bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact on Acute Myeloid Leukemia Relapse in Granulocyte Colony Stimulating Factor Application: A Meta-Analysis
Authors: Feng Xiaoqin , Li Chunfu 
Published: October 2019

Abstract
Objective: This meta-analysis evaluated the impact of granulocyte colony-stimulating factor (G-CSF) added to chemotherapy on treatment outcomes including survival and disease recurrence in patients with acute myeloid leukemia (AML).
Methods: Medline, Cochrane, EMBASE,Google Scholar databases were searched until December 7, 2015 using the following search terms. Randomized control trials (RCTs), two-arm, and prospective studies that investigated patients with AML who underwent stem-cell transplantation were included.
Results: The overall analysis revealed significant improvement in overall survival (OS) (pooled HR= 0.90; 95%CI, 0.83 to 0.98; P = 0.017) and disease free survival (DFS) (pooled HR = 0.85; 95% CI, 0.77 to 0.94; P = 0.002) for patients receiving G-CSF with chemotherapy. Among patients without prior AML treatment, there was significant improvement in DFS (pooled HR = 0.87; 95% CI, 0.77 to 0.98; P = 0.021) and reduction in incidence of relapse (pooled HR = 0.81; 95% CI, 0.68 to 0.96; P = 0.015) for those who received G-CSF. However, subgroup analyses found no significant difference between G-CSF (+) and G-CSF (-) treatments in rates of OS (P = 0.135) and complete remission (CR) (P = 0.357) for patients without prior AML treatment. Among patients with relapsed/refractory AML, there was no significant difference found between G-CSF(+) and G-CSF(-)groups for OS (P = 0.225), DFS (P = 0.209) and CR (P = 0.208).[EG1]
Discussion and Co nclusion: Treatment with chemotherapy plus G-CSF appears to provide better survival and treatment responses compared with chemotherapy alone, particularly for patients with previously untreated AML.

Disclosures
No relevant conflicts of interest to declare.
Predicting Early Mortality in Diffuse Large B-Cell Non-Hodgkin Lymphoma
Authors: Maddox Jamie M 
Published: October 2019

Abstract
It is difficult to find figures for the expected rate of early mortality in diffuse large B-cell non-Hodgkin lymphoma (DLBCL) as many of the patients who are destined to die early do not enter clinical trials. Our own rate of early mortality (death within 100 days of the diagnostic test being performed) was higher than we had anticipated (23%). We undertook a study to look at risk factors for early mortality, and to see if there were any factors which could be improved by altering our investigation and initial management.
Our haematology database has baseline demographic and prognostic information on all cases of haematological malignancy diagnosed in our centre. A two year period was chosen retrospectively from 1st January 2013 until 31st December 2014. This gave 97 registered patients with DLBCL.
Early mortality was significantly related to the patient age, Eastern Cooperative Oncology Group (ECOG) performance status, lactase dehydrogenase value, presence of 2 or more sites of extranodal disease and the presence of B-symptoms. We did not see a significant relationship to the presence of marrow disease or the presence of disease bulk. As the majority of the relevant factors are already part of validated prognostic scoring systems, we evaluated the (International Prognostic Index) IPI, the R-IPI (revised International Prognostic Index) and the NCCN-IPI (enhanced International Prognostic Index) to see which was the best predictor of early mortality. The IPI gave the chance of 100 day mortality as 4% for low or low-intermediate risk patients, 16% for high-intermediate risk patients and 53% for high risk patients. The R-IPI gave the chance of 100 day mortality as 0% for low risk patients, 5% for intermediate risk patients and 48% for high risk patients. The NCCN-IPI gave the chance of 100 day mortality as 0% for low or low-intermediate risk patients, 13% for high-intermediate risk patients and 57% for high risk patients (figure 1). By six months, the mortality rate in high risk NCCN-IPI patients had reached 71% while the low and low-intermediate groups remained at 0%. Some patients were included who were not considered for potentially curative chemotherapy. Even with these patients excluded, the risk of 100 day mortality was still 50% in the high risk NCCN-IPI group.
Some of the risk factors for mortality will likely worsen if the diagnosis or initial treatment are delayed. We therefore looked at the overall pathway from referral until first treatment. We found that those with early mortality tended to have a shorter time course until receiving their first treatment, likely reflecting the fact that they were more unwell when they first presented.

Disclosures
Maddox: Janssen: Other: Funding to attend ASH 2016 (travel, accommodation, registration); Boehringer-Ingelheim: Other: Funding to attend ASH 2014 (travel, accommodation, registration).
Azacitidine As Post-Allograft Maintenance Helps Reduce Relapse Risk in High-Risk MDS and AML
Authors: El Cheikh Jean , Massoud Radwan , Fares Elie , Kreidieh Nabila , Mahfouz Rami , Kharfan-Dabaja Mohamed A , Bazarbachi Ali 
Published: October 2019

Abstract
Purpose: Relapse after allogeneic hematopoietic SCT (allo-SCT) for AML or myelodysplastic syndrome (MDS) remains the main cause of treatment failure and is associated with a very poor prognosis and a short survival despite the type of the salvage therapy. Options include reductions of immunosuppressive therapy, chemotherapy with or without infusion of donor lymphocytes (DLI) or second allo-SCT, but results remain disappointing. Other studies (C Jabbour et al, and Craddock Charlie et al) demonstrated the efficacy and safety of 5-azacytidine (Vidaza) maintenance post Allo-SCT.
Patients and Methods: The aim of our observational study was to evaluate the anti-leukemic effect of 5-azacytidine (Vidaza) as post-transplantation prophylactic therapy to prevent relapse in patients with high risk AML or MDS in our center. We identified 16 patients, 13 AML and 3 MDS. Twelve patients (75%) received a risk-adapted intensity of busulfan at 130mg/m2/day for either 2, 3 or 4 days, with a fixed dose of fludarabine (30mg/m2/day for 5 days), and thymoglobulin (2.5mg/kg/day for 2 days). Our algorithm was based on age, co-morbidity (ies) and disease risk.
Twelve patients (75%) received peripheral blood stem cells (PBSC) from HLA identical siblings, 3 patients (19%) from haplo-identical donor and 1 patient from matched unrelated donor. Azacitidine was started after a median of 60 days post-transplant with a reduced dose of 32 mg/m2/day for 5 days monthly for 5 years. None of the patients experienced graft rejection. Patient and transplant characteristics are outlined in Table 1.
Results: Nine patients (56%) had either a monosomal karyotype or a complex karyotype. Patients received a median number of 8 cycles (1-37) of vidaza. None of our patients stopped definitively vidaza for toxicity reasons. Three patients (19%) discontinued their treatment: one for 3 months because of pneumonia, one for acute GvHD grade II then resumed Azacitidine therapy after 6 months, the third stopped for 2 weeks because of neutropenia. After a median follow-up of 10 months (1-56) from allo-SCT, 13 patients (81%) still alive and 3 patients died; one because of CMV infection, one from disease progression and one from cardiac infarct. At the last follow up 13 patients (81%) remain in complete remission.
Conclusions: Azacitidine prophylactic maintenance therapy appears to reduce the risk of relapse by helping consolidate post-allograft responses in high risk AML or MDS. The toxicity related to this dose of azacitidine was very low. Our findings require validation in a large prospective multicenter randomized study.
Legend: AML, Acute Myeloid Leukemia; MDS, Myelodysplastic Syndrome; CR, Complete Remission; FB2 Fludarabine 2 days Busulfan,;FB3 Fludarabine 3 days Busulfan; FB4 Fludarabine 4 days Busulfan; TBF Fludarabine Busulfan.

Disclosures
No relevant conflicts of interest to declare.
Two Cases Report of Haploid Hematopoietic Stem Cell Transplantation Treatment of Adrenal Leukodystrophy
Authors: Chen Libai , Wen Jianyun , He Yuelin , Feng Xiaoqin , Li Chunfu , Wu Xuedong 
Published: October 2019

Abstract
Background : Adrenal leukodystrophy is one of the beta oxidation peroxidase disease, an x-linked recessive heredity, can lead to very long chain fatty acids in tissue accumulation, result in adrenal and cerebral white matter of the progressive deterioration. Hematopoietic stem cell transplantation (HSCT) is a curative treatment for early childhood cerebral type of X-ALD. We report two cases of haploid hematopoietic stem cell transplantation for the treatment of adrenal leukodystrophy.
Methods: Two patients were male, 5 years old, 6 years old, respectively, by the gene diagnosis of adrenal leukodystrophy.Case 1 received father haploid bone marrow and peripheral blood stem cell(HLA7/10 match)combine with unrelated umbilical cord blood(HLA 9/10 match). Case 2 received sister haploid bone marrow and peripheral blood stem cell(HLA5/10 match)combine with unrelated umbilical cord blood(HLA 7/10 match).Case 1 conditioning regimen use cyclophosphamide, fludarabine and thiotepa.Case 2 conditioning regimen use cyclophosphamide , busulfan ,fludarabine , rabbit anti-human thymocyte immunoglobulin and thiotepa.Case 1 bone marrow infused total nucleated cell dose was 2×108/kg (CD34+:0.75%,CD3+:1.67%), peripheral blood stem cell infused total nucleated cell dose was 29×108/kg (CD34+:0.19%,CD3+:4.96%), unrelated umbilical cord blood infused total nucleated cell dose was 1.16×108/kg (CD34+:0.44%). Case 2 bone marrow infused total nucleated cell dose was 0.89×108/kg (CD34+:0.74%,CD3+:2.29%), peripheral blood stem cell infused total nucleated cell dose was 25.85×108/kg (CD34+:0.5%,CD3+:15.23%), unrelated umbilical cord blood infused total nucleated cell dose was 0.39×108/kg (CD34+:0.93 %). GVHD prophylaxis Case 1 used mycophenolate mofetil,sirolimus,while Case 2 used mycophenolate mofetil,tacrolimus and sirolimus.
Results: The absolute neutrophil count (ANC) greater than 0.5×109/L of two patients were 21 and 23 days , case 1 had a successful engraftment with father donor-derived as case 2 had a successful engraftment with umbilical cord blood donor-derived.Follow-up time of 35 months and 3 months respectively,Case 1 Check head MRI again show a smaller lesionswhile Case 2 progression-free.Two cases' C24:0, C26:0, C24:0 / C22:0, C26:0 / C22:0 of plasma decline than before transplantation.
Conclusion: In the absence of HLA-match donor, haploid bone marrow and peripheral blood stem cell combined unrelated umbilical cord transplantation is a effective method of treatment of adrenal leukodystrophy, but which will successful engraftment need more further studies.

Disclosures
No relevant conflicts of interest to declare.
Adult Lymphoma-Associated Hemophagocytic Syndrome Is a Life-Threatening Disease: Retrospective 10-Year Review of 89 Cases at a Single Center
Authors: Jin Zhili , Wang Yini 
Published: October 2019

Abstract
Lymphoma is classified into Hodgkin's and non-Hodgkin's lymphoma (B- cell or T-cell type). Lymphoma-associated hemophagocytic syndrome (LAHS) is a life-threatening disease with dismal prognosis. To assess the hemophagocytic lymphohistiocytosis (HLH)-related clinical features and prognosis in the immunophenotype of LAHS, we retrospectively evaluated 483 patients with HLH presented at our institution between December 2006 and March 2016. Eighty-nine adult patients were diagnosed with LAHS. Of those, 2 cases (2.2%) were Hodgkin's lymphoma with Epstein-Barr virus infection. Eighty-seven cases (97.8%) were non-Hodgkin's lymphoma consisting 25 cases (28.7%) of B-cell LAHS (B-LAHS) and 62 cases (71.3%) of T-cell LAHS (T-LAHS). There were 17 male and 8 female patients in B-LAHS with a median age of 57 years. There were 40 male and 22 female patients in T-LAHS with a median age of 39 years. T-LAHS patients were associated with younger age which was significantly different with that in B-LAHS patients (p=0.000). Clinical features were summarized according to HLH-2004 diagnosis criteria. For B-LAHS, fever and elevated serum ferritin exhibited in 100% of cases; elevated sCD25 was found in 94.7%; decreased NK cell activity was identified in 42.1%; pancytopenia was found in 80.0%; hemophagocytosis was found in 80.0%; splenomegaly presented in 92.0%; hypofibrinogenemia was found in 20.0%; hypertriglyceridemia presented in 26.1%. For T-LAHS, fever exhibited in 98.4%; elevated serum ferritin was found in 96.3%; elevated sCD25 presented in 87.8%; decreased NK cell activity was identified in 51.3%; pancytopenia exhibited in 80.6%; hemophagocytosis was found in 84.2%; splenomegaly presented in 85.4%; hypofibrinogenemia was found in 59.3%; hypertriglyceridemia presented in 50.0%. The 1-month, 3-month, and 6-month overall survival rate was 88.0%, 67.6%, and 53.1% in B-LAHS patients versus 54.5%, 28.2%, and 18.8% in T-LAHS patients. Ten T-LAHS patients underwent allogeneic hematopoietic stem cell transplantation (HSCT) with survival time of 1, 3, 4, 5, 5, 6, 7, 52, 84, 113 months, respectively. Nine patients with T-LAHS (14.5%) survived up to the end of follow-up, of which 6 patients (66.7%) received HSCT and 3 patients (33.3%) were without transplantation. Our results indicated the HLH-related clinical features present differently between T-LAHS and B-LAHS. Compared with B-LAHS, T-LAHS associate with earlier onset and inferior prognosis. In addition, allogenic HSCT might be an effective treatment approach for T-LAHS patients to achieve long-term survival.

Disclosures
No relevant conflicts of interest to declare.
Enhancers and Transcriptional Regulation
Authors: Wysocka Joanna 
Published: October 2019

Abstract
Interactions between the genome and its cellular and signaling environments, which ultimately occur at the level of chromatin, are the key to comprehending how cell-type-specific gene expression patterns arise and are maintained during development or are misregulated in disease. Central to the cell type-specific transcriptional regulation are distal cis-regulatory elements called enhancers, which function in a modular way to provide exquisite spatiotemporal control of gene expression during development. We are using a combination of genomic, genetic, biochemical, and single-cell approaches to investigate how enhancers are activated in response to developmental stimuli, how they communicate with target promoters over large genomic distances to regulate transcriptional outputs, what is the role of chromatin modification and remodeling in facilitating or restricting enhancer activity and how regulatory sequence change leads to the phenotypic divergence in humans. I will discuss our latest results on the mechanisms underlying enhancer function and gene regulation in development and disease.

Disclosures
No relevant conflicts of interest to declare.
Detection of Leukocyte Antibodies by Means of I131-Labelled, Purified Anti—Human-Globulin Antibody. Problems of Nonspecific Adsorption of Globulin by Leukocytes
Authors: ANDERSON ROBERT E. , WALFORD ROY L. 
Published: October 2019

Abstract
Initial studies of a quantitative method for detecting sensitization of white blood cells by antileukocyte antibodies are presented. The method entails isolating I131-labelled, anti—human-globulin antibody (prepared in rabbits) by adsorption and elution from insoluble antigen, globulinazobenzylcellulose. The degree of adsorption of the labelled antibody by presumably sensitized as opposed to nonsensitized leukocytes is measured by radioactive isotope counting technics. The vexing problem of nonspecific adsorption of human or rabbit globulin by leukocytes is considered, and procedures for partially circumventing this problem are set forth. Seligmann's solution with normal rabbit serum added to a final concentration of 10 per cent appeared to be the most effective washing fluid in most instances for removing nonspecifically adsorbed globulins from leukocytes. The use of purified anti—human-globulin antibody, as opposed to whole Coombs serum, also very favorably affected the ratio between immunologically specific adsorption and nonspecific adsorption. Results of the over-all I131 method as applied to selected positive and negative human sera are detailed.
The Clinical Significance of Fever in Acute Leukemia
Authors: RAAB SPENCER O. , HOEPRICH PAUL D. , WINTROBE MAXWELL M. , CARTWRIGHT GEORGE E. 
Published: October 2019

Abstract
1. The total course of acute leukemia in 55 patients managed in one clinic disclosed 149 febrile episodes.
2. Fever occurred virtually only when the leukemia was in relapse.
3. Infection was the cause of fever in 102 of the 149 episodes of fever.
4. With survival after the onset of symptoms of acute leukemia beyond the mean duration of life characteristic of that kind of acute leukemia, infection appeared to be more often the cause of fever than when survival was less than the mean for that kind of leukemia.
5. Fever due to infection could not be reliably differentiated from fever not due to infection by either the height or character of the fever curve, or by counting the absolute number of mature polymorphonuclear leukocytes in the blood.
6. Infection causing febrile episodes was most successfully detected by means of history, physical examination, chest roentgenogram, blood culture and other cultures as indicated by the preceding maneuvers.
7. Consideration of the fever of acute leukemia from the point of view of present day studies of the pathogenesis of fever did not clearly implicate known mechanisms of pyrogenesis.
8. The interplay of state of leukemia, nature of infecting microorganism and anti-infectious and antileukemic therapies is related to outcome in febrile episodes due to infections. The management of febrile episodes is discussed.
9. Increased survival time in children with acute lymphoblastic leukemia has not been accompanied by increased morbidity.
A Comparative Study of Some Staining Properties of Crystals in a Lympho-plasmocytoid Cell, of Russell Bodies in Plasmocytes, and of Amyloids-With Special Emphasis on Their Isoelectric Points
Authors: GOLDBERG ARTHUR F. , DEANE HELEN WENDLER 
Published: October 2019

Abstract
A staining procedure for determining the approximate isoelectric points of substances has been applied to tissue sections containing (a) intracytoplasmic crystals in a lympho-plasmocytoid cell, (b) Russell bodies of plasmocytes, and (c) secondary and primary amyloids. The same method was also applied to sections of human gamma globulin.
The results indicate the similarity of Russell bodies, the crystals, and gamma globulin, all of which showed an isoelectric range between pH 6 and 7.5. Other staining methods employed tended to confirm this identity.
The discrepancies reported in the literature on the staining properties of Russell bodies are discussed.
All of the amyloids tested had an apparent isoelectric point near pH 5. Various suggestions in the literature about the nature and origin of amyloid are summarized.
A STATISTICAL STUDY OF MORTALITY FROM LEUKEMIA
Authors: SACKS MILTON S. , SEEMAN ISADORE 
Published: October 2019

Abstract
The recorded death rate from leukemia in the United States has risen continuously since 1900, with an accelerated rate of increase since 1930. The rise from a rate of 1.9 per 100,000 population in 1920 to 3.7 in 1940 represents an increase of 94.7 per cent in this twenty-year period. This increase cannot be accounted for by changes in the age distribution of the population, for the age specific death rates have increased in each age group. The factor of increasing recognition of the disease resulting from improved diagnostic technics and greater use of hospitals with their laboratory facilities must be given adequate consideration in an effort to determine the causes for the rising death rate.
White persons are affected at a rate more than twice as great as nonwhites. Some of the difference must be attributed to variations in the availability of diagnostic services. Males experience a rate approximately one-third greater than females.
Leukemia affects persons in the older ages, particularly over 55 years, with the greatest frequency, and the population under 5 years of age experiences a mortality rate higher than any other age under 45 years. In the intermediate ages the death rate falls to the lowest point. In 1940 the death rate from leukemia for all ages was 3.7 per 100,000 population. The highest rate, 15.7 per 100,000 occurred in the age group 75-84 years. Under 1 year the rate was 4.9 per 100,000. The lowest rate, 1.5 per 100,000, occurred in the ages from 15 to 2.4 years.
Figures for the city of Baltimore for the five-year period 1939-1943 indicate an almost equal incidence of lymphoid and myeloid leukemia. Nearly two-thirds of the deaths studied in Baltimore were reported as acute leukemia. Acute myeloid leukemia appears to be more common than acute lymphoid. After age 45 chronic leukemia is more frequently observed; younger persons experience acute leukemia most commonly.
Undoubtedly many deaths result from leukemia in which this disease was neither diagnosed nor recorded on a death certificate. Clinical evidence indicates that the causes in which this failure would occur most commonly are cancer, anemia, and diseases of the spleen. Statistical evidence reveals that these conditions are certified jointly with leukemia in a significant number and proportion of cases.
Comparison of the experience of several countries indicates that the general trends of mortality from leukemia in the United States are common to the other communities. The death rates per 100,000 population in 1931 adjusted for differences in age and sex composition of the population were: United States, 3.5; England and Wales, 3.0; Paris 2.5; and Canada 2.3.
Each year since 1940 more than 5,000 persons in the United States have died from leukemia.
THE IMPROVED DEMONSTRATION OF CIRCULATING ANTIBODIES IN HEMOLYTIC ANEMIA BY THE USE OF A BOVINE ALBUMIN MEDIUM
Authors: NEBER JACOB , DAMESHEK WILLIAM 
Published: October 2019

Abstract
1. Bovine albumin solution as a testing and diluting medium was used for the detection of abnormal iso-antibodies in the serum of various cases of hemolytic anemia.
2. Five patients with idiopathic acquired hemolytic anemia all showed a warm agglutinin, although in 4 of these patients antibody could not be detected by use of the standard saline technic. Higher titres than in salt sDlution were always obtained in the albumin medium. Three patients with congenital spherocytic anemia not in crisis, 2 patients with severe Mediterranean anemia, and 2 with sickle cell anemia failed to show antibody. In the crisis of 1 case of congenital spherocytic anemia an autohemolysin was temporarily found with the use of bovine albumin. Other cases of acquired hemolytic anemia (chemical, symptomatic, hypersplenic) failed to show antibody. Detection of antibody was of distinct value in the diagnosis of acquired hemolytic anemia of the "idiopathic" type. Its continued presence in such a case after splenectomy rendered the prognosis doubtful.
3. In the further differentiation of various types of familial and acquired cases, use was made of the red cell survival time. Parallel determinations of the survival time and of iso-antibodies showed a distinct correlation. Use of the anti-human globulin rabbit serum test to detect iso-antibody adsorbed to the red cell is cited as of further diagnostic aid.