bluuebunny/crossref_metadata_2025 huggingface dataset:
PB1998 PROGNOSTIC VALUE OF PRETRANSPLANT PET/CT IN HODGKIN LYMPHOMA
Authors: Dr Miltényi Z. , Punk E. , Dr Pinczés L.I. , Illés Á.
Published: June 2019

Background:

Autologous stem cell transplant (ASCT) is the standard of treatment in patients with refractory/relapsed Hodgkin lymphoma (HL). Several adverse prognostic factors at relapse are known (stage, anaemia, B signs, Karnofsky score, early relapse etc.) to predict the outcome after ASCT.

Aims:

We analyzed the prognostic value of pre‐ transplant PET/CT and number of salvage therapy retrospectively.

Methods:

Between January 1, 2007 and December 31, 2018 pre‐transplantation 18FDG‐PET/CT scans of Hodgkin‐lymphoma patients were performed. Deauville criteria were used for evaluation of PET/CT scans. Positive PET scans were defined, if Deauville score was 4 or 5. We analyzed the effect of PET/CT results for survival (overall‐, relapse‐ and event free), and investigated differences between PET positive and PET negative groups. Statistical analysis was performed using IBM SPSS 25 programme.

Results:

Sixty‐two Hodgkin‐lymphoma patients (33 men and 29 women) had PET/CT scan before AHSCT. Median age at the time of AHSCT was 35 (19‐65) years. Median follow up time was 55.4 (0‐175) months. There were 49 (79%) PET negative and 13 (21%) PET positive patients. Five‐year overall survival rate was 80% in PET‐ group, and 46.2 % in PET+ group (p < 0.042). Five‐year relapse‐free and event‐free survival rate for negative and positive groups were 85.5% and 43.5% (p < 0.012), and 70.3% and 30.8% (p < 0.006). There were 6 relapse and 9 deaths (3 due to HL) in PET‐ group, and 5 relapse and 6 deaths (due to HL) in PET+ group. Twenty‐five of 49 patients in the PET‐ group got only one type of salvage treatment (DHAP) before AHSCT, against 2 of 13 patients in PET+ group (p = 0.046). Patients who acquired PET negative status after DHAP therapy only, had no relapse. Patients who were treated with 2 or more lines of salvage therapy and acquired PET negative status after these treatments, has no significantly better relapse‐free survival, than patients who remained PET positive.

Summary/Conclusion:

Clinical routine use of PET/CT before AHSCT is highly suggested based on our investigation. PET‐ patients have significantly better OS, PFS and EFS. PET negative status attends better prognosis, if it is reached with first salvage treatment.
PB2002 IMPACT OF AUTOIMMUNE CYTOPENIAS ON THE CLINICAL COURSE AND SURVIVAL OF HODGKIN LYMPHOMA
Authors: Pinczés L. , Szabó R. , Miltényi Z. , Illés Á.
Published: June 2019

Background:

Autoimmune cytopenias (AICP), namely autoimmune hemolytic anemia (AIHA) and autoimmune thrombocytopenia (AITP) often complicate the course of malignant lymphomas. The incidence and clinical significance of AICPs associated with Hodgkin lymphoma (HL) have not been thoroughly defined.

Aims:

Our aim was to retrospectively assess the incidence, clinical features and response to treatment of HL‐associated autoimmune phenomena.

Methods:

Five hundred and sixty‐five HL patients were diagnosed and treated at the University of Debrecen between 1990 and 2017. We compared the clinicopathological characteristics of HL patients developing AICPs with those who had no clinical evidence of autoimmune events. We considered an AICP to be a disease‐defining event if it led to diagnosis or revealed disease progression, relapse or secondary malignancy. Statistical analysis was performed using Fisher's exact test.

Results:

We identified 8 cases of AIHA and 8 cases of AITP among 14 patients altogether, one of them presented with Evans syndrome. Two AICPs preceded the diagnosis of HL, 2 of them developed simultaneously with the disease and 11 AICPs occurred during follow‐up after first line therapy. During more than 5000 person‐years of follow‐up, the incidence of AICPs in HL patients was 2,8%. Eighty‐one percent of AICPs required treatment, 77% of these patients responded well to intravenous steroid. Treatment of the underlying lymphoma with ABVD combination chemotherapy resulted in the effective control of both the underlying disease and the immune condition, in most cases, where AICPs were identified at the presentation of HL. Almost half of the AICPs (46%) were disease‐defining events: 5 cases led to the diagnosis of HL or indicated relapse and 2 events revealed secondary malignancies. AICPs were more frequently observed in patients with advanced stage disease at initial diagnosis (p < 0.004). The association of HL and AICPs had no effect on long‐term overall‐ (OS) and progression‐free survival, however, short‐term (1 year) mortality of HL patients experiencing AICPs was significantly elevated (p < 0.022) compared to the majority of patients, who did not have AICPs. Also, the OS rate of HL patients with AICPs at initial diagnosis was significantly lower (p = 0.033) compared to patients developing AICPs during follow‐up.

Summary/Conclusion:

While AICPs are rare complications of HL, these events can imply clinical significance. Those HL patients who experienced AICPs had a particular disease‐related profile. These cytopenias show a good response to steroid treatment. This large series of consecutive, unselected patients demonstrate that the association of HL and AICPs may increase short‐term mortality. Our results emphasize the importance of taking into consideration the possibility of an underlying hematological malignancy in newly diagnosed AIHA/AITP cases.
PB2016 RESULTS OF TREATMENT PATIENTS OF MANTLE CELL LYMPHOMA DEPENDING ON THE MUTATIONAL STATUS OF THE TP53 GENE
Authors: Koroleva D. , Zvonkov E. , Gabeeva N. , Smolyaninova A. , Gavrilina O. , Shchetsova O. , Biderman B. , Tsygankova S. , Bulygina E. , Rastorguev S. , Nedoluzhko A. , Sudarikov A. , Kovrigina A. , Galtseva I. , Obukhova T. , Kuzmina L. , Parovichnikova E. , Savchenko V.
Published: June 2019

Background:

According to a retrospective study published data in 2017 by the Nordic MCL group, in multivariable analyses, only mutation TP53 showed independent prognostic impact. The median OS for the TP53‐mutated cases was 1.8 years, median PFS was 0.9 years.

Aims:

To assess the incidence of TP53 gene mutation and survival in pts with MCL during of prospective trial MCL‐RUS‐2016.

Methods:

A total 25 pts were enrolled in prospective study MCL‐RUS‐2016 between 2016 to 2019 years. The median age was 52 years (range, 33 to 71 years). Seven pts (28%) were over the age of 60 years. Male:female = 15:10. In all pts the Ann Arbor stage was 4. Among 25 pts in depend pretreatment MIPI score, 36%, 48% and 16%, respectively, were considered as being at low, intermediate and high risk. Seven (28%)of 25 pts had blastoid MCL. Mutation of the TP53 gene determined using by Sanger sequencing of the coding region (exons 1(2)‐11) was present in 4 (16%) pts (TP53mut). Another 21 pts (84%) had wild type mutational status (TP53 wt). Complex karyotype (CK) was indentified in 8 (32%) pts. Three pts had the mutation of p53 and CK. Deletion of 17p was present in 4 (16%) pts, but only 3 of 4 cases with 17p loss displayed TP53 mutation.

Results:

Eighteen pts (TP53 wt) reseived 4 cycles of alternating of rituximab, bendamustine, cytarabine (R‐BAC) and rituximab, high dose cytarabine 12 g/m2 (R‐HA), followed by stem cell mobilization and ASCT. MRD was not detected in all 18 pts at the end of therapy. Eighteen pts achieved and remain in complete remission and 3 pts continue on treatment. The median follow‐up time was 5 months after ASCT (range, 1‐17 months). Pts with MCL, who have TP53 mutations, had a worse prognosis. Two pts with TP53 mutation in our study died for progression disease. Two pts, who underwent allo‐HCT from non‐relative HLA‐matched donors, is a alive in CR, with the time of observation three and twenty‐seven months.

Summary/Conclusion:

The regimens R‐BAC/R‐HA was well tolerated with a manageable safety profile. Allogeneic hematopoietic cell transplantation is only curative treatment for MCL with TP53 gene mutation.
PB2021 GASTRIC MUCOSA‐ASSOCIATED LYMPHOID TISSUE LYMPHOMA: A MONOCENTRIC EXPERIENCE
Authors: Ben Kridis W. , Falleh S. , Charfi S. , Khmiri S. , Toumi N. , Boudawara T. , Daoud J. , Khanfir A.
Published: June 2019

Background:

Mucosa‐associated lymphoid tissue (MALT) lymphoma accounts for 7‐8% of B‐cell lymphoma. Tumor proliferation consists of type B lymphomatous cells of low grade malignancy. They are considered indolent and are part of the marginal zone. They constitute the predominant histological type of non‐Hodgkin's malignant lymphoma of the stomach. Transformation into high‐grade lymphoma is rare.

Aims:

The aim of this study is to describe the clinical characteristics and the therapeutic results of MALT lymphoma.

Methods:

We reviewed retrospectively the records of 18 patients presenting with gastric MALT lymphoma treated between 1993 and 2018. Patients with low‐grade lymphoma in failure after helicobacter eradication had exclusive gastric external radiotherapy. Chemotherapy were indicated in case of high grade lymphoma transformation. Radiotherapy doses range between 30 and 40 Gy (2 Gy per fraction, five fractions per week).

Results:

Median age was 52 years old. All tumours were IE stage. Helicobacter pylori was positive in 15 cases. Three patients had other cancers (gastric adenocarcinoma, breast cancer, mantle lymphoma). All patients received antibiotic therapy (triple therapy in 12 cases and concomitant treatment in 7 cases) with responding residual disease in 6 cases and probable minimal residual disease in 9 cases. Second line antibiotherapy was pylera in 3 cases and levofloxacin with amoxicillin in 2 cases. Seven patients with low‐grade MALT lymphoma had radiotherapy. Four patients with high‐grade transformed lymphoma received chemotherapy. Seventeen patients are in complete remission after treatment achievement. Five and 10‐ year disease‐free survival are 100%.

Summary/Conclusion:

Eradication of Helicobacter pylori is the mainstay of treatment of gastric MALT lymphoma. The levocine‐amoxicillin combination with proton pump inhibitor seems to be effective as a second‐line treatment in case of non availability of the pylera. External irradiation is an effective and well‐tolerated treatment modality in case of resistance to helicobacter eradication. Immuno‐chemotherapy is indicated for diffuse lymphoma (stage III and IV) or in case of transformation into large cell lymphoma.
PB2042 CYTOMEGALOVIRUS INFECTION – A BRAKE IN PLATELET RECOVERY AFTER CHEMOTHERAPY IN ACUTE MYELOID LEUKEMIA PATIENTS
Authors: Popov V. , Balea M. , Patrinoiu O. , Georgescu D. , Dumitru I. , Iova A. , Begu M. , Dobrea C. , Arghir A. , Papuc S. , Soare D. , Abagiu A. , Madalina S. , Popescu G.A. , Bumbea H.
Published: June 2019

Background:

Cytomegalovirus (CMV) infection influence platelet recovery in bone marrow transplantation patients. Patients with CMV infection, primary, reactivated, or latent, require more platelet unit transfusions, this procedure determines increases the risk of transfusion‐related infections. In literature there are many reports regarding CMV implication in bone marrow recovery secondary transplant procedure.

Aims:

The association with CMV infection and slowly recovery of bone marrow secondary chemotherapy in AML was rarely reported

Methods:

We report 2 cases with delay in platelet recovery after intensive chemotherapy‐ consolidation phase of acute myeloid leukaemia patients.

Results:

Patients male 46 years and female 55 years were diagnosed with AML 1. Diagnose was put using WHO criteria and was not identified any genetic abnormalities. We started 3+7 regimen with obtaining complete remission status. After bone marrow recovery we started consolidation phase with high doses Cytarabine 2 applications. After second application we observed delay in platelet recovery (more than 1 months). Bone marrow biopsy indicated severe aplasia. Serology for CMV infection was positive for IgG antibodies, PCR for CMV was positive indicated active CMV infection. Patients were referred to infectionist and was started antiviral treatment – Gancyclovir. During treatment patients presented increases of platelet count and absence of platelet unit transfusion, in 1 month patients had G1 trombocytopenia (improving of CTCAE grade from G4 to G1)

Summary/Conclusion:

The delay in bone marrow recovery after intensive chemotherapy used as treatment of acute myeloid leukemia patient represent a warning to check CMV infection presence. This attitude could avoid complications like infections or/and transfusions related.
PB2105 RESULTS OF BONE DENSITOMETRY IN PATIENTS WITH MULTIPLE MYELOMA DURING TREATMENT
Authors: Sergey A. , Troyan V. , Sergey K. , Rukavitsyn O.
Published: June 2019

Background:

Multiple myeloma is a malignant tumor consisting of plasma cells, with infiltration which increases bone resorption, increases the activity of osteoclasts, changes bone mineral density in the form of osteopenia and osteoporosis

Aims:

to evaluate and compare bone density over time in patients with multiple myeloma after high‐dose chemotherapy with autotransplantation of hematopoietic stem cells.

Methods

Prior to treatment, all patients (n = 64) were densitometry of the spine, both hip joints in a direct projection and repeated after 7‐12 months (m = 10). The results were evaluated by the T‐test in the values of standard deviations (SD): norm (+ 2.5SD> ‐1SD); osteopenia (<‐1SD> ‐2.5SD); osteoporosis <‐2.5SD. The results of densitometry in patients with multiple myeloma were compared before and after high‐dose chemotherapy with autotransplantation of hematopoietic stem cells, and patients who received standard chemotherapy.

Results:

Before treatment, the data of densitometry in the group of patients with chemotherapy (n = 35): in 12 (34.2%) patients the norm (‐0.425 ± 0.078SD); 18 (54.4%) patients had osteopenia (‐1.633 ± 0.056 SD); in 5 (14.2%) osteoporosis (‐2.62 ± 0.033 SD). In the group of patients with stem cell transplantation (n = 29), the following results were obtained: the norm (‐0.4 ± 0.145 SD) in 8 (27.5%) people; osteopenia (‐1.831 ± 0.071 SD) ‐ in 16 (55.1%) patients; osteoporosis (‐2.68 ± 0.033 SD) ‐ in 5 (17.4%) people. In the statistical analysis, the median MTF of both groups was m = ‐1.6SD. After the treatment, 10–12 months later, in the control group with chemotherapy (n = 35), the changes were less pronounced: the norm (–0.467 ± 0.077 SD) in 12 (34.2%) patients; in 18 (54.4%) patients with osteopenia (‐1.472 ± 0.056 SD); osteoporosis (‐2.7 ± 0.063 SD) in 5 (14.2%) people. In the group of patients with transplantation after the treatment, the indicators were as follows: T‐criterion is within normal limits (–0.137 ± 0.135 SD); osteopenia (‐1.83 ± 0.071 SD) osteoporosis (‐2.64 ± 0.022 SD). When analyzing the changes in the density level in each specific patient before and after treatment using the Student's t‐criterion, it turned out that in the group with high‐dose chemotherapy, the dynamics of the increase in the density level were significantly better in the groups of patients with initially normal and osteoporotic groups (= 5.77; (p <0.001) and t = 2.45; (p <0.01), respectively, in the studied groups).

Summary/Conclusion:

After high‐dose chemotherapy with autotransplantation of hematopoietic stem cells, the mineral density of bone tissue increases significantly, which can be assessed by densitometric studies.
PB2136 DO FUNCTIONAL VARIANTS OF MIF AND MBL GENES INFLUENCE OUTCOME IN PATIENTS UNDERWENT AUTOLOGOUS STEM CELL TRANSPLANTATION FOR MULTIPLE MYELOMA?
Authors: Pehlivan M. , Nursal A. F. , Gündeş I. , Oyacı Y. , Kıvanç D. , Pehlivan S.
Published: June 2019

Background:

Multiple myeloma (MM) is a plasma cell malignancy, with wide survival range and multiple risk factors and staging systems linked to survival. Macrophage migration inhibitory factor (MIF) is a potent proinflammatory cytokine. Mannose‐binding lectin (MBL) enhances opsonization and activates complement.

Aims:

This analysis was performed to evaluate the relationships of MIF ‐173G/C and MBL codon 54 variants with clinical feaures and susceptibility in patients underwent Autologous stem cell transplantation (ASCT) for MM.

Methods

A total of 155 patients (Female/Male:74/81) who underwent ASCT and 200 healthy subjects (Female/Male:99/101) were included. The median follow‐up period was 36 months. Genotyping of these variants was determined by PCR‐RFLP. Genotype and allele frequencies were compared between the study groups using χ2‐test. Kaplan‐Meier curves for Progression‐free survival (PFS) and Overall survival (OS) were compared using a log‐rank test.

Results:

The median age at diagnosis is 55 years for patients. In all, median OS was 79 months in patients. OS showed that 16.1% patients died. PFS was associated with gender (p = 0.049, 95% Cl:0.258‐0.998). Individuals with BB genotype showed a significant association with 10.607‐fold increased risk of MM (p = 0.001). The genetic analysis association with survival was performed under a recessive genetic model (CC vs. GG/CG). MIF GC/GG genotype was significantly associated with longer OS (median 5 years) compared to CC genotypes (Log Rank p = 0.016).

Summary/Conclusion:

Our study indicated that the MBL codon 54 functional variant might contribute to MM susceptibility in Turkish population. Also our results imply that the OS in MM patients is associated with the ‐173G/C variant of MIF gene.
PB2182 OUTCOME OF FIRST‐LINE THERAPY FOR PATIENTS WITH SYSTEMIC LIGHT‐CHAIN AMYLOIDOSIS: MONOCENTRIC ANALYSIS
Authors: Fernández R. , Soto A. Silva , Cepeda F. , González A. , Robles V. , Fonseca E. , Sanchez S. , Torres J. , Sarasa M. , Chamorro P. , Álvarez A. , Arias T. , Bobes A. , Fernández A. , Fernández C. , González S. , González M. E.
Published: June 2019

Background:

Systemic light‐chain amyloidosis (AL) is characterised by deposition of misfolded immunoglobulin light chains within organs.

Melphalan or cyclophosphamide with dexamethasone in combination with bortezomib are currently recommended first‐line therapy regimens.

Aims:

To describe the clinical presentation and outcomes for newly diagnosed AL amyloidosis patients.

Methods

This single‐centre retrospective study included all patients diagnosed with AL amyloidosis in our hospital area (300,000 inhabitants) between March 2012 to March 2018. Data regarding demography, diagnosis, treatment and follow‐up were extracted from the clinical history (HC).

Survival curves were constructed according to the Kaplan‐Meier method and compared by logarithmic ranking.

Time to progression (TTP) was defined as the time from the date of diagnosis or the start of a treatment for a disease until the disease worsens.

Results:

We analysed 24 patients (15women, 9 men) with newly diagnosed AL amyloidosis. Median age was 66 years (range 42‐82), and 6 pts were considered ASCT candidates. Involvement of kidney, peripheral nerve, heart, liver and other organs were found in 14 (35%), 13 (32.5%), 11 (24.5%), 1 (2.5%) and 1 (2.5%) cases, respectively.

According to Mayo Stage 2012: stage 2: 25%, stage3: 33.33% and stage 4: 41.66%

First‐line treatments were: regimens based on bortezomib CyBordex (cyclophosphamide, bortezomib and dexamethasone) n =  12, VTD (bortezomib, thalidomide and dexamethasone) n = 2, VMP (bortezomib, melphalan and prednisone) n = 2, BD (bortezomib and dexamethasone) n = 6, MP (melphalan and prednisone) n = 2 and CP (cyclophosphamide and prednisone) n = 1.

Haematological responses of CyBordex, VTD, VMP, BD were 33.33%, 100% and 100% and 16.66% respectively.

The haematological responses were: RC 25%, VGPR 33.33%, RP 8.33%, NR (no response) 33.33%

The organ responses were 45.83% (n = 11). Median follow‐up of 19 months (95% CI 0‐49.9). Median PTT of 19 months (95% CI 0‐41.9).

The rate of premature death within the first six months was 29.16%.

Summary/Conclusion:

Regimens based on bortezomib in newly diagnosed AL amyloidosis show results that seem comparable to those previously published in the literature.

Almost a third of patients show no response, and premature death in six months is significative.

To improve these outcomes, it is necessary to better define the role of proteasome inhibitors the role of new therapies.

Educational interventions are important to optimize the diagnostic process and to reduce the rate of early deaths.
PB2192 GLOBAL COAGULATION CAPACITY OF ESSENTIAL THROMBOCYTHEMIA PATIENTS BY ROTEM ANALYSIS ADJUSTED FOR PLATELET COUNT CORRELATES WITH THROMBOTIC RISK CLASS
Authors: Giaccherini C. , Marchetti M. , Verzeroli C. , Gamba S. , Russo L. , Finazzi G. , Rambaldi A. , Falanga A.
Published: June 2019

Background:

Essential Thrombocythemia (ET) is characterized by hypercoagulability and increased risk of arterial and venous thrombosis. The thromboelastometry profile by ROTEM, a point of care system for assessment of global coagulation in whole blood, has never been investigated in these patients, who have abnormalities in blood cell counts. This approach is attractive in that the test reflects the activity of both soluble and cellular components of hemostasis. Furthermore, the test is rapid, does not require blood sample centrifugation and may be useful in prospective studies of thrombotic risk assessment in ET patients.

Aims:

To evaluate the global clotting process in ET patients by thromboelastometry with ROTEM and establish whether and to what extent elevated platelet count and mutational status affect the global hemostasis evaluation.

Methods

Analysis was performed in 52 ET patients using INTEM and EXTEM reagents, to evaluate the intrinsic and extrinsic pathway, respectively. Maximum clot firmness (MCF, [mm]), which reflects the maximum tensile strength of the thrombus, clotting formation time (CFT [sec]), namely the time that clot takes to increase from 2 mm to 20 mm above baseline, and clotting time (CT [sec]), the time to clot initiation, were recorded. Patient thrombotic risk was classified as, i.e.: very low risk (age≤60 yrs, no thrombosis history, JAK2/MPL−), low risk (age≤60 yrs, no thrombosis history, JAK2/MPL+), intermediate risk (age > 60 yrs, no thrombosis history, JAK2/MPL−), and high risk (thrombosis history or age >60 yrs with JAK2/MPL+).

Results:

ROTEM analysis with both EXTEM and INTEM reagents showed that ET patients had a hypercoagulable profile, characterized by significant (p < 0.01) short CFT and high MCF values compared to healthy subjects. None of the ROTEM parameters per se correlated with classes of thrombotic risk. However, a strong correlation (p < 0.01) was present between platelet count and CFT or MCF (both with EXTEM and INTEM reagents). Therefore, the parameters were adjusted for platelet count. After adjustment, corrected CFT (cCFT) significantly correlated with the patient thrombotic risk category (p < 0.05). Furthermore, corrected MCF (cMCF) was significantly increased in JAK2V617F+/MPL+ compared to CalR+ subjects (p < 0.01).

Summary/Conclusion:

This study confirms the occurrence of a hypercoagulable state in ET patients and shows that ROTEM parameters are significantly influenced by platelet count. Correction of CFT and MCF values allows a better understanding of global coagulation of ET patients and may potentially better reflect the thrombotic risk in these patients.
PB2208 MOLECULAR PROFILE AND TELOMERE LENGTH ARE USEFUL MARKERS FOR DIFFERENTIAL DIAGNOSIS OF PRE‐FIBROTIC PRIMARY MYELOFIBROSIS VERSUS ESSENTIAL THROMBOCYTHEMIA
Authors: Yun J. , Kim J.‐A. , Yang N. , Ryu S. , Jeong D. , Lee Y. E. , Kim S.‐M. , Lim K. M. , Lee D. S.
Published: June 2019

Background:

The 2016 revised WHO classification of MPN newly presented pre‐fibrotic PMF. Diagnostic criteria is based on bone marrow morphology, fibrosis, and clinical features (leukoerythroblastosis, anemia, leukocytosis, increased lactate dehydrogenase, and palpable splenomegaly). Since pre‐fibrotic PMF is a new entity characterized by a unique combination of both thrombotic and hemorrhagic risk, a differentiation from essential thrombocythemia (ET) is pivotal for treatment decision. However, the differentiation is difficult in many cases.

Aims:

In this study, we sought to explore useful markers for the differential diagnosis of ET and pre‐fibrotic PMF. We compared the cytogenetic and molecular profiles, telomere length, survival rate of patients among pre‐fibrotic PMF, overt PMF and ET.

Methods:

We reviewed BM morphology and clinical data of 59 Korean patients diagnosed with MPN in 2005∼2014. We classified MPN subtypes of them in series of 2001∼2016 WHO criteria. G‐banding/FISH (BCR/ABL1, 20q deletion, 13q deletion) (n = 57), targeted sequencing of 88 genes (n = 59), telomere/centromere ratio using quantitative FISH (n = 44), and survival analysis (n = 59) were performed.

Results:

Among 15 patients with MPN‐U by WHO 2001∼2014 classification, 7 patients were re‐diagnosed with pre‐fibrotic PMF, 2 with overt PMF, 6 with MPN‐U by WHO 2016 classification. Based on WHO 2016 classification, cytogenetic abnormalities were detected as 0% in ET, 0% in pre‐fibrotic PMF, and 42.3% in overt PMF. The numbers of mutated genes were 1.5 ± 1.3, 2.4 ± 1.3, 2.0 ± 1.2 in ET, pre‐fibrotic PMF, overt PMF, respectively (p = 0.542). The spectrum of mutate genes expanded from ET to overt PMF. Telomere length (telomere/centromere ratio) were 14.5 ± 1.4, 10.1 ± 3.1, 9.2 ± 3.7 in ET, pre‐fibrotic PMF, overt PMF, respectively (p = 0.042). 5‐year survival rates were 100%, 71.4%, 49.5% in ET, pre‐fibrotic PMF, overt PMF, respectively.

Summary/Conclusion:

Pre‐fibrotic PMF patients were found to harbor more number of mutations than ET. Mutation profile expanded and telomere lengths decreased in order of disease severity. Especially, CSF3R, DNMT3A, SF3B1, SRSF2 mutation can be candidate marker for differential diagnosis between ET and pre‐fibrotic PMF. Telomere length definitely gives information about disease severity, which is a useful indicator in differential diagnosis of MPN.

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PB2259 SIGNIFICANCE OF INCIDENTAL FINDINGS DETECTED ON PET‐CT SCANS PERFORMED IN HAEMATO‐ONCOLOGY: A SINGLE CENTRE EXPERIENCE
Authors: Mackintosh C. , Soutar R. , McCarthy P. , Koumpis A.‐E.
Published: June 2019

Background:

PET‐CTs scans are commonly used in haematological malignancies to stage disease and assess response to therapy. It is not uncommon for PET‐CT to reveal incidental findings, the significance of which is unclear.

Aims:

This study aimed to determine how common incidental findings are in patients with haematological malignancies, and assess the outcome of the investigations into these findings.

Methods:

Reports from 212 patients who had a PET‐CT scan reviewed at the departmental haematology‐radiology meeting of the Beatson Oncology Centre, Glasgow, Scotland between May 2015 and May 2018 were reviewed retrospectively. All scans were undertaken at the same site, the West of Scotland PET Centre. For each incidental finding, follow up, diagnosis and outcome was then reviewed. 57% (n = 121) of patients were male and the median age was 57 years. The majority of patients (93%, n = 196) underwent the PET‐CT scan due to underlying lymphoma, 122 (43%) of these were Non‐Hodgkin and 74 (35%) with Hodgkin lymphoma,16 of the patients had underlying myeloma or other suspected malignancies.

Results:

The study found that 13% (n = 28) of patients that underwent PET‐CT scanning had an incidental finding. The majority of these findings (82%, n = 23) were investigated further. No significant abnormal finding was revealed through further investigation for 43% (n = 10). A pathological finding was found in 57% (n = 13) of scans. Of these 69% (n = 9) had a pre‐malignant or malignant diagnosis: 2 adenocarcinomas and 4 precancerous polyps in the colon and 3 Thy3a in the thyroid. The remaining 4 were benign pathologies including gastric reflux, benign adenomas and a fistula. The incidental findings were in a variety of anatomical sites, the most common being the colon (n = 15 findings), followed by the thyroid (n = 4). Regarding outcome patients with pre‐malignant polyps and adenocarcinomas underwent complete surgical excision, with no disease remaining post operatively. No patient had evidence of progression / relapse of the incidental finding at time of follow up.

Summary/Conclusion:

Incidental findings on PET‐CT were shown to occur commonly in patients with haematological malignancies. Follow up of these incidental findings is indicated, and appropriate, as it often results in the diagnosis of a treatable, pathological condition. Further investigation in patients with haematological malignancy is particularly important in view of the potential high survival rate from the underlying haematological cancer.
PB2270 THE RELATIONSHIP BETWEEN OXIDATIVE STRESS MARKERS, AGE, NEUTROPHIL‐TO‐LYMPHOCYTE RATION AND OBESITY
Authors: Gaman M.‐A. , Epingeac M. E. , Gaman A. M.
Published: June 2019

Background:

Obesity is a complex metabolic disease associated with an excessive accumulation of white adipose tissue (WAT). WAT secretes adipokines, which in turn generate reactive oxygen species (ROS) or decrease the total antioxidant capacity (TAC), and pro‐inflammatory cytokines (TNF‐alpha, IL1, IL6), leading to obesity‐induced inflammation.

Aims:

To evaluate oxidative stress via ROS and TAC measurement and evaluate obesity‐induced inflammation via the neutrophil‐to‐lymphocyte ratio (NLR) in obese patients.

Methods:

We evaluated oxidative stress and NLR in obese subjects vs. non‐obese controls. Patients were divided by age, sex, and degree of obesity. Obesity was diagnosed according to the WHO criteria, based on the body mass index (BMI). Oxidative stress was evaluated using a CR3000 analyzer via the FORT (Free Oxygen Radical Testing for ROS quantification) and FORD (Free Oxygen Radical Defence for TAC measurement) assays. NLR was evaluated as a marker of chronic inflammation (normal values: 0.78‐3.53). Statistical analysis of data was conducted using the student T‐test and a p‐value < 0.05 was considered significant. The study was approved by the Ethics Committee of the University of Medicine and Pharmacy of Craiova (approval no. 40/27.03.2018) and written informed consent was collected from all subjects involved.

Results:

The study group involved 85 obese patients (mean age 61.85 ± 10.60 years, age range 24‐82): 17 males (20.00%, mean age 62.65 ± 8.90 years, age range 43‐77) and 68 females (80.00%, mean age 61.65 ± 10.97 years, age range 24‐82). The control group included 30 non‐obese subjects (mean age 44.60 ± 18.45 years, age range 18‐85). Mean BMI was 36.44 ± 3.63 kg/m2 in obese subjects (men: 35.35 ± 3.41 kg/m2, women: 36.71 ± 3.63 kg/m2) vs. 24.56 ± 1.76 kg/m2 in controls (p‐value < 0.0001). Stratification in obesity classes was: 38 patients (44.70%) ‐ class I obesity, 31 patients (36.47%) ‐ class II obesity, 16 patients (18.83%) – class III obesity. FORT values were increased in obese patients vs. controls (3.09 ± 0.36 mmol/L vs. 2.03 ± 0.14 mmol/L, p‐value<0.001). FORD values were decreased in obese patients vs. controls (0.69 ± 0.15 mmol/L vs. 1.27 ± 0.13 mmol/L, p‐value<0.001). We did not record significant differences in terms of NLR in obese subjects vs. controls (2.46 ± 0.96 vs. 2.31 ± 0.26, p = 0.4036). In obese subjects, we found positive correlations between FORT and BMI (r

s
 = 0.38407, p = 0.00028), NLR (r

s
 = 0.06771, p = 0.5381) and age (r

s
 = 0.06781, p = 0.53748). Negative correlations were recorded between FORD and BMI (rs = ‐0.35083, p = 0.001), age (rs = ‐0.04698, p = 0.66942) and NLR (rs = ‐0.06732, p = 0.54045)

Summary/Conclusion:

In our study group, ROS levels were increased and TAC was decreased in obese patients as compared to healthy controls. ROS levels and TAC correlated with BMI, but not in a significant manner with age or NLR.
PB2364 UNSUCCESSFUL COLLECTION OF AUTOTRANSPLANT DURING THE FIRST SESSION OF LEUKOCYTAPHERESIS IN PATIENTS WITH MULTIPLE MYELOMA AND EFFECTIVE STEM CELL MOBILIZATION
Authors: Kostroma I. , Zhernyakova A. , Romanenko N. , Chubukina Z. , Zapreeva I. , Bessmel’tsev S. , Chechetkin A. , Gritsaev S.
Published: June 2019

Background:

It is well known that the effectiveness of stem cell collection and the possibility to harvest suboptimal CD34+ cells number during the single apheresis session is dependent on the number of CD34+ cells circulating in the peripheral blood (PB), i.e. on the effectiveness of mobilization regimen.

Aims:

To determine the rate of unseccessful collections in patients with multiple myeloma (MM) when the number of CD34+ cells circulating in the PB is in accordance with the optimal level 20/1 mkl or more.

Methods:

Retrospective analyses of autotransplant collection in 55 MM patients have been done. Median age of patients was 56 (31‐67) years. Complete response, very good partial response and partial response were diagnosed in 12 (21.8%), 13 (23.6%) and 30 (54,5%) patients accordingly. 25 (45.5%) patients were treated with lenalidomide previously. Cyclophosphamide 3 g/m2 with granulocyte colony‐stimulating factor (G‐CSF) were used for stem cell mobilization in 28 (50.9%) patients. 26 (47.3%) patients were mobilized with vinorelbine 35 mg/m2 with G‐SCF and G‐SCF monotherapy was used in 1 (1.8%) patient.

Results:

The number of CD34+ cells circulating in PB at the day of the first apheresis procedure was 5‐694/1 mkl (Me 118). Median number of collected CD34+ cells was 5.53 × 10/6/kg (0.27‐29.23). The correlation between number of circulating CD34+ cells and the quantity of harvested CD34+ cells was confirmed: r = 0.503; p < 0.05. At the same time there were 7 (12.7%) cases in which the number of collected CD34+ cells were lower than suboptimal level (0.25‐1.9 × 10/6/kg, Me 1.33 × 10/6/kg) despite the successful mobilization rate: 26‐118/1 mkl (Me 44). The second procedure of apheresis was done on the next day and in all cases except for the one there was the possibility to harvest CD34+ cell number enough to perform a single stem cell transplantation: 2.58‐3.48 × 10/6/kg. The place of central veun catheterization has been changed in all these cases except for the one.

Summary/Conclusion:

We suppose that a reason of unseccessful stem cell collection in MM patients with adequate rate of mobilization may be disturbance of the bloodstream speed in the apheresis system due to the anatomical characteristics of subclavia vein localization. A method to correct the problem is relief the central catheter puncture place.
PB2383 FACTORS ASSOCIATED WITH EFFECTIVE HARVESTING AND ENGRAFTMENT OF AUTOTRANSPLANT IN PATIENTS WITH MULTIPLE MYELOMA
Authors: Kostroma I. , Zhernyakova A. , Chebukina Z. , Semenova N. , Zapreeva I. , Tiranova S. , Bessmel’tsev S. , Chechetkin A. , Gritsaev S.
Published: June 2019

Background:

The effectiveness of autologous stem cell transplantation (AutoSCT) depends on the speed of autotransplant engraftment which in return is adjoined by quantity of harvested and infused CD34+ cells.

Aims:

The aim of the study was to determine predictors of AutoSCT effectiveness in patients with multiple myeloma (MM) as new medicines were introduced in induction therapy and mobilization schemes.

Methods:

Retrospective analyses of autotransplant harvesting in 75 patients and autotransplant engraftment during 112 AutoCST was performed. Cyclophosphamide and vinorelbine in combination with granulocy colony‐stimulating factor (G‐CSF) were used for mobilization. Conditioning regimens were Mel200, Mel140 and Thio/Mel140. All patients received G‐CSF during posttransplant period. Standard criteria of engraftment were used.

Results:

One induction scheme (p = 0.0315) and cyclophosphamide in mobilization regimen (p = 0.0001) were the positive predictors of increased number of CD34+ cells in autotransplant. The rate of engraftment was dependent on the serial number of AutoSCT and number of CD34+ cells infused. The role of the serial number of AutoSCT is attributed to the less intensity of the second conditioning regimen: Mel140 versus Mel200 and Thio/Mel140 during the first AutoSCT.

Summary/Conclusion:

Autotransplant quality and the rate the engraftment in patients with MM are dependent on the fectiveness of induction therapy and intensity of mobilization regimen. So, we conclude that the choice of induction therapy variant and mobilization regimen intensity has to be adapted to the individual patient, prognostic variant of MM, possibility to respond to standad induction therapy and number of planned AutoSCT.
PB2393 FROM NON‐TRANSFUSION DEPENDENCY TO TRANSFUSION DEPENDENCY: LIGHTS AND SHADOWS IN THALASSEMIA
Authors: Ricchi P. , Meloni A. , Pistoia L. , D’Ascola D. , Pitrolo L. , Barone A. , Sanna P. M. G. , Cuccia L. , Righi R. , Peritore G. , Positano V. , Pepe A.
Published: June 2019

Background:

Patients with non‐transfusion dependent thalassaemia (NTDT) can be placed on regular transfusional therapy either for the prevention or for the management of different complications.

Aims:

We retrospectively evaluated the effects of blood transfusions (BT) in the real‐life and quite extensive context of the Myocardial Iron Overload in Thalassaemia (MIOT) network where most of biochemical, cardiac, hepatic parameters and morbidities typical of the NTDT patients could be analysed and compared in a chronologically manner.

Methods:

147 NTDT patients (46.49 ± 12.27 years; 92 females) who started regular BT at the mean age of 21.84 ± 17.85 years were considered. Magnetic Resonance Imaging (MRI) was used to quantify iron overload (T2∗ technique) and biventricular morphological and functional parameters (cine sequences).

Results:

For the 40% of the patients there were more than two indications for the transition to regular BT, with anemia being present in the 92.5% of the cases. The patients reached a pre‐transfusion hemoglobin of 9.64 ± 0.72 g/dl.

The percentage of chelated patients increased significantly after starting regular BT (52.5% vs 91.7%; P < 0.00001).

Table 1 shows the changes (6 months before vs 6 months after starting regular BT) in the haematochemical and iron‐overload parameters. A down‐regulation of all erythropoietic and/or haemolysis indices and a drop‐in platelets and white blood cell count were detected. No changes in serum ferritin, MRI liver iron concentration (LIC) and global heart T2∗ values were detected.

There was a significant decrease of the left ventricular end‐diastolic volume index (101.58 ± 19.67 ml/m2 vs 91.65 ± 20.99; P = 0.050).

After the start of regular BT, patients were followed‐up for 24.08 ± 15.62 years. There was a significant increase in the frequency of endocrinopathies (diabetes, hypogonadism, hypothyroidism and osteopenia), bone pain, infections, and alloimunization, but their prevalence remained lower than 20%.

A positive impact on patients’ health‐related quality of life was detected, with the sense of well‐being passing from 16.4% to 73.0% (P < 0.0001).

Summary/Conclusion:

Following the use of regular BT and chelation therapy, only a mild increase in most of the complications evaluated in the analysis was recorded; we cannot exclude that it could be ascribable to aging per se, as it happens for general population. No increase in iron overload parameters was detected and conversely, we recorded a positive cardiac remodelling. Therefore, in the Italian context, the decision to regularly transfuse patients with NTDT, despite sometimes complex and problematic, may represent a way to prevent or slow down the natural progression of the disease and improve the patients overall quality of life.

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PB2405 PHENOTYPES AND GENOTYPES OF HEMOGLOBINOPATHIES IN AZERBAIJAN
Authors: Asadov C. , Aliyeva G. , Mikayilzadeh A. , Mammadova T. , Gafarova S. , Abdulalimov E. , Guliyeva Y.
Published: June 2019

Background:

Azerbaijan is located in Transcaucasia, which is a high prevalent region of hemoglobinopathies. Besides β‐thalassemia, the local population is also known for the presence of α‐thalassemia and some hemoglobin variants. Several previous studies reported the incidences of α‐thalassemia and hemoglobin variants such as HbS, HbE and HbD, as well as incidence rate and mutation spectrum of β‐thalassemia in the local population. Nevertheless, these were mainly conducted in small study groups and they were limited on β‐globin genotyping, which necessitated a large‐scale screening and genotyping to reveal phenotypes and mutational background of all common hemoglobinopathies in Azerbaijan.

Aims:

The aim of our study was to screen a large sample of population in order to reveal the prevalence of thalassemias and variant hemoglobins as well as their mutational background in Azerbaijan.

Methods:

The sample group included 436,144 individuals (population = 9,982,952) applying for marriage certificate, which were screened via Thalassemia Prevention Program of Azerbaijan. Premarital screening of thalassemia is mandatory since 2015, covering almost all areas of the country. Total hemoglobin (Hb) levels, red blood cell indices and Hb pattern analysis were evaluated in all samples. Genotyping of selected samples were performed via reverse dot blot hybridization and sequencing techniques.

Results:

The screening of more than 4% of the population revealed following carrier frequencies of hemoglobinopathies: α‐thalassemia – 10.1%, β‐thalassemia – 3.71%, HbS – 0.082%, HbC – 0.382%, HbE – 0.087% and HbD Punjab – 0.068%. The frequency of α‐thalassemia was calculated via Hardy–Weinberg equation, based on the count of individuals with HbH. Genotyping of the carriers revealed 33 β‐thalassemia and 9 α‐thalassemia mutations. The most common β‐thalassemia mutations were frameshifts and mRNA processing mutations accounting for β0 phenotype: Codon 8 [‐AA] – 34.7%, IVS‐II‐1 [G > A] – 16.7%, IVS‐I‐110 [G > A] – 9.7%, Codon 8/9 [+G] – 4.8%, and Codon 36/37 [‐T] – 4.3% (N = 1252). The most prevalent α‐thalassemia mutations, on the other hand, were deletions accounting for milder phenotype of HbH disease: 20.5 kb DEL – 43.8% and 3.7 kb DEL – 35.4% (N = 144).

Summary/Conclusion:

This is the largest study to date evaluating phenotypic and genotypic diversity of hemoglobinopathies in Azerbaijan, and we hereby provided the first report on carrier frequencies of hemoglobin variants in the country. The screening and genotyping results revealed that hemoglobinopathies are highly heterogenous in Azerbaijan. β‐Thalassemia, although accounts for a lower frequency comparing to α‐thalassemia, is associated with severe phenotypes, including the possibility of coinheritance with clinically significant variants as HbS and HbE.
PB2410 DEPRESSION AMONG CAREGIVERS OF CHILDREN WITH THALASSEMIA MAJOR
Authors: Sen S. , Sen S. , Tulpule S. , Mullanfiroze K. , Gupta S.
Published: June 2019

Background:

Caregivers of patients with thalasemia devote a significant proportion of their time to meet their ongoing medical needs. This can adversely affect the time dedicated to their other children, and as carriers of the disease, they may be burdened significant feelings of guilt and inadequecy. We evaluated symptoms of depression among parents of these patients by PHQ‐9, a well validated screening tool for assessing depression.

Aims:

To determine the incidence of mental health issues among caregivers of children with thalassemia.

Methods:

Parents and caregivers of patients with thalassemia in a Haemoglobinopathy Clinic were screened over a 2‐month period using the Patient Health Questionnaire (PHQ‐9). Responses were tabulated and analysed and the responses from male and female caregivers were analysed and compared separately.

Results:

Parents of of 98 thalassemia patients were screened during the study. Responses were obtained from 75 fathers and 98 mothers of patients. Overall among all parents, 34% screened positive for minor or major symptoms of depression. Among the fathers, 34% had minor symptoms on screening, but none had any symptoms of major depression. Whereas, among the mothers, only 11% had minor symptoms with 24% had major symptoms. In fact, in this cohort 7% of mothers had severe major depression. No thoughts of self harm were voiced by any caregivers, but 80% of fathers voiced feelings of inadequacy and 34% mentioned anger issues. In contrast, feelings of inadequacy or anger issues were voiced by only 14% of mothers.

Summary/Conclusion:

Our study showed that almost a third of parents of children with thalassemia were suffering from depression and we recommend all parents should have access to proper counselling, with active screening and access to appropriate services. It was concerning to note that mothers were more liable to major depression requiring therapy. Though fathers were noted to have less severe symptoms of depression, more than 80% harboured feelings of guilt and inadequacy. As physicians, we need to be actively aware of the mental health issues of thalassemia parents and be vigilant to help them access appropriate services as required.
PB2436 PLATELET GLYCOPROTEIN (GP IIB/IIIA) GENE POLYMORPHISM AS A RISK FACTOR FOR ISCHEMIC CEREBRO VASCULAR STROKE
Authors: Abdelhamid D.A.E. Saad , Attia F.M. , Hosny A.O. , Elsamahy M. Abdelfatah , Ibrahiem G.A. , Abdelhamid M.A.S.
Published: June 2019

Background:

Recent data which indicate considerable variability in platelet phenotype which accounts for differences in platelet surface receptor function, count and reactivity with subsequent thrombotic events. The identification of a contribution by platelet glycoproteins polymorphism to Ischemic cerebrovascular stroke which is a multifactorial, polygenic pathological process is challenging.

Aims:

Assessment of the genetic platelet glycoprotein (GPIIb/IIIa) polymorphism, as a genetic risk factor in ischemic cerebrovascular stroke patients in Ismailia, Egypt.

Methods:

Study population included: Fifty adult ischemic cerebrovascular stroke patients (acute, recent or old) and fifty‐healthy control group matching the patients group. Hematological and biochemical; Molecular assessment included DNA extraction and purification using micro‐centrifugation technique were done. DNA amplification was carried out by PCR‐RFLP technique. Genotypic determination of the platelet GPIIb/IIIa genotypes was carried out using agarose gel electrophoresis of the PCR products after endonuclease restriction with enzyme Msp‐I.

Results:

Platelet glycoprotein GP IIIa (PlA2/A2) genotypic distribution showed a statistically significant difference in ischemic cerebrovascular stroke patients in comparison with the healthy matched controls (the control group: GPIIIa (PlA1/PlA1: homozygous) 82%, GPIIIa (PlA1/PlA2 heterozygous) 16%, GPIIIa (PlA1/PlA1), and GPIIIa (PlA2/PlA2 homozygous) 2%.While the patients group: GPIIIa (PlA1/PlA1: homozygous) 58%, GPIIIa (PlA1/PlA2 heterozygous) 32%, GPIIIa (PlA1/PlA1), and GPIIIa (PlA2/PlA2 homozygous) 10%. There were statistically significant differences in between study groups regarding Platelet GP IIIa (PlA2/A2)genotypes, smoking, hypertension, diabetes, and dyslipidaemia; dyslipidaemia showed the highest odds ratio of all the risk factors.

Summary/Conclusion:

Conclusions: In this population, the genetic platelet glycoprotein GPIIIa (PlA1/PlA2) polymorphism is a reliable and significant predictor biomarker in the prediction of ischemic cerebrovascular stroke and the platelet glycoprotein GPIIIa (PlA2/PlA2) mutant allele was identified as a risk factor ischemic cerebrovascular stroke.

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