bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studies on the Hemolysin and Agglutinin of Leukemic Leukocytes
Authors: PIROFSKY BERNARD 
Published: October 2019

Abstract
1. Leukocytes from thirteen cases of leukemia were isolated, homogenized, and extracted in 0.88 M sucrose, 0.14 M NaCl, and 2.0 M NaCl solutions. All thirteen 0.88 M sucrose, twelve of thirteen 2.0 M NaCl, and seven of the thirteen 0.14 M NaCl extracts, were found to contain a hemolysin and agglutinin active against normal and trypsinized erythrocytes.
2. The hemolysin and agglutinin of leukemic leukocyte extracts was found to differ from coating antibody eluted from erythrocytes of patients with acquired hemolytic anemia, from β-glucuronidase, and from anti-H agglutinin. In spite of great similarities, the hemolysin and agglutinin differed in certain respects from the lysin-inhibitor complexes that have been extracted from tissues.
3. An inhibitor of the hemolysin and agglutinin of leukemic leukocyte extracts was found in normal serum. This inhibitor is stable at 56° C. for 30 minutes, is not dialyzable, is not exhausted from leukemic sera, and apparently does not permanently change the hemolysin or agglutinin.
4. The possible role of the leukemic leukocyte hemolysin and agglutinin in instituting premature senescene of the erythrocyte resulting in a "hemopathic" type of hemolytic anemia is discussed.
Platelet Functional Defects in Thrombocytopenic Purpura
Authors: BONNIN J. A. , JENNER MISS MAUREEN 
Published: October 2019

Abstract
A defect in a serum thromboplastic component was found in six patients with severe thrombocytopenic purpura in addition to the platelet thromboplastic defect.
The defective sera returned to normal spontaneously upon storage at -20 C. The addition of washed normal platelets during coagulation completely corrected the serum defect in the one instance in which it was possible to carry out the experiment.
It was postulated that a platelet factor was primarily at fault, resulting in the lack of immediate activation of a serum thromboplastic component.
The two thromboplastic defects are cumulative and are possibly dependent upon separate platelet factors.
Leukemia or Lymphoma and Coexistent Primary Malignant Lesions: A Review of the Literature and a Study of 120 Cases
Authors: MOERTEL CHARLES G. , HAGEDORN ALBERT B. 
Published: October 2019

Abstract
A total of 194 cases of leukemia or lymphoma with coexistent primary malignant disease was found reported in the literature. To this we have added 120 new cases from the files of the Mayo Clinic in which the diagnosis was made in the 10 years from 1944 through 1953.
The following observations were made:
1. The presence of leukemia or lymphoma does not seem to predispose to the development of any other specific type of primary malignancy.
2. The incidence of another primary malignant lesion in patients with leukemia or lymphoma is probably comparable to, and perhaps exceeds, that in any segment of the general population of similar age.
3. The coexistence of Kaposi’s sarcoma and leukemia or lymphoma in the same patient probably represents a morphologic variation of the same basic malignant disease of the reticuloendothelial system.
4. Any patient with leukemia or lymphoma who presents signs or symptoms of a focal malignant lesion should be regarded as having another primary lesion until proved otherwise on pathologic examination.
The Role of the Mature Neutrophil in Bacterial Infections in Acute Leukemia
Authors: SILVER RICHARD T. , BEAL GRACE A. , SCHNEIDERMAN MARVIN A. , MCCULLOUGH NORMAN B. 
Published: October 2019

Abstract
Its acute leukemia, phagocytosis of Brucella organisms by mature neutrophils was not impaired. Phagocytosis of these organisms was not altered by antimetabolite therapy or during periods of bacterial infection. The absolute mature neutrophil count when infection developed was found to vary from patient to patient. The onset of bacterial infection in patients with acute leukemia was preceded by dynamic decreases in the number of mature neutrophils in the peripheral blood. Seventeen of eighteen patients had lower mature neutrophil counts immediately prior to the onset of infection as compared to the period free of infection. The median decrease was 54 per cent. As infection did not always follow decreases in mature neutrophils it is suggested that other factors also play a role in the development of bacterial infections in patients with acute leukemia.
The Osmotic Resistance of Leukocytes in Peripheral Blood and Splenic Circulation of the Rabbit
Authors: STORTI E. , BELLESIA L. , LUSVARGHI E. 
Published: October 2019

Abstract
By studying the behavior of the resistance of leukocytes to hypotonic saline solution we have found that leukocytes leaving the spleen are much less resistant than those entering it.
It is felt that the change in resistance affecting leukocytes on their passage through the spleen is in all probability the manifestation of one of the mechanisms by which the spleen regulates the life span of leukocytes.
Serum 2-Hydroxyglutarate Level Is a Prognostic Marker in Acute Myeloid Leukemia
Authors: Wang Jing-Han , Chen Wen-Lian , Chen Tian-Lu , Zhu Yong-Mei , Zhang Wei-Na , Li Yang , Wu Song-Fang , Qiu Yun-Ping , Zhao Ai-Hua , Li Jun-Min , Mi Jian-qing , Jin Jie , Wang Yun-Gui , Huang He , Wu De-Pei , Li Yan , Yan Xiao-Jing , Yan Jin-Song , Li Jian-Yong , Wang Shuai , Huang Xiao-Jun , Jia Wei , Chen Zhu , Chen Sai-Juan 
Published: October 2019

Abstract
Abstract 1433

BACKGROUND
High levels of 2-HG in serum were found among AML cases with IDH1/IDH2 mutations. However, the impact of 2-HG levels on biological characteristics and clinical outcomes has not been systematically evaluated in a large cohort of AML patients.

METHODS
Serum 2-HG levels in 699 patients with hematologic malignancies, including 405 AML patients, were measured by GC-TOFMS. Clinical prognostic power of 2-HG and genetic risk factors associated with 2-HG were also evaluated in AML patients.

RESULTS
Among all patients with hematopoietic malignancies investigated, high serum 2-HG levels were observed only in AML group. 64 out of 405 (15.8%) AML patients displayed aberrantly higher levels (7.14±2.11μg/ml) of 2-HG. Compared to cases with normal 2-HG (3.65±1.02μg/ml), these patients showed a higher prevalence in AML-M0/M1 subtypes, a closer correlation with mutated IDH1/2 genes, a distinct gene expression profile and an aberrant DNA methylation status in bone marrow blasts. Additionally, the patients with high 2-HG were associated with higher serum levels of α-ketoglutarate (α-KG) and glutamate, suggesting presence of impaired metabolic pathway involved in the biosynthesis of 2-HG. Univariate and multivariate analyses indicate that high level of 2-HG is among the most significant negative indicators for complete remission (CR) rate, overall survival (OS) and event-free survival (EFS) either in all AML cases or in cases with cytogenetically normal AML (CN-AML).

CONCLUSIONS
Serum 2-HG is an independent prognostic marker in AML. Patients with high 2-HG had significantly higher frequency of IDH1/IDH2 gene mutations and unfavorable prognosis compared to those with normal 2-HG.

Disclosures:
No relevant conflicts of interest to declare.
Incidence and Outcomes of a Rare Translocation t(3,5) in Patients (pts) with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
Authors: Alattar Mona Lisa , Kantarjian Hagop M. , Cortes Jorge E. , Kadia Tapan M. , Borthakur Gautam , Ohanian Maro , Ravandi Farhad , Garcia-Manero Guillermo , Quintas-Cardamas Alfonso , Jabbour Elias , Daver Naval , Pierce Sherry A. , Brandt Mark , Faderl Stefan , Pemmaraju Naveen 
Published: October 2019

Abstract
Abstract 1456

Background:
Cytogenetic analysis of large pt cohorts allows us to evaluate the prognostic impact of rare and unique translocations. Little is known about the clinical outcomes of pts with t(3,5), which generally results in fusion of NPM and MLF1 in pts with MDS and AML.

Methods:
We retrospectively reviewed the charts of 8,215 pts with a diagnosis of MDS or AML evaluated at our institution from 1985–2011.

Results:
A total of 17 pts with a t(3,5) either at diagnosis or post-treatment were identified (10 pts, as the sole cytogenetic abnormality, and 7 pts, as part of other/complex karyotype). Among evaluable cases (15/17), frequently occurring breakpoints included q25;q34 (n=4), p21;q15 (n=2), and p21;q13 (n=2).10 pts had MDS with IPSS of Int-1(n=5) and Int-2(n=5), and 7 pts had AML. Four pts had therapy-related MDS (3 pts with prior lymphoma, 1 pt small cell lung cancer) and one pt with MDS had PNH. Median age was 56 years (range, 20–78) at diagnosis. Four pts (24%) had a FLT3-ITD mutation (3 with AML and 1 with MDS), 1 of these FLT3-mutated pts had additional mutations in c-KIT and NRAS mutation, 9 pts were tested and negative for molecular abnormalities, and 4 pts did not have molecular analysis available. Therapies were diverse, with two most common: cytarabine-based regimens (n=6) and hypomethylating agent-based therapy (n=6). Overall, median number of therapies for all pts was 1 (range, 0–5), including 2 pts treated with upfront stem cell transplant (SCT) and 1 pt treated with only growth factors/supportive care. Six pts (35%) (MDS 3 pts, AML 3 pts) underwent SCT during their course of therapy (including 1 cord blood, 1 SCT with NK cells, and 4 allogeneic MUD SCT). Overall median survival for pts with MDS was 8.1 months (range, 1–57) and for pts with AML, 21 months (range, 2–53). CR was achieved overall in 12 pts (71%) with median CR duration of 3.2 months (range, 1–60 months). Three (18%) pts were refractory to all chemotherapy and one pt died during induction chemotherapy (infection and diffuse alveolar hemorrhage). One pt never received treatment.

Conclusions:
Survival is particularly poor among patients with MDS and t(3;5) while those with AML have survival comparable to normal karyotype (NK) AML. Further investigation with novel treatment approaches is warranted in this subpopulation of MDS/AML pts.

Disclosures:
No relevant conflicts of interest to declare.
Long-Term Efficacy of Low-Dose All-Trans Retinoic Acid Plus Individually Adapted Chemotherapy Induction Followed by Arsenic Trioxide Based Post-Remission Therapy in Adults with Newly Diagnosed Acute Promyelocytic Leukemia
Authors: Lou Yinjun , Jin Jie 
Published: October 2019

Abstract
Abstract 1480
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myelogenous leukemia (AML), which usually presents with pancytopenia, coagulopathies and bleeding. Molecular studies have revealed that it was caused by leukemogenic PML-RARA fusion gene resulting from a specific chromosomal translocation t(15;17). The administration of target agent all-trans-retinoic acid (ATRA) combined with anthracycline-based chemotherapy for induction and consolidation followed by ATRA plus low-dose chemotherapy maintenance is the standard strategies for patients with newly diagnosed APL. However, despite the high cure rate, early death and leukemia relapse are the two main important obstacles. We evaluated the efficacy of low-dose All-trans-retinoic acid (ATRA) plus individually adapted chemotherapy for induction followed by arsenic trioxide (ATO) based post-remission therapy in newly diagnosed acute promyelocytic leukemia (APL). From January 2004 to September 2011, 109 patients with APL were enrolled the study. The complete remission (CR) rate was 96.3%. The early death rate was 0.9%. Two arms were assigned according to post-remission protocols: ATO group cases were treated with standard chemotherapy, ATO, and ATRA. Without ATO group cases were subsequently treated with chemotherapy and ATRA only. Patients were monitored by reverse transcriptase-polymerase chain reaction (RT-PCR) during and after treatment. The six-year relapse-free survival (RFS) was significantly better for patients in ATO group than in without ATO group, 94.4% versus 50.6% (P < 0.0001) and the six-year overall survival (OS) rate was 95.7% versus 64.1%, in two groups (P = 0.003). This study shows that low-dose ATRA plus tailored chemotherapy is effective in induction therapy, and the addition of ATO to post-remission therapy significantly improves the long-term outcome.

Disclosures:
No relevant conflicts of interest to declare.
Tumor Associated Macrophage Expression, CD163, Is Associated with Poorer Outcome in Diffuse Large B-Cell Lymphoma
Authors: Bohn Olga L. , Maragulia Jocelyn C. , Crispin Hilda , Gonzalez Camille , Miething Cornelius , Zelenetz Andrew D. , Teruya-Feldstein Julie 
Published: October 2019

Abstract
Abstract 1583

Background:
Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma with various subtypes. Recent data of Tumor Associated Macrophages (TAM) in DLBCL have shown association with poor overall survival. We were interested in assessing these markers, in particular, for practical daily clinical use at a high volume cancer center. We therefore performed a retrospective study to evaluate expression of macrophage markers (CD68 and CD163) in DLBCL and determine overall survival (OS) and event free survival (EFS).

Design:
A total of 128 DLBCL cases were reviewed. Tissue microarrays (TMA) were constructed with cores in triplicate. CD163 and CD68 expression was assessed by immunohistochemistry (IHC) using anti-CD68 (KP-1, Ventana) and anti-CD163 (Vector Laboratories) performed on the automated Ventana XT platform according to manufacturer protocols (Tucson, AZ). The assessment of intratumoral CD163 infiltration was performed at objective magnification 40X by three observers (OB, HC and JTF) and a consensus was obtained. The number of CD163 macrophages was counted in three cores. The mean was calculated and the results were scored as follows: 0 (0 to 25 positive cells); 1 (between 26 to 50 positive cells); 2 (51 to 75 positive cells); 3 (76 to 100 positive cells). CD68 expression was assessed by IHC and the degree of intratumoral infiltration was scored as follows: 0 (less than 5% positive cells); 1 (between 5% to less than 50% of positive cells); 2 (more than 50% positive cells). Of 128 patients, 13 had limited clinical data, 23 were biopsies at relapse, and 92 were evaluable for OS and EFS from initial therapy. EFS was defined as progression of disease, secondary malignancy, or death due to disease or any other reason. OS was calculated from date of death or last follow-up date to date of diagnostic biopsy. EFS was calculated from event date or date of last follow-up to end of treatment date. SPSS software was used to calculate Kaplan Meier survival curves and statistics.

Results:
There were 51 (55%) males and 41 (45%) females (M:F ratio 1.2). The median age was 60 years (range from 10 to 90). A high number of tumor infiltrating CD163 expression (scores 0 [n=19], 1 [n=6], 2 [n=9] vs 3 [n=58]) was associated with significantly poorer OS (p=0.028) and EFS (p=0.005). A statistically significant difference was observed in patients with tumors that had abundant tumor associated macrophages with CD163 (score 3 >75 positive cells) on IHC. CD68 expression did not correlate with OS and EFS.

Conclusion:
High CD163 expression is statistically significantly associated with decreased OS and EFS in DLBCL. Because of cleaner staining, scoring on a daily practical basis in a high volume center is useful. Our data supports initial few prior reports of this marker in DLBCL.

Disclosures:
No relevant conflicts of interest to declare.
Salvage Treatment with Ofatumumab and ESHAP (O-ESHAP) for Patients with Relapsed or Refractory Classical Hodgkin's Lymphoma After First-Line Chemotherapy: Interim Analysis of a Phase II Trial of the Spanish Group of Lymphoma and Bone Marrow Transplantation (GELTAMO)
Authors: Martinez Carmen , Rodriguez-Calvillo Mercedes , Terol María José , Xicoy Blanca , García-Sanz Ramón , Perez-Ceballos Elena , Cantalapiedra Alberto , Domingo-Domènech Eva , Hernández Miguel , Sampol Antonia , Espeso Manuel , Briones Javier , Lopez Javier , Sureda Anna 
Published: October 2019

Abstract
Abstract 1630
The management of recurrent or refractory Hodgkin's lymphoma (HL) remains challenging. Previous published data have suggested that infiltrating normal B lymphocytes in classic HL lesions may contribute to the survival of Hodgkin and Reed-Sternberg cells in vivo. The objective of this prospective, multicenter, phase II trial was to investigate the activity of an anti-CD20 monoclonal antibody, ofatumumab, in combination to a standard platinum-based salvage regimen, ESHAP (O-ESHAP) followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) for patients with classical HL failing to first line chemotherapy. Forty- five patients (25 M / 21 F, median age 34 years, range 18–66) were enrolled in the study between June 2010 and June 2012. Treatment consisted on three cycles of ESHAP plus ofatumumab 1,000 mg days 1 and 8 on first cycle and day 1 on second and third cycles. At the time of study entry, 66% of patients had III-IV Ann Arbor stage, 16% bulky disease, 18% B symptoms, 40% extranodal HL and 52% ≥3 involved nodal areas. We respect to response to first-line therapy, 46% patients had achieved a completed response (CR) and then relapsed, 6% had a partial remission (PR), whereas the remaining 48% were primary refractory. Eighty-one percent patients have received 3 cycles of O-ESHAP as scheduled, three patients 2, and five 1 cycle (1 patient due to toxicity, 1 patient's decision, 2 HL progression, and 4 treatments ongoing). Grade 3–4 WHO hematological toxicity was observed in 16%, 19%, and 20% after cycles 1, 2, and 3, respectively. Non-hematological toxicity was reported in 32%, 10%, and 20%, respectively. Overall response (OR) rate was 63% (49% CR and 14% PR). Response to O-ESHAP according to prior response to first-line chemotherapy is shown in table 1. Adequate PBSCs collection was achieved in 94% mobilized patients. Twenty-six out of 33 patients have already proceeded to ASCT. Two patients died of neutropenic sepsis after ASCT and HL progression, respectively. Preliminary results of this ongoing trial suggest that addition of ofatumumab to ESHAP is safe and has a promising clinical activity in patients with relapsed/refractory HL candidates to ASCT.
Table 1. Response to O-ESHAP according to previous response to first-line treatment Response to first-line chemotherapy Relapsed or partial response (n=17) Refractory (n=16) Response after O-ESHAP OR 16 (94%) 7 (44%) CR 14 (82%) 3 (22%) PR 2 (12%) 4 (22%) Refractory 1 (6%) 9 (56%)

Disclosures:
No relevant conflicts of interest to declare.
A Single Nucleotide Polymorphism in the Coding Sequence of BIM Is Associated with Poor Prognostic in Chronic Myeloid Leukaemia Treated by Imatinib
Authors: Mahon Francois-Xavier , Augis Vanessa , Airiau Kelly , Josselin Marina , Turc Beatrice , Belloc Francis 
Published: October 2019

Abstract
Abstract 1683
BIM is a pro-apoptotic protein essential to tyrosine kinase inhibitors (TKI) response in chronic myeloid leukaemia (CML) patients. Thus, mutations in BIM sequence could lead to imatinib resistance independently of BCR-ABL mutations. Recently, a deletion polymorphism in intron 2 of BIM was demonstrated to confer intrinsic TKI resistance in asiatic patients (Ng et al, nature medicine, 2012). However the Caucasian population is not concerned by this intronic deletion polymorphism. So, in the current study we performed BIM coding sequence analysis in 72 CML imatinib-treated patients and among them 40 were resistant to imatinib in our center from French population of patients. For twenty patients, the disease evolved in either acceleration or blastic phases at least once during the study. We did not find any mutation with amino-acid change in the BIM coding sequence. However, we observed a silent single nucleotide polymorphism (SNP) c465C>T (rs724710) in the region coding for the active BH3 domain. A strong statistic link was found between the presence of the T allele of this polymorphism and the Sokal high risk group (p=0.0065). The frequency of the T allele was found higher in non responsive patients than in a local healthy donor reference population (p=0.0049). Similarly, the analysis showed an association of this T allele with the frequency of mutations on the tyrosine kinase domain of BCR-ABL (p<0.001) but not with additional chromosomal alterations. Moreover, the presence of the allele T significantly lengthened the time of achievement of major molecular remission. Finally, the presence of the T allele was found related to a decreased basal expression of the Bim mRNA in the circulating mononuclear cells of healthy donors. These results suggest that analysis of the c465C>T SNP of BIM could be useful for predicting the outcome of CML patients under imatinib treatment.

Disclosures:
Mahon: Novartis Pharma: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy.
The IRON2 Study. A Retrospective Observational Study to Describe the Evolution of Iron Overload in Patients with Low-Risk Myelodysplastic Syndrome
Authors: Remacha Angel , Arrizabalaga Beatriz , Villegas Ana , Duran Maria Soledad , Hermosin Lourdes , de Paz Raquel , García Marta , García Regina , del Cañizo Consuelo , Sanz Silvia , Sanz Guillermo 
Published: October 2019

Abstract
Abstract 1723

Introduction and Objective:
A large number of patients with low-risk myelodysplastic syndrome (MDS) need blood transfusions, being iron overload an inevitable consequence that may cause hepatic fibrosis and cirrhosis, diabetes or myocardiopathy unless it is not treated. The main objective of this study is to describe the evolution of iron overload in transfusion-dependent patients with low-risk MDS. Secondary objectives include the evaluation of the impact of iron chelation therapy on Event Free Survival (EFS) (including infections, arthropathy, diabetes mellitus, hepatic and cardiac complications), Overall Survival (OS) and Leukemia Free Survival (LFS).

Methods and Patients:
Retrospective observational study carried out in Haematology Departments of 47 Spanish hospitals between March 2010 and March 2011. Transfusion-dependent patients with low/intermediate-1 IPSS risk who had received ≥10 red blood cell (RBC) transfusion during at least 12 months previous to study entry were eligible.

Results:
A total of 263 patients were evaluated [age at diagnosis, 74 ± 10.5 years]. IPSS classification was available in 82.9% included patients (lack of cytogenetics in 37 patients), classified as low risk (86%) and int-1 risk (14%). At diagnosis, 25.5% of patients had serum ferritin (SF) levels >500ng/ml, 8.7% SF>1,000ng/ml, and 22% TSI>50%. The median number of RBC transfusions per month was 2.35 RBC/month; during the course of the disease, 82.4% of patients reached SF levels >1,000ng/ml. Cardiac complications worsened/appeared in 24.4% of patients, having received a median RBC transfusions of 22 (7–92), and showing a median SF levels of 1,365 (735–3,025) ng/ml. One-hundred forty-seven (55.9%) patients started iron chelation therapy (85.5% with deferasirox) with a median number of RBC transfused of 23 (14–38) and a median SF levels of 1,570 (1,231.5–2,195) ng/ml. 71% of patients with SF>1,000ng/ml were on iron chelation therapy. Table 1 shows the results of univariate analysis of EFS, OS and LFS. As part of this study, we are currently performing a multivariate analysis whose results will be presented in forthcoming congress.

Conclusions:
The results of this study show that a high percentage of transfusion-dependent patients with low-risk MDS (82.4%) reach SF levels >1,000ng/ml during the course of their disease. Patients on iron chelation therapy show a higher cardiac EFS, OS and LFS compared with those not treated, being deferasirox the most frequently used chelating agent in clinical practice.

Disclosures:
Sanz: Novartis Farmaceutica S.A.: Employment.