedure, and the maternal unit, with respect to the number of recovered cells, specifically with CD34+ the viable ones as well as the totals.
Figure 1. Bayesian Analysis between neonatal and process factors. Weight baby (PRN); sex (SRN); cord blood unit collected volume (ml); initial white cell (GBTI); total final white cell(GBTF); % total CD34+ ( PCD34T); % viable CD34+ (PCD34V); total CD43+ (CD34T); viable CD34+ (CD34VA); ginecology unit (UH); time hour (TH). Figure 1. Bayesian Analysis between neonatal and process factors. Weight baby (PRN); sex (SRN); cord blood unit collected volume (ml); initial white cell (GBTI); total final white cell(GBTF); % total CD34+ ( PCD34T); % viable CD34+ (PCD34V); total CD43+ (CD34T); viable CD34+ (CD34VA); ginecology unit (UH); time hour (TH).
Results of the first 300 units process with these technology
Initial nuclear cells/ml Collectionvolume Initial total nuclear cells % CD 34total Viable% CD 34 Recovery% Average 11.4 x 106/ml 102.8 ml 12.2 x108 0.32 0.31 80 Acceptance criterion 7–20 x 106 &gt; 75 ml &gt;8 x 108 0.1– 0.3 0.1– 0.3 &gt;60%
Clinical Results of a −80°C Simplified Cryo-Preservation Method.
Authors: Escoboza Jose R. Borbolla , Lopez-Hernandez Manuel A. , Garza Marcos E. , Baez Enrique , Trueba Elvira , Hernandez Roberto , DeDiego-FloresChapa Jose E. , Baltazar Severiano , Alvarado Martha , Villareal Gerardo , Gonzalez-Avante Mauricio C. , De Leon Rosa E. , Cedillo Jose L. , Penniecook Jason A. , Tovar Yara E. , Leon Maria I. , Ramirez-Assad Cecilia 
Published: April 2020

Abstract
Introduction: Autologus Stem Cell Transplant (ASCT) has found it’s place in the therapy of some common neoplastic diseases such as lymphoma, Hodgkin’s disease and multiple myeloma, and is still under research in a many other malignant and non-malignant diseases such as autoimmune disorders. One common problem for centers performing these procedures in the developing world is the remote possibility of acquiring the controlled-rate freezing and liquid Nitrogen storage apparatus.
Method: We have previously described a simple cryopreservation technique that does not require controlled-rate freezing nor liquid Nitrogen, and only utilizes common hospital equipment (Borbolla, et al. Blood 2000,96;11:1654a).
Results: Our group has performed 35 Autologus stem cell transplants in three different hospitals, using this cryopreservation method. All transplants were performed using peripheral blood stem cells obtained by apheresis. Mean CD34+ cell counts before cryopreservation were 2.72 X10^8 (SD:±1.07). Mean number of days between cryopreservation and transplant was 23.31 (SD:±15.66). Mean cell viability using Trypan blue method was 95%. One heavily treated and irradiated patient had engraftment failure. Mean number of days to neutrophil engraftment (ANC&gt;500 cells/μL) was 14.55 (SD:±4.54); and for platelet engraftment (Plt&gt;20,000/μL) was 23.18 (SD:±6.85).
Conclusion: Our cryopreservation method is comparable to other more expensive and cumbersome variants. Despite the fact that there is controversy surrounding some new indications for ASCT, some indications are already established and increase significantly the possibilities of a great number of patients to be cured from many malignant diseases such as NHL, Hodgkin’s disease, multiple myeloma, germ cell cancers and Ewing’s sarcoma, among others.
While there is no centralized data, the number of ASCT procedures performed in developing countries is known to be staggeringly low. The authors believe that behind these very low numbers, are economic issues and not professional capabilities of our health personnel. With the help of a Humanitarian Service Institution (Rotary International) we are currently working with a hospital in a Caribbean country to help them start performing ASCT using this cryopreservation method. Just as we did in our year 2000 meeting poster, we encourage Hematology departments in developing countries to get in touch with us (borbolla@itesm.mx) in order to arrange for this free technology transfer which will enable them to offer this procedure to their patients.
Nonmyeloablative Hematopoietic Stem Cell Transplantation for the Treatment of Systemic Sclerosis.
Authors: Shiratsuchi Motoaki , Motomura Seiichi , Ikuta Takuya , Ohno Hirofumi , Shiokawa Satoshi , Nishimura Junji 
Published: April 2020

Abstract
Systemic sclerosis (SSc) is an autoimmune disease which is characteristic of diffuse scleroderma and visceral organ fibrosis. Various kinds of therapies including immunosuppressive drugs have been attempted yet all proved ineffective. In order to reconstitute the immune system and cure SSc patients, we started a clinical trial of nonmyeloablative hematopoietic stem cell transplantation (NST) for the treatment of SSc. The inclusion criteria consisted of an age younger than 70 years, SSc as defined by Ministry of Health, Labor, and Welfare, a duration of less than 4 years since the diagnosis of SSc, a skin score of more than 15 points, and moderate organ failure. We herein describe the first patient to take part in this trial. A 52-year-old female suffered from scleroderma and we diagnosed to have SSc in 2000. Although she was treated with prednisolone, cyclophosphamide, penicilamine, and prostagrandin, the scleroderma was progressive (skin score 30 points) and the interstitial pneumonia also worsened (%VC 66.5 %, serum KL-6 level 1080 U/mL). In November 2003, we enrolled her as the first patient to undergo NST after her informed consent was obtained. After conditioning therapy consisting of low dose TBI (200 cGy) and fludarabine (30mg/m2, 3days), G-CSF-mobilized peripheral blood stem cells from an HLA- identical brother were infused.
Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. No blood transfusion was performed. Complete donor chimerism was obtained and has continued since 1 month after NST. The cyclosporine dosage was tapered gradually, and no apparent acute or chronic GVHD was seen. Three months after NST, the patient’s skin score improved to 19 points and a skin biopsy showed mild lymphocyte infiltration. At 8 months after NST, the area of interstitial pneumonia decreased according to the computed tomography findings and the %VC levels and serum KL-6 level were both found to have substantially improved (70.3 % and 746 U/mL, respectively). Although the duration after NST is still short, the clinical course for this patient is presently appears to be promising.
Preliminary Data on Once-Daily IV Busulfan at 3.2 mg/kg/day Indicate That It Is Safe as a Component of the Conditioning Regimen for Hematopoietic Stem Cell Transplantation.
Authors: Brunvand Mark W. , Rifkin Robert , Matous Jeffry V. , McSweeney Peter , Bearman Scott 
Published: April 2020

Abstract
Busulfan is a useful chemotherapy in many stem cell transplant regimens. Data support the use of buslfan in transplant patients, especially if they have had prior treatment with radiation therapy. The dose of the busulfan used in myloablative stem cell transplantation has traditionally been sixteen oral doses of 1mg/kg/dose. The oral dosing has been limited by unreliable oral absorption of busulfan tablets. Transplant related mortality and incidence of venocclusive disease are directly related to high peak levels of busulfan. Relapse has been associated with low peak levels of busulfan.
Recently, busulfan has become available as an IV preparation and preliminary data indicate that the peak busulfan levels are predictable via the IV administration route. The bulk of the data available on outcomes after transplantation using IV busulfan have used a QID dosing schedule of 0.8mg/kg/dose for sixteen doses. A smaller data base has utilized IV busulfan for stem cell transplantation as a single daily dose of 3.2mg/kg/day for 2–4 days. We present data on 19 patients treated at RMBMTP for hematological malignancies with the 3.2mg/kg/day dosing for stem cell transplantation. Sixteen of the 19 patients underwent allogeneic stem cell transplantation from related or unrelated donors from April 2003 to March 2004. Three patients underwent autologous stem cell transplants using the IV busulfan 3.2 mg/kg/day with cyclophosphamide 120 mg/kg total dose. None of the autologous transplant patients developed VOD or death during the first 100 days. 8 of the 16 patients undergoing allogeneic stem cell transplant have died: 4 patients died of relapsed disease, 2 died of GVHD, 1 patient died of sepsis, and 1 died of GVHD, relapse and a fungal infection. No autologous or allogeneic stem cell transplant patients died of regimen related toxicity.
This single daily dose regimen has been well tolerated with no increase in transplant related mortality or VOD. The 3.2 mg/kg/day dose appears adequate to assure engraftment of allogeneic stem cells. The patients presented had high-risk hematological malignancies. Although the followup is short, the OS survival of 100% for the autologous stem cell transplants and 50% for the allogeneic stem cell transplantation is consistent with published data for transplantation of high-risk hematological malignancies. There does not appear to be a higher transplant related mortality, GVHD or VOD rate for patients treated with busulfan at 3.2 mg/kg/day as a single dose.
ABO Incompatible Allogeneic Stem-Cell Transplantation Following Reduced-Intensity Conditioning: Close Association with Thrombotic Microangiopathy.
Authors: Worel Nina , Greinix Hildegard T. , Mitterbauer Margit , Schulenburg Axel , Hoecker Paul , Keil Felix , Kalhs Peter 
Published: April 2020

Abstract
Thrombotic microangiopathy (TM) is a severe complication of stem cell transplantation (SCT) associated with high mortality rates. One of the major risk factors for the development of TM is the toxic effect of high-dose chemo-radiotherapy, heavy pretreatment and the use of unrelated donors (URD) grafts. To reduce transplant related mortality in patients at risk non myeloablative conditioning regimens have been introduced.
We reviewed data on 83 consecutive patients given sibling (n=44) and URD (n=39) SCT after reduced intensity conditioning and graft versus host (GvHD) prophylaxis with CsA and mycophenolate mofetil with respect to occurence of TM. Diagnoses consisted of ALL (n=5), AML (n=31), CML (n=8), MDS (n=6), MM (n=11), NHL (n=17), renal cell cancer (n=4) and n. ovarii (n=1). A group of 565 patients undergoing high-dose conditioning followed by sibling (n=372) an URD (n=193) SCT served as control. The majority of these patients received CsA and MTX as GvHD prophylaxis. The diagnoses of TM was confirmed by renewed thrombocytopenia, coombs negative hemolysis, increased LDH-levels and fragmented red cells in peripheral blood smears. TM occured in 9 of 83 patients (11%) after RIC compared to 25 of 565 patients (4,4%) after high-dose conditioning, respectively. All but one patient in the RIC group received an ABO-incompatible stem cell graft (p&lt; 0.05). The median time of onset of TM was 62 days after SCT (range, 9 to 906 days) in this group. Donor source (sibling/URD) had no influence on the risk of developing TM (p=0.07). TM was associated with severe acute GvHD (n=2), chronic extensive GvHD (n=3), sepsis (proteus mirabilis n=1), herpes virus infection (n=1), severe hemolysis after minor ABO-incompatible SCT (n=1) and computed tomography approven atypical pneumonia (n=1). First line treatment consisted of withdrawal of cyclosporine A and plasmaexchange treatment (median exchange procedures 14, range 8 to 30). Overall, 5of 9 (55%) patients responded, 3 patients died due to GvHD and TM, 1 of multi- organ failure. One patient who responded to plasmaexchange died 1 year later due to relapse.
Posttransplant TM is a common severe complication and seems to increase after reduced-intensity conditioning. Fludarabin, a major constitute of RIC, is not reported to cause TM. How far GvHD-prophylaxis without MTX plays a role in the development of TM remains unclear. Of particular importance is that patients receiving ABO-incompatible stem cell grafts have a significant higher risk to develop TM after allogeneic SCT following reduced-intensity conditioning.
The Impact of Monitoring Epstein Barr Virus PCR in Paediatric Bone Marrow Transplant Patients: Can It Successfully Predict Outcome and Guide Intervention.
Authors: Greenfield Hayley M. , Gharib Maged I. , Turner Andrew J.L. , Coussons Mary L. , Will Andrew M. , Jarrett Ruth F. , Macheta Mario P. , Wynn Robert F. 
Published: April 2020

Abstract
Epstein Barr Virus (EBV) associated Lymphoproliferative Disease (LPD) is a complication of allogeneic haemopoietic stem cell tranplantation (HSCT). In certain groups (congenital immunodeficiency, unrelated and mismatched donor transplants, T cell depletion) the risk may be as high as 25% with significant morbidity and mortality. Strategies to predict such illlness and allow early intervention have therefore assumed importance.
We have routinely screened peripheral blood of paediatric, transplanted patients by quantitiative PCR. We report the results of such analysis of 28 successive patients and the EBV serial quantitation in 4 patients with EBV LPD. The median age at time of transplant was 6.5 years. 17 patients received an unrelated donor transplant and one patient received a haplo-identical transplant. The remainder (n=9) received a matched family donor transplant. 23 patients received either Alemtuzumab (n=19) or ATG (n=4). 13 patients had leukaemia, 5 had mucopolysaccharide syndrome, 4 for congential immune deficiency and 6 for non malignant haeamtological conditions.
9 (32%) patients showed no evidence of EBV reactivation using serial PCR monitoring. 10 patients had low level EBV reactivation as defined with a PCR log[copy number] &lt;4.5 copies/ml. 9 patients had a higher level of EBV reactivation. 2 patients had clinical EBV LPD and 2 additional LPD patients with LPD and with archived serial blood samples were also analysed.
All patients with clinical LPD fell in the high level reactivation group. All patients with high level reactivation had received either Alemtuzumab or ATG. Patients within this high level group with LPD had a higher PCR log value again than those without LPD (all patients with EBV LPD had levels &gt; 6, whilst the highest level without disease was 5.2). All 4 patients responded to therapy for EBV LPD, with a combination of rituximab, withdrawal of immune suppression or administration of donor lymphocytes - DLI). At higher EBV levels the quantitative PCR had increasing positive predictive value for clinical LPD.
We therefore conclude that EBV serial quantitative PCR is useful in discriminating those who will develop LPD from those that will not. Our data suggest that it is possible to use EBV PCR quantitation further to discriminate asymptomatic EBV reactivation that will resolve without therapy from EBV reactivation that will require intervention. This prevents over exposure of patients to treatments (rituximab, DLI, immune suppression withdrawal) with significant associated toxicity (prolonged B cell aplasia, graft versus host disease).
Pseudomembranous Colitis Following Autologous Stem Cell Transplantation.
Authors: Hickey Joanne M. , Tompkins Kirsty A. , Duggan Peter R. 
Published: April 2020

Abstract
Introduction: Diarrhea is a well established cause of morbidity post autologous stem cell transplantation (ASCT), occurring in 50–90% of patients - particularly in the first 20–30 days. Clostridium difficile toxin overproduction is a cause of diarrhea and can lead to serious morbidity and mortality. However, previous studies have demonstrated an incidence of C. difficile toxin positive diarrhea post ASCT of only 4%–7%. Our aims were to retrospectively identify the prevalence of C. difficile positive diarrhea in our population of ASCT patients in the first 30 days post transplant, and to retrospectively identify the prevalence of empiric antibiotic treatment for C. difficile diarrhea in these patients during the same time period.
Methods: All patients who received ASCT or immediate post transplant care at the General Hospital, Health Sciences Centre between April 1996 and March 2004 were identified and the results of any stool cultures sent in the first 30 days post transplant were recorded. In addition, the use of metronidazole during the same time period in any patient with a stool culture sent was identified.
Results: A total of 101 patients received ASCT or post transplant care between April 1996 and March 2004. Of these, 63 patients (62%) had a total of 75 stool cultures sent for culture and sensitivity as well as C. difficile toxin analysis. A total of 3 cultures from 2 patients (2%) were positive for C. difficile toxin. No other bacteria were isolated from stool samples. Of the 63 patients having C. difficile toxin analysis, 30 (48%) were treated with a course of metronidazole.
Conclusions: Our population of ASCT patients have similar rates of C. difficile positive diarrhea as previously studied populations. Despite the very low frequency of C. difficile diarrhea in our patients, there was a high prevalence of empiric antibiotic treatment with metronidazole. Based on this data, we feel that it is safe to forego empiric antibiotic treatment pending stool culture results and to use anti-diarrheal agents to achieve symptomatic relief in patients with diarrhea immediately post ASCT.