bluuebunny/crossref_metadata_2025 huggingface dataset:
PB1662 INTEGRATION OF GENOME‐WIDE ANALYSIS INTO CLINICAL DIAGNOSIS OF ACUTE LYMPHOBLASTIC LEUKEMIA: HOW MUCH CAN WE IMPROVE CYTOGENETIC TESTING?
Authors: Othman M. , Melo J. , Carreira I. , Grygalewicz B. , Silva M. , Liehr T.
Published: June 2019

Background:

Acute lymphoblastic leukemia (ALL) is a heterogeneous, aggressive disease, and most common in children. It is a leading cause of cancer death in young and adult, too. However, about 30% of pediatric and 50% of adult ALL patients still lack defined genetic hallmarks of biological and clinical significance. In addition, complex karyotype‐ALL (CX‐ALL) promoting a wide spectrum of diverse genetic alterations with striking genomic instability, are overall often neglected by research.

Aims:

The overall goal of this study was to characterize karyotypes and genetic content of 25 ALL cases and to rule out if one single molecular approach may be sufficient to detect genomic aberrations in these patients.

Methods:

ALL cases were retrospectively studied by multitude multicolor banding (mMCB), fluorescence in situ hybridization (FISH) using selected locus‐specific probes and array‐comparative genomic hybridization (aCGH).

Results:

Most strikingly, 13 of the studied 25 ALLs (∼55%) revealed abnormal karyotypes, applying mMCB: structural abnormalities were present in 12 and even numerical ones were identified in 2 cases. Overall, 123 copy number alterations (CNAs) were identified as loss (∼80%) or as gains (∼20%). Furthermore, highly complex karyotypes were detected by aCGH and mMCB in 4 out of the 13 aberrant cases. The latter four patients had either deletions or amplifications in genes involved in lymphoid development, cell cycle, Hematopoietic stem cells development and/or DNA repair (IKZF1, CDKN2A/B, PAX5, BIRC3, ATM, RB1, RUNX1), as shown by FISH, and also presented acquired marker chromosomes.

Summary/Conclusion:

Molecular approaches are suited to identify cryptic aberrations and potential target genes involved in leukemogenesis and progression of the disease. The present work demonstrated that aCGH is a highly efficient tool for detection of CNAs in ALL. However, while aCGH provide data on imbalanced genomic alterations, molecular cytogenetics additionally detects different leukemic subclones within one sample, as well as balanced translocations leading to tumor‐specific fusion genes. Thus, still no single approach is sufficient to comprehensively characterize all acquired aberrations in ALL.
PB1673 FEASIBILITY AND OUTCOME OF ALLOGENEIC BONE MARROW TRANSPLANTATION IN ADULT PHI NEGATIVE ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: Fakhfakh Y. , Frikha I. , Abdeljlil N. Ben , Tojmen L. , Hdiji S. , Mdhaffar M. , Ladab S. , Kassar O. , Ghorbel M. , Benothmen T. , Elloumi M.
Published: June 2019

Background:

Acute lymphoblastic leukemia (ALL) is a rare disease in adults. Despite the novels therapies, clinical outcomes remain unsatisfactory. Bone marrow allograft still holds its place as a consolidation treatment for patients in complete remission in order to improve the prognosis and lengthen survival.

Aims:

We study in this work the feasibility and outcome of bone marrow allograft for adult Philadelphia chromosome negative ALL.

Methods:

Our study is retrospective including the cases of high‐risk adult ALL (HR) diagnosed in the hematology department of Hédi Chaker Hospital of Sfax during the period from January 2004 to December 2015. These patients were treated according to protocols inspired by GRAALL 2003 and 2005. The indication of bone marrow allograft is systematic in patients whose age are <50 years and having a compatible intrafamilial donor. For our patients we studied the allograft indication, the search for a family compatible HLA donor, the feasibility of the allograft and finally the result of this one which was carried out at the national center of bone marrow transplantation in Tunis.

Results:

Among the 36 cases of adult phi negative ALL treated with the GRAALL 2003 and 2005 protocols, 28 patients were in complete remission (CR) and 22 patients (79%) were classified as HR. Twenty patients had indication of bone marrow allograft (2 were> 50 years of age). Of the 20 patients who had an HLA study, 14 patients (70%) had a compatible HLA family donor. Allogeneic bone marrow allograft could only be performed for 9 patients: 64% of patients with a compatible HLA donor and 45% of patients with CR. For the 5 others the transplant could not be done for: relapsed before allograft for 2 cases and severe comorbidities for the 3 others. The median time to completion of the allograft was 15 weeks. Among the allografts, 6 patients (67%) were living in CR after a follow‐up of 74 months, one patient relapsed at 6 months post‐transplant and 2 patients died of acute GVH. Of the 19 non‐allograft CR patients, 6 patients were living in CR (31%) and 1 died during consolidation therapy and 12 relapsed. The 5‐year DFS of both allografted and non‐allografted patients was 72% and 21%, respectively.

Summary/Conclusion:

Despite the cost‐effectiveness of the intra‐familial HLA study (70% donor) in our study, allografting could only be performed for a small number of patients (45%), hence the need to expand the indication of allograft for subjects over 50 years old or perform a mini allograft, do the same haplo transplant and even expand donor sources on files (pheno‐identical donors). Two‐thirds of the allografted patients in our series did not relapse, an interesting result and comparable to the literature.
PB1683 INCIDENCE AND DEMOGRAPHIC CHARACTERISTICS OF THE MAJOR SUBGROUPS OF PRECURSOR B‐CELL ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN – A BULGARIAN SINGLE CENTER STUDY
Authors: Yurukova N. , Balatzenko G. , Konstantinov D. , Jordanova M. , Avramova B.
Published: June 2019

Background:

The detection of genetic aberrations is used to risk‐stratify patients with acute lymphoblastic leukemia (ALL), decide on the treatment protocol, and to estimate therapeutic effect through the detection of minimal residual disease.

Aims:

The aim of this study was: 1) to determine the frequency of the most common and significant genetic anomalies in children with ALL ‐ t(12;21)(p13;q22)/TEL‐ AML1, t(1;19)(q23;p13)/E2A‐PBX1, t(4;11)(q21;q23)/ MLL‐AF4 и t(9:22)(q34;q11.2)/BCR‐ABL; 2) to compere the incidence with that described in other studies; 3) to describe the demographic characteristics of the different genetic subgroups.

Methods:

For a thirteen year period, in 271 patients with established ALL, molecular‐genetic studies (RT‐PCR) were performed to search for the most common fusion genes.

Results:

In the study population of 271 patients, the incidence of TEL‐AML1 (+) OLL was 21%, E2A‐PBX1 (+) ALL was 5%, BCR‐ABL (+) was 3%, and MLL‐AF4 2.5%. A tendency for a characteristic demographic profile emerges for each genetic subgroup.

Summary/Conclusion:

This study is the first in Bulgaria. The results obtained are comparable to those published by other authors.
PB1738 NUCLEOPHOSMIN‐1 GENE MUTATION DETECTION: COMPARATIVE IMMUNO‐STAINING STUDY FOR BONE MARROW (BM) BIOPSY VERSUS BM ASPIRATE & BM CLOT IN DE NOVO ADULT ACUTE MYELOID LEUKEMIA PATIENTS AMONG EGYPTIANS
Authors: Elgamal B. , El Gammal M. , Badawy R. , Abdelghaffar E. , Rasheed E. , Elkafoury M. , Hamdy M.
Published: June 2019

Background:

NPM1 gene mutation is a well‐known prognostic marker in AML, probably related to its cytoplasmic localization. NPM1 gene mutation detection could be done by either molecular genetics or its protein product by immunohistochemical staining of bone marrow (BM) biopsy.

Aims:

This study aimed to compare the detection rate of the immuno‐staining technique for mutated nucleophosmin‐1 gene when applied on the standard BM biopsy versus BM aspirate or BM clot biopsy in adult de novo patients of acute myeloid leukemia.

Methods:

Forty adult patients (18‐60 years) with newly diagnosed AML were enrolled into this study. Detection of nucleophosmin localization either nucleolar or cytoplasmic was performed using monoclonal mouse anti‐human nucleophosmin (clone 376) by conventional immunohistochemical technique on BM biopsy, BM aspirate & BM clot biopsy.

Results:

The study included 40 AML patients, 23 males, 17 females. The complete remission (CR) rate was 70%. Median overall survival (OS) was 2.5 month (0.1‐40 months). Median disease free survival was 6 month (0.2‐39). NPM1 was detected in 11/40 patients by conventional immunohistochemical technique on BM biopsy, 11/39 patients by BMA technique, and 9/29 by BM clot technique. The BMA technique had Sensitivity of 100%, Specificity of 78.6%, positive predictive value of 64.7%, negative predictive value of 100%, and diagnostic accuracy of 84.6%. The BM clot technique had sensitivity of 77.8%, specificity of 90.0%, and positive predictive value of 77.8%, negative predictive of 90.0%, and diagnostic accuracy 86.2%.

Summary/Conclusion:

The BMA technique had good sensitivity and so could be used as a cheap screening method even in patients with profound thrombocytopenia. BM clot technique had good specificity. Both BMA and BM clot techniques could be a reasonable cheap option if combined together in cases in which BM biopsy could not be done.

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PB1772 TUMOR‐FORMING PLASMACYTOID DENDRITIC CELLS IN ACUTE MYELOMONOCYTIC/MONOCYTIC LEUKEMIA
Authors: Zhu L. , Wang P. , Zhang W. , Li Q. , Deng X. , Liu S. , Liu Y. , Kong P. , Rao J. , Zhang X.
Published: June 2019

Background:

lasmacytoid dendritic cells (PDCs) act as a link between innate and adaptive immunity, PDCs infiltration has been reported in infectious diseases, autoimmune diseases and neoplasms. Our previous work reported PDCs infiltration could occur in AML patients, but the clinical significance of PDC in AML was rarely investigated, based on DC induction from hematopoietic stem cells, myeloid progenitors and monocytes, we presume acute myelomonocytic/monocytic leukemia cases share PDCs phenotypes originally.

Aims:

To clarify the conception andevaluated the expression of PDCs in bone marrow.

Methods:

80 acute myelomonocytic leukemia(AML‐M4) and 83 acute monocytic leukemia (AML‐M5) patients was included in this study for the examination of PDCs expression.

Results:

62 cases were positive for PDCs, which were closely associated with cycles of chemotherapy before achieved CR, patients’ WBC count, Hb concentration, platelet count and bone marrow blasts, and the patients with PDC infiltration had a shorter survival time, meanwhile, allo‐HSCT could abrogated the side effects of PDCs on AML patients.

Summary/Conclusion:

PDC infiltration has a possible role in risk stratification for patients AML‐M4/M5, and our work emphasizes the significance of heterogeneity of AML‐M4/M5.
PB1781 THE OUTCOME OF PREGNANCY‐ASSOCIATED HEMATOLOGICAL CANCERS IN TAIWAN
Authors: Li S.‐S. , Hsu Y.‐T. , Yen C.‐C. , Wu P.‐Y. , Chen Y.‐W. , Li C.‐Y. , Chen T.‐Y.
Published: June 2019

Background:

Pregnancy‐associated cancers, usually defined as cancers diagnosed during pregnancy or one year after delivery, is a diagnostic and therapeutic challenge to doctors. Hematological malignancies are among the most common types of cancer in women of child‐bearing age. However, the impact of pregnancy on the maternal and neonatal outcome is largely unknown.

Aims:

To investigate the impact of pregnancy on the outcome of patients with pregnancy‐associated hematological malignancies.

Methods:

We identified patients with pregnancy‐associated cancers by intersecting the Taiwan Cancer Registry with the Birth Certificate Application. Patients were grouped into pregnant (diagnosed during pregnancy) and lactating (diagnosed within one year after delivery) group. Female patients of child‐bearing age (16‐49 years) who were not pregnant at the diagnosis of cancer were used as a control.

Results:

From the year 2001 to 2015, cancer was diagnosed during pregnancy and one year after delivery in 512 and 2151 patients, respectively. Lymphoma and leukemia are the 5th and 6th most common subtype of pregnancy‐associated cancer. Survival is not significantly different between pregnant, lactating, and non‐pregnant leukemia patients (p = 0.49). A higher proportion of aggressive B‐cell lymphomas is observed in lymphomas diagnosed during pregnancy (73.6%), as compared with the lactating (38.6%) and non‐pregnant (39.5%) group (p < 0.01). The proportion of advanced stage lymphoma in the pregnant or lactating group was not different from that in the non‐pregnant group (Odds ratio [OR] 0.87 & 0.98, p = 0.85 & 0.97, respectively). Compared with the non‐pregnant group, the survival in pregnancy group was not significantly different (Hazard ratio [HR] 1.41, p = 0.40), while the survival in the lactating group is markedly better (HR 0.19, p < 0.01). After controlled with age, stage, year of diagnosis, and histology, lactating status remained an independent prognostic marker (HR 0.12, p = 0.03).

Summary/Conclusion:

Lymphoma diagnosed within one year after delivery carries a good prognosis. Further study is needed to investigate the effect of lactation‐associated hormones in lymphoma.

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PB1782 TWO‐YEAR SURVIVAL WITH AXICABTAGENE CILOLEUCEL IN RELAPSED OR REFRACTORY LARGE B‐CELL LYMPHOMA: AN UPDATED ANALYSIS
Authors: Diakite I. , Lin V.W. , Klijn S. , Navale L. , Purdum A.G. , Fenwick E. , Botteman M. , van Hout B.
Published: June 2019

Background:

Relapsed/refractory large B cell lymphoma is historically associated with a poor prognosis, with a median overall survival (OS) of 6.3 months. In the 2‐year update of the ZUMA‐1 trial of axicabtagene ciloleucel (axi‐cel), median OS was not reached after a median follow‐up of 27.1 months. Prior analysis at 1‐year suggests that traditional parametric survival models cannot accurately estimate long‐term OS with axi‐cel when a large proportion of patients achieve durable remissions, thereby supporting the use of a mixture cure model (MCM) for survival extrapolations (Bansal, et al. Biol Blood Marrow Transplant. 2018).

Aims:

We analyzed the updated 2‐year ZUMA‐1 data to further explore the robustness of MCM.

Methods:

The ZUMA‐1 data were analyzed using a traditional parametric model, MCM, a general mixture model (GMM), and an integrated Markov cure model (IMCM). The MCM assumed patients with long‐term OS would have similar mortality as the age‐adjusted general population. The GMM relaxed this assumption by separately fitting and then combining parametric survival functions for poor‐ and good‐prognosis patients in a single survival function. The IMCM simultaneously accounted for OS and disease progression in a single framework. All parameters were estimated via maximum likelihood estimations, and model fit was assessed via Akaike information criterion (AIC).

Results:

The best‐fitting traditional model estimated a mean OS of 10.6 years (AIC = 444.3). The best‐fitting MCM estimated a mean OS of 13.5 years, with a 51.0% long‐term OS fraction (AIC = 439.3). The best‐fitting GMM produced a mean OS of 13.5 years, with a 52.7% long‐term OS fraction (AIC = 442.1). The best‐fitting IMCM estimated a mean OS of 13.4 years, with a 50.5% long‐term OS fraction (AIC = 916.6). The higher AIC for GMM and IMCM is partly because of specifying more parameters than MCM.

Summary/Conclusion:

Analyzing the updated ZUMA‐1 2‐year data, both the GMM and IMCM showed good model fit and results consistent with those of the MCM. These results support the long‐term survival associated with axi‐cel in relapsed/refractory large B cell lymphoma driven by the ≥ 50% long‐term OS rates.
PB1808 THE LEVELS OF SERUM FERRITIN CAN BE A PREDICTIVE FACTOR FOR SURVIVAL OUTCOMES IN DIFFUSE LARGE B CELL LYMPHOMA PATIENTS WITH ANEMIA
Authors: Lee H.S. , Jeong J.Y. , Jo J.‐C. , Lee W.S. , Lee J.H.
Published: June 2019

Background:

There are many clinical and molecular factors used to predict outcomes in patients with malignant lymphomas. Some studies have shown that serum ferritin levels correlated with tumor mass and closely followed disease activity in patients with hematologic malignancies such as malignant lymphoma and acute leukemia. And serum ferritin has frequently been used as a surrogate marker for systemic iron stores, but may also be elevated in specific circumstances without excess iron stores, such as in inflammation. Nevertheless, in actual clinical practice, the patients with malignant lymphoma, who are anemic and have high serum ferritin levels, are considered to suffer from anemia of chronic disease (ACD). To date, no studies have reported the survival differences between the ferritin and Hemoglobin (Hb) levels.

Aims:

Therefore, we investigated the clinical significance of high serum ferritin level in DLBCL patients with ACD.

Methods:

A total of 312 patients who were diagnosed with DLBCL between 2010 and 2016 were retrospectively analyzed. Patients were divided into four groups based on their ferritin (<500 and ≥500 ng/ml) and hemoglobin (Hb, <12 and ≥12 g/dL) levels. Progression free survival and Overall survival were calculated with the use of the Kaplan‐Meier methods.

Results:

In this study, several factors were demonstrated as independent prognostic factors for survival outcomes. IPI risk is an independent prognostic factor for the 5‐year PFS and 5‐year OS (relative risks (RR) = 0.458, 95% confidence interval [CI]: 0.277–0.758, p = 0.002 and RR = 0.297, 95% CI: 0.152–0.578, p < 0.001, respectively). Non‐bulky mass (<10 cm) (RR = 1.995, 95% CI: 1.140–3.448, p = 0.015) and female sex (RR = 1.848, 95% CI: 1.141–2.997, p = 0.013) were independent good prognostic factors for the 5‐year PFS. Low Hb and high ferritin were also independent poor prognostic factor for the 5‐year PFS (RR = 2.411, 95% CI: 1.063–5.473, p = 0.035: compared with high Hb and low ferritin levels and RR = 2.124, 95% CI: 1.072–4.209, p = 0.031: low Hb and low ferritin). Nevertheless, the groups based on Hb and ferritin levels did not significantly differ for 5‐year OS. In addition, the survival outcomes based on the ferritin level in patients with anemia (Hb < 12.0 g/dL) indicated statistically significant difference. The 5‐year PFS values were 59.3% and 40.9% in low and high serum ferritin levels (<500 and ≥500 ng/ml), respectively (p = 0.01), and the 5‐year OS values were 78.4% and 51.9% in the low and high ferritin levels, respectively (p = 0.006).

Summary/Conclusion:

High serum ferritin levels may prove to be efficient predictive markers for survival outcomes in DLBCL patients with anemia looks like ACD. In DLBCL patients with anemia, that is, considered as ACD, high ferritin level may not indicate a simple ACD but may be a prognostic factor for poor survival.
PB1834 PRALATREXATE EXPERIENCE IN NON HODGKIN LYMPHOMA
Authors: Enciso‐Olivera L. , Patiño B. , Diaz M. , Martinez H. , Otero D. , Spirko P. , Acon C.
Published: June 2019

Please indicate where the abstract has been published before: Third National Congress of clinical investigation. Colombian Association of Oncology and Hematology (ACHO)

Background:

Pralatrexate is an antimetabolite used mainly in the treatment of relapsed or refractory peripheral T‐cell lymphoma. However, due to its low prevalence rate, and a small population analyzed in the trials, there is not a trial which evaluated results in ordinarily practice in our knowledge.

Aims:

To study the treatment with Pralatrexate in a 10 patients series with T‐cell lymphoma, both nodal and cutaneous, attended in our institution.

Methods:

Case series. Patients older than 18 years old, with a diagnosis of T‐Cell lymphoma, any subtype, treated with at least one cycle of Pralatrexate with available information for following up and treatment evaluation. All the analysis were made in the statistic package R (Version 3.4.3) and STATA 15.

Results:

Ten patients were included, 50% were men. The median was 47.8 years (IQR 17.04). The 50% had a Mycosis Fungoides (MF) diagnostic, being the most frequent histologic type. Five patients had the diagnosis of T Cell Lymphoma NOS which, one (10%) T cell Lymphoma ALK‐negative, one (10%) angioimmunoblastic lymphoma and one (10%) primary cutaneous anaplastic lymphoma.

All the patients had received a prior treatment based on anthracyclines. The number of treatment received prior to the Pralatrexate beginning was a mean of 2,8 (SD 1.03). The 30% (three patients) suffered grade 3 mucositis in at least one cycle. Four patients required to be admitted at least in a cycle due to complications related to the treatment, and a patient required to be admitted in an intensive care unit requiring vasopressor support. None opportunistic infections were reported nor febrile neutropenia related to the other treatment cycles.

A patient (10%) reached out complete response, two patients were in stable disease. Six patients (60%) progressed during the treatment after a mean of 2.8 cycles (1 to 4). At the last evaluation time, five (50%) of patients had started a new treatment line.

Summary/Conclusion:

The pralatrexate treatment in our patients with T cell lymphoma diagnosis offers a low response and short duration rates. Despite its good tolerance, also there is a high risk of complications, mainly mucositis.
PB1835 A PHASE 1/1B DOSE‐ESCALATION TRIAL EVALUATING CPI‐818, AN ORAL INTERLEUKIN‐2‐INDUCIBLE T‐CELL KINASE INHIBITOR, IN PATIENTS WITH RELAPSED/REFRACTORY T‐CELL LYMPHOMA
Authors: Mobasher M. , Miller R.A. , Janc J. , Kwei L. , Barker C. , Mohammady A. , Luciano G. , Khodadoust M. , Radeski D. , Horwitz S.M. , Kim Y.H.
Published: June 2019

Background:

Interleukin‐2‐Inducible T‐Cell Kinase (ITK) is a Tec‐family, non‐receptor tyrosine kinase expressed in T cells that plays a key role in T‐cell receptor (TCR) signaling, which is required for development of T‐cells. In T‐cell lymphoproliferative disorders, expression of the TCR and its downstream signaling components are maintained, which suggests that malignant cells may exploit this growth and survival pathway to their advantage. Professional antigen‐presenting cells abundant in the lymphoma microenvironment may provide antigen to drive TCR signaling through ITK, which is expressed in a variety of T‐cell lymphomas including PTCL, CTCL, ALCL, and in a subgroup of T‐lymphoblastic leukemia/lymphoma. CPI‐818 is a first‐in‐class, irreversible, covalent‐binding ITK inhibitor with a high degree of selectivity for ITK. By inhibiting ITK, CPI‐818 blocks signaling pathways that are essential to inflammatory responses and has shown to inhibit tumor growth in animal models.

Aims:

To test the effect of CPI‐818 clinically, a phase 1/1b dose‐escalation trial of CPI‐818 is initiated in subjects with relapsed/refractory T‐cell lymphoma.

Methods:

The trial will include patients with various types of T‐cell lymphoma (PTCL and CTCL) who have progressed on, refractory to, relapsed, or intolerant to at least 2 standard therapies; age ≥ 18 yo; have ECOG status 0‐1; adequate organ function; and without any other condition that would contraindicate the use of the investigational product. Dose Escalation with 3 + 3 (+ optional 3) design will consist of up to 6 ascending dose levels (100,200, 400, 600, 900, and 1200 mg BID) of CPI‐818. In the Dose Expansion phase, there will be 4 disease‐specific expansion cohorts (AITL, PTCL‐NOS, CTCL and other T‐cell lymphoma), and each cohort may enroll up to a maximum of 28 subjects/cohort based on a 2‐stage expansion design‐ Figure.

The objectives of the study are to evaluate the safety and tolerability of CPI‐818; establish the maximum tolerated dose or the maximum administered dose of CPI‐818; evaluate pharmacokinetics and pharmacodynamics of CPI‐818 in humans; assess the anti‐tumor activity of CPI‐818 and identify potential biomarker signals. Study schema in the figure.

Approximately 151 subjects will be enrolled at approximately 35 sites in the US, South Korea, and Australia.

Results:

None. Trial in progress

Summary/Conclusion:

None. Trial in progress

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PB1838 EPISTAXIS IN PEDIATRIC TERTIARY OUT‐PATIENT CLINIC: COULD IT BE AN ALARMING SIGN?
Authors: Elalfy M. , Tantawy A. , Badr Eldin B.E. , Ebeid F. , Mekawy M.A. , Mohammad Y.
Published: June 2019

Background:

Epistaxis could be an alarming bell to diagnose a hemostatic disorder.

Aims:

To detect those with possible bleeding tendencies using simple tools of assessment.

Methods:

A prospective study for children attended tertiary pediatric out‐patient clinic (POPC) over a one year; who had been presented with epistaxis of non‐apparent cause. They underwent clinical assessment and parents answered pediatric bleeding questionnaire and epistaxis severity score. Complete blood count and coagulation profile, platelet function screening tests.

Results:

100 patients less than 18 years with epistaxis (53 females and 47 males), estimated annual frequency of epistaxis was 1 in 300 children attended Ain Shams University out‐patient clinic. Half of them were younger than six years. 76 had recurrent epistaxis and 12 had systemic comorbidities. 90% presented by anterior nasal bleeding and the majority had been controlled just by nasal compression. 43 patients presented with epistaxis only; 15% had definite local cause, 85% of them were considered idiopathic on initial evaluation. 57 presented with other bleeding manifestations; 82% of them had a definite hemostatic disorder and ten percent needed further assessment. There was a positive family history for epistaxis in half of those with definite hemostatic disorders. A bleeding score of ≥2 showed significant value in suspecting hereditary hemostatic disorder as a cause of epistaxis.

Summary/Conclusion:

Epistaxis as a presenting symptom to the POPC is not uncommon; the use of pediatric bleeding questionnaire was helpful to detect those with an underlying hemostatic disorder. Epistaxis was a presenting symptom for a hemostatic bleeding disorder in half of the referred cases. Still around 20% of epistaxis with suspected hemostatic disorder need further studies to reach a definite diagnosis.
PB1846 ANTHROPOMETRIC AND HORMONAL PARAMETERS IN COMPARISON WITH BONE MINERAL DENSITY IN MEN WITH HAEMOPHILIA FROM LOWER SILESIA ‐ PRELIMINARY REPORT
Authors: Biernat M.M. , Jędrzejuk D. , Urbaniak‐Kujda D. , Prajs I. , Podolak‐Dawidziak M. , Wróbel T.
Published: June 2019

Background:

In patients with haemophilia, recurrent episodes of bleeding lead to joint deterioration and bone resorption. To date, the effect of various risk factors on the bone mineral density (BMD) reduction have found conflicting results.

Aims:

The aim of the study was to analyze the impact of certain parameters, such as: viral status of patients, estradiol, testosteron, parathormone and vitamin D levels in relation to bone density.

Methods:

24 men with moderate and severe haemophilia, aged 18‐35 were enrolled. BMD at the lumbar spine, trabecular bone score (TBS) and total body densitometry were measured using dual X ray absorptiometry method (DXA) (densitometer Horizon, Hologic, 2017). Blood analyses were performed for morphology parameters, liver and kidney function parameters, HCV, HBV, HIV viral status, estradiol, testosteron, DHEA‐S, TSH, parathormone and Vitamin D levels.

Results:

The study population included 24 men with haemophilia A, who had been receiving prophylactic factor replacement therapy. HCV seropositivity was found in 6/24 patients (25%), whereas HBV seropositivity was detected in 4 patients (16,7%). There was no patient infected with HIV virus. No statistical correlation was found between BMD and viral serological status. It was found that in 15/24 patients BMD was normal with a Z‐score of > ‐1 (62,5%), whereas in 9/24 patients (37,55%), BMD was decreased. In hemophilic patients with normal BMD Z‐score, the increased BMI, androidal fat deposit (AFD), gynoidal fat deposit (GFD), fat mass index (FMI), free fat mass index (FFMI), Estimated visceral adipose tissue (Est VAT) mass were detected. Among all analyzed hormones, only serum estradiol concentration was statistically higher in patients with normal BMD. In 17/24 examined patients Vitamin D deficiency (<20 ng/ml) was detected (71%), although Vitamin D insufficiency (<30 ng/ml) was found in 4/24 patients (16,7%). Three patients (12,5%) had a normal Vitamin D concentration.

Summary/Conclusion:

The higher BMD in haemophilic patients is related with certain anthropometric parameters, such as body‐fat‐, free‐fat‐mass indexes and visceral fat tissue. BMD negatively correlated with % body fat, androidal fat mass and PTH, whereas TBS negatively related with androidal/visceral fat mass. We found that Vitamin D deficiency is very common in haemophilic patients, however there was no correlation between Vitamin D levels and BMD.
PB1883 GLYCOPROTEIN STRUCTURES OF LEUKEMIC B‐LYMPHOCYTES AND CD38 EXPRESSION IN CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: Shalay O. , Lebed H. , Barilka V. , Zotova O. , Valchuk M. , Loginsky V.
Published: June 2019

Background:

Glycoprotein cell structures (glycocode) play an important part in intercellular interaction. Changes in their structure may determine the ability of leukemic cells to spread (expansion), and impact the exposure of membrane antigen, which transmit pro‐ and antiapoptotic signals.

Aims:

The aim of this study was to conduct research of leukemic lymphocytes glycocode in chronic lymphocytic leukemia (CLL) and its interconnection with the expression of prognostically significant CD38 antigen.

Methods:

Carbohydrate determinants of leukemic lymphocyte membrane were studied in 65 CLL patients using panel of 12 lectins with main carbohydrate specificity, and CD38 expression.

Results:

27% of lymphocytes of CLL patients were identified as containing Thomsen–Friedenreich antigen (PNA+), absent in normal lymphocytes. Leukemic lymphocytes are characterized by a significantly lower level of I and II type N‐glycans’ glycosidic chains (RCA). The lymphocytes of the CLL patients reacted weaker with GalNAca‐specific SBA lectin, Mana‐specific PSL lectin and GlcNAcb‐specific lectins (WGA і STL), polyspecific lectin PHA.

We researched the correlation between lectin receptors expression level and CD38 antigen. The patients were divided into groups with low and increased antigen expression level. In the low CD38 expression level group (≤30%) no statistically significant changes in interaction with lectins were detected as compared to the general patients group. Leukemic lymphocytes with increased CD 38 expression (>30% CD38+ cells) exhibit a significantly higher interaction level with PNA lectin (T antigen) and decreased interaction level with RCA; they have more terminal Fucα residues (H antigen, LAL lectin).

A correlation analysis has been done between the percentage of leukemic cells that bind lectins and the number of CD38+ lymphocytes. A high level of CD38 expression correlates with increased A antigen disaccharide content (GalNAAcα1→3Galβ; SBA lectin), decrease of GlcNAcβ sialylated residues (WGA lectin, r = –0,702; STL lectin, r = –0,503), and sialic acid (SNL lectin). They have less polyantennae N‐glycans (PHA lectin, r = –0,701).

Summary/Conclusion:

A higher CD 38 expression level is accompanied with an increased number of cells containing Thomsen‐Friedenreich antigen (PNA lectin) and corelates positively with antigen A level (SBA lectin) and terminal Fucα (LAL lectin) and a decreased level of Galβ glycosidic residues (RCA lectin); it correlates negatively with a decrease of GlcNAcβ sialylated residues (WGA, STL lectin), and residues of neuraminic acid (NANA, SNL lectin) and polyantennae N‐glycans (PHA‐L lectin).
PB1907 IBRUTINIB THERAPY IS ASSOCIATED WITH SERIOUS INFECTIONS IN PATIENTS WITH B‐CELL MALIGNANCIES ‐ A SINGLE CENTER EXPERIENCE
Authors: Misura Jakobac K. , Milunovic V. , Kursar M. , Mandac Rogulj I. , Ostojic Kolonic S. , Radic‐Kristo D.
Published: June 2019

Background:

Ibrutinib is an irreversible inhibitor of Bruton tyrosine kinase (BTK). Recently, ibrutinib has become available in Croatia for chronic lymphocytic leukemia (CLL) with del17p aberration or in early relapse and for relapsed/refractory mantle cell lymphoma (MCL) pretreated with bendamustine and rituximab. BTK inhibition can lead to immunosuppression through B‐ and T‐cell inhibition resulting in an increase in infections. In literature, systematic meta‐analyses have shown higher incidence of infections in B‐cell malignancies treated with ibrutinib, however the results for CLL are diverse.

Aims:

The main aim of this retrospective study was to retrospectively review all infections associated with ibrutinib in patients treated with B‐cell malignancies and characterized the grade and possible predisposing factors at single center institution.

Methods:

We retrospectively reviewed the medical charts for all patients treated with ibrutinib in era from 2015‐2018 to estimate the rate and grade of infections and possibly underlying factors predisposing these patients to infections.

Results:

A total number of patients included was 32, mainly the patients treated for CLL (28). Median line of previous therapies was 2 with only two patients being treatment naïve. The dosage of ibrutinib was according to the standard of care with median exposure to ibrutinib being 8.5 months. Any grade of infections occurred in 41.9% (N = 18) of our sample with median time to first infection being 82.5 days. The most common type of infection was sepsis (33.3%) followed by pneumonia (22.2%). The specific microbiological agents were isolated in 8 patients. Most of infections were mild (grade I/II according to NCI CTCAE nomenclature) estimated to be 41.2% in our sample. Grade III‐IV infections occurred in 35.3% of sample and grade V infections occurred in 4 patients. It is important to note that re‐infection occurred in 4 patients. Ibrutinib therapy was temporally withdrawn in 9 patients with median time off therapy being 30 days while it was discontinued indefinitely due to infection in 3 patients. Previous fludarabine therapy (p = 0.024) was the only factor associated with the occurrence of infection unlike previous number of therapy, neutropenia, leukopenia and levels of immunoglobulin G. In survival analysis, infections in general were not associated with poorer outcome (p = 0.265), but the grade of infection was associated with poorer outcome (p = 0.003)

Summary/Conclusion:

Our findings show, however, higher grade of serious infections than pivotal RESONATE trial with expected incidence early in the treatment course. The role of temporary ibrutinib withdrawal due to an infection should be explored in the greater samples possible through the larger observational studies.
PB1921 COMPREHENSIVE ANALYSIS OF MOLECULAR RESPONSE IN TUNISIAN CML PATIENTS FOR TREATMENT DISCONTINUATION
Authors: Frikha R. , Elloumi M. , Kamoun H.
Published: June 2019

Background:

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by a balanced genetic translocation, t(9;22)(q34;q11.2) and the generation of a BCR‐ABL1 fusion oncogene. Assessment and monitoring of BCR‐ABL1 levels by quantitative PCR (qPCR) is essential for the management of CML patients treated with TKIs.

Currently, deeper molecular response (DMR: BCR‐ABL1 ≤0,01% IS) is considered to be the gateway to treatment‐free remission, which is becoming a high‐priority goal of CML treatment. Thus, achieving deep molecular response is a requirement for a successful treatment discontinuation.

Aims:

This study was carried out to identify patients with chronic myeloid leukemia (CML) treated with TKI therapy in routine clinical practice in Tunisia potentially eligible for treatment discontinuation, based on a molecular response (MR) on the international scale (IS).

Methods:

It was a 2 years retrospective study of 114 CML patients who attended the hematology department at the Hospital University of Sfax, south of Tunisia. Quantitative assessment of the BCR‐ABL transcript was performed using the Cepheid Xpert BCR‐ABL ultra assay.

Results:

Most patients (67,5% i.e 77/114) had an optimal response according to the European LeukemiaNet 2013 guidelines. Among them; 58,4% were in deep molecular response at their last visit and had been receiving TKI for at least 4 years.

Summary/Conclusion:

Despite the limit of our study, the available real‐life molecular responses with TKI therapy should be considered to identify potentially CML patients eligible for discontinuation of TKI therapy.
PB1956 COEXISTENCE OF BCR/ABL1 AND JAK2 MUTATION IN MYELOPROLIFERATIVE NEOPLASMS
Authors: Luciano L. , Crisci S. , Trastulli F. , Fatigati M. , Izzo B. , Pane F. , Frigeri F.
Published: June 2019

Background:

Chronic Myeloid Leukemia and Myeloproliferative neoplasms were considered mutually exclusive. However some recent reports have described the co‐occurrence of BCR/ABL1 and JAK2 mutation in patients with CML phenotype. Generally, in the few reported cases, clinical and laboratory data suggest the presence of two different clones.

Aims:

Here we describe the clinical and molecular data of 3 patients showing the presence of BCR/ABL1 and JAK 2 mutation, with CML phenotype in 1 and myeloproliferative phenotype evolving in CML in the others.

Methods:

BCR/ABL1 transcript were identified and quantified by Rq‐PCR according to ELN recommendations; JAK2 mutation were evidenced by PNA clamping PCR in one patient and by ASO‐PCR in the others.

Results:

Patient clinical characteristics are summarized in table 1. Patient 1 showed CML phenotype with coexistence of BCR/ABL1 and JAK2 mutation at diagnosis. He started Dasatinib treatment at standard dose (100 mg/die) but after 6 months because of intolerance, he switched to Ponatinib obtaining a major molecular response. Patient 2 was diagnosed Thrombocytemia carrying V617F JAK2 mutation, after a portal vein thrombosis and started anticoagulant therapy combined to Hydroxiurea treatment. After 2 years, he switched to IFN therapy and in 2011 (after 2 more years) he showed CML feature with the appearance of BCR/ABL1 hybrid transcript. Imatinib treatment was added to Interferon and combination therapy was sustained for 7 years. Because of intolerance to IFN, in 2018 patient switched to Ruxolitinib at the dose of 30 mg BID, while also maintaining Imatinib. Patient 3 was diagnosed Thrombocytemia carrying V617F JAK2 mutation in 2009 and received IFN treatment. In 2017 he developed leukocytosis with the appearance of e1a2 BCR/ABL1 hybrid transcript. At that time, he stopped IFN therapy and started Imatinib at the standard dose of 400 mg per day with control of both diseases. Molecular monitoring showed a simultaneous decrease of both abnormalities in patient 1 who got a deep molecular response (MR 4). Patient 2 reached a deep molecular response (MR 4.5) but still needs of Ruxolitinib treatment for thrombocytemia, suggesting the presence of two different clones. Patient 3 got a deep molecular response (MR 5) and it is ongoing the evaluation of JAK2 mutation.

Summary/Conclusion:

Coexistence of BCR/ABL1 and JAK2 mutation is rarely reported so far but a widely use of molecular techniques could increase the number of patients with both abnormalities. At least in patient 3 of our series, clinical and molecular data suggest that both abnormalities are present in the same clone and V617F JAK2 mutation is the first occurred one. Digital PCR experiments could clarify if a single cell express both molecular abnormalities. Such cases are relevant to better understand the pathogenesis of myeloproliferative neoplasms.
PB1976 MICROANGIOPATHIC HEMOLYTIC ANEMIA DUE TO HEART VALVE PROSTHESIS
Authors: Andrade Luís D. , Afonso S. , Loureiro B. , Silva Gomes J. , Barreira R. , Maia Magalhães T. , Ribeiro M.L.
Published: June 2019

Background:

Microangiopathic hemolytic anemias (MAHA) are characterized by the presence of hemolytic anemia (HA), related to red blood cell (RBC's) fragmentation, thrombocytopenia and hemosiderinuria due the intravascular hemolysis. The term thrombotic microangiopathy (TMA) is also used to describe syndromes characterized by AHMA, thrombocytopenia, and thrombotic lesions in small blood vessels such as Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic uremic syndrome (HUS). Although TTP and HUS are the prototypes of TMA / MAHA, there are other causes that should not be forgotten, such as MAHA by valvular leak.

Aims:

Perform the casuistry of the Hematology Service of a Central Hospital for a rare cause of hemolytic anemia.

Methods:

Parameterized search for the data of patients with MAHA and hemosiderinuria evaluated at a Hematology out patients clinic at a Central Hospital between January 2007 and March 2018.

Results:

9 patients with MAHA were identified with valvular leak, the mean age at diagnosis was 68 years and 6 were men (66%). All patients had mechanical heart valves: 66% mitral valve, 22% aortic valve and 11% both valves. The time from surgery to diagnosis of AHMA was ∼ 2 years. The mean Hb value was 8.4 mg/dL. All patients had RBC fragmentation. The mean value of DLH was 3773U/L, total bilirubin (TBil) was 1.9 mg/dL. 88% patients were supplemented with oral iron. Only 3 patients increase ∼ 1.5 g of Hb after 3 months of therapy. 1/3 patients were supplemented with EV iron; 1/3 needed blood transfusion. 66% underwent valvular leakage correction and of these 50% significantly improved Hb and hemolysis.

Summary/Conclusion:

A careful clinical history and the RBC morphology play a central role in the diagnosis of anemia. The MAHA due to leak valvular is a rare entity, but with a tendency to increase. Despite the small number of patients, the authors consider pertinent to present these data because this is a potentially reversible cause of anemia. The disproportionate high DHL level in relation to the TBilis a possible clue to the differential diagnosis of HA.
PB1980 IMPROVING HEALTHCARE PROVIDERS’ KNOWLEDGE REGARDING THE PRINCIPLES OF GENE THERAPY FOR HEMOPHILIA THROUGH ONLINE EDUCATION
Authors: Hurst S. , Warren C. , Kadkhoda H. , VanLaar E. , Pierce G.
Published: June 2019

Background:

Gene therapy offers the hope of a functional cure for hemophilia. To prepare healthcare providers (HCPs) for this potential paradigm shift in care, National Hemophilia Foundation (NHF), European Haemophilia Consortium (EHC), the World Federation of Hemophilia (WFH), and Medscape Education collaborated to develop a multi‐modal, online, continuing medical education (CME) curriculum.

Aims:

The current study assessed the ability of online CME to improve HCPs knowledge regarding the scientific principles underlying gene therapy overall and its study in hemophilia.

Methods:

A 15‐minute, CME‐certified video commentary with synchronized slides was developed and launched online on 8/3/2018. Educational effectiveness was assessed with a repeated‐pairs pre‐/post‐assessment study design, in which each individual served as his/her own control. Responses to 3 multiple‐choice, knowledge questions and 1 self‐efficacy confidence question were analyzed. A chi‐squared test assessed changes pre‐ to post‐assessment. P values <0.05 are statistically significant. Effect sizes were evaluated using Cramer's V (<0.05 modest; 0.06‐0.15 noticeable effect; 0.16‐0.26 considerable effect; >0.26 extensive effect).

Results:

To date, 1634 HCPs (958 physicians) have participated in this activity. This analysis presents data from the subset of hematologists/oncologists (n = 77; hem/oncs) and pediatric oncologists (n = 69) who answered all pre‐/post‐assessment questions during the initial analysis period of 8/3/18‐9/5/18; data collection is ongoing. Significant improvements were observed overall (hem/oncs: P = .0007; V = .156) and in the following areas,

‐ Correct identification of transient transaminitis as the most common adverse event observed in gene therapy trials: hem/oncs: 45% vs 73% (62% relative increase), P = 0.0006, V = .277; and pediatric hematologists: 26% vs 43% (% relative increase), P = .032, V = .181

‐ Recognition of the relatively low homology between the adeno‐associated virus (AAV) vector used in gene therapy trials for hemophilia A (AAV5) and other primate AAVs: hem/oncs: 36% vs 55% (53% relative increase), P = 0.023, V = .182

‐ Pediatric hematologists exhibited a small increase in knowledge, but this change was not statistically significant: 33% vs 41% (24% relative increase), P = NS

‐ Both of hem/oncs (39%) and pediatric hematologists (32%) indicated increased confidence in their understanding of the science underlying gene therapy in hemophilia

Lastly, the findings uncovered educational needs, such as the understanding of the FIX construct currently under study in hemophilia B trials.

Summary/Conclusion:

Participation in this online activity significantly improved knowledge among hem/oncs and pediatric hematologists with regard to the adverse events, viral vectors, and gene constructs in current clinical trials for gene therapy in hemophilia.
PB1996 PROGNOSTICATION OF HODGKIN'S LYMPHOMA BY IPET AND IPS: UPDATE DATA OF 8 HEMATOLOGICAL UKRAINIAN CENTERS.
Authors: Novosad O. , Skrypets T. , Pastushenko I. , Kadnikova T. , Ulianchenko K. , Gorbach A. , Ashykhmin A. , Kmetyuk Y. , Karpova O. , Mykhalska L. , Kindrakevych O. , Kozlov V. , Novikov N. , Kosinova V. , Oliinichenko E. , Kostiukova N. , Tkachenko O. , Karnabeda O. , Stratienko V. , Kriachok I.
Published: June 2019

Background:

PET‐CT has completely changed and improved treatment approaches in patients with Hodgkin Lymphoma (HL) for the last years. Recent studies are evaluated predictive role PET for survival rate. The major idea is to identify patients from a high‐risk group who can have early relapse/refractory disease using iPET and IPS to guide the choice of chemotherapy.

Aims:

To evaluate the prognostic role of iPET in patients with HL.

Methods:

The cohort consisted of 132 patients of up to 69 years of age with newly diagnosed HL were treated with ABVD or BEACOPP‐14/esc based on their stage and risk group. Metabolic PET‐CT imaging was performed to routine protocols using Deauville criteria for response assessment. Interim PET was performed at 15.5 ± 3 days (range, 5‐26) after 2‐3d and 4th cycles of treatment in 81% and 19% cases, respectively (p < 0.05). The main endpoints of study were to assess the correlation between IPS, iPET findings and clinical outcome (relapse/death).

Results:

The ORR (CR, PR) in this group of patients was 85.6%. The maximum follow‐up period was 70 months (median 16 months). Under the follow‐up there are still 96.9% (128/132) patients.

81.8% (108/132) and 18.2% (24/132) of patients had 1–3 and 4–5 scores of iPET by Deauville 5‐PS scale, respectively (p < 0.05). In total, disease progression was documented in 20.8% (5/24) iPET‐positive (iPET+) and 13% (14/108) iPET‐negative (iPET‐) patients (p < 0.05). There were two deathss from refractory disease. The 5‐year EFS of iPET+ patients vs iPET‐was 50% and 80%, respectively (p < 0.05).

We divided patients by IPS groups: 71(53.8%) with ≤2 and 61(46.2%) with ≥3 risk factors (low and high‐risk group, respectively, p < 0.05).Patients in low‐risk group were associated with significant improvement in 5‐year EFS compared with patients in high‐risk group (80% vsthe 65%, respectively, longrank test, p = 0.01).The estimated 5‐year EFS was 80% in iPET‐ vs 65% with iPET+ in low risk group (p < 0.05). The 5‐year EFS was significantly better in high‐risk patients who achieved iPET‐ status compared to iPET+ status (70% vs 55%, p < 0.05).

Summary/Conclusion:

In our study, we found that IPS correlates with iPET results. Moreover, it could predict treatment outcomes in patients with HL.