bluuebunny/crossref_metadata_2025 huggingface dataset:
PB2043 UPPER AND LOWER GASTROINTESTINAL ENDOSCOPY FINDINGS IN PATIENTS WITH ISOLATED FERRITIN DEFICIENCY
Authors: Bahadir A. , Sağ E. , Çakır M.
Published: June 2019

Background:

Iron deficiency without anemia is the most common nutritional disorder in children. Iron balancing is provided by intestinal absorption and iron transfer mechanisms. The most common causes of anemia are chronic blood loss from the gastrointestinal tract (peptic ulcer, hemorrhoids, parasites), inadequate dietary intake, gynecological problems (menorrhagia), decreased gastrointestinal mucosal absorption (celiac disease), Helicobacter pylori (Hp) infection and autoimmune gastritis. In the literature, there are not many studies about iron deficiency without decreasing hemoglobin (Hg) levels in the early period of iron deficiency.

Aims:

In our study, we aimed to evaluate the lower and upper endoscopic findings of patients with normal Hg levels and low ferritin levels.

Methods:

A total of 2391 patients aged between 0‐18 years and had normal Hg levels were included into the study performing upper and lower gastrointestinal system (GIS) endoscopy by the pediatric gastroenterology‐hepatology department between 2009 and 2018. The patients were divided into two groups as Hb level was normal, ferritin level below 15 mg / dl (group 1; n = 549) and Hb level was normal, ferritin level was above 15 mg / dl (group 2; n = 1143). In group 1, upper GIS endoscopy was performed to 520 patients, lower GIS endoscopy to 56 patients. In Group 2, upper GI endoscopy was performed to 1095 patients and lower GI endoscopy to 120 patients. All endoscopy results of the patients were evaluated and compared.

Results:

The most common complaint was abdominal pain in both groups (63%, 67.4%, respectively). And the most common endoscopic findings in both groups were reflux esophagitis in the esophagus (9.6%, 9.1%, respectively, p>0.05), gastritis in the stomach (32.1%, 37.9%, respectively, p > 0.05). Hp gastritis was the second most common endoscopic finding in group 1. When the both groups were compared, there was a significant difference between group for Hp gastritis (24%, 27.6%, respectively, p = 0.002). In duodenum findings, celiac disease was higher in group 1 and there was a significant statistically between group for celiac disease (6%, 2.1%, respectively, p = 0.000). In colonoscopic examination, lymphoid nodular hyperplasia and polyp were higher in group 1 and there were statistically significant between groups (14.3%, 5%, and 10.7%, 3.3% respectively, p = 0.03, 0.04).

Summary/Conclusion:

In the literature, generally the studies are about anemia and upper GIS findings. In our study, the patients with decreased ferritin and normal Hg levels and undergoing upper and lower GIS endoscopy were investigated. The risk of Hp gastritis and celiac disease was found to be increased in patients with ferritin deficiency without anemia (group 1). In addition, lymphoid noduler hyperplasia and polyps were also caused ferritin deficiency.
PB2056 ORBITAL LYMPHOMA: CLINICAL AND EPIDEMIOLOGICAL PATTERNS WITHIN THE UNITED STATES
Authors: khalafAllah M. , gouda M.
Published: June 2019

Background:

Lymphomas are relatively common tumors that may affect the orbit through tissue infiltration. However, data available about tumors possibly originating in orbit (also called orbital lymphoma) are scarce.

Aims:

In this study, we aimed to spotlight on this type of malignancy using the using data from American National Cancer Institute, Surveillance, Epidemiology, and End Results (SEER) Program.

Methods

We used SEER∗Stat version 8.3.5, Microsoft Excel, as well as SPSS IBM SPSS Statistics for Windows, Version 25.0 for data analysis. In SEER∗Stat, we used the (Incidence ‐ SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2017 Sub (1973‐2015 varying)) database to obtain data. We included cases diagnosed with lymphoma between 2006 and 2015 at site related to orbital cavity C69.0‐C69.9.

Results:

A total of 2340 cases were identified with a median age of 65.2. Females and patients of white race represented the majority of the analyzed cohort (n = 1249, 53.4%; n = 1846, 78.9%, respectively). Age‐adjusted Incidence rate was 3 per 10,000. 5‐years observed survival was 82% (95% CI: 79.8% ‐ 84%) while the 5‐years relative survival was 94.3% (95% CI: 91.3% ‐ 96.2%). The most common pathology of studied cases was extranodal marginal zone lymphoma of mucosal‐associated lymphoid tissue (MALT) (n = 1310, 56%) [Table 1]. Median survival was not reached at the study cutoff (Figure 1).

Summary/Conclusion:

Orbital lymphoma has an incidence rate of 3 per 10,000. These tumors are more likely to occur in old age, females, and white race. Survival data are relatively good with the 5‐years relative survival being 94.3%.

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PB2063 HAIRY CELL VARIANT–LABORATORY FINDINGS OF A CASE SERIES
Authors: Chereghini A. , Gonclaves M. , Daniel D. , Silva R. , Maekawa Y. , Muramoto F. , Tamashiro N. , Takao T. , Sandes A. , Silva M.
Published: June 2019

Background:

Hairy cell leukemias are rare mature B‐cell neoplasms that morphologically present cytoplasmatic projections. According to the most recent World Health Organization Classification, they can be Classic (HCL) or Variant (HCLv). These two diseases present important clinical and laboratory differences. HCLv is the rarest of them with an incidence of less than 1 case:1.000.000 inhabitants/year. Unlike HCL, HCLv generally presents with elevated blood counts, there is no monocytopenia and the abnormal cells present an identifiable nucleolus. HCLv cells do not express CD25 or present BRAF mutation mutations, findings that are almost universally present in HCL.

Aims:

The aim of this study was to describe the laboratory findings of all HCLv cases diagnosed at Grupo Fleury from 2015 to 2018.

Methods

A retrospective descriptive study of the laboratory findings of all HCLv cases diagnosed at Grupo Fleury from 2015 to 2018. Complete blood counts were obtained with a Sysmex XE 5000 counter and submitted to morphology review. Blood or bone marrow immunophenotypic prophiles were obtained using an 8‐color FACS Canto II cytometer for acquisition and Inifinicyt for analysis. Antibodies against CD3, CD4, CD5, CD8, CD10, CD11c, CD19, CD20, CD22, CD23, CD25, CD38, CD45, CD56, CD79b, CD103, CD123, CD200, KAPPA, LAMBDA, FMC7, IgM, IgD, IgG and IgA were used.

Results:

7 cases were diagnosed during this period (0.04% of all of suspected oncological cases submitted immunophenotyping). Median age was 86 years old (range: 58‐89), and 3 were males. Median CBC values were [median (range)]: hemoglobin = 10.1 g/dL (8.8‐12.7); lymphocytes = 2.4 × 109/L (1.4‐16.5); monocytes = 0.53 × 109/L (0.2‐3.1); platelets = 91 × 109/L (76‐97, and an outlier of 1.106 × 109/L). No cases presented monocytopenia Flow cytometry (5 of peripheral blood and 2 of bone marrow aspirate), demonstrated universal positivity for CD19, CD20, FMC‐7, CD103, and CD11c (partial expression in one case). No case demonstrated CD5, CD10, CD25, CD38 or CD123. Of note, CD200 expression was negative or mild in all cases. Five cases were IgM+/IgD+, one IgM+, and the other was IgG+. Two demonstrated kappa expression and 5 were lambda light chain restricted. Karyotype was normal in all of the 3 cases analyzed.

Summary/Conclusion:

Flow cytometry, along with morphology, was the main sources of diagnosis, as no specific genetic alteration is known. The presence of CD103 and CD11c in the absence of CD123 and CD25 suggest HCLv, excluding classical HCL. CD200, classically strongly expressed in classical HCL was negative or only weakly expressed in HCLv and may help on diagnosis.
PB2064 USE OF RNASCOPE TECHNOLOGY TO DETERMINE STAT‐3 EXPRESSION IN HUMAN DIFFUSE LARGE B‐CELL LYMPHOMA
Authors: Tamma R. , Gaudio F. , Ingravallo G. , Albano F. , Perrone T. , Annese T. , Ruggieri S. , Maiorano E. , Specchia G. , Ribatti D.
Published: June 2019

Background:

Diffuse large B‐cell lymphoma (DLBCL) is the most common and one of the most heterogeneous lymphomas. Therefore, it is critical to further stratify cases of DLBCL into biologically similar and clinically meaningful subgroups, which will not only guide prognostic assessment and facilitate therapeutic decisions, but also stimulate further research to understand the pathogenesis and develop potential novel treatments.

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that exerts important biological functions related to cell proliferation, differentiation, survival, angiogenesis and immune response.

Aims:

In this study, we used RNAscope technology in order to evaluate STAT3 RNA expression in human DLBCL in selected groups of activated B‐cell–like DLBCL (ABC‐DLBCL) patients and germinal center B‐cell–like DLBCL (GBC‐DLBCL) patients.

Methods

This retrospective study reviewed data from patients diagnosed with DLBCL collected from the archive of the Section of Pathology of the University of Bari, Hospital Policlinico, Bari, Italy, between 2009 and 2013. All patients had pathologically confirmed DLBCL. Tumors were divided into two histological subgroups: one that includes ABC patients and another that includes GCB patients.

Results:

The results have shown that ABC DLBCL tissue samples contained more STAT3‐positive cells as compared with GCB tissue samples. Moreover, the immunofluorescence analysis showed that tumor vessels in ABC samples appeared lined by endothelial cells expressing both FVIII and STAT3 signals, while in GCB samples, only few vessels expressed both FVIII and STAT3. These data confirm other reports showing that STAT3 is highly expressed and activated in ABC‐DLBCL samples and the tumor vessels appeared lined by endothelial cells expressing both FVIII and STAT3.

Summary/Conclusion:

An improved understanding of tumor biology and the role of the tumor microenvironment has led to advances in the diagnosis, classification, prognostics, as well as novel treatments of patients with hematologic malignancies. Ongoing dynamic and correlation studies of tumor biology and the contribution of the tumor microenvironment should be promoted in the context of novel drug development in order to identify optimal therapies for various lymphomas, and improve the curability of these diseases.
PB2066 DAMAGE OF THE TP53 GENE POLYADENYLATION SIGNAL IN DLBCL
Authors: Voropaeva E. , Pospelova T. , Voevoda M. , Maximov V. , Kolesnikova M.
Published: June 2019

Background:

Single nucleotide replacement rs78378222 lead to change of the normal TP53 gene polyadenylation signal and cause disorders of processing of 3′‐end of mRNA. The experimental data have suggested that rare allele C of the rs78378222 leads to much lower level of TP53 expression and decrease the apoptosis induction level in cells under the influence of genotoxic agents in comparison with allele A. Thus, rs78378222 is thought to be the unique allele variant of TP53 gene with the reduced p53 function.

Aims:

The purpose of the present study was to reveal the frequency of the rs78378222 of TP53 in tumor tissue of the patients with diffuse large B‐cell lymphoma (DLBCL).

Methods

Genomic DNA was isolated from formalin‐embedded paraffin blocks of lymph nodes and extranodal tumor lesions biopsies of 92 patients with DLBCL by phenol‐chloroform extraction method using guanidine. The tissue sections containing at least 70‐80% of the tumor cells were taken. Genotyping of the rs78378222 was performed by the PCR‐RFLP method. To confirm the presence of rare allele C of the rs78378222 Sanger's direct sequencing was performed.

Results:

The frequency of the rs78378222 in DLBCL tumor tissue was 9/92 (9.8%). It was noted that 5 of 9 patients had minor allele C in the homozygous state. Since the detection of cases of the rare homozygous genotype C/C of the rs78378222 in normal tissue has not described previously, the received results indicated a loss of heterozygosity in the TP53 gene in DLBCL tumor tissue of rs78378222 carriers. Only two of these cases were combined with mutations in the gene. In three cases ‐ loss of heterozygosity was the only aberration in TP53.

Summary/Conclusion:

Aberrations in 3′‐UTR of TP53 gene may be a universal carcinogenesis mechanism, playing role in pathogenesis of DLBCL as well. The loss of normal allele A rs78378222 stimulates the significant growth of cells malignant potential.
PB2076 MOLECULAR CYTOGENETIC ANALYSIS OF CHROMOSOME 7 ABERRATIONS IN MYELOID DISEASES
Authors: Ransdorfova S. , Onderkova M. , Brezinova J. , Sarova I. , Valerianova M. , Svobodova K. , Lhotska H. , Pavlistova L. , Lizcova L. , Michalova K. , Zemanova Z. , Jonasova A. , Stopka T. , Cermak J.
Published: June 2019

Background:

Complete or partial loss of chromosome 7 is a recurrent chromosomal aberration frequently found in myeloid disorders such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). This finding is an important prognostic indicator associated with poor response to the treatment and faster disease progression.

Aims:

(1) to determine the breakpoints on the long and short arm of chromosome 7 using FISH with locus‐specific probes; (2) to specify the frequency of these rearrangement; and (3) to evaluate overall survival [OS] of patients with chromosome 7 alteration.

Methods:

Diagnostic bone‐marrow samples of 46 adults with AML/MDS and with chromosome 7 aberration were examined. Karyotypes were analyzed using conventional and molecular cytogenetic techniques: FISH (Abbott, Kreatech), mFISH/mBAND (MetaSystems) and array CGH/SNP (Illumina, Agilent).

Results:

Monosomy 7 as a sole chromosomal abnormality was found in seven patients. Isolated deletion 7q was proved in one case only. In 38 cases, chromosome 7 aberrations were detected in combination with other changes (n = 16) or as a part of complex karyotype (n = 22). The most frequently altered regions on the long arm were identified in bands 7q22, 7q31 and 7q33‐7q36. In 17 patients (37%), deletion of the EZH2 tumor suppressor gene located in band 7q36.1 was found. The most frequently altered regions on the short arm were identified in bands 7p11‐p12. Rearrangements of 7p were always associated with other chromosomal alterations, the isolated 7p aberration was not proved. In 14 patients (30%), structural aberrations of both short and long arm 7p/7q were detected. In two cases, acquisition of additional clonal aberrations was observed during the disease. OS of the whole group was 6.45 months.

Summary/Conclusion:

In our cohort, the rearrangement of 7p as a sole aberration was not observed. A large heterogeneity of breakpoints was confirmed on the long arm 7q. High instability of chromosome 7 together with other chromosomal changes represent a marker of poor prognosis and is associated with rapid disease progression. In patients with myeloid malignancies, early detection of 7p/7q aberrations is important to precise prognostication and treatment decision.

Supported by MH CZ‐DRO (IHBT, 00023736), RVO‐VFN64165, GACR P302/12/G157, Progres Q28/LF1.
PB2079 INCIDENCE OF MBL AT MDS DIAGNOSIS AND CLINICAL IMPLICATIONS
Authors: Pardalis V. , Dimou M. , Iliakis T. , Bitsani A. , Papaioannou P. , Koudouna A. , Kalyva S. , Markopoulos A. , Grafakos I. , Kyrtsonis M.‐C. , Panagiotidis P.
Published: June 2019

Background:

Monoclonal B lymphocytosis (MBL) which is characterized as asymptomatic monoclonal expansion of< 5 × 109/L circulating B cells has been reported in 5.5% of adults > 65 years of age in the general population (Ghia P et al. Blood 2004). MBL can have the immunophenotype of CLL (CD5+, CD23 + )‐CLL like, however less than 20% have non‐CLL phenotype (CD5‐, CD23‐). They rarely progress to CLL or lymphoma and do not require treatment (Xocheli A et al. Blood 2014). Coexistence of MBL and myelodysplastic syndromes (MDS) is a known phenomenon (Cauwalier et al. Leuk Lymphoma 2002); however the true incidence and the clinical impact of this phenomenon is poorly studied.

Aims:

We analysed the incidence of concurrent diagnosis of MBL and MDS in the whole cohort of newly diagnosed MDS patients (pts), who referred at our centre between 1/2014 and 1/2019.

Methods

We retrospectively collected data from all the newly diagnosed MDS pts in our centre between 1/1/2014 and 2/1/2019. In particular, we focused on patients’ demographics (gender, age), MDS risk category, incidence of random detection of an MBL population either with immunophenotype or immunohistochemistry in bone marrow and/or peripheral blood and treatment data.

Results:

Eighty one pts were referred and diagnosed with MDS in our centre during the aforementioned period: 23 female and 52 male with median age of 76 years (range 44‐92), 23 (28.4%) low, 33 (48,1%) Intermediate‐1, 17 (21%) Intermediate‐2 and 2 (2.5%) high IPSS risk score. In 7 (8.6%) pts concurrent MDS and MBL was found. In 4 (4.9%) pts an MBL CLL‐like population and in 3 (3.7%) a non‐CLL‐like population was detected. Six of these 7 pts were treated for MDS: 4 with azacytidine, one with lenalidomide (del 5q MDS) and 1 with danazol. One of those pts was diagnosed with Diffuse Large B cell Lymphoma of peritoneal cavity 15 months after the initiation of azacytidine for MDS and he died after 2 cycles of R‐CHOP regimen. MDS status at the time of death was partial response. No evolution of MBL was presented in the other 6 patients.

Summary/Conclusion:

Coincidence of MBL in MDS patients in our centre was 8.6%, which is higher than the reported rate for the general population of the same age (5.5%). Despite the fact that in only one patient with MDS, MBL transformed to DLBCL, question between the relationship of MDS and MBL still remains. Issues like impact of MDS therapy to the possibility of transformation of MBL to aggressive B cell lymphomas and relationship between age and coexistence of MBL in MDS patients have to be further elucidated.
PB2082 PHENOTYPIC ALTERATIONS IN CHRONIC MYELOMONOCYTIC LEUKEMIA: SIMILARITIES AND DIFFERENCES MYELODYSPLASTIC SYNDROMES
Authors: Marques J. R. , Pereira‐Cunha F. G. , Duarte G. B. O. , Lorand‐Metze I.
Published: June 2019

Background:

Recently, 3 types of monocytes have been characterized by immunophenotyping in chronic myelomonocytic leukemia (CMML). Increase in monocytes in bone marrow (BM) may also be found in myelodysplastic syndromes (MDS). In a previous study using multiparameter flow cytometry to study BM myeloid precursors in MDS we found monocyte increase in 21% of the patients, with similar frequencies in RAEB and low risk MDS, but this was associated with a worse overall survival.

Aims:

to study the phenotypic characteristics of BM myelomonocytic precursors and CD34+ progenitors in CMML and compare them with findings observed in MDS.

Methods

we studied cases of CMML and low risk MDS entering our Laboratory in 2018. Bone marrow (BM) was collected at the diagnostic work‐up. Diagnosis and classification of the cases was made by WHO 2016 criteria based on peripheral blood counts, BM morphology and cytogenetics. Cases of transitory peripheral cytopenias presenting normal results were used as controls. Immunophenotyping of BM cells was made with and 8‐color platform according to Euroflow. A minimum 300000 cells were acquired.

Results:

We examined 24 cases of MDS (age 27‐88 years), and 19 CMMLs (age 55‐90 years) which were compared with 12 controls (age 25‐79 years). Concerning immunophenotypic features, SSC of granulocytic precursors/SSC of lymphocytes <6 was seen in 10 MDS and in 9 LMMC cases. Abnormal antigen expression in granulocytic precursors was observed in 11/23 MDS (0 alterations = 12, 1 = 5 and 2 = 6) and 11/17 CMML (0 alterations = 7, 1 = 7 and 2 = 5). Total monocytes were increased in all CMMLs but also in 15 cases of MDS, with similar proportions of classical monocytes (median 94.7% and 93.1% respectively), but increase in monocytes in CMML was mostly dependent on increase in classical monocytes, while in MDS both classical and non‐classical forms increased. Myeloid CD34+ progenitors were >2% in 4 cases of CMML but in none of the MDS cases. Total lymphocytes increased in MDS, but decreased in CMML. In these later, the decrease was more prominent in mature B‐cells, but occurred also in T CD4+ cells.

Summary/Conclusion:

Immunophenotyping of BM in CMML discloses several abnormalities of monocytic but also of granulocytic precursors, similar to MDS. Besides, decrease in lymphoid cells is similar to what has been described in juvenile myelomonocytic leukemia but different from those seen in low risk MDS.
PB2085 ENVIRONMENTAL AND OCCUPATIONAL DETERMINANTS OF MYELODYSPLASTIC SYNDROMES: EXPOSURE, ASSOCIATION AND RISK: A CASE CONTROL STUDY FROM PAKISTAN
Authors: Anwar N. , Arshad A. , Fatima N. , Sharif S. , Zaidi M. , Shamsi T.
Published: June 2019

Background:

Myelodysplastic syndromes are heterogeneous group of haematopoietic stem cell disorders and have a variable reduction in the production of red cells, platelets, and mature granulocytes. Previous studies have emphasised the possible association of disease with environmental and occupational factors.

Aims:

In Pakistan and the surrounding regions, patients do not have access to prompt diagnostic and treatment facilities. Moreover, the characteristics of many patients, such as a low literacy rate, exposure to hazardous chemicals, inadequate access to milk and water, and habitual narcotics use, make them more vulnerable to diseases like MDS at an early age compared with patients in the western world. In this regard, we hypothesised to sketch a roadmap for our patients to identify risk factors in their daily routines and make them aware of related causal factors that ultimately could lead to life threatening disorders like MDS and thus minimise their disease burden. With this background and rationale, we conducted a case control study that evaluated environmental and occupational determinants as risk factors for MDS patients. To the best of our knowledge, this is the first study conducted in Pakistan in this context.

Methods

This was a case control study carried out at the National Institute of Blood Diseases and Bone Marrow Transplantation. The participants included 153 de novo MDS cases and 447 age and sex matched controls. Disease characteristics, sociodemographics and exposure to chemicals were collected through a questionnaire. The chi squared test was applied for finding associations between categorical variables, and binary logistic regression was applied to find odds ratios for significant variables.

Results:

Among the study participants (n = 600), there was a significant association between cases and controls regarding marital status, type of job, educational status and arsenic (p < 0.0001). There was also significant difference found in study group with language (p = 0.037) and benzene (p = 0.021). The association with residency in rural and urban areas, and milk and water source was not found significant.

Summary/Conclusion:

We concluded that people in developing countries such as Pakistan could be at higher risk than those in industrialized countries of getting diseases like MDS owing to the unrecognised exposure to perilous environmental and occupational factors. This study will be helpful to understand the aetiology of MDS in Pakistani population.
PB2086 LOW RISK MYELODYSPLASTIC SYNDROMES (LRMDS) RESPONSE TO ERYTHROPOIETIN MIGHT BE ENHANCED BY DIFFERENT IRON FORMULATION INFLUENCING BONE MARROW METILATION PATTERNS AND MACROPHAGES POLARIZATION
Authors: Giordano G. , Lucchesi A. , magri M. , niro G. , gasperi M.
Published: June 2019

Background:

Iron status influences dna methylation. External factors as liposomes may switc‐off bone marrow macrophages M1 polarization that is related to inflammatory status. These things are important in ineffective hemopoiesis in LRMDS.

Aims:

To see if sucromial iron and sodium ferrigluconate support in LRMDS shows different dna metilation patterns and macrophages polarization in bone marrow.

Methods

This study is a retrospective nonrandomized study. 45 patients with low risk refractory anemia receiving support with erythropoietin 40000 UI two times/week, b12 300 mg/day and folate 15 mg/day were divided in 3 group of 15 patients. Group A received i.v. sodium ferrigluconate 65 mg/day for 7 days/month, group B received sucrosomial iron tablets every other day, group C don’t received iron. No significant differences among median Hb level (9.5 g/dl), median age (65 yo), sex, karyotype, sEpo, ferritin, Tsat, IPSS, transfusion need, were in the three groups.

Follow‐up period was 6 months.

The bone marrow M1 proinflammatory macrophages (iNOShigh/CD163low/CD14 + ) and M2 antiinflammatory (iNOSlow/CD163high/CD14‐) were analyzed by cytofluorimetry and dna methylation with methylation‐specific PCR.

Bone marrow aspiration, M1 and M2 count, dna methylation, Hb level, transfusion need, ferritin and tsat level, CRP were recorded bimonthly.

Results:

All results were recorded at time 0, 2, 4 and 6 months.

M1% was 1, 0.8, 0.7, 1 in group A, 1.2, 0.9, 0.6, 0.4 in group B, 0.8, 0.8, 0.9, 1 in group C.

M2% was0.4, 0.5, 0.3, 0.4 in group A, 0.4, 0.5, 0.5,0.6 in group B, 0.3, 0.3, 0.4,0.3 in group C.

% of methilated cytosine was 6% in group A, 3% in group B, 5% in group C.

CRP (ng/ml) was 6, 8, 10, 12 in group A, 7, 5, 3, 2 in group B, 8, 6, 5, 5 in group C.

Hb concentration (g/dl) was 9, 9.8, 11.5, 11.8 in group A, 9, 10.2, 11.5, 12.5 in group B, 9.5, 10, 10.5, 10.9 in group C.

Transfusion need (units) was 2 in group A, 2 in group B, 2 in group C.

Summary/Conclusion:

In LRMDS iron support improves erythropoietin effectiveness and reduces dna methylation. Sucrosomial iron reduces macrophages M1 polarization and CRP, improving effective hemopoiesis.

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PB2106 LOCKED NUCLEIC ACID MODIFIED OLIGONUCLEOTIDE MIMICKING MIR‐15A SUPPRESSES TUMOR CELLS PROLIFERATION IN VITRO
Authors: Li Z. , Lai Y. , Qiu L. , Hao M.
Published: June 2019

Background:

Recent studies have highlighted not only the importance of these genetic events but also epigenetic aberrations including DNA methylation, histone modifications, and non‐coding RNAs in the biology of multiple myeloma (MM). Our previous study has shown that non‐coding RNA miR‐15a inhibited the proliferation and promoted the apoptosis of MM cells. The level of miR‐15a was down‐regulated in MM cells and correlated with poor survival of myeloma patients. So, we speculated that up‐regulation the level of miR‐15a would promote MM cells death and prolong patient survival.

Aims:

To identify whether oligonucleotide mimicking miR‐15a (OMM‐15a) would be worked as an effective agent in the treatment of multiple myeloma and other cancer cells.

Methods

OMM‐15a was artificial synthesized in two different forms, the native form and the modified form with locked nucleic acid at the both end of native OMM‐15a (LNA‐OMM‐15a). The anti‐tumor proliferation effects of OMM‐15a and their modified ones were detected in MM cell lines ARP1, OCI‐My5 and breast cancer cell line MCF7. The OMM‐15a was transfected into these cells. At the different time point after the transfection (24 hrs, 48 hrs and 72 hrs), the cell proliferation and apoptosis was detected. The quantitative real‐time PCR and western blot were performed to detect the down‐stream signaling pathway of miR‐15a.

Results:

Our data indicated that the native form of OMM‐15a could work as hsa‐miR‐15a, but its function was weak and short duration. It could only downregulate part of the target genes expression of hsa‐miR‐15a, PHF19 and BCL2. Only PHF19 in one (ARP1) of the 3 cell lines was downregulated in the protein level at the 24 hrs point after transfection. It could not suppress tumor cells proliferation and increase their apoptosis. However, LNA modification at the both ends of the native form OMM‐15a could increase the stability and the function of OMM‐15 and prolonged their anti‐tumor effects. After modification, VEGFA were downregulated in addition to PHF19 and BCL2. And what's more, the proteins of PHF19 and BCL2 were all downregulated in all the 3 cell lines. Moreover, the LNA‐OMM‐15a showed significant effects on suppression of the tumor cells proliferation and on promotion of cells apoptosis.

Summary/Conclusion:

Treatment with LNA‐OMM‐15a significantly inhibited the proliferation of tumor cells. Cell apoptosis were up‐regulated notably in MM and other tumor cells. This preclinical study indicates that the LNA‐OMM‐15a would be work as a potential effective agent for tumor treatment.
PB2141 FEATURES OF THE DIRECT ANTIGLOBULIN TEST IN PATIENTS WITH MULTIPLE MYELOMA
Authors: Poponina E. , Butina E. , Yovdiy A. , Zaitseva G. , Vaneeva E. , Paramonov I.
Published: June 2019

Background:

The direct antiglobulin test (DAT) is used to detect autoantibodies that are fixed on the surface of red blood cells. A differentiated DAT allows to estimate the amount of absorbed immunoglobulins, describe their class and subclass, and detect the components of the complement on the membrane of red blood cells. This information helps to predict the risk of hemolysis and suggest the cause of anemia in a particular patient.

Aims:

To study the frequency and features of positive DAT in patients with multiple myeloma (MM).

Methods

The results of differentiated DAT were analyzed in 80 patients first hospitalized at the Institute clinic in 2018–2019 with the diagnosis MM. DAT was performed by gel method using anti‐IgG/C3d, DC‐Screening I and DAT IgG1/IgG3 cards (BioRad, USA). The frequency of positive DAT in patients was compared with the same in 200 healthy residents of the region–donors of blood components.

Results:

All blood donors were DAT‐negative. Autoantibodies to red blood cells were detected in 27.5% (22) of patients with MM (p < 0.05).

The intensity of the reaction (+) was observed in 50.0% (11) of patients with positive DAT, (++)–in 50.0% (11). DAT (++ + ), (++ + +) was not revealed. In the 100% of cases immunoglobulins G subclasses 2,4 were fixed on the surface of red blood cells, associated with a low risk of immune hemolysis. None of the patients was positive due to immunoglobulins classes A, M and complement components, which could contribute to the development of hemolytic complications. No clinical and laboratory signs of hemolysis were observed in the patients with positive DAT.

Positive DAT was more frequently found in the group of patients with MM older than 60 years (48.0%), whereas in the group of patients younger than 60 years it was 18.2% (p <0.05).

When observing patients with MM with positive DAT, it was noted that in one third of patients receiving chemotherapy, the result of DAT becomes negative within 5 months.

Autoantibodies can interact with test and donors red blood cells, being detected in an indirect antiglobulin test (IAT). Positive IAT was in 9.1% of patients with positive DAT and in 3.4% ‐ with negative. These patients had difficulties in donor's selection due to non‐specific agglutination.

Summary/Conclusion:

Even though positive DAT is often found in patients with MM, not in every case it should be regarded as a sign of autoimmune hemolysis. To correctly assess the risk of hemolysis, physicians should analyze other laboratory and clinical data. Positive DAT may be correlated with the difficulties of selection of the donor for such patient.
PB2143 HEPATITIS B VIRUS INFECTION MIGHT CONTRIBUTE TO MULTIPLE MYELOMA PROGRESSION THROUGH 1Q21 AMPLIFICATION
Authors: Xu P. , Guo D.
Published: June 2019

Background:

Hepatitis B virus (HBV) is not only a hepatotropic virus but also a lymphotropic virus. The association between HBV and hematologic malignancies has also been described, but the correlation between HBV infection and multiple myeloma (MM) has remained controversial.

Aims:

This study aimed to assess the prevalence of HBV infection in patients with MM and investigate their characteristics and prognostic significance.

Methods

The clinical data of 165 patients with MM receiving at least four cycles of chemotherapy from April 2008 to February 2017 in Nanjing Drum Tower Hospital were collected. HBV markers were determined by an enzyme‐linked immunosorbent assay.

Results:

The rates of an acute or chronic HBV infection and resolved HBV infection in patients with MM were 12.12% and 26.06%, respectively. The gain of 1q21 was statistically significant in HBV‐positive and HBV‐negative patients (54% vs. 38.2%, P = 0.048), and the level of alanine transaminase (ALT) in HBV‐infected patients was significantly higher than that of the non‐infected group (63.29 vs. 24.66 U/L, P = 0.043). Lactate dehydrogenase, serum creatinine, and serum calcium levels were found as significant risk factors of overall survival. The progression‐free survival (PFS) of HBV‐positive patients was shorter than that of HBV‐negative patients (18.97 vs. 29.67 months P = 0.006), and HBV positive was considered an independent prognostic factor of PFS.

Summary/Conclusion:

HBV infection might contribute to MM progression through 1q21 amplification, and HBV markers should be closely monitored in patients with MM.
PB2156 RISK FACTORS ASSOCIATED WITH EARLY MORTALITY IN PATIENTS WITH MULTIPLE MYELOMA
Authors: Novikova A. , Nakastoev I. , Balzhanova Y. , Ryzhko V. , Grachev A. , Danilina A. , Kanaeva M. , Klyasova G. , Gribanova E.
Published: June 2019

Background:

Early mortality (EM) in multiple myeloma (MM) ranges from 4% to 25% mostly depending on the patients included and on treatment options. EM tends to be lower in clinical trials including younger, transplant‐eligible patients or in bortezomib‐ and lenalidomide‐based regimens in comparison with elderly patients and conventional chemotherapy treatment.

Aims:

To estimate risk factors associated with EM in patients with newly diagnosed MM.

Methods

Patients with newly diagnosed MM were included into the study (from Jan 2013 to Feb 2019). EM was defined if it occurred within 1 year of entry into the study. Adverse cytogenetic abnormalities were specified as gain(1q), t(4;14), t(14;16), t(14;20) or del(17p).

Results:

A total of 174 patients with newly diagnosed MM (82 male, 92 female; median age 61 years) were involved in the study. Follow‐up period was 1‐71.4 months (median 8 months). The majority of patients developed an advanced stage of disease (Duriе‐Salmon stage 3–141 (81.1%), ISS stage 3–99 (56.9%)). All patients received chemotherapy regimens containing proteasome inhibitors as first‐line therapy and immunomodulatory drugs, intensive and conventional chemotherapy regimens as second‐ or next‐line therapy. During follow‐up period fatal outcome was observed in 45 (25.9%) of 174 patients, of them 16 (9.2%) patients with EM. Median early mortality was 4.7 months. The age of patients with EM and patients survived > 1 year was comparable (median age 64.5 vs. 61, respectively). A larger proportion of patients with EM had Durie‐Salmon stage 3 (93.8% vs 79.7%), ISS stage 3 (75.0% vs 55.1%). Fish in situ hybridization analysis was conducted in 126 (72.4%) patients, adverse cytogenetic abnormalities were present in 4/8 (50.0%) patients with EM and 33/118 (27.9%) patients survived >1 year. Risk factors assotiated with EM were ECOG performance status ≥ 3 score (87.5% vs 40.5%, p = 0.0003), C‐reactive protein level > 10 mg/L (62.5% vs 26.6%, p = 0.007), high lactic acid dehydrogenase activity (81.3% vs 46.2%, p = 0.008), platelet count < 150 × 109/L (43.8% vs 18.9%, p = 0.047) (tab.). For the 16 patients with EM, 11 (68.8%) of deaths were related to MM progression, 4 (25.0%) were due to infections and 1 (6.2%) ‐ heart failure.

Summary/Conclusion:

EM in patients with newly diagnosed MM was 9.2%. Risk factors associated with EM were poor performance status, elevated serum LDH activity, low platelet count, high serum C‐reactive protein.

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PB2160 REAL LIFE EXPERIENCE OF TREATMENT WITH POMALIDOMIDE, CYCLOPHOSPHAMIDE AND DEXAMETHASONE COMBINATION IN ADULT PATIENTS WITH RELAPSED AND REFRACTORY MULTIPLE MYELOMA
Authors: Alarcón‐Payer C. , Sánchez M. E. Clavero , Collado C. García , Chacón M. Jurado , Morales A. Jiménez
Published: June 2019

Background:

Multiple myeloma is a plasma cell malignancy that accounts for 1% of all cancers. Despite available therapies, the disease remains uniformly fatal, and patients who have received prior lenalidomide and bortezomib have a median overall survival of 9 months. Pomalidomide and low‐dose dexamethasone (PomDex) is standard treatment of lenalidomide refractory myeloma patients who have received >2 prior therapies. Combination therapy is often used in clinical practice in an attempt to overcome drug/clone resistance.

Aims:

Evaluate in daily clinical practice the effectiveness and safety of the combination pomalidomide, cyclophosphamide and dexamethasone (PomCyDex) in adult patients with relapsed and refractory multiple myeloma (RRMM).

Methods

Four‐year prospective observational study on 33 cases of RRMM. To measure the health outcomes obtained with the PomCyDex combination in a third level hospital we used the median progression free survival (PFS) as the main variable to assess if the combination is effective. Age, number of previous treatment lines and most frequent adverse reactions were also measured.

Results:

33 RRMM cases were analyzed, (57.6%: women; 42.4%: men). The mean age was 68 years. The health outcomes measured in our clinical practice were as follows: 39.4% of the patients were treated with PomCyDex in the 3rd line, 15.1% in the 4th line, 24.3% in the 5th line, 18.2% in the 6th line and 3% in the 7th line. The mean number of PomCyDex cycles received was 9. The median PFS was 5.5 months. PomCydex combination was shown to improve PFS by an additional 1.5 months compared to PomDex‐only patients receiving a 4 month PFS (MM‐003). The most frequent adverse reactions observed were neutropenia (38%), anaemia (11%) and thrombocytopenia (5%).

Summary/Conclusion:

Treatment with PomCyDex is an effective combination in the treatment of adult patients with RRMM. Also, PomCyDex combination is well tolerated in most patients and is therefore considered a safe treatment.
PB2162 INCIDENCE & SEVERITY OF BORTEZOMIB‐INDUCED PERIPHERAL NEUROPATHY WITH THE USE OF GENERIC BORTEZOMIB IN MONOCLONAL GAMMOPATHIES: A PROSPECTIVE STUDY FROM INDIA
Authors: Nath U. K. , Vaniyath S. , Chetia R. , Chattopadhyay D.
Published: June 2019

Background:

The proteasome inhibitor Bortezomib is one of the most effective frontline drugs in the therapeutic armamentarium against monoclonal gammopathies. However, drug‐induced peripheral neuropathy is the major dose‐limiting toxicity and adversely affects quality of life. Generic preparations of bortezomib are mainstay of therapy in resource‐poor countries due to significantly higher cost of original brand of bortezomib.

Aims:

The present study aims to analyze the incidence & severity of bortezomib‐induced peripheral neuropathy (BIPN) in patients of monoclonal gammopathies receiving generic bortezomib in a resource‐poor setting.

Methods

This non‐randomized, prospective study enrolled total 73 bortezomib‐naïve patients of monoclonal gammopathies between July 2016 & February 2019. Both newly diagnosed & relapsed patients of symptomatic multiple myeloma (MM), Waldenstrom macroglobulinemia (WM) & primary amyloidosis, who had no baseline evidence of peripheral neuropathy were included. Patients having disease‐related neuropathy & patients who had earlier received thalidomide or other neurotoxic drugs were excluded. All study patients received one of the generic bortezomib brands available in India. Bortezomib was initially administered at 1.3 mg/m2 dose, by subcutaneous injection, on days 1,8,15,22 of each 28 days’ cycle. Patients were clinically evaluated for BIPN before each cycle, & at onset of BIPN symptoms. Bortezomib dose was modified according to grade of BIPN (Table 1). Bortezomib was discontinued in grade 3‐4 neuropathy, & restarted after BIPN symptoms improved to < grade 3.

Results:

Median patient age was 58 years (32‐76 years). Majority (62/73 patients, 85%) had MM, eight patients had WM & three patients had Primary Amyloidosis. Twenty‐seven patients in the study (37%) developed BIPN during treatment. Severity of BIPN in study is shown in Table 2. BIPN symptoms were reversible in 90% patients after discontinuation of bortezomib. Median follow up was 7 months (2‐18 months).

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Summary/Conclusion:

In our study, approximately one‐third of patients with monoclonal gammopathies treated with subcutaneously administered generic bortezomib developed bortezomib‐induced peripheral neuropathy. The incidence of severe (grade 3‐4) BIPN was about 12%, leading to temporary/permanent discontinuation of bortezomib and also interfering with quality of life.

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PB2175 LONG TERM FOLLOW‐UP OF MAINTENANCE THERAPY WITH INTEREFRON ALPHA AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANT IN MULTIPLE MYELOMA PATIENTS–SINGLE CENTER EXPERIENCE
Authors: Batinic J. , Bašić‐Kinda S. , Pulanić D. , Ostojić A. , Dreta B. , Hude I. , Sertić D. , Seiwerth R. Serventi , Duraković N. , Rončević P. , Bojanić I. , Gjadrov‐Kuveždić K. , Dubravčić K. , Batinić D. , Ilić I. , Aurer I. , Nemet D.
Published: June 2019

Background:

Maintenance therapy after autologous hematopoietic stem cell transplantation (AHSCT) in multiple myeloma (MM) patients was a matter of debate until recently, when lenalidomide in this setting proved to increase overall survival (OS). Before lenalidomide interferon alpha (IFN) was standard maintenance therapy.

Aims:

The aim of this analysis was to determine the impact of maintenance therapy after AHSCT on progression free survival (PFS) and OS in MM patients treated at our institution between 1993 and 2014.

Methods

We performed a retrospective analysis of outcomes of MM patients autografted at our institution between 1993 and 2014. We identified 274 pts. who had PFS at least 6 months posttransplant; median age was 57, range 28‐71, 48% were male. 124 of them received tandem and 150 single AHSCT. Median follow‐up was 62 mo. Posttransplant 200 patients received IFN, 44 thalidomide and 30 no maintenance according to physicians’ choice.

Results:

Patients receiving IFN had longer 5‐year PFS compared to patients receiving thalidomide or no maintenance (52% vs. 34% vs. 31%, respectively, p < 0.001). OS was best in the IFN group, intermediate in the thalidomide and worst in the no maintenance group (67% vs. 59% vs. 32%, respectively, p < 0.001). The difference was limited to patients receiving tandem transplants. In this group 5‐year PFS was 61% vs. 35% vs 0% (p < 0.001) and OS 85% vs. 67% vs. 65% (p = 0.003) in the IFN, thalidomide and no maintenance group respectively. In patients that received a single transplant 5‐year PFS was 43% vs. 33% vs 36% (p = 0.157) and 5‐year OS 70% vs. 75% vs. 54% (p = 0.06) in the IFN, thalidomide and no maintenance group respectively.

Summary/Conclusion:

Our results indicate that maintenance therapy has beneficial effects on OS and PFS in MM patients treated with tandem, but not single AHSCT. IFN is superior in this setting to thalidomide and could be considered as a treatment option when lenalidomide is not available.
PB2176 DIAGNOSIS AND MANAGEMENT OF SYSTEMIC AL AMYLOIDOSIS IN REAL WORLD
Authors: Sirvent M. , Ondarra L. , Segues N. , Sarasqueta C. , Alkorta A. , Hernandez M. , Caminos N. , Perez E. , Romero P. , Zeberio I. , Aranbarri A. , Otero I. , Lombardi C. , Iriondo J. , Altuna A. , Araiz M.
Published: June 2019

Background:

Light‐chain (AL) amyloidosis is the most common form of systemic amyloidosis, accounting for 70% of patients with amyloidosis. It is characterized by deposition of a misfolded monoclonal light‐chain that is secreted from a malignant plasma cell clone, and interferes with an organ's normal function. Clinical features depends on organs involved. To continue improving patient prospects, early and accurate diagnosis and meticulous treatment choices are essential. Immunohistochemistry of abdominal fat aspirates is the most widely available method for amyloid typing, and it has to be done by a highly specialized pathologist, combined with clinical data and genotyping, it may lead to accurate amyloidosis classification. Delayed diagnosis remains a major obstacle to initiating effective therapy.

Aims:

To describe retrospectively the diagnosis and management in our hospital, of twenty five patients with biopsy‐proven systemic AL amyloidosis (included between 05/2011‐01/2019).

Methods

Median age at diagnosis was 64 years (range 45‐84). 44% patients were male and 56% female. At baseline evaluation, λ free light chains was shown in 92%, median bone marrow plasma cells was 10.9% (5 patients had associated MM), 12% had unfavorable genetic. Mayo stage was distributed as follows: I (8%), II (20%), III (28%), IV (44%). 20 pts (80%) had cardiac involved and 12 (60%) had typical pattern of delayed gadolinium enhancement in magnetic resonance. Median left ventricle thickness was 16.7 mm.

Results:

The histological diagnosis was in 28% by renal biopsy, 20% minor salivary gland, 16% fat aspiration, 8% cardiac, and proceeds with mass spectroscopy in 2 patients. Fat aspiration was performed in 15 pts (60%), but only 4 (26%) were positive. 44% received one regimen of treatment [0‐6 lines]. Bortezomib and lenalidomide were the most used drugs in first and second line (80% and 32% respectively). 20% underwent ASCT (only 2 directly). 16% received doxycycline. The hematologic and organic response for each line and PFS is shown in table 1. Median PFS was decreasing with Mayo stage (1‐2 stage: 16 month, 3: 9.7 months, 4: 7 months. Median OS was 4 years [95% CI 1.5‐6.4] with median follow up of 7.8 years, and median OS in patients achieving RC/VGPR was 4.9 years [95% CI 1.7‐8].

Summary/Conclusion:

1) Our series PFS and OS are worse comparing with literature, in real world AL amyloidosis is still diagnosed late, in advance Mayo stage (72%), and cardiac involvement. 2) The fat aspiration is not the diagnosis tool in the most cases. 3) Early diagnosis is the key to managing the disease and improves de survival of these patients. 4) It could be recommendable to start therapy, if clinical‐analytic suspicious is high, although without histological confirmation, but it has to be provided in further studies.

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