bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iron Overload in Acute Myelogenous Leukemia after Bone Marrow Transplantation.
Authors: Pakbaz Zahra , Fischer Roland , Noonan Nancy , Shiota Sherrie , Harmatz Paul , Vichinsky Elliott , Walters Mark C. 
Published: October 2019

Abstract
Children with acute leukemias typically receive RBC transfusions during the course of their treatment. However, the severity and significance of transfusional iron overload is not known in this patient population. Earlier, we reported elevated serum ferritin (SF) in 5 patients with AML who received HLA-identical sibling bone marrow transplantation (BMT). However, SF has a wide predictive interval for liver iron concentration (LIC) in thalassemia and sickle cell disease and the current recommendation is to measure LIC to estimate total body iron burden. Further exploration of the SF-to-LIC ratio (SF/LIC) to investigate the relationship between SF and LIC has shown ratio differences by specific disease (SCD, thalassemia, genetic hemochromatosis), transfusion status and use of chelation. The reasons for these differences are not presently known. In this study LIC was measured within 2 weeks of serum ferritin (SF), in 8 AML patients after transplantation, to explore the significance of the elevated SF and to determine the range and character of the SF/LIC ratio after BMT for AML. LIC was measured (1–4 year after BMT) by a low temperature SQUID biosusceptometer system (Ferritometer®) under the standardized Hamburg-Torino-Oakland protocol. The range for LIC in healthy individuals measured by SQUID is 90–340 mg/g wet weight. The median serum ferritin was 1227 (582–1723) μg/l and the median LIC was 1284 (751–1612) mg/g wet weight or approximately 4 times greater than the upper limit of normal. ALT was measured in 4 patients of which 2 were mildly elevated. Neither LIC nor SF changed over the interval of follow-up extending to 3 years in 2 patients (aged 11.5y and 14.5 y) who returned annually for LIC measurements. The ratio of SF/LIC ranged from 0.5 to 1.4 (median: 0.9) in the patients with AML. This compares to ratios of 1.2 (0.6–2.6) in regularly transfused sickle cell disease patients (n=45), 0.87 (0.23–2.7) in transfusion dependent thalassemia patients and 0.32 (0.05–0.57) in transfusion independent thalassemia patients. These preliminary observations suggest that children with acute leukemias who undergo bone marrow transplantation develop significant transfusion related iron accumulation. Additional investigation should be undertaken to determine if AML patients would benefit from iron reduction therapy by phlebotomy after BMT.
Transplantation for 37cases of Refractory Acute Lymphocytic Leukemia.
Authors: Ma Xiao , Wu De Pei , Su Ai - Ning 
Published: October 2019

Abstract
Objective: To explore the efficiency and toxicity of allo-geneic hematopoietic stem cell transplantation (Allo-HSCT) for refractory acute lymphocytic leukemia.
Patients and Methods: Thirty-seven patients of refractory acute lymphocytic leukemia received allo-geneic hematopoietic stem cell transplantation containing 18/37 cases from HLA-identical siblings donors, 8/37 cases from HLA-identical unrelated donors and 11/37 cases from haplo-identical donors of the mother. The tolerance, transplant related complications, survival rate were observed and analyzed. A myeloablative conditioning regimen included TBI and Cyclophosphamide. Cyclosporine A combined MTX were used to prevent graft versus host disease (GVHD) and G-CSF was administered after Allo-HSCT.
Result: All 37 patients tolerated the therapy well and Slight or moderate mucositis was happened. Nineteen patients had light abnormal liver function and two had renal disfunction lightly, one patient had epilepsy during the therapy. Fatal infection complications were occurred in 6 patients (including idiopathic pneumonia in 2 patients). Severe acute GVHD was presented in 5 patients. Chronic GVHD was occurred in 16 patients. Hemorrhagic cystitis was happened in 1 patient, and 9 patients relapsed again after transplantation. Venoocclusive liver disease, host versus graft disease, substantia alba encephalopathy, fatal hemorrhage, secondary tumor and dysphrenia were not occured. Hematopoietic reconstitution obtained on days 12 to 25(day 17 on average). In the follow-up duration of 9 to 55 months (34 months of mid position), most of these patients had a complete chimerical state. Twenty of 37 patients are alive (54.1%). Disease free survival is 48.6%.
Conclusion: Allo-HSCT is an effective therapy in the treatment of refractory acute lymphocytic leukemia. Relapse again after transplantation, fatal infection, and severe acute GVHD are the main reasons of failure.
A Low Intensity Protocol of Fludarabine, Busulfan and Cyclophosphamide Reduces Toxicity without Compromising Engraftment in Children Undergoing Allogeneic Bone Marrow Transplantation for Beta Thalassaemia Major.
Authors: George Biju , Mathews Vikram , Viswabandhya Auro , Chandy Mammen , Srivastava Alok 
Published: October 2019

Abstract
Busulfan (Bu) and Cyclophosphamide (Cy) based conditioning protocols are associated with significant morbidity and mortality in Class III (Pesaro classification) patients with beta thalassaemia major undergoing allogeneic stem cell transplantation. After IRB clearance and informed consent, we have developed a new low intensity protocol using fludarabine 30mg/m2/day for 5 days (Day - 15 to Day -11), busulfan 14 mg/kg over 4 days (Day -10 to -7) and cyclophosphamide 160 mg/kg over 4 days (Days -5 to -2). Graft versus host disease (GVHD) prophylaxis consisted of cyclosporine (5mg/kg/day) in 2 divided doses starting Day -4 and methotrexate 10 mg/m2 on Day +1 followed by 7 mg/m2 on Day +3, +6 and +11. Between January and July 2006, 14 children with Class II (n = 5) or Class III (n = 9) beta thalassaemia major were treated with this protocol. The median age was 10 years (range: 3 – 13). All patients had HLA matched related donors [sibling (13) or family (1)] with a median age of 4 years (range: 2 – 35). Ten (71%) of these transplants were sex mismatched. One patient expired on Day +10 due to an intracranial bleed while 13 (92.8%) engrafted. The median time to ANC > 500/mm3 was 17 days (range: 14–20) and platelet count > 20,000/mm3 was 25 days (range: 11 – 49). One patient had graft rejection. Two patients (14%) had grade 2 hemorrhagic cystitis and veno-occlusive disease each that resolved with conservative management. None of the patients had grade IV mucositis while 1 patient has a grade II gastro-intestinal bleed lasting 2 days that resolved with transfusion support. Acute GVHD (grade I – II) was seen in 5 patients (41.6%) and resolved in all with corticosteroids. Febrile neutropenia occurred in all but only 2 patients had a documented infection. The day 30 chimerism was complete in 10 patients (77%), > 90% donor chimerism in 2 (15.3%) with rejection in 1 patient (7.7%). At a median follow up of 4 months (range: 1–6), the overall survival (OS) is 92.8% and the disease free survival is 85.7%. We compared engraftment and toxicity with 167 patients with Class II and III Thalasssaemia treated with Bu16/Cy200 (n=116) or Bu600 mg/m2/ Cy200 (n=51) and found that the engraftment was not delayed but there was significant reduction in VOD (14% vs 53%; p=0.005) and gastrointestinal bleeding (7% vs 39%; p=0.021) with this new protocol.
Conclusion: A low intensity protocol incorporating reduced doses of busulfan and cyclophosphamide in combination with fludarabine is associated with reduced toxicity and improved survival in children undergoing allogeneic BMT for Thalassaemia. Long term follow up is required to assess late toxicity and graft function.
Comparative Analysis of Matched Related Donor (MRD) and Matched Unrelated Donor (MUD) Hematopoietic Stem Cell Transplantation in Treatment of Patients with Chronic Myeloid Leukemia.
Authors: Styczynski Jan , Gil Lidia , Zaucha Jan Maciej , Czyz Anna , Bieniaszewska Maria , Wysocki Mariusz , Hellmann Andrzej , Komarnicki Mieczyslaw 
Published: October 2019

Abstract
Allogeneic HSCT offers a long term remission for CML patients. We compared results of MRD and MUD HSCT in 82 pts with CML, treated between 1999 and 2005. In MRD group, 61 pts (median age 39, range 8–54 yrs) were conditioned with BuCy2 regimen. 50 pts were in chronic, 7 in acceleration and 4 in 2nd chronic phase. 38 pts received peripheral blood (PB) and 23 bone marrow (BM) cells. Prophylaxis of graft versus host disease (GVHD) consisted of cyclosporin (CsA) and methotrexate (MTX). 21 pts (median age 31, range 11–51 yrs) transplanted from MUD were conditioned with BuCy2 (n=13) or TBI-based regimen (n=8). All MUD patients received thymoglobulin. This group comprised of 14 pts in chronic and 3 with accelerated, 1 in blastic phase and 3 in 2nd chronic phase. 10 pts received PB and 11 BM cells. CsA+MTX was given as GVHD prophylaxis. MUD group differed from MRD group by following factors: younger age (p=0.020), longer time to HSCT (p<0.001), use of imatinib before HSCT (p=0.039), and higher pre-transplant (Gratwohl) risk score (p<0.001). Results: Hematopoietic recovery occurred in all pts in MRD group, and in 95% in MUD group. Probability of overall survival for all pts was OS=0.72±0.05. 42 pts developed acute GVHD >2 grade (26 in MFD and 16 in MUD) and 27 pts extensive chronic GVHD (23 in MFD and 4 in MUD). Mean survival, estimated 5-yrs OS, probabilities of GVHD incidence, relapse and non-relapse mortality (Kaplan-Meier method) with respect to transplantation method, are shown in Table.
TABLE: Results of transplantation in MRD and MUD groups Probability MRD-HSCT (n=61) MUD-HSCT (n=21) P Mean survival (years) 5.6 (95%CI=4.9–6.3) 3.6 (95%CI=2.4–4.7) 0.0020 Overall survival 0.75±0.05 0.60±0.11 0.0759 Relapse incidence 0.12±0.04 0.25±0.12 0.1950 Non-relapse mortality 0.22±0.05 0.41±0.11 0.0311 Acute GVHD≥2 0.45±0.06 0.79±0.10 0.0175 Chronic extensive GVHD 0.47±0.07 (n=57) 0.35±0.14 (n=15) 0.3103
Factors predicting negative outcome by multivariate analysis were: acute GVHD≥2 (p=0.0097, HR=1.81, 95%CI=1.12−2.94), and pre-transplant risk score >2 (p=0.0280, HR=1.61, 95%CI=1.06−2.00). MUD-HSCT or use of imatinib before HSCT did not predict for OS. Conclusion: In the era of tyrosine kinase inhibitors, results of MRD− and MUD-HSCT show that HSCT still remains an important therapeutic option for CML patients.
The Long Term Survival of the Patients with Refractory Leukemia Treated by Related HLA Haploidentical Stem Cells Transplantation.
Authors: Wu Bingyi , Kunyuan Guo , Hu Haiyan , Yang Yuliang , Deng Lan 
Published: October 2019

Abstract
To assess the Long Term Survival of patients with refractory leukemia treated by HLA haploidentical stem cells transplantation. We analysed the outcomes of 35 patients with refractory leukemia who underwent HLA haploidentical peripheral blood stem cells transplantation from August, 1998 to December, 2005. Thirty five patients with refractory leukemia including 16 cases of acute non-lymphocytes leukemia, 11 cases of acute lymphocytes leukemia, 7 cases of chronic myeloid leukemia and 1 case of IV phase of non-Hodgkin lymphoma underwent HLA haploidentical peripheral blood stem cells transplantation. The median age was 25 years old (3– 52 years old). Fourteen patients received stem cells from parent donors, four from daughter and one from son donor, the others from sibling donors. Three HLA locus mismatched in thirteen cases, Two HLA locus mismatched donors in fifteen cases, One HLA locus mismatched in six cases. The conditioning regime consisted of fludara (25mg/m2 ×5d), busufan (4mg/kg ×4d) and cyclophsphamide(60mg/kg ×2d). Rabbit anti-human lymphocyte globulin (5mg/kg ×5d) was added in some patients in conditioning regime. A mean of 5.0 × 108/kg (2.97×108/kg-8.0×108/kg) mono-nucleated cells was grafted. The mean CD34+ cells number was 5.5 ×106/Kg (3–6.5 ×106/kg). Ten patients received 400ml donor derived bone marrow beside donor peripheral stem cells. Thirty-two patients were successfully grafted and one failed to graft and one died with severe fung infection at day 2, and one died from severe veno-occlusive disease at day 28. The mean time of white cell count more than 1×109/L was 14(11–18) days and platelet count more than 20×109/L was 15 (11–18) days. All patients got complete remission in 32 successful grafted patients. Severe acute graft versus host disease occurred in seven patients, and four died. Eight patients suffered from chronic graft versus host disease. Eight patients relapsed and died. The median relapse time was 10 (3–24) months. Fourteen patients are still disease free survival. The three years disease free survival rate was 40%. We concluded from our observation that HLA haploidentical peripheral blood stem cells transplantation may be an effective therapy for refractory leukemia. Some patients with refractory leukemia treated by HLA haploidentical stem cells transplantation could survive with free diseases; Though graft versus leukemia effect may be strong in HLA haploidentical blood stem cells transplantation, leukemia will probably be relapse when the patient without complete remission at transplant.
Hematopoietic Stem Cell Transplantation (HSCT) for Malignancies Using Plasma Depleted Umbilical Cord Blood (UCB) That Were Not Red Blood Cell Depleted.
Authors: Petz Lawrence , Nademanee Auayporn , Rosenthal Joseph , Graham Michael , Eames Gretchen , Karanes Chatchada , Chan Lee Lee , Tan Ah Moy , Tan Poh-Lin , Wang Brian , Tseng Peggy , Chow Tiffany , Wu Tina , Jaing Tang-Her , Gjertson David , Tan Patrick , Chow Robert 
Published: October 2019

Abstract
Cell dosage is a limiting factor for UCB HSCT, especially for adult patients. Most UCB banks practice red cell depletion (RCD) techniques to save storage space, which incur significant nucleated cell loss after processing. One method to minimize cell loss and still reduce volume after processing is to deplete plasma (PD), but not the red blood cells. Not washing UCB (NW) after thawing also minimizes cell loss. A large racially diverse PD UCB inventory of over 25,000 units is now available on stem cell registries. There were 70 ALL, 54 AML, 19 CML, and 45 others transplanted for malignant indications. A retrospective audited analysis was performed on 170 patients with engraftment and/or survival information. Of the ALL/AML/CML cases with available information, there were 32 1CR/CP, 33 2CR, and 13 3CR/CP. The median age of patients was 13 years old (range 05–59); median weight 50 kg (range 5–137); male 45%. Transplant characteristics indicated a median # HLA ABDR matches of 4.0; median pre-freeze TNC dose 4.1 × 107/kg; median post-thaw TNC dose as reported by TC 3.7 × 107/kg; median pre-freeze CD34 dose 1.4 × 105/kg; transplants outside of U.S. 34%; double unit transplant 30%; non-myeloablative 16%. Sixty-one percent of the transplanted UCB were washed post-thaw (W), 39% were infused without post-thaw wash (NW), with 20% of the units without available post-thaw data. Kaplan-Meier estimates of 3-month ANC500 and 6-month platelet 20K and 50K engraftment are 89±3%, 81±5%, and 73±5% respectively. Median time to engraftment for ANC 500, platelet 20K, and 50K were 22 days (range 7–69 days), 52.5 days (range 12–181 days), and 64 days (range 25–374 days) respectively. Median time to engraftment for post-thaw washed units (W) versus PD CBU not washed and infused directly after thawing (NW) were 24 vs. 22 days for ANC500, and 57 vs. 48 days for platelet 20K respectively. The incidence of reported grade II-IV and III-IV acute GVHD were 32% and 14% respectively. Twelve percent developed limited chronic GVHD and 14% developed extensive chronic GVHD. With a median follow-up of 170 days (range 4–1402 days), the Kaplan-Meier estimates of 1-year TRM, OS and relapse-free survival were 31±4%, 51±4% and 47±4% respectively. These results demonstrate that HSCT using unrelated PD UCB can be performed safely and effectively in patients with malignancies, and post-thaw wash may not be necessary.
Results of High Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Acute Myeloid Leukemia.
Authors: Ault Kenneth A. , Case Delvyn Caedren , Boyd Marjorie A. , Ervin Thomas J. , Aronson Frederick , Ebrahim Kurt S. , Hedlund Jacquelyn A. 
Published: October 2019

Abstract
43 patients with acute myeloid leukemia have undergone transplantation at our institution over the past 14 years. Patient selection criteria included age less than 70 years, creatinine less than 2mg/ml, no active infection, cardiac ejection fraction >40%, DLCO > 50% of predicted and no other co-morbid conditions that would jeopardize survival. 39 patients were in first remission, 4 were in second or higher remission. 3 patients had favorable cytogenetics, 40 had intermediate or unfavorable cytogenetics. After achieving remission for at least 30 days, patients were consolidated with Etoposide and AraC, followed by G-CSF. Hematopoietic stem cells were collected when the WBC rebounded to at least 10,000/μl. The target dose of CD34 positive cells was 5×106/kg. The minimum dose given was 2.3 × 106/kg). High dose therapy consisted of Busulfan 1mg/kg and Etoposide 60mg/kg. The average age at transplantation was 42 years (range 20 to 61). Days of neutropenia (AGC<500/μl) ranged from 2 to 10 (average 5.2). The median length of follow up is 4.0 years. Kaplan-Meier progression-free survival is 38% at 5 years and 35% at 10 years. Currently 26 patients are alive, and 23 are free from progression. Overall survival is 60%.
Maine Medical Center Autologous HPC Transplant Program Acute Myelogenous Leukemia Maine Medical Center Autologous HPC Transplant Program Acute Myelogenous Leukemia
Pretreatment of the Esophagus with Manganese Superoxide Dismutase Plasmid/Liposome Complex (MnSOD-PL) before Irradiation Results in Increased Migration and Proliferation of Marrow-Derived Stem Cell Progenitors in the Esophageal Squamous Epithelium.
Authors: Epperly Michael W. , Niu Yunyun , Shen Hongmei , Greenberger Joel S. 
Published: October 2019

Abstract
Irradiation of the mouse esophagus increases production of superoxide, nitric oxide, peroxynitrite, and other reactive oxygen species (ROS) for weeks after exposure. ROS production in the esophageal microenvironment may be toxic to cells migrating in to repair irradiation damage. MnSOD-PL gene therapy decreases ROS production. We tested whether such treatment increased the engraftment of circulating marrow origin cells involved in repair of esophageal irradiation damage. C57BL/6NHsd female mice were treated with intraesophageal MnSOD-PL and irradiated 24 hr later along with control mice to 29 Gy to the thoracic cavity. Subgroups of mice were sacrificed at days 1, 2, 3, 4, or 5 days after irradiation, esophagus removed, frozen in OCT and sectioned. Sections were stained and apoptosis quantitated. Low level apoptosis was detected for the first 3 days with significant apoptosis on day 5. Mice pretreated with MnSOD-PL had reduced apoptosis (3 ± 1%) compared to control irradiated mice (20 ± 7%) (p= 0.010). Female mice in each 29 Gy esophagus irradiated group were injected I.V. 5 days later with 1 × 105 bone marrow cells from male ROSA mice. Subgroups received MnSOD-PL (100 ug plasmid DNA in 100 ul) 24 hr before irradiation. ROSA donor cells were differentiated from recipient C57BL/6NHsd cells by Y probe and LacZ positive staining and resistance to G418 follows explants in vitro. At sacrifice 14 days after irradiation, esophagus was removed and sorted into side population (SP) and non-side population cells (NSP). Mice that received MnSOD-PL before irradiation, had 42.3 ± 5.3% of NSP cells LacZ+ compared to 10.9 ± 1% in the irradiation only group (p < 0.0001). SP cells from MnSOD-PL treated mice demonstrated 26.5 ± 4.8% LacZ+ cells compared to 9.3 ± 2.0% in the irradiation control group (p = 0.0021). Serial transfer of donor ROSA marrow origin esophageal “stem cell candidates” was carried out by I.V. transfer of 1st generation SP and NSP harvests to 29 Gy thoracic irradiated female recipients. Second generation recipients pretreated with intraesophageal MnSOD-PL who received ROSA male SP cells isolated from first generation mice (also pretreated with MnSOD-PL) demonstrated the highest number of LacZ+ cells (4.7 ± 1.6%). In contrast, no LacZ+, ROSA cells were detected in second generation irradiation control recipients. Therefore, intraesophageal delivery of MnSOD-PL increases stable migration of bone marrow derived progenitors of esophageal squamous epithelium and improves the stability of serially transferred marrow origin, esophageal stem cell candidates.
Development of an Effective Safety Switch for Selective Elimination of Human T Cells In Vivo after Adoptive Transfer.
Authors: van Meerten Tom , Rozemuller Henk , Mackus Wendy J.M. , Parren Paul W.H.I. , van de Winkel Jan G.J. , Claessen Marie-Jose , van Rijn Rozemarijn S. , Hagenbeek Anton , Martens Anton C.M. , Ebeling Saskia B. 
Published: October 2019

Abstract
Adoptive transfer of T cells is frequently associated with unwanted side effects. In order to tackle these effects one could introduce a safety switch into the cells that permits their selective in vivo elimination. The human CD20 gene in combination with CD20 antibodies was recently proposed as a novel safety switch. In such a system, T cells may be genetically modified with a CD20-encoding vector prior to adoptive transfer. If necessary, CD20-transgenic cells can be eliminated in vivo through administration of CD20 antibodies, such as the chimeric antibody rituximab (RTX) that is currently used to treat CD20+ lymphoma. RTX activates the complement system and recruits immune effector cells, resulting in rapid death of CD20+ cells. Recently, a novel human CD20 antibody, Humab 7D8, was shown to have superior activity over RTX.
In this study a set of CD20-encoding retroviral vectors was generated, which either lacked or contained one or both of two regulatory elements:
the woodchuck posttranscriptional regulatory element (WPRE) to increase CD20 expression, and the chicken hypersensitivity site 4 insulator element (INS) to achieve a position independent expression of CD20 and to increase the safety profile of the vector by preventing activation of cellular (onco)genes by the retroviral enhancer.
We found that the level of CD20 expression obtained with vectors containing INS was 2-fold lower than with vectors lacking INS. Additional inclusion of WPRE restored the level to that of the vector without INS. In addition, INS greatly enhanced the homogeneity of CD20 expression in T cells. Moreover, after 3 months in culture, all cells generated with CD20-INS had retained CD20 expression, while 60% of cells transduced with the control CD20 vector had lost CD20 expression.
Complement dependent cell kill (CDC) of both RTX and HuMab 7D8 was dependent on the level of CD20 expression (p<0.01). However, while very low CD20-expressing cells were completely resistant against RTX they could be effectively killed by HuMab 7D8. For maximal kill of CD20-high cells, a 100-fold lower dose of HuMab 7D8 was required, compared to RTX. In vivo efficacy was studied through bioluminescent imaging of luciferase+ CD20-transgenic T cells. After transfer of CD20+ cells in immune deficient RAG2−/−gamma c−/− mice, both CD20 antibodies were capable of eliminating >99% of CD20+ cells, prolonging survival of mice from 20 till 42 days.
In conclusion, we developed a safe vector that leads to homogeneous and stable expression of CD20 on human T cells. These cells can be killed effectively in vivo with HuMab 7D8, a recently developed CD20 antibody. This system will be applicable to other approaches that require inclusion of a safety switch in ex vivo modified cells.