bluuebunny/crossref_metadata_2025 huggingface dataset:
PB1769 INTERLEUKIN‐10 (1082G/A) GENE POLYMORPHISM IS ASSOCIATED WITH RISK OF ACUTE MYELOID LEUKEMIA IN SUDANESE POPULATION
Authors: Osman I.
Published: June 2019

Background:

Acute myeloid leukemia (AML) is a cytogenetically and molecularly heterogeneous diseases, and description of transforming genetic events is becoming increasingly significant. Interleukins (ILs) are a diverse set of small cell signaling protein molecules. Single nucleotide polymorphisms (SNPs) of ILs alter their function, increasing predisposition to different illnesses.

Aims:

We investigated the association between a single nucleotide polymorphism (SNP) in IL‐10 ‐1082G/A (rs1800896) in Sudanese acute myeloid leukemia patients

Methods:

A total of 30 patients with Acute Myeloid Leukemia and 30 control subjects were enrolled in this study. Blood samples were collected from all participants in EDTA containing tubes. Genomic DNA was extracted from all blood samples using salting out method. The genotypic variants of IL‐10(‐1082G/A) polymorphism were detected by allele specific‐PCR.

Results:

We found that (36.7%) of patients have homogenous GG genotype, (43.3%) have heterogeneous GA genotype and (20.0%) have AA genotype. GA genotype was significantly higher risk of AML compared with the homozygous, there is no association between IL‐10(‐1082G/A) polymorphism and AML sub‐type, gender, age group, mean of hematological parameter (TWBCs, Blast%, Hb and platelet count).

Summary/Conclusion:

In summary we conclude that GA genotype of IL‐10 ‐1082G/A (rs1800896) polymorphism is a risk factor for AML and G allele is insignificantly higher than A allele in AML patient. No association between IL‐10(‐1082G/A) polymorphism and AML sub‐type, gender, age group, mean of hematological parameter (TWBCs, Blast%, Hb and platelet count).
PB1778 ESTIMATION OF PROTEIN Z LEVEL IN ADULT NAÏVE ACUTE MYELOID LEUKEMIA PATIENTS
Authors: Mohamed H. , Hegab H. , El Razazz M.
Published: June 2019

Background:

The occurrence of various coagulation abnormalities in acute leukemia is well established, but there are no data assessing the role of protein Z (PZ), a vitamin K‐dependent plasma protein in hemostatic disorder in hematology cancers, including acute leukemia, The potential role of alterations of PZ levels in the pathogenesis of disorders of coagulation has been investigated and revealed conflicting results as Protein Z (PZ) deficiency may induce bleeding as well as thrombosis.

Aims:

to estimate the level of protein Z in Acute Myeloid Leukemia (AML) patients and its correlation with bleeding tendency or thrombosis

Methods:

PZ level was measured by ELISA kits in 60 adult naïve (AML) patients aged above 16 years old and 30 healthy controls after informed consent from Clinical Hematology Unit, Ain‐Shams University Hospital and correlated it with bleeding and thrombotic episodes. Patient on oral anti‐coagulant regularly, Inherited bleeding disorder, Inherited thrombophilia were excluded.

Results:

The median PZ level was lower in AML Patients in comparison to healthy controls{205ng/L (150 – 340) vs 349.5ng/L (274 – 400) with p value < 0.001}.

No statistically significance correlation between protein Z level with initial platelet count(P value 0.323).

A statistically significant correlation was detected between episodes of bleeding and PZ level (P value 0.008). By utilizing ROC curve, the best cutoff value for protein Z as a predictor for bleeding episodes during induction was found >350ng/L.

Summary/Conclusion:

Conclusion: The results suggest that PZ level was lower in AML patients than healthy control and it was correlated with bleeding episodes. can be a cofactor associated with an increased bleeding tendency in AML patients.

Summary: PZ can be a cofactor associated with an increased bleeding tendency in AML patients.
PB1783 PROGRAMMED CELL DEATH‐1 AND PROGRAMMED CELL DEATH LIGANDS EXPRESSION IN NODAL PERIPHERAL T‐CELL LYMPHOMA
Authors: Asawapanumas T. , Tungnantachai N. , Assanasen T. , Polprasert C. , Bunworasate U. , Intragumtornchai T. , Wudhikarn K.
Published: June 2019

Background:

Program cell death‐1/Program cell death ligands (PD‐1/PD‐Ls) is an important element of immune response regulation in human. Activation of PD‐1/PD‐Ls results in an inhibition of cellular mediated immune response. Several cancers including lymphoma exhibit abnormal PD‐1/PD‐Ls expression which may contribute to treatment failure and worse outcome. However, data of PD‐1/PD‐Ls expression in peripheral T cell lymphomas (PTCLs) has been sparsely described. Herein, we described expression patterns of PD‐1/PD‐Ls in PTCLs and explored their correlation with clinical parameters.

Aims:

To describe expression features of PD‐1/PD‐Ls in PTCLs and explore their correlation with clinical characteristics and outcomes

Methods:

We included 51 adult PTCLs diagnosed and followed up at King Chulalongkorn Memorial Hospital between 2550 and 2561. Medical records were abstracted for detailed clinical data. Paraffin embedded tissue archives were further stained for PD‐1, PD‐L1 and PD‐L2 which were independently interpreted for expression level and intensity by two hematopathologists. Membranous staining more than 5% was used as a positive cut off criteria. Correlation with clinical parameters was then analyzed.

Results:

Of 51 PTCLs, PD‐1, PD‐L1 and PD‐L2 were seen in 27.5%, 49.0% and 68.6% of PTCLs respectively. The expression patterns and frequency of PD‐1/PD‐Ls have varied among different histologic subtypes. There was no significant difference in baseline clinical characteristics between PD‐Ls expression status. With median follow up duration of 15 months, the 1‐year event free survival (EFS) and overall survival (OS) were 43.9 % and 61.6% respectively. Neither EFS nor OS was different among PD‐L1 or PD‐L2 expression cohort (1‐year EFS 39.3% in negative PD‐L1 lymphoma vs 46.9% in positive PD‐L1 lymphoma, 1‐year EFS 40.5% in negative PD‐L2 lymphoma vs 49.5% in positive PD‐L2 lymphoma) (1‐year OS 55.2% in PD‐L1 negative lymphoma vs 59.5% in PD‐L1 positive lymphoma, 1‐year OS 57.7% in PD‐L2 negative lymphoma vs 56.8% in PD‐L2 positive lymphoma). Univariate cox regression analysis showed that performance status was the only prognostic factor for survivals. PD‐1 and PD‐Ls expression status, either on lymphoma cells or non‐tumor stroma, were not predictive factors for treatment outcomes.

Summary/Conclusion:

Aberration expression of PD‐1/PD‐Ls could be seen in PTCLs and was varied among histologic subtypes. Clinical characteristics, treatment response and survivals were not statistically different among PD‐1 and PD‐Ls expression patterns.

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PB1799 HOW TO PREDICT EARLY PROGRESSION IN PATIENTS WITH DIFFUSE LARGE B CELL LYMPHOMA
Authors: Nakaya A. , Ishii K. , Fujita S. , Satake A. , Nakanishi T. , Azuma Y. , Tsubokura Y. , Saito R. , Konishi A. , Hotta M. , Yoshimura H. , Ito T. , Nomura S.
Published: June 2019

Background:

Even in the rituximab era, the survival rates of patients who obtain complete remission and later experience disease recurrence remain unsatisfactory. The treatment strategy for early progression has not been taken into consideration.

Aims:

The aims of the present retrospective study were to extract DLBCL patients with early progression and to detect characteristic findings.

Methods:

530 patients diagnosed with DLBCL from April 2002 to November 2017 were enrolled in the study. Primary treatment included R‐CHOP or R‐CHOP‐like regimens. Early progression was defined as progressive disease or a transient response with disease progression within 6 months after completion of treatment.

Results:

Among 530 patients, 149 patients (28%) showed early progression. Survival of early progression patients were significantly worse (12.1 months vs 152.9 months, p = 3.26e‐66). In multivariate analysis, NCCN‐IPI, elevated LDH, and PS >3 were significant factors affecting survival. Patients who received salvage ASCT(n = 16) showed better prognosis than patients without ASCT (30.5 months vs 10.6 months, p = 0.012).

Summary/Conclusion:

In the rituximab era, we could use NCCN‐IPI to identify patients at high‐risk of early progression.

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PB1800 PROGNOSTIC RELEVANCE OF PROTEIN EXPRESSION, CLINICAL FACTORS, AND MYD88 MUTATION IN PRIMARY TESTICULAR DIFFUSE LARGE B‐CELL LYMPHOMA
Authors: Xu Y. , zhou R. , Chen B.
Published: June 2019

Background:

Primary testicular diffuse large B‐cell lymphoma (tDLBCL) is a rare, clinically aggressive form of extranodal lymphoma confined to the testis. It is known to have a poor prognosis, with an outcome inferior to nodal DLBCL. Only a few studies of tDLBCL have included immunohistochemical and molecular investigations, and little is known about the prognostic significance of the in situ tissue antigen expression profiles in tDLBCL.

Aims:

We performed a mutation analysis of the MYD88 L265P mutation in 17 tDLBCL patients and investigated the immunophenotypic biomarkers and clinicopathological factors associated with tDLBCL.

Methods:

Clinical date and paraffin‐embedded material from 17 patients presenting with tDLBCL were retrieved from the archives of the pathology department at the Nanjing Drum Tower Hospital.Immunohistochemistry was used to examine the expression of CD10, Bcl2, Bcl6, MUM1, C‐myc, P50, P65, P53, PSTAT3, OCT4, PIM1, CXCR4 and JAK2. MYD88 gene mutation analysis and complete clinical data evaluation were carried out and linked to overall survival time.

Results:

High expression of B‐cell lymphoma 2 was detected in 7/17 tDLBCL patients and was associated with a poor prognosis in a univariate model. Most of these patients (6/7) also expressed c‐myc. P50, JAK2, PSTAT3, PIM1 and CXCR4 were also upregulated in tDLBCLs. There were seventeen cases of tDLBCL; in total, 82.4% (14/17) of patients exhibited an activated B‐cell‐like phenotype (ABC), 56.3% (9/16) of patients harbored the MYD88 L265P mutation and showed a correlation between the MYD88 L265P mutation and the ABC phenotype (p = 0.009). However, there was no association between the MYD88 mutation status and overall survival.

Summary/Conclusion:

We demonstrated that clinical factors such as age, IPI score, stage, lack of B symptoms and the over‐expression of Bcl‐2 are independent prognostic factors determining overall survival and that the over‐expression of P50, JAK2, PSTAT3, PIM1 and CXCR4 may promote the pathogenesis of tDLBCL. Moreover, we found a high prevalence of the MYD88 L265P mutation in tDLBCL, which may reflect a fairly consistent genetic feature in tDLBCL.
PB1802 INCREASED RISK OF HIP FRACTURES IN YOUNG WOMEN WITH LYMPHOMA, RESULTS FROM A SWEDISH POPULATION BASED STUDY
Authors: Johansson P. , Lewerin C. , Kristjansdottir H. , Johansson H. , Mellström D.
Published: June 2019

Background:

Blood cancer is the third most common cancer in Sweden and lymphoma is the most common of hematologic malignancies. A significant proportion of lymphoma patients are cured and others are living many years with disease. Bone loss has been noted in lymphoma patients. However, the incidence of fracture, the most devastating outcome of osteoporosis, and in particular hip fracture is not known in this group of patients.

Aims:

To determine the risk of hip fracture in patients with lymphoma diagnosed between 1995 and 2015

Methods:

We conducted a retrospective population based cohort study of Swedish lymphoma patients older than age 18 years, diagnosed from 1995 to the end of 2015 to determine the risk of hip fracture. Patients were identified from the National Cancer Register and from inpatient registers including all Swedish hospitals. They were followed up to 22 years (mean follow up 5.5 years). Fracture risk in lymphoma patients was compared with the Swedish population registry during the same time of period and adjusted for age, sex and calendar year.

Results:

37236 lymphoma patients were identified (45% women). 2.2 % of the men and 4.7% of women developed a hip‐fracture, in mean time 4.9 years after they were diagnosed with lymphoma. The incidence of hip‐fracture was higher in women than in men, increased by age and decreased by calendar year. The risk (hazard ratio‐HR) for hip fracture was increased in lymphoma patients compared with the Swedish general population, especially in younger women. The HR was 2.80 (95% CI 1.95‐4.03) in females aged 40 years in 2016 and for men corresponding HR was 1.70 (95% CI 1.44‐2.00). There was a trend to lower HR with increasing calendar year and older age. However, in elderly men (80 years of age) the risk for hip fracture was even lower, HR 0.83 (95% CI 0.81‐0.85) compared with the Swedish population. No differences between hip fracture incidence in patients with Hodgkin lymphoma or diffuse large B‐cell lymphoma compared with other lymphomas was noted (p>0.30). In multivariate analysis, unmarried men had a two times higher risk for hip‐fracture compared with men with other marital status with lymphoma (HR; 2.02 95% CI 1.63‐2.50).

Summary/Conclusion:

We conclude that lymphoma patients, especially younger women, are at higher risk of hip fracture than the general population independently

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PB1807 RESULTS OF TREATMENT BY REGIMENS R‐MPV/TBC FOR PATIENTS WITH PRIMARY CNS LYMPHOMA
Authors: Zvonkov E. , Koroleva D. , Gabeeva N. , Smolyaninova A. , Gavrilina O. , Shchetsova O. , Gubkin A. , Kovrigina A. , Galstyan G. , Klyasova G. , Savenko T. , Parovichnikova E. , Savchenko V.
Published: June 2019

Background:

High‐dose MTX‐containing chemotherapy and autologous stem sell transplantation (HDC‐ASCT) is a potentially curable options for patients with primary central nervous system lymphoma (PCNCL). In our prospective study, pts with newly diagnosed PCNSL were treated with R‐MPV (rituximab, methotrexate, vincristine and procarbazine) chemotherapy, followed by consolidation HDC‐ASCT with TBC (thiotepa, busulfan and cyclophosphamide). After completion of therapy all pts reseived maintenance treatment with temozolomide every 3 months for a total of 2 years.

Aims:

To assess the efficacy and safety of regimens R‐MPV/TBC for patients with PCNSL.

Methods:

A total 19 pts were enrolled in prospective study between 2015 to 2019 years. The median age was 43 years (range, 20 to 62 years), with a total of 2 (10%) ≥ 60 years of age. Male:female = 13:7. In four pts (21%) the ECOG status was ≥ 2. The MSKCC prognostic class was as follows: 17 pts (91%), class 1; 2 pts (9%), class 2; 0 pts, class 3.

Results:

Following 3‐5 R‐MPV cycles 16 pts were in CR and 3 pts in PR. All pts were undegro stem‐sell harvest after the second cycle. All pts eventually received HDC‐ASCT with TBC. Treatment‐related mortality was 0%. All pts achieved haemotopoietic regeneration: the median times neutrophil and platelet recovery were 9 and 14 days, respectively. Seventeen pts are alive and well in complete remission at a median follow‐up of 12 months (range 1‐40). Two pts with progressive disease (+6 months) went on to received second‐line treatment: both had received chemotherapy and WBRT.

Summary/Conclusion:

Regimens R‐MPV/TBC was associated with favorable safety and high preliminary efficacy.
PB1817 A STUDY OF SERUM ALBUMIN AND CALCIUM IN 93 PATIENTS WITH SECONDARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS
Authors: Gao X. , Qiu H. , Wang J. , Duan L. , Tian T.
Published: June 2019

Background:

Hemophagocytic lymphohistiocytosis is a fatal syndrome of overactive inflammation, which is caused by excessive cytokines released by abnormal cytotoxic T cells, NK cells and macrophages. According to the etiology, it can be divided into primary HLH and secondary HLH.

Aims:

To investigate the clinical significance of serum albumin levels and calcium concentrations in patients with secondary hemophagocytic lymphohistiocytosis.

Methods:

The clinical and laboratory data of 93 patients with newly diagnosed sHLH in 2013.4 to 2017.5, and 20 healthy controls were retrospectively analyzed. The patients were classified as the clinical remission group and the progression group according to the response criteria. To explore the changes of serum calcium concentrations and albumin levels in the patients, its correlations with other laboratory indexes and the impact on survival.

Results:

(1) The serum calcium concentrations and albumin levels in lymphoma‐related HLH group and non‐tumor HLH group were lower than control group (P < 0.001); The serum calcium concentrations and albumin levels in the clinical remission group after treatment was higher than that before treatment (P < 0.001), while in the progression group the serum calcium concentrations and albumin levels after treatment did not changed significantly (P > 0.05,P = 0.101). (2) The serum calcium concentrations in newly diagnosed sHLH patients was positively correlated with ANC, PLT, HGB (P < 0.05); The overall survival (OS) was significantly longer in patients with serum calcium concentration ≥1.88 mmol/L than that<1.88 mmol/L (P = 0.006). (3) The serum albumin levels in newly diagnosed sHLH patients was positively correlated with ANC, HGB (P < 0.05); The overall survival was longer in patients with serum albumin level ≥25.2 g/L than that<25.2 g/L (P = 0.005).

Summary/Conclusion:

The serum calcium concentrations and albumin levels have clinical significance for disease diagnosis, decision‐making therapy and treatment outcomes in the patients with sHLH.
PB1818 CLINICAL FEATURES AND PROGNOSTIC FACTORS OF PRIMARY TESTICULAR DIFFUSE LARGE B‐CELL LYMPHOMA (PT‐DLBCL): EXPERIENCE OF 35 PATIENTS FROM FUSCC
Authors: Liu Y.‐Z. , Luo P. , Zhang Q.‐L. , Xue K. , Cao J.‐N. , Hong X.‐N. , Lv F.‐F.
Published: June 2019

Background:

Primary testicular lymphoma (PTL) is a rare extranodal lymphoma, with diffuse large B cell lymphoma (DLBCL) as the predominant histological subtype. Factors that contribute to precise stratification and guide the treatment of this disease are still not well understood.

Aims:

This study aims to identify clinical features and prognostic factors of PT‐DLBCL patients.

Methods:

A total of 35 patients were included in this retrospective study who were diagnosed as PT‐DLBCL and treated in Shanghai Cancer Center, China from March 2007 to May 2018. The demographic details, clinico‐pathologic characteristics of the patients were summarized. Kaplan‐Meier survival curves were constructed for survival analyses.

Results:

The median age of the patients was 59 (range 36‐76) years old. All patients presented with testicular swelling, two had the presence of B symptoms. 33(94%) patients underwent orchiectomy. All patients received combination chemotherapy for 4‐6 cycles and central nervous system prophylaxis consisting of MTX for 4‐6 doses. 87% (28/32) patients achieved complete response, and ORR was 96.9% (31/32). 21 patients continued contralateral testis irradiation in our hospital. The median follow‐up time was 980 days (range 156‐2976 days). Median overall survival (OS) was not reached at the time of reporting. The estimated 5‐year PFS and OS rate were 67% and 84%. None of the 21 patients who received radiotherapy to the contralateral testis experienced relapse in that location in our study. All three patients who suffered from central nervous system relapse had the germinal center B‐cell subtype of DLBCL. Kaplan‐Meier analysis showed that PT‐DLBCL patients characterized by late stage (Stage III/IV) (P = 0.003), higher IPI score (IPI≥ 2) (P = 0.001) had a shorter progression free survival (PFS). More importantly, we found that patients with the ratio of the LDH level in CSF to the serum LDH level more than 6.5 suffered from a worse PFS (P = 0.032).

Summary/Conclusion:

Our work revealed that staging III/IV, IPI score ≥ 2 were adverse factors of PT‐DLBCL patients’ PFS. Significantly, the PT‐DLBCL patients with ratio of LDH level in CSF to the serum LDH level > 6.5 were indicated to have a worse PFS.
PB1830 CLINICAL IMPACTS OF INFLAMMATORY MARKERS IN PATIENTS WITH LIMITED STAGE UPPER AERODIGESTIVE TRACT NK/T CELL LYMPHOMA
Authors: Chung J.‐S. , Kim D.‐Y. , Song M.‐K. , Joo Y.‐D.
Published: June 2019

Background:

In localized extranodal natural killer/T cell lymphoma (ENKTCL), traditional prognostic models had a limited prognostic value to predict survivals. Especially, clinical data is limited to find out what the most meaningful inflammatory marker among them is and determine whether the meaningful inflammatory marker would be useful to reinforce prognostic limitations of the traditional prognostic models in ENKTCL

Aims:

The present study was performed to find out the most meaningful factor among available inflammatory markers and to evaluate whether the inflammatory marker would improve predictive ability of traditional models in patients with limited stage UAT ENKTCL.

Methods:

We evaluated prognostic value of inflammatory makers in 157 patients with limited stage upper aerodigestive tract (UAT) ENKTCL. Diagnosis of ENKTCL was according to the presence of histologic findings and immunophenotypes such as CD3+, CD20‐, CD56+ and positive Epstein‐barr virus by fluorescence in situ hybridization.

Statistical Analysis

Chi‐square test or Fisher's exact test were used as appropriate to analyze categorical variables. Progression‐free survival (PFS) and overall survival (OS) were estimated using the Kaplan‐Meier method and the 2‐tailed log‐rank test. PFS was defined as the time between the beginning of salvage therapy until disease progression or death. Meanwhile, OS was defined as the time from the start of salvage therapy until death. Cox proportional hazard model was used to evaluate prognostic impacts of several prognostic factors. Hazard ratios (HRs) of prognostic factors were used to measure the differential risks of progression and death. Receiver operating characteristic (ROC) curves were prepared to estimate the accuracy of predicting the ideal cut‐off values of continuous variables. The statistical analysis was carried out with SPSS software version 18.0 (SPSS Inc., Chicago, IL, USA). A p‐value < 0.05 was considered significant.

Results:

Among several inflammatory markers, mean platelet volume (MPV) was most meaningful predictive value for progression‐free survival (PFS) and overall survival (OS). Ideal cut‐off value of MPV was 8.8 in Receiver operating characteristic analysis. In univariate and multivariate analysis, only two factors such as low MPV (< 8.8) (PFS, HR = 2.483, 95% CI = 1.182‐4.601, p = 0.009; OS, HR = 3.412, 95% CI = 1.949‐6.990, p = 0.008) and high international prognostic index (IPI) score (IPI ≥ 2) (PFS, HR = 3.339, 95% CI = 1.323‐8.430, p = 0.011; OS, HR = 3.317, 95% CI = 1.046‐6.892, p = 0.010) were significantly associated with both PFS and OS. interestingly, the MPV value could significantly subdivide low IPI score group (PFS, p = 0.006; OS, p = 0.021).

Summary/Conclusion:

We found that Low MPV and high IPI can significantly predict poor prognosis in localized ENKTCL.

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PB1831 PRELIMINARY RESULTS OF THE COMBINED TREATMENT PRIMARY NON‐HODGKIN ORBITAL LYMPHOMAS
Authors: Jazyltayeva A. , Jazyltayeva A. , Gabbasova S. , Karakulov R. , Kemelbekov N. , Sagyndikov G. , Nassipov B. , Akanov A. , Taktybayeva A.
Published: June 2019

Background:

Non‐Hodgkin Lymphomas (NHL) effected organ of vision compose 8–12 % of all primary extranodal NHL, and may be the first and only sign of the disease.

Aims:

To estimate a therapy of patients with extranodal orbital lesion in our cancer center.

Methods:

Since 2014 to 2018 in our center treated 17 patients with extranodal damage to the orbit of the eyes. The age of patients ranged from 23 to 92 years, the average age of patients was 57 years. The number of men were 8 people, women ‐ 9. Unilateral orbital damage was registered in 15 patients, bilaterally in 2 patients. In 12 cases process localized in the anterior part of the orbit, in 5 ‐ in the middle and deep parts of the orbit with the spread in the maxillary sinus. Clinical sings of NHL characterized with exophthalmos in varying degrees of severity, difficult reposition, displacement of the eyeball and restriction of its mobility, swelling of the eyelid. By all the observations: to 12 patients performed biopsy of the tumor, 4 patients underwent therapeutic and diagnostic orbitotomy by Killian, to 1 patient ‐ eye orbit exentation. Histological variants: MALT‐ lymphomas – 4 patients, Diffuse B‐cell Lymphoma – 8, Mantle Cell Lymphoma – 2 and Follicular Lymphoma ‐ 2 patients.

Results:

All patients underwent 6 courses of chemotherapy according to the R‐EPOCH protocol. Complete answer registered in 16 cases, partial answer in 1 of cases, and this patient received a course of radiation therapy on the affected area. Observation median was 3 years (15 month‐5 years).

Summary/Conclusion:

Therefore, treating orbital NHL requires complex multidisciplinary approach, allowing determining the correct diagnosis and prescribing adequate treatment. Standart first line therapy achieved good results of relapse‐free survival. Chemotherapy showed the same results as the combined treatment (chemotherapy and orbitotomy).
PB1839 SUCCESSFUL PERIOPERATIVE HEMOSTATIC MANAGEMENT FOR SURGERY IN PATIENTS WITH CONGENITAL FACTOR IX DEFICIENCY: A SINGLE CENTER EXPERIENCE
Authors: Park Y.S.
Published: June 2019

Background:

Hemophilia B is an X‐linked recessive bleeding disorder resulting from factor IX (FIX) deficiency. Prevalence of hemophilia B is one in 20,000 live male births, a quarter that of hemophilia A. While coagulation factor replacement is essential in surgical intervention in hemophilia B patients, evidence in support of the perioperative management is more lacking than hemophilia A.

Aims:

This study provides an updated evaluation of the safety and effectiveness of coagulation FIX concentrates in treating perioperative bleeding.

Methods:

We reviewed the records of hemophilia B patients without inhibitors who underwent surgery between June 2006 and May 2017 using coagulation FIX concentrates at a single center. The first bolus of [80 IU/kg X 1.2‐1.4] was given 30 min before surgery to achieve a preoperative FIX level of 80 % under the supervision of a multidisciplinary hemophilia team of our institute. Approximately 50% of the initial dose was administered every 12 h and the dosing intervals were increased to 24 h.

Results:

In total, 109 surgeries (93 orthopedic, 16 other) were conducted in 70 hemophilia B patients. The median age of the patients was 35.5 years (range, 6–78). The median duration of hospitalization was 14.3 days (range, 2–47), and median duration from operation to discharge was 11.5 days (1‐42). Recombinant FIX concentrates were administered in all cases except 2 patients. The major surgical procedures, that were defined as one that required hemostatic support for periods exceeding 5 consecutive days, were 94 cases (89.5%). Median difference between preoperative and postoperative hemoglobin was 2.35 g/dL (range, 0‐7.7). Total 18 cases of patients required packed RBC transfusion after surgery. In most cases, bleeding stopped or was well controlled; however, one patient expired after emergent surgery for intracranial hemorrhage. No thromboembolic event and development of antibody to FIX were observed in any case.

Summary/Conclusion:

Good control of hemostasis can be achieved using FIX concentrates in hemophilia B patients who are undergoing surgery. Thorough planning is needed before elective surgery and more active and aggressive management may be needed for emergency surgery.
PB1843 EFFECT OF ADHERENCE TO PHYSICAL THERPY REGIMEN ON JOINTS OUTCOMES FOR HEMOPHILIAC CHILDREN AT ZAGAZIG UNIVERSITY HOSPITALS
Authors: Hesham M. , El‐Dakhakhny A. , Hanfy M. , Abo‐Elsoaud A.
Published: June 2019

Background:

The maintenance of healthy joints and muscles is crucial to the quality of life of patients with hemophilia. Clotting factor replacement may stop or even prevent bleeds but it does not restore joint or muscle function. Only regular movement and exercise and adherence to them can do that. Physiotherapy aims to bring relief from pain, restore muscle power and control, restore range of joint movement and prevent further injury to a target joint. Enhancing adherence, joint function and decreasing pain by using physiotherapy is the major hope for all hemophiliac patients, especially in developing countries with limited access to treatment.

Aims:

to Identify the effect of adherence to physical therapy regimen on joint outcomes for children with hemophilia.

Methods:

A quasi–experimental study was conducted on a sample of “35” children were suffering from hemophilia “A” or “B” at the Pediatric Hematology outpatient clinic at Zagazig University Hospitals. The knee joint was selected to perform the physiotherapy regimen Tools was composed of three parts Part I: a structured interview sheet. Part II assessment of adherence using (attendance at clinic appointments, SIRASa and Patient Self‐Report Scale of their Home‐Based Rehbiltation adherence). Part III was the assessment of the musculoskeletal status and joint evaluation using (Gibert score, FISH© and the musculoskeletal data sheet).

Results:

‐ There was a significant statistical relation and improvement in the mean score of functional ability of the studied group throughout the intermediate and post‐test phases than the pre‐test phase.

‐ There was a significant statistical improvement in the studied sample adherence and knee joint outcomes throughout the study phases.

Summary/Conclusion:

the adherence to physiotherapy have a profound effect on improving joint outcomes. So,we recommend encouraging the awareness of hemophiliac patients about physiotherapy and its beneficial role in decreasing the musculoskeletal complications.
PB1847 CONGENITAL COMBINED DEFECTS OF COAGULATION FACTORS FVII AND FX: ABOUT A TUNISIAN FAMILY.
Authors: Maalej S. , Megdiche F. , Ghorbel M. , Kacem S. , Kassar O. , Fakhfakh Y. , Kotti F. , Chaabane H. , Mbarek L. , Elloumi M. , Kallel C.
Published: June 2019

Background:

Combined factor VII (FVII) and factor X (FX) deficiency is considered as an extremely rare bleeding disorder. Only a few cases have been reported all over the world. According to the WFH (World Federation of Hemophilia) 2014, the global populations’ prevalence of combined defects of coagulation factors (CDCF) is close to 1:2 000 000. These recessively inherited coagulation disorders, are usually associated with a high consanguinity's rate. Unfortunately, diagnosis is still underestimated, mainly due to the important heterogeneity of clinical and biological phenotypes which may induce difficulties in the disease's management in patients.

Aims:

The aim of this study was to report two cases presenting a combined FVII‐FX deficiency diagnosed in the South of Tunisia.

Methods:

Biological investigation included prothrombin time (PT), activated partial thromboplastin time, FVII and FX analysis by coagulometric methods and fibrinogen by the Clauss method.

Results:

An 11‐year‐old female was referred to our laboratory to realize routine screening tests before a tonsillectomy. Haemostasis has been checked and results showed a prolonged PT (PT = 45%, normal range:70‐100%) (aPTT and fibrinogen were normal), which prompted to realize further tests. Our patient, offspring of a consanguineous marriage, reported, since an early age, recurrent epistaxis and abundant gingivorrhagia. Laboratory analyses showed a combined FVII and FX deficiency with a mild decrease of both FVII and FX coagulant activities as follows: (FVII:C = 52%, normal range: 55‐170%) and FX:C = 36%, normal range: 70‐120%) which required a family screening. It was then revealed that she had an older sister (17 years old) with a combined FVII and FX deficiency (FVII:C = 53%, FX:C = 47%). Clinically, the sister presented gingivorrhagia since an early age. With regard to the parents, the plasma levels of the father revealed that he was probably a carrier of FX deficiency (FX:C = 51%) and he complained about gingivorrhagia and epistaxis too. However, the mother and two other sisters had normal coagulant activities and didn’t suffer from any abnormal bleeding disorder.

Summary/Conclusion:

In accordance with the recent reports, the presence of two clotting defects in a patient may cause diagnostic difficulties. For that, firstly, an acquired vitamin K deficiency should be excluded by getting normal clotting activities of both factors II and IX. Secondly, to avoid a misdiagnosis, it's recommended to investigate both FVII and FX in cases with prolonged PT, especially that patients belonging to the South of Tunisia are known by high rates of consanguineous marriages. Added to that, it's important to explore the mutational spectrum of F7 and F10 and its associated phenotypes in order to attest the combined defects and to guarantee a better genetic counselling.
PB1860 A TURKISH CHILD PRESENTED WITH NEONATAL THROMBOCYTOPENIA ASSOCIATED WITH GNE MUTATION WITHOUT ASSOCIATED MUSCLE WASTING
Authors: Yilmaz E. , Ozcan A. , Verboon J.M. , Karakukcu M. , Sankaran V.G. , Unal E. , Patıroglu T.
Published: June 2019

Background:

Mutations in the glucosamine (UDP‐N‐acetyl)‐2‐epimerase/N‐acetyl mannosamine kinase (GNE) gene have previously reported in children with myopathy, however, recently GNE gene mutations were reported to be causative in nine children with thrombocytopenia without associated muscle wasting.

Aims:

Here we share our experience of a child with macrothrombocytopenia without muscle wasting associated with GNE.

Methods:

The clinical and genetic features of child with GNE is reported

Results:

A 30‐day‐old male was referred to Pediatric Hematology Clinic of Erciyes University with complaints of generalized petechial rash, ecchymoses just after birth and it was learned that he received intravenous immunoglobulin and platelet transfusions due to suspected neonatal allo‐immune thrombocytopenia at another medical center. His parents were first cousins. He was referred to our hospital NICU with thrombocytopenia. Blood count analyses revealed a hemoglobin of 10.6 g/dL, leukocyte count of 7810 x109/L, and platelet count of 6 x109 /L. The blood smear showed giant platelets. The bone marrow aspiration showed mild granulocyte maturation. He developed severe transfusion depended mucosal bleedings due to severe thrombocytopenia and neutropenia, so hematopoietic stem cell transplantation was planned. As no matching donor was found from the family or unrelated family, alpha beta depleted haploidentical hematopoietic stem cell transplantation (HSCT) from his father was performed. Although myeloid and platelet engraftments were achieved at +14, +13 days consequently, the chimerism decreased and the patient underwent a second haploidentical HSCT with mesenchymal stem cell support. Nevertheless, the chimerism did not improve and the patient died despite supportive treatment. Using whole exome sequencing, we identified a predicted pathogenic missense variant in the GNE gene (chr9:36219976:C>T, p.590:Gly>Arg) present in the heterozygous state in both parents and homozygous in the affected child.

Summary/Conclusion:

GNE mutations must be kept in mind for children with macrothrombocytopenia. Although our experience is limited, we speculate that there may be some underlying bone marrow micro‐environmental problem that resulted in early rejection after HSCT.
PB1865 SINUS BRADYCARDIA AS A SIGN OF CENTRAL NERVOUS SYSTEM INVOLVEMENT IN A CHILD WITH GRISCELLI SYNDROME TYPE 2
Authors: Kilic O. , Ay Tuncel D. , Gorkem B.S. , Ozcan A. , Akyol S. , Yuregir O.O. , Pamukcu O. , Unal E. , Karakukcu M. , Patıroglu T.
Published: June 2019

Background:

Hemophagocytic syndrome is often fatal in Griscelli syndrome type 2, and the only cure is hematopoietic stem cell transplantation.

Aims:

We aimed to emphasize the importance of sinus Bradycardia as a sign of Central Nervous System Involvement in a Child with Griscelli Syndrome Type 2

Methods:

A 6‐year‐old female Syrian refugee with gray hair was referred to Erciyes University for hematopoietic stem cell transplantation (HSCT) for Griscelli syndrome type 2. Her parents were consanguineous, and one of her siblings had the similar hair color and died when she was 9 months old.

Blood count analyses revealed a hemoglobin of 5 gr/dl, leukocyte count of 810x109/L and platelet count of 2x109/L. Bone marrow aspiration and biopsy showed hemophagocytosis with normal cellularity. Sinus bradycardia was detected on the first day of her admission on ECG (50/min). Because of sinus bradycardia, a cranial magnetic resonance imaging (MRI) was done. A homozygous pathogenic c.514_518delCAAGC (p.Gln172Asnfs∗2) (pQ172Nfs∗2) variant was detected in the molecular analysis of RAB27A gene.

Results:

After the diagnosis of Griscelli syndrome type 2, she was treated according to the HLH 2004 protocol with additional intrathecal chemotherapy. The bradycardia recovered in three days. Six weeks after this treatment the patient showed complete improvement but her parents refused further treatments.

Summary/Conclusion:

Different types of arrhythmia can be seen in different types of diseases that may affect the CNS. According to best of our knowledge, this is the first reported case of a child with Griscelli syndrome type 2 who presented sinus bradycardia as a sign of CNS involvement. It should be considered that sinus bradycardia in a child with partial oculocutaneous albinism may be an important predictor for CNS involvement of GS‐2.
PB1866 SUCCESSFUL MANAGEMENT OF A CHILD FOR PAROXYSMAL NOCTURNAL HEMOGLOBINURIA WITH LONG‐TERM ECULIZUMAB THERAPY
Authors: Aydogan G. , Salcioglu Z. , Akici F. , Yilmaz E. , Tahtakesen T.N. , Bayram N. , Ozdemir N.
Published: June 2019

Background:

PNH arises from a genetic mutation of hematopoietic stem cells which leads to the acquired nonmalignant clonal expansion of cells lacking glycosyl phosphatidylinositol‐anchored proteins (GPI‐APs). Lack of GPI‐APs translates into PNH's most significant clinical features: bone marrow failure, intravascular hemolysis and thrombosis. PNH rarely occurs in children and has been reported to have a distinct clinical presentation compared to the adult population. Most of the pediatric patients in the litearture have arisen in a previous setting of bone marrow failure. There are few pediatric case reports presented with reccurrent hemolytic episodes.

Aims:

There is a paucity of published data on outcomes in children with PNH treated with eculizumab. Therefore, we find it significant to share our experience regarding the use of eculizumab for a pediatric patient, who was diagnosed as PNH at 5.5 years of age and have been managed successful by eculizumab for more than 9 years at Kanuni Sultan Süleyman Education and Research Hospital.

Methods:

The case is retrospectively evaluated.

Results:

The patient was diagnosed in March 2008 with immunphenotyping and verified with FLAER method. She had been given blood transfusions, hyperhydration therapy, low‐dose oral prednisolone continuously initially and then during hemolytic attacks. During follow‐up, attacks had become more frequent and recurred at 2‐3 weeks intervals. With the informed consent of the family, eculizumab therapy was commenced in December 2011. She was 9 year old at this time.The dose of eculizumab was set according to the weight of the child as 600 mg/week for 4 week, then 900 mg/every other week parenterally. After introduction of eculizumab, both the frequency and the severity of the attacks had declined significantly. She has been under eculizumab therapy for more than 9 years without any considerable advers effect. Reoccurence of hemolytic attack was observed, when the patient had infections or the treatment was interrupted due to problems in obtining drugs.

Summary/Conclusion:

Depending on our experience, eculizumab may have a substantial role in controlling hemolytic episodes and preventing thrombotic complications and improving quality of life in children similiar to adults.
PB1870 IBRUTINIB PLUS VENETOCLAX SYNERGISTICALLY REDUCES SIGNALING AND VIABILITY IN CLL: IMPLICATIONS FOR BIOMARKER DISCOVERY
Authors: Skånland S.S. , Cremaschi A. , Bendiksen H. , Hermansen J.U. , Raj D.B.T.G. , Munthe L.A. , Tjønnfjord G.E. , Taskén K.
Published: June 2019

Background:

Recently, several small molecule drugs have been approved for the treatment of chronic lymphocytic leukemia (CLL). These drugs have significantly improved the management of this patient group. However, knowledge about how to combine the novel therapies for optimal effects and what patients will best benefit from them is still lacking.

Aims:

The aims of this study were to investigate whether drug synergies can be identified by single cell signaling analyses, and to identify potential signaling biomarkers for response to therapy.

Methods:

We investigated the effects of idelalisib, ibrutinib and venetoclax on 35 protein epitopes by phospho flow cytometry in CLL patient samples. Cell viability was monitored with internal markers for apoptosis in the phospho flow assays and with independent drug sensitivity screens.

Results:

The activity of proteins in the B cell receptor signalosome and the phosphatidylinositol 3‐kinase pathway were altered upon drug exposure. Combined treatment with ibrutinib and venetoclax give promising results in clinical studies and we show that this combination exerted synergistic inhibitory effects both on cell signaling (Figure 1a) and on cell viability (Figure 1a, b). Our analyses indicate that the standard dosages of ibrutinib and venetoclax can be lowered without loss of efficacy, potentially reducing drug costs and toxicities. Observed correlation between cell signaling and cell viability indicates that signaling molecules could serve as biomarkers to predict response to therapy.

Summary/Conclusion:

We suggest that phospho flow should be considered as a novel approach for dose and synergy prediction in a precision medicine setting for CLL.

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PB1897 MANAGEMENT OF AUTOIMMUNE CYTOPENIA COMPLICATING CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: Vyhovska O. , Yevstakhevych Y. , Maslyak Z. , Yevstakhevych I. , Pelenyo N. , Semerak M. , Vyhovska Y.
Published: June 2019

Background:

Chronic lymphocytic leukemia (CLL) in 4.3‐9.7% of patients is complicated with immune cytopenia (IC). Timely diagnostics of IC is important, as the therapeutic tactics in patients with IC is significantly different from standards of treatment of patients with CLL without immune complications.

Aims:

Determination of the peculiarities of the course of IC in patients with CLL and assessment of different treatment regimens.

Methods:

Under our observation, there were 83 patients with CLL complicated with IC: 38 patients with autoimmune hemolytic anemia (AIHA), 26 patients with immune thrombocytopenia (ITP), 15 patients with Fischer‐Evans syndrome, 3 patients with partial red cell aplasia, one patient with immune neutropenia.

The prognostic markers of the disease were determined: expression of CD38, ZAP70, β2 MG level, Coombs’ test, FISH analysis (del11q 22.3 and del17p 13.1). 58 patients received drug therapy (the first line ‐ steroid hormones, further: the schemes of COP, CHOP or RCOP, RCHOP or monotherapy with rituximab (rituximab at a dose of 375 mg / m2 / day, 4 injections with a weekly break), 25 patients underwent splenectomy.

Results:

The most severe course of the disease was observed in patients complicated with Fischer‐Evans syndrome (the median overall survival of 75 months). Insignificantly better results were observed in patients with AIHA (the median overall survival of 78 months). In patients with ITP, the median overall survival has not been achieved (observation time 12‐133 months). In case of steroid hormones use, as the first line of treatment, most patients experienced short‐term remissions.When using monotherapy with rituximab, the median progression‐free was 20 months. Conducted course therapy, based on RCOP or RCHOP regimens, was effective in 82% of patients. The median progression‐free survival has not been achieved in patients of this group (observation time 12‐57 months).

The median of overall survival for CLL with ITP after splenectomy was 135.0 months, for CLL with AIHA it was 69.6 months, and for CLL complicated with Fischer‐Evans syndrome it was only 49.5 months.

Summary/Conclusion:

Treatment of patients with CLL complicated with immune cytopenias should be individualized:

1. For patients with CLL that runs without significant enlargement of lymph nodes and spleen, low lymphocytosis, in case of occurrence of AIHA or ITP the use of monotherapy with rituximabis is optimal.

2. In case of occurrence of AIHA, ITP or Fisher‐Evans syndrome in patients with CLL that runs with enlargement of lymph nodes, spleen, significant lymphocytosis, the use of R‐COP or R‐CHOP schemes, 4‐6 courses, is the most effective.

3. In case of resistance to drug therapy and the presence of splenomegaly in patients with CLL, complicated with IC, splenectomy is indicated.
PB1909 HYPOGAMMAGLOBULINEMIA AS A PREDICTOR OF SURVIVAL IN OLDER PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: Umit E. , Baysal M. , Bas V. , Gulsaran S. , Demirci U. , Kirkizlar O. , Demir A.M.
Published: June 2019

Background:

chronic lymphocytic leukemia (CLL) is the most frequent leukemia of adults and has a median age of 71 years at diagnosis. Approach to CLL patients may include watchful waiting as well as chemotherapy and recently, immunotherapy and small molecules. As life expectancy in general population increases, a significant increase in patients who are accepted as old is also expected. As fitness is not a simple concept, explained with chronological age alone, older patients are suggested to be assessed individually and thoroughly in terms of cognition, comorbidity and mental health.

Aims:

We aimed to investigate the factors which may be related with survival and should be improved in older patients with CLL.

Methods:

104 patients who were 65 years and older diagnosed and treated for CLL were enrolled in the study in a retrospective manner. Demographic and survival data were recorded from files.

Results:

Mean age of our patients was 76,69 years (65‐91). 45 patients were female (43,3%) while 59 were male (56,7%). Median duration of watchful waiting period was 18 months (0‐74). 13 patients were Rai Stage 0 (12,5%) while 36 were Stage I (34,6%), 40 were Stage II (38,5%), 5 were Stage III (4,8%) and 10 were Stage IV (9,6%). Median lymphocyte count was 19.750/μL, median hemoglobin level 12,7 g/dL and median platelet count was 193 x106/L.

Median survival was 46 months (2‐86 months). 40 patients had hypogammaglobulinemia (38,5%). 23 patients have developed a secondary malignancy (22,1%). 40 patients had immune thrombocytopenia (ITP) (38,5%) and 5 patients had autoimmune hemolytic anemia (AHA)(4,8%).

Regarding the relation of complications during the course of disease, only hypogammaglobulinemia was observed to be related with survival. In patients who had hypogammaglobulinemia, mean survival was 42,25 months while in patients who did not have hypogammaglobulinemia, mean survival was 61,3 months (p < 0,05).

Summary/Conclusion:

Hypogammaglobulinemia should be sought in every older CLL patient and be supported if found. Survival of patients who have hypogammaglobulinemia is shorter, which may be explained with increased rates of infections as well as secondary malignancies due to the immune compromisation status.