bluuebunny/crossref_metadata_2025 huggingface dataset:
PB2186 IMPACT OF CYTOGENETIC ABNORMALITIES ON RESPONSE IN A COHORT OF INDIAN MULTIPLE MYELOMA PATIENTS–IS 13Q DELETION THE NEW 17P IN DISGUISE?
Authors: Mirgh S. P. , Mahapatra M. , Seth T. , Dhawan R. , Aggarwal M. , Saxena R. , Pati H. , tyagi S. , Kothari S. , Halder R.
Published: June 2019

Background:

R‐ISS (Revised International Staging System) incorporates cytogenetic abnormalities for risk stratification of multiple myeloma. High‐risk cytogenetic abnormalities in R‐ISS include 17p deletion, t(4;14),t(14;16). Detection of these abnormalities by interphase FISH (Fluorescence in‐situ hybridisation) has become a popular modality owing to its targeted detection ability in non‐mitotic cells.

Aims:

The aim of this study was to observe the frequency of cytogenetic abnormalities in the Indian setting and their co‐relation with treatment outcomes.

Methods

Retrospective single‐centre study conducted at a single tertiary care centre from North India. Multiple myeloma FISH panel comprising of 5 abnormalities ‐ 13q deletion, 17p deletion, t(4;14), t(11;14), t(14;16) were done in all patients with multiple myeloma, either at diagnosis or when they were referred for relapse or progression of disease. Records of patients in the last two years (January 2016 ‐July 2018) were analysed.

Results:

Over a period of 30months, myeloma FISH panel was done in 49 patients. Of these, abnormalities were detected in 52% (n = 25) patients. 90% patients belonged to ISS stage‐3. FISH panel was done at diagnosis, first relapse and disease progression in 77.5% (n = 38), 7.3% (n = 3) and 19.5% (n = 8), respectively. The most common abnormality was 13q deletion (36.7%). 17p deletion,t(4;14) and t(11;14) were seen in 8.2%(n = 4),4%(n = 2) and 2.4% (n = 1) patients, respectively. Response to treatment could be evaluated in 46 patients which was graded as per IMWG (International Myeloma Working Group) response criteria. The overall response rate (CR/VGPR/PR) of patients in different groups–Normal, 13q deletion, 17p deletion was 79.2%, 50%, 50% respectively. This implied that nearly half of the patients (n = 8) in 13q deletion group did not respond to therapy. Of these, 4 patients (50%) had 13q deletion at baseline. The possible reasons for this may be ‐ detection of 13q deletion in relapsed/refractory patients, concomitant t(4;14) on FISH panel, associated 13q deletion detection on conventional karyotyping and lack of 1q amp detection in our panel which could have let to an unfavourable outcome.

Summary/Conclusion:

IgH translocations are rare in Indian patients. 13q deletions, akin to the 17p group, are associated with high beta‐2 microglobulin levels (ISS‐3), poor responses to bortezomib based therapy and are seen on disease progression.
PB2193 GENE EXPRESSION PROFILE IN PRIMARY MYELOFIBROSIS: ROLE OF ASXL1
Authors: Sosa S. Sánchez , Sieyro C. Bilbao , Ortega Y. Florido , Pérez E. González , Perdomo M. D. L. N. Saez , Stuckey R. , Santana G. Santana , Labarta M. T. Molero , Ferrer J. F. Loro , Casares M. T. Gómez
Published: June 2019

Background:

Primary myelofibrosis (PMF) is a BCR‐ABL1‐negative myeloproliferative neoplasm characterized by aberrant differentiation of all myeloid lineages and profound disruption of the bone marrow niche. The presence of JAK2, CALR or MPL [R1] mutation supports the diagnosis. In approximately 10% of cases classified as PMF, the genetic cause remains unknown and they are known as triple negative. Recent prognostic scores like GIPSS or MIPSS recommend the analysis of other mutations in non‐driver genes, such as ASXL1, SRSF2, EZH2, IDH1/2 and U2AF1Q157, since they influence the risk stratification.

Aims:

To analyze the mRNA expression profiles of EZH2, ASXL1, RB1 and TET2 genes in a series of PMF patients with known mutational status of JAK2V617F, CALR and MPL

Methods

Our series consisted of 21 PMF patients, 6 females and 15 males, with a mean age of 70 years (range 41–87), diagnosed and treated between 1996 and 2018 at the Hospital Universitario de Gran Canaria Dr. Negrín, Spain. Four patients of our series were triple negative, 13 JAK2V167mut, 3 CALRmut and 1 MPLmut. mRNA expression levels were determined by real time PCR in a LightCycler 480 Instrument II (Roche) using ABL as a control gene. Results were normalized with a cDNA pool from the peripheral blood of 10 healthy donors, which was introduced as an internal control in each experiment. SPPS V.23 software was used for statistical analyses.

Results:

We found that ASXL1 expression levels were significantly higher in patients with JAK2V617F mutated compared with JAK2V617F non‐mutated (mean 0.47 vs. 0.25, p = 0.037, Mann–Whitney U test). In the study of progression free survival, we detected a 36% decrease in the probability of progression to AML or death per unit of ASXL1 expression (p = 0.007, Cox regression test). No significant associations were found between expression levels of the other genes studied (RB1, TET2 and EZH2) and triple negative status.

Summary/Conclusion:

ASXL1 mutations are common in myeloid diseases and, in these cases, ASXL1 mutations are associated with worse overall survival and leukemia‐free survival. While the impact of ASXL1 mutations has been well‐studied, the impact of ASXL1 expression levels on patient outcome is less studied. The positive association between higher ASXL1 expression plus JAK2V617Fmut and better progression free survival is in agreement with the fact that the opposite, that is, inactivating ASXL1 mutations plus triple negative status, contribute to poor prognosis. These preliminary results should be confirmed in further studies with a larger series.
PB2196 ANTIPLATELET THERAPY IN ESSENTIAL THROMBOCYTHEMIA: LABORATORY STUDY OF LOW‐DOSE ASPIRIN
Authors: Cacciola R. , Vecchio V. , Cacciola E. Gentilini , Cacciola E.
Published: June 2019

Background:

The essential thrombocythemia (ET) is a myeloid neoplasm characterized by platelet hyperreactivity and thrombosis. The daily low‐dose aspirin (ASA) is a cornerstone in the prevention of the thrombotic events. In the ET an accelerated platelet turnover translates in a renewal of the drug target shortening the duration of cyclooxygenase (COX‐1) inhibition and may dictate new dosing strategies particularly in ASA “low‐responders” patients.

Aims:

Therefore, we evaluated platelet count, β‐thromboglobulin (β‐TG) and platelet factor 4 (PF4), as markers of platelet activation, the platelet function activity (PFA), as indicator of ASA platelet sensitivity, the clotting time (CT), clot formation time (CFT) and maximum clot formation/firmness (MCF), as indicators of aspirinated platelet contribution to clot firmness.

Methods

We studied 60 patients (20 men, 40 women; mean age 51 years, range 32‐70) with ET according to WHO criteria. The mean duration of disease was 11 years. All patients were on ASA 100 mg once daily. Of the 60 patients, 45 were on anagrelide hydrochloride (daily dose 1.5 mg) (10 men, 35 women), 15 were on hydroxyurea (daily dose 2 mg) (10 men 5 women). None had inherited or acquired thrombotic risk factors. Sixty subjects served as controls. Platelets were measured by automated analyzer. β‐TG and PF4 were determined by ELISA. ASA platelet sensitivity and CT, CFT and MCF were measured by Platelet Function Analyzer (PFA‐100) and by ROTEM delta, respectively.

Results:

The mean platelet count was 455 ± 200 × 109/L. All patients had normal β‐TG and PF4 (12 ± 5 IU/ml and 4 ± 1 IU/ml), prolonged C/EPI closure time (T, unit: s, n.v. 84‐160 s) (249 ± 40 s), normal CT (CT, unit: s. n.v. 100‐240 s) (110 ± 20 s), normal CFT (CFT, unit: s, n.v. 30‐110 s) (45 ± 5 s) and normal MCF (MCF, unit: mm, n.v. 50‐72 mm) (61 ± 2 mm).

Summary/Conclusion:

These findings suggest that in ET patients the daily low‐dose ASA represents an optimal dosing strategy.
PB2213 SPLANCHNIC VEIN THROMBOSIS IN MYELOPROLOFERATIVE NEOPLASMS; A PROSPECTIVE ANALYSIS OF THROMBOSIS OUTCOME
Authors: Danaee A. , Yu D. , Chen F. , Patch D. , Tripathi D. , Karkhanis S. , Sekhar M.
Published: June 2019

Background:

Splanchnic vein thrombosis (SVT) includes extrahepatic portal vein obstruction (EHPVO), Budd‐Chiari syndrome (BCS) and mesenteric vein thrombosis. Myeloproliferative neoplasms (MPN) account for the majority of non‐cirrhotic SVT and are diagnosed in 30% of patients with EHPVO and 40% with BCS. SVT in MPN patients is associated with significant morbidity and mortality. There have been no prospective studies looking at this subset and there is very little in the way of guidance in managing this complex patient group.

Aims:

MASCOT is a prospective observational longitudinal study of patients with MPN related splanchnic vein thrombosis. The primary end points of the study are to describe morbidity/portal circulation in the patient group over 18‐24months from baseline, assess any changes in end points clinically and radiologically.

Methods:

29 patients from two centres were recruited and followed up for 24 months. Radiological primary endpoints, examined changes in initial thrombus, including thrombus extension or recurrence, recanalization in patients without cavernoma and changes in spleen size.

Results:

The male: female (M:F) was 13:16 with an average age of 48 years (25‐72). The majority of patients had an underlying diagnosis of polycythaemia vera (PV) 13 (45%), followed by essential thrombocythaemia (ET) 9 (31%) and the remaining patients had primary myelofibrosis (PMF), MPN‐unclassified (MPN‐U), post essential thrombocytosis‐MF (PET‐MF). Two patients did not have evidence of MPN on bone marrow histology. 27/29 had the JAK2v617f mutation; 2 had CALR mutation.

Summary/Conclusion:

In this prospective study of patients we did not observe recurrence or extension of SVT, however a small proportion of patients went on to develop further thrombotic complications whilst on anticoagulation. The study aims to follow patients for duration of five years with repeat imaging and clinical data.
PB2225 ARTIFICIAL INTELLIGENCE AIDING IN DIAGNOSIS OF JAK2 V617F NEGATIVE PATIENTS WITH WHO DEFINED ESSENTIAL THROMBOCYTHEMIA
Authors: Belcic T. , Cernelc P. , Sever M.
Published: June 2019

Background:

Smart Blood Analytics (SBA) is an artificial intelligence program using machine learning algorithm in order to provide a list of most probable disease diagnosis in numerical order based on patient's blood test results. It was successfully tested in diagnosing hematological diseases and is especially targeted for medical doctors without detailed knowledge in the field of hematology.

Aims:

Our aim was to determine the applicability of SBA algorithm in patients with suspected essential thrombocythemia (ET).

Methods:

We analyzed 237 patients that presented at UMC Ljubljana between 04/2011 and 09/2016 with the referral diagnosis of ET. Based on the presence of CALR or MPL mutation and bone marrow examination we defined patients with true ET according to WHO 2008 or modified WHO criteria. All 237 patients were subsequently analyzed by SBA algorithm in order to determine the most probable hematologic diagnosis based on patients’ blood test results obtained at the time of referral. The diagnosis of interest according to ICD10 classification was D47 describing other neoplasms of uncertain behavior of lymphoid, hematopoietic and related tissue, including ET. We defined sensitivity and specificity of ET diagnosis by using SBA machine learning algorithm.

Results:

10.5% (25/237) of patients were diagnosed with ET according to WHO 2008 or modified WHO criteria. 22 patients were CALR positive, 1 patient was MPL positive and 3 patients were triple negative. 89.4% (212/237) of patients were diagnosed with either secondary thrombocythemia or other neoplastic disease, such as myelodysplastic syndrome. The sensitivity of SBA algorithm to detect patients with ET was 100% and the specificity was 50.4%.

Summary/Conclusion:

The number of patients with true ET referred to our center was low. An improved referral and diagnostic approach for patients with thrombocythemia should be used. The SBA machine learning algorithm could be useful, especially in circumstances where hematologic consultation is not available. Further development of SBA machine learning algorithm is warranted.
PB2237 THE RED BLOOD CELL COUNT AND THE SEDIMENTATION RATE IN THE DIAGNOSIS OF POLYCYTHAEMIA VERA?
Authors: Skov V. , Nersesjan V. , Zervides K. A. , Kjaer L. , Sørensen A. L. , Hasselbalch H. C.
Published: June 2019

Background:

This retrospective cross‐sectional study investigated the effects of microcytosis on the hematocrit (HCT) value in Polycythemia Vera (PV) patients. Since iron deficiency is frequent in PV, and the HCT is a derived value from the Red Blood cell Count x Mean Corpuscular Volume (RBC x MCV), it is reasonable to question if low MCV in PV affects the validity of the HCT value. In addition, we evaluated the Erythrocyte Sedimentation Rate (ESR) as a possible additional diagnostic marker for PV.

Aims:

To evaluate RBC, hematocrit and the ESR in the diagnosis of PV.

Methods:

This study included 182 subjects (39 with PV, 27 with Essential Thrombocythemia (ET) and 116 suspected of MPN disease with a secondary cause for either thrombocytosis or erythrocytosis (hereafter named “MPN‐suspects”). The frequencies of microcytosis and low ferritin (<15ug/L) in PV patients were compared to subjects suspected of having a MPN disease. Correlation studies were performed to compare the HCT versus RBC in all subgroups. The ESR was evaluated as a diagnostic marker for PV by a contingency table and a ROC‐curve analysis.

Results:

In the MPN suspects, 4 of 117 (3 %) had plasma ferritin < 15 ug/L, compared with 6 of 38 (16 %) in the PV‐group (P < 0.05). In the MPN suspects, we found that 3 of 115 (3%) as compared to 6 of 39 (15%) in the PV‐group had MCV < 82 (p < 0.05). Poor linear correlations of RBC versus HCT were found in the PV group compared to the MPN suspects (R2 = 0.62 and R2 = 0.76, respectively). When subjects with microcytosis were excluded, better correlations were observed (R2 = 0.87 in PV and R2 = 0.82 in the MPN suspect group). We found a specificity of 97,7% and a sensitivity of 37,1% for ESR < 2 mm by a ROC‐curve analysis when used for diagnosing PV when PV was suspected. The area under the curve (AUC) was 0,71 (95% CI: 0.60‐0.82), indicating a fair test accuracy for ESR as a diagnostic test.

Summary/Conclusion:

The HCT is not a valuable parameter in the assessment of expanded RCM in PV, since HCT is falsely lowered due to iron deficiency with microcytosis, which are common findings in patients with PV. The RBC is a simple measurement that may more precisely reflect the total red cell mass which also impacts the ESR as reflected by a low ESR (< 2 mm) in 13 of 35 (37 %) of PV patients at the time of diagnosis. Importantly, the ESR might also be a valuable diagnostic biomarker for PV with a high specificity in patients with elevated HCT, Hb or RBC. A combination of RBC and ESR as simple measures to substitute the Hb‐concentration and the HCT in the diagnosis of PV should be addressed in future well‐designed prospective studies, including the value of the RBC and the ESR in deciding when to phlebotomize patients with PV.
PB2248 FIRST KOREAN CASE OF THROMBOCYTHEMIA 1 WITH THPO MUTATION (C.13+1G>A, SPLICING) DIAGNOSED BY TARGETED EXOME SEQUENCING
Authors: Jung N. , Shim Y. J. , Kim H. S.
Published: June 2019

Background:

Thrombocythemia is a kind of myeloproliferative disorder characterized by excessive platelet production and increased numbers of circulating platelets. Thrombocythemia is also associated with thrombotic or hemorrhagic episodes and leukemic transformation. Thrombocythemia 1 (THCYT1) is a very rare autosomal hereditary thrombocythemia caused by heterozygous mutation in the thrombopoietin gene (THPO) on chromosome 3q27.

Aims:

We introduce the first Korean boy who was confirmed as thrombocythemia 1 with a THPO gene mutation by next generation sequencing.

Methods:

We performed targeted exome sequencing to find out genetic cause to induce thrombocytosis. Library preparation was performed by the TruSight One sequencing panel (Illumina, USA). Massively parallel sequencing was conducted by NextSeq (Illumina, USA). An identified variant was confirmed by Sanger sequencing of the patient and his parents.

Results:

A 25 day‐old male infant who had congenital absent distal phalanges of left hand was referred to our medical center for the evaluation of leukocytosis – white blood cell (WBC) count 32,700/ μL. His older sister had a history of persistent thrombocytosis with unknown etiology from her age of 5 months in another hospital. In his laboratory test, WBC count gradually increased to 57,610/μL and the monocyte count in peripheral blood increased over 1,000/μL. His bone marrow study showed increased myeloid series with some blasts (5.1%). At first, we suspected that he had juvenile myelomonocytic leukemia (JMML), but his clinical and genetic evaluations were insufficient for the diagnostic criteria of JMML. He was followed up for laboratory tests at the outpatient clinic regularly. At his 4 months of age, leukocytosis resolved spontaneously. On the other hand, platelet count increased to more than 1,000,000/μL and sustained. The second bone marrow study revealed megakaryocyte hyperplasia. The genetic evaluations for ET (JAK2, MPL, and CALR gene sequencing) were performed, and there was no pathogenic variant in them. Based on his history and laboratory findings, we performed targeted exome sequencing for his family. Finally, at the 11 months of his age, the patient was confirmed as THCYT1 with a THPO gene mutation (NM_000460.2:c.13+1G>A, splicing) which is also found in his father, as mosaicism, and his sister who was had a history of thrombocytosis. Also, of the 4 of his family, thrombocytosis was only detected in his older sister. The pedigree suggested that the disease was in herited in an autosomal dominant manner. He has been followed over a period of 15 months up to now with treatment of low dose acetyl salicylic acid. No thrombotic or hemorrhagic events developed during the follow up period.

Summary/Conclusion:

This is the first report of thrombocythemia 1 patient with THPO gene mutation in Korea.

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PB2254 QUALITY OF LIFE AND DEMOGRAPHICS OF PATIENTS WITH IMMUNE THROMBOCYTOPENIA (ITP); DATA FROM THE PLATELET DISORDER SUPPORT ASSOCIATION (PDSA) PATIENT REGISTRY
Authors: Kruse A. , Kruse C. , Potthast N. , Boulanger V. , Seebald A. , Rossov S. , Milligan K.
Published: June 2019

Background:

Patients with the autoimmune disease ITP suffer from bleeding events as a result of low platelet counts. These events may manifest as bruises, petechiae, blood blisters, bloody stools, blood in urine, or even bleeding in the brain. Treatments vary by severity of disease but include medications (steroids, immunosuppressants, IVIG, TPO‐receptor agonists) and splenectomy. Both the disease and the treatments themselves impact quality of life for these patients, who commonly state concerns of anxiety and fatigue.

Aims:

In 2017, PDSA in collaboration with NORD launched the ITP Natural History Registry to understand patient characteristics, their disease, disease management, and quality of life. Here, we describe the demographics and quality of life for registrants to date.

Methods:

The PDSA Registry contains 6 surveys covering patient demographics, medical and diagnostic information, treatment utilization, disease progression, and quality of life. As of February 2019, 538 patients have completed 1,975 surveys.

Results:

Patients in the registry are mostly white (89%, 470/528), female (76%, 399/528), and reside in the US. 34% (170/499) of patients have Medicare, Medicaid, or both, while 62% (311/499) have commercial insurance. Average (median) age at diagnosis was 32 (31) years with 25% (125/502) younger than 18 years. Time from onset of symptoms to diagnosis was more than one year for 32% (169/528) of patients. In response to specific questions regarding anxiety and fatigue, 11% (32/285) of patients stated they were often or always feeling like they needed help for their anxiety and 36% (99/277) said that their fatigue bothered them quite a bit or very much. Of the 538 registrants, 288 provided data on treatment and 27% (78/288) indicated receiving a splenectomy. For patients who received a splenectomy, quality of life was rated as poor to fair for 23% (18/78) of patients. For patients who had not had a splenectomy, 19% (40/210) rated their quality of life as poor to fair, which is improved but not statistically different from the splenectomy group (z = 0.758, p = 0.447).

Summary/Conclusion:

Respondents in the PDSA ITP Natural History Registry are predominantly female, white, and diagnosed while young, with a fourth of patients under 18 at time of diagnosis. Disease awareness is suboptimal as indicated by the prolonged time to diagnosis, >1 year, for a third of registrants. QoL is impacted in patients with ITP with it directionally worse, though not significantly different, for those who have had a splenectomy compared to those without. Data collection continues through the registry with the intent of raising disease awareness and understanding the impact of the disease.
PB2257 USE OF ARGATROBAN AS AN ANTICOAGULANT TREATMENT ALTERNATIVE IN CRITICAL PATIENTS WITH HEPARIN‐INDUCED THROMBOCYTOPENIA. EXPERIENCE IN A THIRD LEVEL HOSPITAL.
Authors: Salvador E. , Villalba M. , García A. , Pinzón S. , Fernández N. , Calvo J. M. , Delgado P.
Published: June 2019

Background:

Heparin is a widely used drug. The most frequent complication derived from its use is the haemorrhage. However, an uncommon but potentially serious adverse effect is heparin‐induced thrombocytopenia (HIT). The goal of treatment of HIT is to reduce platelet activation and thrombin formation to decrease the risk of thrombosis. Argatroban is the drug of choice in HIT patients as an alternative anticoagulant treatment in critically ill patients with high risk of haemorrhage, postoperative cardiac events or renal failure, since it allows close control of anticoagulation.

Aims:

To analyze the clinical, laboratory and therapeutic characteristics of patients treated with Argatroban by HIT in our hospital

Methods:

Retrospective analysis or patients treated with Argatroban for diagnosed HIT during the last year.

Results:

Four patients have required treatment with Argatroban for HIT since they required maintenance of anticoagulation due to mitral prosthesis, unstable angina, DVT in the right lower extremity and acute ischemia in the left lower extremity. Median age 68 years (43‐79). All of them were diagnosed with HIT according to the 4T score during their admission to the Intensive Care Unit. PF4/Heparin antibody testing was positive in the four patients.

The median number of days from the start of Heparin treatment (2 with unfractioned and 2 with low molecular weight) to the onset of thrombocytopenia was 6 days (1‐8). Median platelets at diagnosis were 73x109/L (49‐82). Median number of days from the start of Argatroban to platelet recovery was 6 days (3‐12). Median number of days of treatment with Argatroban was 9.5 days (2‐18). Argatroban dose was adjusted to maintain aPTT at 1.5‐3.0 times baseline. 3 patients presented thrombotic events, 2 directly related to HIT (1 ischemic stroke and 1 acute ischemia of right upper extremity) and 1 with worsening of reperfusion of the limb. 2 patients required amputation of the limb. No adverse events associated with Argatroban, including haemorrhage, were observed.

Summary/Conclusion:

HIT is a potentially catastrophic complication of heparin treatment which requires urgent detection and treatment with a non‐heparin anticoagulant such as Argatroban should be initiated. Even in critically ill patients, Argatroban anticoagulation improves clinical outcomes in patients who have HIT, without increasing bleeding risk.
PB2258 ERYTHROPOIESIS STIMULATING AGENTS (ESAS) IN MANAGEMENT OF MYELODYSPLASTIC SYNDROMES: RECAMDS TRIAL
Authors: Cerchione C. , Martinelli G. , Soriente I. , D’Arco A. M. , Danise P. , Cerciello G. , Pane F. , Alfinito F.
Published: June 2019

Background:

Erythropoiesis stimulating agents (ESAs) are the frontline treatment in low‐risk anemic MDS patients and an employment of this therapy in the earlier stage of the disease can delay the need for RBC transfusion, hypothetically by slowing the disease course. It's matter of debate whether the clinical response is a result of proliferation and maturation of the dysplastic clone or stimulation of residual normal erythropoiesis by ESAs.

Aims:

Macrocytosis is one of the cytological hallmarks of dyserithropoiesis in MDS: an analysis of the erythropoietic response to ESAs therapy in a cohort of anemic non trasfusion‐dependent MDS patients, enrolled in a retrospective register, RECAMDS, subgroup of Italian register, was performed.

Methods:

183 patients, treated with standard‐dose ESAs, have been retrospectively analyzed (Table 1). Data analysis was performed, according to IWG 2006 criteria, at the baseline, after 3 and 6 months of continuous treatment, with a subanalysis of the patients according to WHO and R‐IPSS risk stratification. ESAs were started at mean Hb concentration of 9.31 g/dl, mean serum EPO concentration: 51 mU/L, after a mean time from diagnosis of 6 months (r.1‐118).

Results:

Overall response rate (ORR) was 83.6% (153/183), no difference among WHO and IPSS subgroups was found: 132/183 (72.1%) achieved response after 3 months of treatment, while other 21/183 (11.2%) after 6 months. 19 patients with stable disease (non‐responders, according to IWG criteria), in which treatment was continued, achieved response after 9 months. In the macrocytic‐responders group 83.2% exhibits again macrocytosis after 3 months, while 16.8% become normocytic. In the normocytic‐responders group 89.8% exhibits again normocytosis, while 10.2% become macrocytic: in these patients, after 3 months, there was a contemporary worsening in neutropenia and thrombocytopenia, with transfusion‐dependence, regarded as first signs of progression of disease. Non‐responders were 30/183 (16.3%): in the macrocytic non‐responders group 89% exhibit again macrocytosis after 3 months, while 11% become normocytic; in the normocytic group 76% exhibits again macrocytosis, while 24% become normocytic.

Summary/Conclusion:

These preliminary data can suggest that, in the majority of MDS patients responsive to ESAs, the increase of Hb concentration occurs mainly stimulating erythroid production in MDS clones; in the minority of patients probably it happens recruiting residual polyclonal erythropoiesis.

It is interesting to note that stimulating effects of ESAs last even when the expression of dysplasia progresses.
PB2271 POMALIDOMIDE‐DEXAMETHASONE IN THE MANAGEMENT OF HEAVILY PRETREATED MULTIPLE MYELOMA
Authors: Cerchione C. , Martinelli G. , Nappi D. , Pareto A. E. , Di Perna M. , Ferrara K. , Ferrari A. , Simonetti G. , Pane F. , Catalano L.
Published: June 2019

Background:

Pomalidomide is a new generation IMID, with a very good compliance, thanks to oral administration, which can be used also in heavily pretreated patients, in a domestic setting.

Aims:

In this retrospective observational trial, It has been evaluated efficacy and tolerance of pomalidomide plus dexamethasone (PD) as salvage regimen in heavily pretreated patients with relapsed and refractory MM (rrMM), whose prognosis is particularly severe.

Methods:

33 patients (19 M/14 F), with rrMM, median age at diagnosis 69 years (r. 52‐84), and median age at start of treatment 76 years (r.56‐89) treated with several lines of treatments (median 7, r. 2‐11), every refractory to all the drugs previously received (also Bortezomib, Thalidomide and Lenalidomide), received Pomalidomide‐Dexamethasone (Pomalidomide 4 mg for 21 days, Dexamethasone 40 mg days 1,8,15,22, pegfilgrastim day +8) every 28 days, until progression. ISS was equally distributed, and cytogenetic at relapse was evaluable in 14 patients. All the patients had previously been treated with schedule containing bortezomib and IMIDs. 60% (20/33) of them had undergone at least to a single ASCT. All patients were relapsed and refractory to last therapies received before PD.

Results:

Pomalidomide was well tolerated, with grade 3 anemia in 51% (17/33) of patients, 36.3% (12/33) grade 3 neutropenia (pegfilgrastim in primary prophylaxis was given, no hospitalization was required, no septic shocks were observed), 30.3% (10/33) grade 3‐4 thrombocytopenia without hemorrhagic events and transfusion‐dependence. No severe extra‐hematologic toxicity was observed. According to IMWG, ORR1 (≥PR) was 45.4% (15/33: 4 CR, 5 VGPR, 6 PR), but, considering that we are evaluating a cohort of heavily pretreated patients, with poor prognosis, another parameter should be considered, ORR2 (≥SD), considering stable disease as a successful result in progressive MM. ORR2 was 78.7% (26/33: 4 CR, 5 VGPR, 6 PR, 11 SD). These can be considered as impressive result in this subset of patients. Oral treatment gives a really good compliance, in frail and unfit patients, and response, when present, is always really fast (median time to response: 2 months (r.1‐6)), median OS from diagnosis was 92 months (range 21‐234), median OS from start of pomalidomide was 9 months (range 1‐25).

Summary/Conclusion:

Pomalidomide‐dexamethasone has shown significant efficacy and a very good compliance, thanks to oral administration, in a particularly severe setting of heavily pretreated patients, relapsed and refractory to all available therapeutic resources.
PB2279 EFFECT OF EDUCATIONAL TRAINING PROGRAM ON IMPROVING PEDIATRIC ONCOLOGY NURSES, PRACTICE REGARDING NON PHARMACOLOGICAL PAIN MANAGEMENT
Authors: Hesham M. , Dakhakhny A. El‐ , Ramadan R. , besheer M.
Published: June 2019

Background:

Pain in cancer children poses a significant challenge for health professionals. It is most often not adequately treated because of inexperience and unfounded fears of analgesic treatment. Non pharmacological interventions support patients in coping with the disease consequences and in playing an active role in the management of their condition. Nurses are the professionals most responsible for caring for patient's pain and play a critical role in efficient pain management.

Aims:

to identify the effect of an educational training program on improvement of pediatric oncology nurses’ practice regarding non‐ pharmacological pain management.

Methods:

A quasi‐experimental study design was conducted on a sample of 23 nurses who were working in in Pediatric Hematology and Oncology unit at Zagazig university children hospitals. Two tools were used in the present study at three phases (pretest, post‐test and follow up after 2 months); first: a questionnaire interview sheet to assess nurses’ knowledge related to pain and non‐ pharmacological pain management, the second: a structured observational checklist for nurses’ practice.Educational training program was developed to train pediatric oncology nurses about non‐pharmacological pain management in children (Massage technique,Reflexology massage,Hotand cold Pack Application,Slow rhythmic breathing).

Results:

from the present study we revealed that none of the studied nurses had good knowledge score before implementation of the program. This percentage increased to 100.0% after implementation of the program and decreased to 52.2% at follow up phases of the program. Pediatric oncology nurses practice had been improved significantly after implementation of the educational training program either immediately or 2 months later.

Summary/Conclusion:

it was concluded that educational training program to pediatric oncology nurses had improved their knowledge and practice regarding non pharmacological pain management as there was a statistical significant difference throughout the three phases of the study. Based on the results of the present study continuous formal training programs for updating the knowledge and practice of pediatric oncology nurses about non‐pharmacological pain management was recommended.
PB2292 ROLE OF SMOKING ON HEMATOLOGICAL PARAMETERS AND FERRITIN LEVELS
Authors: Çiftçiler R. , Guven A. , Haznedaroglu I. , Aksu S.
Published: June 2019

Background:

Cigarette smoking is associated with an increased risk of cardiovascular diseases, including coronary artery disease, peripheral vascular disease, ischemic heart disease, atherosclerosis, myocardial infarction and stroke. Our aim was to define possible effects of smoking on hematological parameters as well as ferritin and transferrin saturation.

Aims:

In this study, we evaluated the association between hematological parameters and smoking status. Our aim was to define the possible effects of smoking on hematological parameters as well as ferritin and transferrin saturation.

Methods:

This study has been performed in a retrospective manner. One hundred and forty nine patients who admitted to Hacettepe University Hospitals between September 2018 and November 2018 were evaluated. Inclusion criterion in this study were ≥ being older than 18 years of age, having no chronic diseases such as diabetes mellitus, ischemic heart disease, peripheral vascular disease, active liver and kidney disease, chronic pancreatitis, gastrointestinal disease, inflammatory bowel diseases, hypertension, any infectious or debilitating illness. In addition, patients who were on medications such as antibiotics, steroids, thiazide diuretics, aspirin, non‐steroidal anti‐inflammatory drugs, immunomodulatory drugs and drugs that may interfere with ferritin and CBC parameters were excluded from the study.

Results:

There were 95(63.7%) healthy non‐smokers and 54 (36.3%) healthy smokers included in this study. The median age was 32 (18‐61) years for all groups. There were 47 (31.5%) males and 102 (68.5%) females in this study. Hemoglobin (p<0.001), HCT (p<0.001) and MCV (p = 0.002) were statistically significantly higher in smokers group than in non‐smokers group. Leukocyte (p<0.001), neutrophil (p = 0.001) and lymphocyte (p = 0.04) counts were statistically significantly higher in smokers group compared to non‐smokers group.

Summary/Conclusion:

In conclusion, our study showed that cigarette smoking has severe adverse effects on hematological parameters such as hemoglobin, leucocytes, lymphocytes, MCV and HCT. These alterations might be associated with a greater risk of developing secondary polycythemia, atherosclerosis, chronic obstructive pulmonary disease and cardiovascular diseases.

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PB2299 AN INVESTIGATION INTO THE PRESENCE OF COMPLEMENT PROTEINS ON ERYTHROCYTE VESICLES IN SICKLE CELL DISEASE
Authors: Obieze C.
Published: June 2019

Background:

A single amino acid substitution in the globin gene segment is the underlying genetic defect in sickle cell disease (SCD) creating a haemoglobin molecule which polymerizes on deoxygenation. Recent insights into the pathophysiology of the disease have pointed to the roles inflammation and hypercoagulability play in disease manifestation and severity caused, in part, by increased phosphatidylserine exposure and extracellular vesiculation by sickle red cells.

Current works have identified some of these vesicles as those released from reticulocytes in the process of maturation to the red blood cell. These vesicles are termed ‘inside‐out’ autophagic vesicles as they are the result of the fusion of endocytosed parts of the cell membrane with autophagic endosomes and are positive for intracellular glycophorin A (GPA) epitope using BRIC163 antibody. Further analysis has shown that some of these vesicles are also positive for extracellular GPA epitope using BRIC256 antibody raising the possibility that the vesicle membrane may have become permeabilized. One possible permeabilizing mechanism is the membrane attack complex of the complement system.

Aims:

The aim of this project was to investigate the presence of complement proteins on vesicles isolated from plasma or attached to erythrocytes using flow cytometry and confocal microscopy

Methods:

Vesicles were isolated from SCD plasma (n = 2) and healthy control (n = 1) using 2 different techniques: membrane‐based isolation technique and fluorescent‐activated cell sorter (FACS) and studied with flow cytometry using BRIC163, BRIC256, C3, C4, C3c and C3d antibodies. Cultured reticulocyte (n = 2), sickle red cells (n = 3) and healthy control red cells (n = 2) were analyzed with confocal microscopy using Annexin‐V, BRIC163, C3, C4, C3c and C3d antibodies.

Results:

Results show the presence of complement proteins on vesicles in both SCD plasma and healthy control in levels as high as 100% for BRIC163 vesicles in healthy control. Confocal analyses reveal this deposition is also present on vesicles prior to release and is associated with PS exposure.

Summary/Conclusion:

Complement proteins are present on vesicles in plasma and erythrocytes and may suggest activation and formation of the MAC complex. Further work is required to determine the involvement of these proteins in vesicle formation and release.
PB2308 THE EFFECT OF SICKLE CELL DISEASE ON PREGNANCY IN AL‐AHSA, KSA 2012‐2017
Authors: Abdulrahman S. , Alsaleh E. , Algadeeb S. , Algadeeb J. , Algadeeb M. , algadeeb R.
Published: June 2019

Background:

Pregnant women with SCD are at an increased risk for maternal and fetal morbidity and mortality (1,2). The numerous potential maternal complications include anaemia, acute crisis, preeclampsia, eclampsia, urinary tract infection, pneumonia, and acute chest syndrome (3,4,5,6). In addition, Pregnant women with SCD had lower maternal weight and gestational weight gain (7,8).

Aims:

The aim of this study was to compare the pregnancy outcomes between pregnant women with Sickle Cell Disease and pregnant women without Sickle Cell Disease and to measure the difference in weight gain between two groups.

Methods:

A quantitative retrospective cohort study carried out between January 2012 and December 2017 in Maternal and Children Hospital and Primary Health Care centres in Al‐Ahsa, an eastern region of the Kingdom of Saudi Arabia (KSA). The study population included all SCD patients who were registered for antenatal care follow up in the MCH and, on the other side, pregnant women without SCD from the primary health care centres depending on inclusion and exclusion criteria. The total sample size was 429. One hundred forty‐three pregnant women with Sickle Cell at the Maternity and Children Hospital and 286 pregnant non‐Sickle Cell from PHCCs were recruited by matching in residency. The data collection sheet used to gather patient information was prepared based on the card of antenatal care in the Ministry of Health and literature review.

Results:

Weight, BMI, and haemoglobin level at the first antenatal visit showed a significant difference between the two groups (P < 0.001). Forty‐three present of women with SCD had cesarean sections, compared to 13.9% of women without SCD, and there was a statistically significant association between them (P < 0.001). Maternal weight gain was lower in women with Sickle Cell Disease and showed statistically significant (P < 0.001). Women with Sickle Cell Disease had an increased risk of Caesarean section (AOR = 3.807, 95%CI = 2.074‐6.987, P < 0.001).

Summary/Conclusion:

Women with Sickle Cell Disease are more likely to have adverse pregnancy outcomes compared to women without Sickle Cell Disease. Women with Sickle Cell Disease had lower weight gain during pregnancy.
PB2312 PANORAMA OF HEMOGLOBINOPATHIES IN THE ANNABA REGION OF ALGERIA
Authors: Djenouni A. , GRIFI F.
Published: June 2019

Background:

Various national studies and some multicenter studies have been conducted in the past, highlighting the different foci of hemoglobinopathies. The North‐East of the country, essentially the border area with Tunisia, is an endemic area of sickle cell disease, posing many public health problems.

Aims:

The objectives of our work are:

Census of hemoglobinopathies supported at our level

Determine their epidemiological and evolutionary characteristics

Methods:

This is a retrospective study, extending from January 1988 to December 2017. A regular monitoring is carried out at varying rates depending on the type of hemoglobinopathy with annual impact assessments.

Results:

during this period a total of 1709 cases of hemoglobinopathies, was followed and each type its epidemiological characteristics:

Major sickle cell syndromes: 1550 cases (90.7%)

Homozygous form: 960 cases (61.94%)

Double heterozygosity S / C: 99 cases (6.4%)

Double heterozygosity S / B Thalassemia: 491 cases (31.68%)

Epidemiological data: the current average age: 30.3 years [1 ‐ 69 years], the Sex ratio: 0.84, the majority of our patients come from Algerian‐Tunisian border area (79%). Inbreeding is present in 35.35% of cases, 70% of patients had at least one similar case in siblings.

Hemoglobin C: 70 cases (4.1%)

Epidemiological data: the current average age: 36 years [11 ‐ 69 years]; the Sex ratio: 0.70. Inbreeding is present in 59.69% of cases, 63% of patients had at least one similar case in siblings.

The β Thalasemia: 89 cases (5.2%)

Major form: 68 cases (76.4%)

Intermediate form: 21 cases (23.6%)

The epidemiological characteristics: the current average age: 19 years [03 ‐31 years], Sex ratio: 1.04. Inbreeding is present in 51% of cases and is 1st degree in 33.33%.

Summary/Conclusion:

Hemoglobin abnormalities are common in our region, mainly major sickle cell syndromes, posing a major health problem. Many efforts must be made at different levels to reduce the frequency of these abnormalities in this region and to provide adequate and above all multidisciplinary care for these patients.
PB2317 CHOICE OF VENOUS ACCESS FOR CHRONIC RED CELL EXCHANGE IN CHILDREN WITH SICKLE CELL DISEASE
Authors: Velasco P. , Guillen G. , de Heredia C. Diaz , Fernandez J.
Published: June 2019

Background:

Among the options of chronic transfusion regimen in sickle cell anemia (SCA), red cell exchange (RCE) is the most efficient method.

In pediatrics, permanent venous accesses minimize venous punctions and improve the quality of life. Port‐a‐cath (PAC) are the devices with the least infectious complications.

The recommended size of the PAC is related to the patient's age and weight

Patients with SCA have a higher risk of thrombotic complications.

Aims:

Our objective is to select the most versatile and small PACs, to reduce thrombotic risk, which allow adequate flows to perform RCE.

Methods:

Selection of PAC marketed in Europe with one and two lumen, depending on the size of the reservoir, catheter, speed and availability in Europe

Ex vivo analysis of the maximum flows tolerated by the ”Spectra Optia“ machine during the RCE procedure, using expired red blood cell concentrates and Gripper needles of 19 and 20G.

Implantation of the device and analysis of the efficacy of the procedure in 2 patients with SCA in a chronic transfusion regimen for 2 years

Results:

After a first screening, the Cardiva PHS Medical 10.5fr double‐lumen PACs were analyzed; Bard 9.5 fr and Vortex Angyodinamics 11.4 fr. As a PAC of single lumen, the Smart Port CT mini Angyodinamics of 6.6 fr was analyzed, in order to use an extraction PAC and a return one for the same vessel.

The catheters that showed better results were those of Angyodinamics, using Gripper of 19G and reaching flows of 25‐30 ml / min.

Among these PACs, we selected the 6.6 fr of single lumen for the following reasons: smaller reservoir (more suitable for small and thin children), separate devices that allow only one of them to be replaced if a light is obstructed and because a Single‐light PAC could be sufficient if in the future Spectra Optima allows the unipuncture mode.

In vivo, we successfully implanted the 2 PAC of single lumen selected in 2 patients of more than 40 kg, in which we were able to perform RCE every 6 weeks, during the last 2 years. The procedure is performed in an average of 3 hours. There have been no complications of thrombosis, obstruction or infection to date.

Summary/Conclusion:

The exvivo test allowed to discard devices not suitable for the procedure and to select a single lumen PAC model of 6.6 fr that allows sufficient flows to perform the chronic RCE in pediatric patients of any age and weight, minimizing the associated infectious and thrombotic risks to permanent accesses in patients with ACF.
PB2327 SUBSTITUTING CARMUSTINE WITH BENDAMUSTINE IN BEAM RESULTS IN DELAYED PLATELET RECOVERY AND LESS MUCOSITIS WITH SIMILAR EFFICACY – A MATCHED PAIR ANALYSIS
Authors: Aurer I. , Zekanovic I. , Durakovic N. , Batinic J. , Dreta B. , Bašić‐Kinda S. , Sertić D. , Roncevic P. , Radman I. , Rincic G. , Bojanic I. , Periša V. , Lozic D. , Petrovic J. , Valkovic T.
Published: June 2019

Background:

Due to availability and pricing problems recently many transplant centers substituted carmustine in the BEAM regimen (carmustine, etoposide, cytarabine, melphalan), used for conditioning of lymphoma patients undergoing autologous stem cell transplantation (ASCT), with bendamustine (BeEAM). Very few comparisons of the toxicity and efficacy of these two conditioning regimens have been reported.

Aims:

Describe the toxicity and efficacy of BeEAM and compare it to that of BEAM.

Methods:

We analyzed outcomes of 35 patients with frequent lymphoma types (B‐large cell, follicular, Hodgkin (HL), T‐cell and mantle‐cell) conditioned with BeEAM in 2016 and 2017 and compared them to 37 patients conditioned with BEAM between 2011 and 2015 matched by age, sex, diagnosis and risk according to standard prognostic indices. Bendamustine was administered at a total dose of 160 mg/m2 divided over two days. Etoposide, cytarabine and melphalan were given as usual.

Results:

Median follow‐up of BeEAM conditioned patients was 18 mo and BEAM conditioned 46 mo. Number of reinfused CD34+ cells/kg body weight was similar between the groups (median 5.87 vs. 5.56 × 106, p = 0,412). One of the BeEAM conditioned patients died of cardiac shock and one progressed before hematologic recovery, no such events occurred in those conditioned with BEAM. There was a trend towards lower incidence of infections and febrile neutropenia (80% vs. 95%, p = 0.0719) and significantly less mucositis in the former group (11% vs. 51%, p = 0,0002). Neutrophil recovery was similar (median 11 days, range 8‐16 vs. median 10 days, range 7‐18; p = 0,215), but platelet recovery was slower after BeEAM (median 16 days, range 8‐29 vs. median 12, range 8‐27; p = 0.00132). Hospitalization duration was similar (median 16 days, range 12‐32 vs. median 17 days, range 12‐24; p = 0.215). OS was almost identical (85% vs. 86% at 2 years, p =  0.781). There was a non‐significant difference in EFS in the whole cohort in favor of BEAM (Fig) (66% vs. 76% at 2 years, p = 0.39), but this was limited to HL (2‐year EFS 61% vs. 82%, p = 0.257). 2‐year EFS of NHL patients was 70% vs. 73%, p = 0.808.

Summary/Conclusion:

Substituting carmustine in BEAM with bendamustine, at least in the dose of 160 mg/m2, results in somewhat delayed platelet recovery but less mucositis and possibly infectious complications. Efficacy in NHL seems maintained. However, reduced efficacy of the BeEAM conditioning regimen in HL cannot be excluded and additional studies, preferably multicenter, in a larger patient population are needed.

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