bluuebunny/crossref_metadata_2025_split huggingface dataset:
HE2100 (androst-5-ene-3β, 17β-diol), an Adrenal Hormone, Protects Rhesus Macaques from Lethal Total Body Irradiation (TBI)- Induced Severe Neutropenia and Thrombocytopenia.
Authors: Stickney Dwight R. , Dowding Charles , Authier Simon , Garsd Armando , Onizuka-Handa Nanette , Reading Chris , Frincke James 
Published: October 2019

Abstract
HE2100 (androst-5-ene-3,17β-diol) is a naturally occurring adrenal steroid hormone being developed for the treatment of acute radiation syndrome (ARS). Previous studies of lethally irradiated rodents demonstrated a significant survival advantage for HE2100 treated groups (Whitnall et. al., Int. J. Immunopharm. 2000). In HE2100 treated rhesus macaques we have previously reported a tri-lineage recovery (neutrophils, platelets and red blood cells) of bone marrow following sublethal irradiation and a reduction in lethality following 6.00 Gy 60Co TBI. Studies were conducted to further investigate the effects of this compound to prevent very severe radiation induced cytopenias and to enhance survival following TBI. Results refer to absolute neutrophil count <500 cells/μL and platelet count <20,000 platelets/μL. We report a meta-analysis of five studies involving 100 animals receiving TBI in the range of 6.00 – 6.34 Gy 60Co. Animals were either untreated, or given vehicle, or 5–15 mg/kg of HE2100 IM for 5 consecutive days starting 2–3 hours after TBI. No clinical support such as transfusions or antibiotics was given in any of the studies. Animals were continuously monitored for core body temperature with an implanted telemetric thermometer. Blood counts were measured daily during expected cytopenic days. Studies were performed after Institutional Animal Care and Use Committee review and approval, observing strict euthanasia criteria. HE2100 afforded protection of the unsupported animals from lethal irradiation, decreasing the lethality overall, from 42% in the control group to 22% in the HE2100 treated group (mid-p=0.044). All deaths occurred between Study Days 14 and 26. The majority of animals (28/32, 87.5%) died by Study Day 20 reflective of ARS. Based on an analysis of days at risk, the cumulative incidence of days of severe neutropenia was reduced by 1.10 days (p=0.002), whereas the cumulative incidence of days of thrombocytopenia was reduced by 2.31 days (p=0.02). No cytopenias were recorded after Study Day 26 on surviving animals. Death in these animals correlated with severe thrombocytopenia and opportunistic infections from the gut and skin flora leading to hemorrhagic sepsis as the primary cause. HE2100-related increases in cellularity were noted in the bone marrow, spleen, and lymph nodes on Study Day 40. HE2100 appears to stimulate multi-lineage recovery, via early bone marrow hematopoietic stem cell progenitors following TBI injury in rhesus macaques.
Correlation of Acute GVHD with CD4+CD25+ Regulatory T Cells of the Donates and Receipients in Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Min Zhai Zhi 
Published: October 2019

Abstract
Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (aHSCT). CD4+CD25+ T cells are characterized in suppression of autoimmunity and induction of transplantation tolerance. Recently several studies have shown that CD4+CD25+ T cells from donor are able to effectively suppress acute GVHD (aGVHD) in murine models. However the relationship of aGVHD with the levels of CD4+CD25+ T cells in donor and receipients undergoing aHSCT in human is not clear. Here we examined the CD4+CD25+ T cells in both donors and receipients after aHSCT.
Methods: donors and receipients were divided into two groups: group 1 without or with grade I aGVHD and group 2 with aGVHD above grade II. Age match with donors and receipients of normal peoples were taken as control separately. aGVHD was diagnosised and graded according to standard criteria. The peripheral blood was obtained from the donors 1 week before aHSCT, and receipients 4weeks after aHSCT for treatment of malignancy, mostly chronic myelogenous leukemia. CD4+CD25+ T cells and CD4+CD25+ bright were assessed by double color immunoflurecence labeling and FACScan. The ratio of CD4+CD25+ T cells and CD4+CD25+ bright in CD4 T cells was calculated.
Results: There is no difference in CD4+CD25+ T cells between normal control and group 1 of the donors who’s stem cells were infused into the receipients underwent grade I aGVHD. CD4+CD25+ T cells were significantly decreased in group 2 of donors compared to normal control and group 1 of donors (see table 1). CD4+CD25+ T cells and the CD4+CD25bright T cells subpopulations in group 2 of receipients were significantly lower than normal control and group 1 of receipients (see table 2).
Summary: the severity of aGVHD is correlated to the levels of CD4+CD25+ T cells in both donors and receipients after aHSCT. aGVHD occur less in the donor with normal levels of CD4+CD25+ T cells. Lower levels of CD4+CD25+ T cells in receipients indicate high incidents of server aGVHD. These data suggested that CD4+CD25+ T cells could have important role in prevention of aGVHD.
Table 1. lymphocytes, CD4+ T cells, CD4+CD25+ and CD4+CD25bright T cells (%) in donates lymphocytes lymphocytes CD4+ CD4+CD25+ CD4+CD25bright *P<0.01 vs normal control and group 1. **P< 0.001 vs normal control and group 1 Normal control n=10 34.27±8.62 37.25±5.38 11.29±1.89 1.36±0.53 Group 1 donate n=6 33.65±10.06 36.43±9.50 11.23±1.69 1.41±0.76 Group 2 donate n=4 23.90±11.67 32.57±3.40 5.64±1.57** 0.69±0.48* Table 2. WBC count, CD4+CD25+ and the CD4+CD25bright T cells in receipients (%) WBC(×109) CD4+CD25+ CD4+CD25bright *P<0.01 vs normal control and group 1. **P< 0.001 vs normal control and group 1 Normal n= 10 6.38±1.23 11.29±1.89 1.36±0.53 Group 1 n= 6 5.16±4.49 17.10±4.19 2.23±1.52 Group 2 n=4 4.34±2.85 1.52±0.61** 0.00±0.00*
Patterns of Early Infectious Complications in Adult Unrelated Cord Blood Transplantation (UCBT). A Single Center Experience.
Authors: Benn Howard , Maroules Michael , Ojha Rakesh , Arcilla Theresa , Nath Rajneesh 
Published: October 2019

Abstract
The major cause of non-relapse transplant related mortality (TRM) in UCBT continues to be infectious, with blood stream infections (BSI) constituting the majority of these events. However, CMV antigenemia and BK virus associated late onset hemorrhagic cystitis (LOHC) are increasingly important causes of morbidity and mortality. We review our single institution experience. We identified 13 patients with hematological malignancies in our database that had undergone UCBT in the period June 2002 - January 2005 and analyzed these data to document the incidence and patterns of infectious complications. The median age was 48 (range 19–62) years. All patients received infectious prophylaxis with Ciprofloxacin, Acyclovir, Voriconazole, Bactrim/nebulized Pentamidine. Eleven patients underwent conditioning with standardized Thiotepa/Busulfan/Cytoxan and GVHD prophylaxis with Tacrolimus/Mycphenalate Mofetil/ATG and the remaining 2 patients received TBI based conditioning. The median total nucleated cell (TNC) was 1.70E+07 and the median CD34 (+) cell count was 8.0E+04. The HLA matches were 4/6 in 9, 5/6 in 3 and 6/6 in 1 patient. All patients engrafted with a median time to neutrophil engraftment (TNE) of 25 (range 16–34) days. Twelve of thirteen patients achieved full donor chimerism at day 30 and 10 of 12 patients with full chimerism at day 100. Five patients developed grade II-IV acute GVHD requiring additional steroid therapy and 1 patient died of steroid refractory GVHD at day 50. Four patients had positive blood cultures at transplant. All patients developed documented bacterial infections: Gram positive in 12 (92%) (VRE in 23%, Steotrophomonas maltophilia in 31%); Gram negative in 8 (61%) (E. cloacae in 15%, Acinobacter spp. in 2 cases). Ten patients were CMV seropositive and 9 of these developed antigenemia requiring Gancyclovir/Foscarnet therapy. Nine patients had documented BK viruria with consequent late onset hemorrhagic cystitis (LOHC) and 5 patients developed BK viremia. There was 1 case of fungal BSI, while 8 patients had documented fungal tongue cultures. Four patients had positive bronchial washings (3 bacterial, 1 C. glabrata). Twelve (92%) patients were alive at day 100. Of note 62% of BSI and all cases of LOHC and CMV antigenemia developed after neutrophil engraftment. In our series of patients, viral infections (CMV, BK virus) were the most significant causes of morbidity. The high rate of BSI, especially after myeloid recovery, argues for a major influence of impaired immune recovery.
Successful Reversion of Chronic Myelogenous Leukemia with Myelofibrosis by Allogeneic Peripheral Blood Stem Cell Transplantation.
Authors: Pang Ying , Hua Jiaye , Chen Ruizhen , Feng Ying 
Published: October 2019

Abstract
Objective: To observe the effect of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) on hematopoietic reconstitution of chronic myelogenous leukemia (CML) and reversion of myelofibrosis (MF).
Methods: A 39 years old male patient diagnosed with CML complicated with MF and hepatitis B carrier condition (HBsAg+)underwent allo-PBSCT. The donor was the patient’s sibling, his 48 years old sister. Six loci on HLA-A, B, and DRB1 were completely matched with that of the recipient and HbsAb(+). Four days after the administration of G-CSF (250ug/day), PBSCs were collected from the donor for 3 consecutive days. A total volume of 168 ml was harvested. A median nucleated cell (MNC) count of 8.54 ×108/kg with 5.1 ×106 /kg of CD34+ cells were actually administered to the recipient. The conditioning regimen was busulfan/cyclophosphamide (BU/CY). The recipient was started on intravenous infusion (IV) of cyclosporine A (CSA) on Day -1 and a plasma concentration of 150–250 ng/L was maintained. IV methotrexate (MTX) 10mg/m2 was given on Days +1, +3, +6, and +11. Oral mycophenolate mofetil (MMF)was given from Days +1 to +28 for prophylaxis of acute graft-versus-host disease (GVHD). If the concentration of hemoglobin (Hb) decreased to less than 70 g/L and/or platelet count (BPC) less than 10×109 /L, the recipient was transfused with 60Co 25cGy irradiated and leuko-depleted red blood cells (RBCs) and/or single-donor platelets. Started from Day +3, the recipient was given G-CSF until white blood cells (WBC) increased to at least 3.0× 109 /L. EPO and Interleukin-11 were also given to stimulate the proliferation of the progenitors of erythrocytes and megakaryocytes. The recipient also received anisodamine with a 24 hour-maintenance dose to improve the microenvironment of hematopoiesis in bone marrow.
Results: DNA-STR on Day +30 indicated a complete chimerism in the recipient. Bone marrow biopsy on Day +50 showed a dramatic decrease of myelofibrosis in the ground substance and active hematopoiesis. Reticulinfibers reduced to 1+. No significant change on splenomegaly was observed but the hepatitis B antigen had turned negative and HBsAb had appeared.
Conclusion: 1. In order to prevent aggravation of MF, Allo-PBSCT needs to be considered as early as possible once the diagnosis of CML complicated with MF is made. 2. Transfusion with a large quantity of donor hematopoietic stem cells is beneficial for engraftment. 3. Strict Immunoinhibition of the recipient will decrease the incidence and degree of GVHD and improve engraftment. 4. The addition of agents which improve the microenvironment of hematopoiesis will enhance engraftment. 5. Recovery of the platelet count is promising post-transplantation whereas significant changes on splenomegaly was not observed. 6. Allo-PBSCT may be a promising therapy for hepatitis B.
High Dose Chemotherapy and Autologous Stem Cell Transplantation in Multiple Myeloma: Comparison of Four Preparative Regimens.
Authors: Alessandrino Emilio P. , Bragotti Letizia Zenone , Colombo Anna A. , Algarotti Alessandra , Bernasconi Paolo , Maffioli Margherita , Caldera Daniela , Corso Alessandro , Rumi Elisa , Troletti Daniela , Lazzarino Mario 
Published: October 2019

Abstract
From 1996 to 2003, 113 consecutive patients with multiple myeloma were treated with four different high dose approaches rescued by autologous peripheral blood progenitor cells (PBPC) after four cycles of VAD or other combinations. The median age was 53 years 31–68), 58% were male and 42% female, the median interval from diagnosis to transplant was 252 days (range 160–3116 days).
Twenty-five patients received as preparative regimen Carmustine, Etoposide and Melphalan (BVM) at the total dose of 600 mg/m2, 900mg/m2 and 140–180 mg m2 respectively. Nineteen pts had as preparative regimen Thiotepa and Melphalan at the total dose of 10 mg/kg and 140–180 mg/m2 respectively, 38 pts received a double transplant with Melphalan given as a single agent at the dose of 200 mg/m2, while 31 pts received a single transplant with Melphalan 200 mg/m2. In patients with poor performance status at transplant or previous history of infection or renal impairment, the dose of melphalan was reduced by 20% respect to the standard planned dose.
in the group of 25patients treated by BVM, 10 had progressive disease, 6 stable disease (SD), 7 partial remission (PR), 1 very good partial remission (VGPR). At day +90 from transplant, 17 patients were in CR or PR (68%). The actuarial probability of overall survival and event free survival at 5 years were 40% and 20%, respectively. One pt died of transplant, one developed a solid tumor 24 mos after transplant. in the group of 19 pts treated with TT and Mel (TT-Mel), 3 pts were with progressive disease, 3 with stable disease, 6 in partial remission, 3 with minimal response, 3 in VGPR, 1 in CR. At day +90, 15 pts were in CR or PR (78%). The actuarial probability of survival was 50% at 5 years, and event free survival 28%. in the group of 38 pts who received a double transplant, 7 pts were with progressive disease, 3 with stable disease, 14 in PR, 12 in VGPR or CR. At day +90 after the second transplant, 31 of 38 patients (81%) were in CR or PR. Overall survival and event free survival was respectively 48% and 20% at five years. in the group of 31 pts receiving a single transplant with Melphalan alone, 8 were with progressive disease, 1 with stable disease, 6 in VGPR, 1 in CR, 13 in PR. At day +90, 21 of 31 patients (67%) were in CR or PR. Overall survival and event free survival was respectively 45% and 22% at five years. In conclusion, double transplant seems better than one transplant with melphalan alone in terms of EFS and OS (p<0.03); the BVM combination produces high response rates, the regimen, however, is toxic with a high rate of life threatening mucositis. the addition of Carmustine and Vepeside or Thiotepa to Melphalan does not produce significant improvement of OS and EFS.
Transfusion and Iron Overload in Thalassemia and Sickle Cell Disease: Impact of Infusion Chelation Therapy on Quality of Life.
Authors: Abetz Linda , Baladi Jean Francois , Jones Paula , Rofail Diana 
Published: October 2019

Abstract
Introduction: Blood transfusions are required as supportive care in thalassaemia and sickle cell patients. Regular blood transfusions may result in iron overload (IO) and, left untreated, in morbidity and earlier morality. Current infusion chelation therapy (ICT) requires 8–12 hour infusions, 5–7 days per week, potentially limiting quality of life (QoL) and inhibiting adherence in patients already limited by thalassaemia and sickle cell disease.
Methods: To assess the impact of ICT on the QoL of patients with thalassemia and sickle cell disease and adherence, a literature review in Medline (539 abstracts; 130 articles), analysis of IO patient transcripts (4 thalassaemia, 1 sickle cell disease) and five IO clinical expert interviews were conducted.
Results: Few published studies (11) used validated QoL instruments and even fewer assessed IO in thalassaemia (4) and sickle cell patients (7). No IO-specific QoL instruments were found. ICT in sickle cell patients may cause additional needle-site pain/discomfort, and may impact on evening social life and sleep, recreational activities, as well as emotional and physical well-being, occupational capacity and feelings of independence. ICT in thalassaemia patients may impact on emotional wellbeing such as self-esteem and worry about the future, family relationships and development of intimate relationships. Published articles and patient and clinician input suggested that QoL impact inhibited prescription of and adherence to ICT and therefore there is a need for easier, efficacious and safe oral chelation therapy (OCT).
Discussion: Limited empirical studies assessed ICT’s impact on QoL in patients with thalassaemia or sickle cell disease, though results indicated that ICT’s QoL impact is significant and prescription and adherence rates would likely improve with OCT. We recommend further qualitative and empirical studies to assess the impact of ICT and OCT in IO patients with thalassaemia and sickle cell patients, using validated instruments.
Influence of Age and Needle Gauge on Bone Marrow Biopsy Specimen Adequacy.
Authors: Goldenberg Alec , Kelley Priscilla , Ibrahim Sherif , Sen Filiz , Liu Cynthia 
Published: October 2019

Abstract
Introduction. The quality and length of bone marrow biopsy core specimens should facilitate accurate diagnositic interpretation of marrow histopathology. A 11G specimen of length 1.6 cm or greater is considered adequate for pathologic evaluation by some authors. The length of specimens recovered with 11G needles appears to depend on needle design. We explored the possibility that the adequacy of bone marrow biopsy specimens may be influenced by patient age and the gauge of biopsy needles.
Methods. 88 bone marrow core specimens were recovered from 72 patients using 11G SNARECOIL bone marrow biopsy needles. The mean age of these patients was 61.4 and the m/f ratio was 45/27. The clinical diagnoses were isolated anemia, cytopenias, leukemia, lymphoma, myeloma and other in 18.0%, 33.3%, 13.8%, 13.8%, 5.5% and 15.2% of the patients, respectively. 10 patients underwent multiple procedures (2–6) for evaluation of treatment efficacy. 106 patients underwent 127 bone marrow biopsy procedures using 8G SNARECOIL needles. The m/f ratio was 56/50 and the mean age of the patients was 63.1years. The clinical diagnoses were isolated anemia, cytopenia, leukemia, lymphoma, myeloma or other in 22.2%, 19.6%, 14.9%, 21.2%, 12.5% and 9.4% patients respectively. 13 patients underwent multiple procedures (range 2–4) for evaluation of response to treatment.
Results. Although the mean length of the 11G and 8G specimens were statistically significantly the same (mean±SEM, 1.97±0.07 cm vs. 1.99±0.05 cm, respectively, p = 0.8), the distribution of specimen lengths was asymmetric or skewed for the 11G specimens (skewness(skw) =0.52) and nearly normal for the 8G specimens (skw =0.04). The deviation from a normal distribution suggested additional variable(s) might be effecting specimen length. The possible influence of age on specimen length relative to needle gauge was considered. The mean age of the patients biopsied with 11G needles was 61.4. The m/f ratios of the patients ≤64 and ≥65 were statistically the same (27/12 vs. 18/15, respectively, p = 0.2). The mean age of the patients biopsied with 8G needles was 63.1. The m/f ratios of the patients ≤64 and ≥65 were statistically the same (30/26 vs. 26/23, respectively, p =0.5). 11 G specimens from younger patients, ≤64, were more frequently adequate (1.6 cm or greater) (39/53 = 73.5%) than specimens from older patients ≥ 65 (18/35 = 51.4%), p = 0.03. Conversely adequate 8G specimens were recovered as frequently in older patients ≥65 years (40/55 = 72.7%) as they were in younger patients ≤64 years, (59/72 = 81.9%) p = 0.21. Moreover, in older patients, adequate biopsy specimens were recovered more frequently by 8G needles then by 11G needles (40/55=72.7% vs. 18/35 = 51.4%, respectively, p = 0.04).
Conclusions. 1. Age influences the rate of recovery of adequate bone marrow core biopsy specimens. 2. 8G needles recover adequate specimens more frequently than 11G needles in older patients.
Are We Ready? A Case for Making Hematology Fellows Competent in Treating the Booming Culturally Diverse Minority Populations.
Authors: Iqbal Uzma 
Published: October 2019

Abstract
United States is at an important phase of its growth since the dawn of the new century. US population has grown by 13% from 248 million to 281 million between 1990–2000. Projected increase in population by mid century will be 460 million. According to 2000 census, 11% of US population is foreign born and 17.9% speaks a language other than English at home. Population demographics indicate very significant trend changes. The projected race and ethnic changes are occurring sooner because of higher than expected increase in immigration rates. By 2050 the minorities will make about 50% of US population. Ethnically and culturally diverse minorities are projected to grow exponentially. Asians are expected to grow by 213% to 60 million, while Hispanics will increase in their ranks by 188% to 102.6 million i.e. roughly one quarter of the population. The black population will see a 71% increase to 61 million while Whites will grow by 7% to 210 million. These trends indicate that Asian and Hispanic populations will triple in number by mid century. This poses special challenges to the health care industry and physicians in particular. The Hematologists will be diagnosing and treating a much larger number of the diseases common in these ethnic groups e.g. Sickle cell disease, hemoglobinopathies including Thalassemias and thrombotic and hypercoaguable disorders etc. interaction with these ethnically and culturally diverse clients will be challenging for the Hematology fellows since no formal training in cultural competency training is incorporated in fellowship program structure. Review of the curricula of the training programs has revealed most of these are deficient in this regards. Some awareness of the issue is found in nursing training literature. There is awareness regarding the cultural competency issue at a national level where Health and Human Services have issued national standards for culturally and linguistically appropriate services in health care (CLAS). This initiative can be used as a road map for providing cultural competency training to Hematology fellows. This will enable them to appreciate, think and act in ways that acknowledge, respect and build upon ethnic, socio cultural and linguistic diversity. Fellows can be trained and evaluated during their training in core competencies such as self-awareness, effective communication, cultural knowledge, humility and proper use of interpreters. In conclusion I emphasize that I order to deliver quality health care to ethnically diverse populations and to decrease disparities in health care, cultural competency should be an integral part of Hematology training programs.