bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delivery of Autologous Bone Marrow Precursor Cells into the Spinal Cord Via Lumbar Puncture Technique in Patients with Spinal Cord Injury.
Authors: Callera Fernando 
Published: October 2019

Abstract
Alternative and less invasive routes for delivering hematopoietic stem cells in animals models of spinal cord injury (SCI) were described and the advantages of the percutaneous lumbar puncture (LP) technique have been recently demonstrated. (Bakshi A et al. 2004, Lepore AC et al. 2005) This proposition has not been described in humans. We therefore tested it by examining whether autologous bone marrow precursor cells can be delivered into the spinal cord via LP in patients with SCI. Seven patients with SCI (four had paraplegia and three had quadriplegia) were enrolled. The median age was 24 years and the mean duration of injury was 3 years. Patients received G-CSF (10microg/Kg) for five consecutive days and 100mL of bone marrow cells (BMC) were aspirated from the posterior iliac crest on day 6. Patients provided written informed consent. Mononuclear cells were separated by a Ficoll-Hypaque gradient, washed and resuspended in PBS. Flow cytometric enumeration of CD34+ cells was performed as previously described. (Gratama JW et al. 2001) Transplantation was performed 4 hours after bone marrow aspiration. CSF samples were collected before and seven days after the transplantation. For each patient, 15x106 mononuclear cells were injected via LP; the median number of CD34+ cells was 2.5x105 (1.8–5.0x105). Cell viability before transplantation was superior to 90% in all samples. Patients had no adverse events. CSF examination was normal in both times. Bone marrow precursor cells are clinically attractive because they can be obtained in patients at bedside raising the possibility of an autologous model of cell therapy for SCI. However, the potential therapeutic effects of these cells for SCI are poorly understood. What is the optimal CD34+ cell dosage? Will multiple doses of CD34+ cells be more efficacious? Is CD34+ the most appropriate BMC subset? Will BMC subsets combinations be more efficacious? The follow-up of our patients will probably provide some information. The absence of cells in CSF samples obtained after seven days is also intriguing. Although high speculative, a possible explanation is that cells home toward the injured spinal cord. All these issues need to be resolved in carefully designed experiments. Finally, our study demonstrated the possibility of delivering autologous bone marrow precursor cells via LP in patients with SCI. This procedure is feasible, safe and well-tolerated in humans. The potential therapeutic effects of these cells for SCI remain to be elucidated.
Effect of Plasma Exchange on Acute Graft Versus Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Cai Zhen , Zhen Gaofeng , He Huang , Li Li , Xie Wanzuo , Shi Jimin , He Jingsong , Lin Maofang 
Published: October 2019

Abstract
Acute graft versus host disease (aGVHD) is one of the major complications after allogenic hematopoietic stem cell transplantation (allo-HSCT) with high morbidity and mortality. Myeloablative treatment and the application of immuno-suppressive drugs (such as CsA, FK506 and MMF) are the main methods of prevention and cure. As it can separate pathogen, toxin, antigen and antibody from the plasma, plasma exchange (PE) is widely used to prevent and treat autoimmune disease, the rejection of stereo-organ transplantation, acute intoxication, severe hepatitis and acute hepatic failure. But up to now, PE is still rarely used to treat aGVHD. Here we present our review of cases where PE was accepted as a treatment modality for refractory aGVHD at our center. From October 2001 to March 2004, eight patients underwent PE due to aGVHD after Allo-HSCT with little response to immuno-suppressive drugs. Four of them had initial diagnosis of chronic myeloid leukemia (CML), and the other four were diagnosed with acute myeloid leukemia M2a,M4,M5,M6 respectively. The age of patients was from 14 to 38 years old (median 31). The “BuCY2” scheme (MMF+MTX+CsA) was used to prevent GVHD. After transplantation, all of them developed II-IV degree aGVHD. Each of them underwent 1 or 2 times of PE, with a volume ranging from 2500ml to 4000ml for a single PE. The overall response rate is favorable (fever, tetter, bellyache, diarrhea and liver function were ameliorated with various degree), with 3 cases (37.5%) having overt response, which was especially seen in patients with intestinal tract symptoms. Also, the level of TNF-α in the serum of the patients after plasma exchange was lower than that of the patients before plasma exchange(P=0.018). These results suggested that intestinal tract plays an important role in magnifying illness and “cytokine storm”, and TNF-α is the pivotal cytokine in the Intestinal tract GVHD. And the non-immunity aspects of GVHD can be described as an inflammatory process. PE may block this kind of inflammation by decreasing the cytokines, especially the level of TNF-α in serum after PE. Thus, the combination of PE and immuno-suppressive drugs is a rather good therapeutic method to control the symptoms of refractory aGVHD after allo-HSCT.
Evaluation of a New Program for PBSC Collection with Fresenius COM.TEC Blood Cell Separator.
Authors: Del Fante Claudia , Perotti Cesare , Viarengo Gianluca , Bergamaschi Paola , Marchesi Andrea , Parisi Cristina , Salvanesci Laura 
Published: October 2019

Abstract
Introduction: At moment PBSC collections can be performed using semiautomated or automated cell separator devices. The collection with semiautomated methods implies an augmented working load for the dedicated personnel and is strongly influenced by the operator. On the contrary, the automated methods offer the advantages of a diminuished working load for the dedicated personnel and an high standardization of the collection procedure. Herein we report our experience on 60 PBSC collections employing the new automated COM.TEC Fresenius autoMNC program that provides the possibility to predict the total number of CD34+ cells collected basing on the CD34+ cell count (x μL) pre-leukapheresis (LKF) collection in peripheral blood.
Materials and Methods: 39 patients affected with various onchohematological diseases and10 healty donors were mobilized with chemotherapy + G-CSF or G-CSF alone, respectively, and subsequently underwent LKF collection for auto or allotransplant. According to our internal protocol 60 LKF collections were performed starting with a CD34+ cell count in peripheral blood at least of 20/μL. Net weight of the final LKF product and its CD34+ cell content were evaluated at the end of each PBSC collection procedure and then compared to the expected data calculated by the cell separator device. Moreover a post collection peripheral blood Plt count was evaluated for each patient/donor.
Results: The mean starting WBC count was 25.86x103/μL (range: 4–82.3), Plt count was 151.38x103/μL (20–395), CD34+ cells was 96.63/μL (20–332). The mean WBC and CD34+ cells in the LKF collection were 224.78x103/μL (20.71–425.3) and 565.45x106 (59.3–1609.3), respectively. The mean volume of the LKF collection was 237.28 ml (120–503). The mean estimated CD34+ cell content was 498.37x106 while the real mean CD34+ LKF cell content was 623.32x106. The mean CD34+ cell collection efficiency was 91% (66–126). Finally, the mean post procedure Plt count in patient/donor was 77.91x103/μL (12–164).
Conclusions: The automatized PBSC collection with the new program COM.TEC Fresenius autoMNC demonstrated a very high CD34+ cell collection efficiency. Moreover the possibility to predict the CD34+ cell yield permits an optimal management of the LKF collection, reducing the number of procedures per patient/donor. The difference observed between the mean estimated CD34+ cells and the real CD34+ cell content may be due to the intra-procedure stem cell mobilization phenomenon. Finally, this new automatized collection system demonstrated to limit the collection related thrombocytopenia either in patient or in donor.
Cellular Composition of Allogeneic and Autologous PBPC Grafts and Patient Engraftment.
Authors: Barbosa Isabel L. , Benevides Patricia A. , Sousa Claudia C. , Machado Lopes Sergio B. , Tavares Ana R. , Campilho Fernando , Campos Antonio , Vaz Carlos P. , Sousa Susana R. , Pimentel Pedro , Carvalhais Alzira 
Published: October 2019

Abstract
We studied the influence of graft populations on the hematological recovery of PBPC transplants. The data shown is a retrospective study of 36 patients (median age 41, range 16–67) who underwent allogeneic transplant from HLA-matched siblings and 29 patients (median age 25, range 20–68) who underwent autologous PBPC transplants between June 2002 and July 2005. The cell populations studied were: total nucleated cells (TNC), CD34+ cells, T cells (CD3+) and NK cells (CD3−/CD56+). The hematological engraftment was evaluated by the following parameters: time to absolute neutrophil count (ANC)>0.5x109/L, platelets>20x109/L, absolute lymphocyte count (ALC)>0.5x109/L and ALC at day +15. The median cell doses infused in patients are summarised in Table 1
Table 1- PBPC cell population infused per Kg of patient body weight TNC x 108 CD34+ cells x 106 T cells x 108 NK cells x 106 *median **range Allogeneic 12.8 * 7.5 3.2 36.8 3.6 – 30.7 ** 3.4 – 10.5 0.7 – 9.8 4.2 – 136.6 Autologous 12 3.26 3.5 29 4.1– 51.0 2.2 – 7.0 0.1– 0.4 7.4 – 351
Spearman correlation analysis showed for the allogeneic PBPC grafts, correlation between TNC and NK cells collected (p=0.002), whereas for the autologous grafts there was correlation between TNC and NK cells (p=0.000) and CD34+ cells (p=0.004) collected.
To asses the importance of cell dose infused in the hematologic engraftment of the two patient groups, neutrophil, platelet and lymphocyte recovery was determined (Table 2).
Table 2- Patient engraftment Day to ANC>0.5x109/L Day to platelets>0.2x109/L Day to ALC>0.5x109/L ALC day +15 cell/μl *median **range Allogeneic 11 * 12 11 715 8 – 15 ** 8 – 29 2 – 14 190 – 4670 Autologous 11 11 12 1178 7 – 13 8 – 18 10 – 21 230 – 4410
For both groups of patients, engraftment occurred within the expected time and ALC day +15 cell/μl was different (median 715 cell/μl and 1178 cell/μl for allogeneic and autotransplanted patients respectively).
For the allogeneic transplanted patients, Spearman correlation analysis showed that the dose of NK cells infused was significantly correlated with ALC at day +15 (p=0.021). There was also correlation between the time to platelets and ANC engraftment (p=0.008) and time to platelets engraftment and ALC at day +15 (p=0.046).
For the autologous patients there was no correlation between cell populations of the grafts and the hematologic engraftment. Our data provide evidence that in allogeneic transplants the NK dose influences early ALC recovery. However, it is important to continue this study to balance the importance of cell population doses both in allogeneic and autologous transplants.
Intravenous (i.v.) or Oral (os) Busulphan (BUS) in Children Prior to Autologous (Auto) or Allogeneic (Allo) Stem Cell Transplantation (SCT): Pharmacokinetics (PK), Toxicity and Compliance.
Authors: Prete Arcangelo , Bartoli Antonella , Castellini Claudia , Rondelli Roberto , Masetti Riccardo , Pession Andrea , Regazzi-Bonora Mario 
Published: October 2019

Abstract
Introduction: High dose BUS is an important component of pre-transplant conditioning regimen in children with advanced hematological malignancies or solid tumor undergoing allogeneic or autologous stem cell transplantation. Variable intra and inter systemic drug exposure as measured by area under curve (AUC), can occurs following oral administration and may be influenced by age, body weight, absorption variability and, particularly in infants, by difficulties to assumption.
Aims: to compare the PK, the toxicity and the compliance of iv versus oral BUS administration in children undergoing pre-transplant conditioning regimen.
Patients and methods: 12 patients (pts), median age 37 (7–177) mos, body weight 6–69 kg, affected by AML (3), ALL (4), NB (3), Thalassemia (2), undergoing to autoSCT (4) or alloSCT (8), received as preparative regimen oral BUS at the dose of 1 mg/kg every 6 hours for a total of 16 doses (6 pts, GR1), or 2 hours i.v. infusion of BUS at the dose of 0.8 mg/kg every 6 hours for a total of 16 doses (6 pts, GR2). Four out of 6 GR1 pts (7–30 mos) had a nasogastric radiolus to allow BUS assumption. PK studies were performed after the first dose of BUS on blood samples collected at 0, 1, 2, 4, 6 hours after first administration in GR1 and at 0, 2, 3, 4, 6 hours from the beginning of the first infusion in GR2. BUS plasma level was determined by high-performance liquid chromatography as described by Henner et al.
Results: GR were comparable as for age (p= 0.07) and body weight (p= 0.14). Comparison of PK median values (+SD) in GR1 versus GR2 didn’t highlighted statistically significant differences as for AUC (p= 0.20) and for T1/2 (p= 0.11). Peak concentration was higher in GR2 (p= 0.058). Bioavailability was 0.61. Variation factor (VF%) were constantly low in GR2. No pt showed acute or late treatment-related extra-medullary toxicity and all pts developed a rapid and sustained hematopoietic recovery.
Conclusions: systemic exposure to 0.8 mg/kg iv BUS versus 1 mg/kg oral BUS is overlapping. Low VF% highlight a smaller interpatient variability in exposure compared to oral BUS. Moreover allows to avoid assumption difficulties in younger pts.
Detection of Cytomegalovirus Specific Cytotoxic T Lymphocyte in Allogeneic Hematopoietic Stem Cell Transplant Recipients.
Authors: Sun Jing , Huang Tao , Yi Zhengshan , Liu Qifa , Xu Dan , Ye Changxiong , Meng Fanyi 
Published: October 2019

Abstract
T lymphocyte reconstitution of allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients was limited in the counts of T lymphocyte subgroup or T receptor recombination exclusion circles (TRECs). The function of T lymphocyte reconstitution is more important. Cytomegalovirus (CMV)-specific CD8 cytotoxic T lymphocytes (CTL) have the predominant role in protection against CMV. HLA-peptide Pentamer (Pentamer) and enzyme-linked immunospot (ELISPOT) have allowed direct visualization of CMV specific CTL. Both assays are highly specific and sensitive and had been applied to other areas.
29 patients with ANLL (9 cases), ALL (4 cases), CML (14 cases) and NHL (2 cases) were eligible for study. All patients received alloHSCT with 19 sibling-donors and 10 unrelative-donors in follow-up median 25 months, median age is 29 (range 11–52) and male/female is 16/13. CMV-IgG serologic status: 30 pairs were donor negative /recipient negative and 2 pairs were donor positive /recipient negative. The blood samples were collected from alloHSCT recipients with HLA-A2 at pre-HSCT and at 3, 6, 9, 12 month after alloHSCT. Detection of CMV-specific CTL in CD8 using HLA-A2-pp65495–503 pentamer complexes was performed with the fluorescence activated cell-sorter flow cytometer. IFN-gamma ELISPOT assay was performed in 96 bottomed-well microplates in which added 4×105 MNC /well and incubated with CMV pp65 (10ug/ml). T lymphocyte subgroup reconstitution was detected at same time.
24/29 (82.8%) recipients suffered CMV antigenemia once or more times after alloHSCT. The median time of onset CMV antigenemia is at 78d (range 31–476d) after alloHSCT. The counts of HLA-A2-pp65-specific CTL were continuously increased in 12 month after alloHSCT. The counts of HLA-A2-pp65-specific CTL at 3 month after alloHSCT were lower than at pre-HSCT and 6 month (p=0.000), 9 month (p=0.022), 12 month (p=0.013) post-HSCT obviously. The numbers of spots within 6 month post-HSCT detected for CMV-specific CTL by IFN-gamma ELISPOT was lower than that after 6 month post-HSCT (p=0.004). It mean that CMV-specific CTL grew more quick from 3–6 month than after 6 month. But analysis the reconstitution of CMV-specific CTL in every recipients were showed increasing or decreasing individually, which affected only by aGVHD (r=0.725, p=0.042) and cGVHD (r=0.843, p=0.036).
Benefit of Early Switch to Liposomal Amphotericin B in Patients with Amphotericin B Deoxycholate-Induced Nephrotoxicity Versus Late Switch.
Authors: Isnard Françoise , Laporte Jean P. , Chevallier Patrice , Pigneux Arnaud , Tilleul Patrick , Lafuma Antoine , Mahi Lamine , Deray Gilbert 
Published: October 2019

Abstract
Amphotericin B deoxycholate (AmBd) nephrotoxicity increases morbidity and mortality however there are no clear guidelines when to switch to liposomal amphotericin B (LAB). We evaluated the benefit of Early Switch (ES) to LAB in patients with AmBd compared to Late Switch (LS).
In this prospective randomized multicenter trial, standard AmBd 1mg/kg/d is initiated in neutropenic patients with haematological malignancies as empirical antifungal therapy (V0). If serum creatinine (SCr) increased of 30% from baseline V0, they were randomized (V1) to LAB 3mg/kg/d (ES) or to pursue AmBd (no switch). In a second step, AmBd treated patients were switched to LAB (LS) if their serum creatinine doubled from V0 or reached a value ≥ 170 μmol/l up to the end of treatment (V2). The analysis included 29 patients [ES=14; no switch=15 with late switch for 9 of them]. Demographics and mean duration of AmBd treatment prior randomization were similar in both groups. Early switch allowed a statistically significant (p=0.04) decrease in serum creatinine (−3.1%) from V1 to V2 as compared with a mean increase of +16.2% in the LS + no switch groups and also demonstrated a significant (p=0.04) increase (+5.1%) in creatinine clearance (ml/min) compared to a decrease (−10.3%) in the LS + no switch groups. This randomised trial demonstrated that an early switch to LAB improves and preserves renal function compared with late switch. Significant reduction of drug-induced nephrotoxicity may impact positively clinical outcomes and provide patients with greater options for chemotherapy treatments.
Evolution of renal function Criteria (mean) ES LS + no switch p SCr at V0 (μmol/l) 67.2 67.3 NS SCr at V1 (μmol/l) 109.0 108.2 NS SCr at V2 (μmol/l) 104.5 123.1 0.08 Evolution of SCr V1 - V2 (%) − 3.1 + 16.2 0.04 Evolution of ClCr V1 - V2 (%) + 5.1 − 10.3 0.04
Results of Non Myeloablative Geno-Identical Transplants in Adults with AML: Influence of the Doses of Peripheral Stem Cells Infused (on Behalf of the Acute Leukemia Working Party of EBMT).
Authors: Gorin Norbert C. , Labopin Myriam , Frassoni Francesco , Rocha Vanderson 
Published: October 2019

Abstract
In adult patients with acute myelocytic leukaemia receiving a conventional myeloablative allogeneic stem cell transplantation, several studies have shown that the higher the doses of hemopoietic stem cells infused, the better the outcome, with a lower transplant related mortality (TRM), a lower relapse incidence (RI) and a better leukaemia free survival (LFS). We wondered whether this observation was transposable in the context of non myeloablative transplants with peripheral blood stem cells where graft versus leukaemia (GVL) is the only anti tumor mechanism generated by the procedure in an effort to control the disease. In this particular situation, one might postulate that increasing the doses of peripheral blood T cells infused in an effort to increase GVL might increase GVHD and TRM. Further, one might speculate on the existence of an optimal range of stem cell and T cell doses to infuse. From January 1998 to December 2003, 253 patients with de novo AML, who received a non myelo ablative transplant with peripheral blood from a genoidentical donor, were reported to the ALWP registry with the dose of cells infused available. The sex ratio of the patients was 56% male /female. Patient age was 55 years (18–72). 141 patients were transplanted in first remission (CR1), 47 in second remission (CR2) and 65 patients had refractory disease or were transplanted in relapse. The pretransplant reduced intensity regimens were variable but 91% included fludarabin and Total body irradiation (TBI) was used in 23% of the patients at a dose<5 Gy. The median dose infused was 9.09 x 108 nucleated cells/kg (1.23–24). The follow up was 17 months (2–67). The LFS of the total population at 2 years was 41± 4%. For patients transplanted in CR1, CR2 and more advanced disease, the LFS were 49 ± 6%, 50± 8% and 23± 6% and the RI 37±4%, 34±7% and 69±6% respectively. Patients transplanted in CR had a significantly lower RI (p< 10−4, RR= 0.43 (0.29–0.65)) and better LFS (p< 10−5, RR=0.49 (0.35–0.7)) than those transplanted with advanced disease. Patients receiving doses of peripheral blood nucleated cells above the median had a trend towards a lower RI (42±5% versus 47±4%; p=0.06, RR=0.67 (0.45–1.02)) and a significantly higher LFS (46±5% versus 37±5%; p=0.04, RR= 0.68 (0.48–0.98)). Higher doses of nucleated cells were associated to a higher incidence of chronic GVHD (59 ± 5% versus 41 ± 5%, p=0.01, RR= 1.75 (1.12–2.73)). Interestingly, the use of TBI was associated to a higher RI (51± 8% versus 43±4%; p=0.02, RR=1.8 (1.1–2.9)). There was no relationship with the doses expressed in CD34+ cells infused. We conclude that in the context of non myeloablative transplants for adult AML, infusing higher doses of PB nucleated cells is beneficial to the patients.
Radiotherapy Post Autologous Stem Cell Transplantation in Patients with Lymphoma Not Reached Complete Response.
Authors: Chang Naibai , Gu Xichun , Zhu Ling , Wei Jianping , Zhao Shengming , Jin Liqing 
Published: October 2019

Abstract
Objective: Anthracycline-based chemotherapy induces 50%–70% of CR in patients with lymphoma, but only 30%–40% of long-term disease-free survival. Salvage chemotherapy with autologous stem cell rescue is required in patients with aggressive disease or never achieve CR with conventional chemotherapy,but the relapsed rate is still high. The purpose of this study was to evaluate radiotherapy post autologous stem cell transplantation in such group of patients.
Methods: 15 patients who underwent autologous stem cell transplantation during 1992–1998 were enrolled in this study. Conditioning regimen was CBV (cyclophosphomide + carmustine + etoposide). Radiotherapy was started on day +50(31–90). All patients were followed up until January 2005. Kaplan-Mier survival analysis was made by using SPSS10.0 software.
Results: There were 14 patients with non-Hodgkin lymphoma and 1 with Hodgkin disease enrolled. Male:female=11:4. Median age was 40 (30–64). At least 6 cycles of induction chemotherapy were given before transplantation. There were 3 patients in progression disease, 1 in stable disease, and 11 in partial remission before transplantation. Three patients received total lymph node irradiation (TLI). Seven patients received TBI(200cGY)+involved field irradiation therapy(IFIT). Five were treated with IFIT. All patients acheaved complete response(including 1 CRu) after radiotherapy. Three patients relapsed. One patient treated with TBI+IFIT relapsed at 6 months later. Two patients treated with IFIT relapsed at 8 and 36 months later respectively. The mean disease-free survival and overall survival were 10.84(SD1.37,95%CI) years and 11.89(SD1.35,95%CI) years respectively. The estimatrd 10-year disease-free survival and Overall survival were both 73%. One patient developed AML at 86 month. Grade III–IV hematologic toxicity was seen in 2 patients.
Conclusions: Post ASCT radiotherapy is safe and tolerated. Relaps rate is low. Patients who received TLI or TBI+IFIT seem to have better outcome than that received IFIT only.