bluuebunny/crossref_metadata_2025 huggingface dataset:
PS1486 INTERLEUKIN‐33 IN PEDIATRIC PATIENTS WITH IMMUNE THROMBOCYTOPENIA: RELATION TO PROGNOSIS AND TREATMENT OUTCOME
Authors: Tantawy A. , Adly A. , Ismail E.
Published: June 2019

Background:

The pathogenesis of thrombocytopenia in immune thrombocytopenia (ITP) has shifted from the traditional view of increased platelet destruction mediated by autoantibodies to more complex mechanisms where both impaired platelet production and T‐cell‐mediated effects play a role. Interleukin‐33 (IL‐33) is a newly identified cytokine of the IL‐1 family. There is increasing evidence to suggest that IL‐33 is a key inflammatory mediator in a complex network of immune cells and non‐immune cells. IL‐33 signals via its ST2 receptor and is involved in several autoimmune diseases by regulating T cell immune responses.

Aims:

To assess the level of IL‐33 in children and adolescents with ITP and correlate it with disease severity, treatment response and outcome.

Methods:

Fifty young patients with ITP were compared with 40 age‐ and sex‐matched healthy controls. Patients were studied stressing on bleeding manifestations, organomegaly/lymphadenopathy and therapy. Bleeding score was calculated to each patient according to the ITP Bleeding Scale (IBLS). The studied ITP Patients were further classified into 3 subgroups: “newly diagnosed ITP” (ITP within 3 months from diagnosis), “persistent ITP” (ongoing ITP between 3 and 12 months from diagnosis), and “chronic ITP” (ITP lasting more than 12 months). ITP Patients were also classified into active ITP defined as platelet count below 100 x 109/L accompanying with or without bleeding episode or complete response (CR) which was defined as any platelet count of at least 100 × 109/L and absence of bleeding.

Results:

IL‐33 levels were significantly lower in ITP patients than controls (median [IQR], 150 [100 – 230] versus 210 [180–260] pg/mL; p = 0.011). Levels were also lower in chronic than newly diagnosed ITP. IL‐33 levels are lower among active ITP (median [IQR], 105 [85 – 120] pg/mL) compared with those in complete remission (median [IQR], 240 [200 – 250] pg/mL) and healthy controls (p < 0.001) while no significant difference was found among the two latter groups (p = 0.197). Patients who had splenectomy had lower IL‐33 levels than non‐splenectomized ones. Lower IL‐33 levels were found among patients with corticosteroid‐dependence and relapse (p < 0.05). No significant difference as regards IL‐33 between treated and un‐treated patients with active ITP. IL‐33 was positively correlated to platelet count at sampling (r = 0.714, p < 0.001).

Summary/Conclusion:

Conclusions: Alterations of IL‐33 levels in pediatric patients with ITP highlight the role of T‐cell immune response in the pathogenesis of ITP. It may be considered as a potential prognostic marker for the development of chronic ITP as it correlates with disease activity. Further studies investigating the role of IL‐33 in the pathogenesis of ITP may provide a new therapeutic target for ITP.
PS1574 HLA‐DRB1∗15 INCREASES THE RISK OF RED BLOOD CELLS ALLOANTIBODIES IN PATIENTS WITH BETA THALASSEMIA MAJOR
Authors: Mashaykhi L.A. Al , Al‐Khabori M.K. , Al‐Riyami H. , Al‐Rawahi B. , Wali Y. , Daar S.
Published: June 2019

Background:

The cornerstone of the management of Beta Thalassemia Major (B‐TM) is lifelong Red Blood Cells (RBC) transfusion. This is associated with the development of RBCs alloantibodies. Human Leukocyte Antigen (HLA) is considered a risk factor for a number of autoimmune disorders. We hypothesized that HLA impacts the rate of alloantibody formation in patients with B‐TM.

Aims:

To assess the impact of HLA alleles on the risk of RBC alloimmunization in patients with B‐TM.

Methods:

This is a retrospective cohort study of patients with B‐TM managed at Sultan Qaboos University Hospital (SQUH) between January 1996 till December 2016. All adult and paediatric patients with B‐TM with available HLA typing results were included. Patients with missing data were excluded. Chi‐squared test was used to assess the impact of HLA alleles on alloimmunization and the effect size was estimated using odd ratio (OR). HLA testing was performed using polymerase chain reaction – specific sequence of oligonucleotides (PCR‐SSO). Gel card technique (BIORAD ID‐System; DiaClon, Bio‐Rad, DiaMed GmbH, Switzerland) was used to screen for the RBC alloantibodies.

Results:

One hundred and sixty‐five patients fulfilled the inclusion criteria without missing information. The median age of all patients was 14 years. Females constituted 48% of the sample and 45% of patients were O RhD positive. The median RBC transfusion was 17 times per year. Patients were first detected to have RBC alloantibody at a median age of 16 years. The commonest RBC alloantibodies found in these patients were anti‐K (50%) and anti‐E (58%). The commonest HLA allele in loci A, B, C, DQ and DRB1 were HLA‐A∗02 (21%), HLA‐B∗51 (14%), HLA‐C∗7 (18%), HLA‐DQ∗05 (47%) and HLA‐DRB1∗16 (32%) respectively. HLA‐DRB1∗15 and HLA‐DQ∗6 were associated with a higher risk of RBC alloantibody formation (HLA‐DRB1∗15: OR 3.57, P = 0.047; HLA‐DQ∗06: OR 4.37, P = 0.025). None of the remaining common alleles (>5%) in Omani population were associated with the risk of alloantibody formation (p values >0.05).

Summary/Conclusion:

HLA‐DRB1∗15 and HLA‐DQ∗06 increases the risk of RBC alloantibody formation in patients with B‐TM. We recommend extended RBC phenotyping and extended antigen matched blood transfusion in patients carrying these two alleles. These findings will need to be confirmed in a larger multicenter study.
PS1584 A PHASE II DOSE‐FINDING STUDY OF DALTEPARIN IN CHILDREN WITH VTE WITH OR WITHOUT CANCER
Authors: Hartman L. , Nurmeev I. , Svirin P. , Sherman N. , Wolter K. , Yan J.L. , Jani D. , Goldenberg N.
Published: June 2019

Background:

Venous thromboembolism (VTE) is an important clinical concern in children with or without cancer. Experience with dalteparin, a low molecular weight heparin, in the treatment of VTE in adults with cancer has been extensively published, but data in children are limited.

Aims:

We sought to determine the twice‐daily dalteparin dose required to achieve target Anti‐Xa levels of 0.5–1.0 IU/mL, as well as its pharmacodynamics (PD), efficacy, and safety in the treatment of VTE in children <19 years old, with or without cancer.

Methods:

This prospective, multi‐center, Phase 2, open‐label study consisted of 3 phases: 1) Dose Adjustment Phase of up to 7 days, in which Anti‐Xa levels were measured following the first, second or third dose of dalteparin, until achievement of the target level; 2) PD Phase of up to 7 days, to obtain 2 randomized PD plasma samples for Anti‐Xa determination; and 3) Follow‐Up Phase, to complete up to 90 days of anticoagulant therapy. Patients were assessed for symptomatic new or progressive (i.e., recurrent) VTE as well as clinically relevant bleeding during treatment. Surveillance VTE imaging was performed at 90 ± 14 days.

Results:

The safety population consisted of 38 patients who received at least 1 dose of dalteparin (<2 years: n = 3; ≥2 to <8 years: n = 8; ≥8 to <12 years, n = 7; ≥12 to <19 years: n = 20). Twenty‐six patients (68%) had a diagnosis of cancer at baseline, of which 23 (88%) were haematological malignancies. The median [range] dalteparin dose required to achieve target Anti‐Xa levels decreased with age (<2 years: 207.5 IU/kg [201.5–213.5 IU/kg]; ≥2 to <8 years: 128.15 IU/kg [123.9–180.3 IU/kg]; ≥8 to <12 years: 125 IU/kg [124.5–152.6 IU/kg]; ≥12 to <19 years: 116.7 IU/kg [99.1–159 IU/kg]) (Figure). Therapeutic Anti‐Xa levels were achieved in 90% of patients within a mean (SD) of 2.6 days (1.54 days); the mean (SD) number of dose adjustments per patient was 0.7 (0.98). One patient (3%) developed symptomatic recurrent VTE. No patients reported clinically‐relevant bleeding. Four patients (11%) had treatment‐related serious adverse events. 62% of patients had complete resolution of their VTE at the end of the 90‐day reporting period.

Summary/Conclusion:

Twice‐daily dalteparin dosing achieved therapeutic levels in 90% of children with or without cancer, with a satisfactory tolerability profile. The median therapeutic doses of dalteparin were higher for the two youngest age cohort groups (<2 years and 2 to <8 years).

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NCT00952380

Sources of Research Support: This study was sponsored by Pfizer Ltd.
PS1590 CENTRAL VEIN CATHETERIZATION IN ONCOHEMATOLOGICAL PRACTICE: RISK OF COMPLICATIONS
Authors: Romanenko N. , Schmidt A. , Glazanova T. , Shilova E. , Chebotkevich V. , Voloshin S.
Published: June 2019

Background:

The insertion of the central venous catheter (CVC) is a vascular access method used in resuscitation and oncohematology and it is required during intensive infusion and chemotherapy. However, due to the invasiveness of the procedure, complications are possible due to the procedure and course of the underlying disease.

Aims:

Assess the frequency of complications related to central vein catheterization in patients with hematology malignancies (HM).

Methods:

We have analyzed 2506 cases of CVC performed to patients with HM for the period from 2003 to 2018. All patients underwent catheterization of the right (82%), left (17.6%) subclavian vein or v. Jugularis externa (0.4%). Bacteriology tests were performed if a catheter‐related infection was suspected (n = 353).

Results:

Out of 2506 catheterizations bloodstream infections in the form of sepsis or bacteremia were documented in 2.5% of patients (n = 63), phlebitis, thrombophlebitis and infiltrate at CVC area were revealed in 2.6% (n = 66), lymphorrhea – in 1.3% (n = 33), catheter bleeding – in 3.9% (n = 73), haematoma – in 4.3% (n = 109), artery puncture (a. Subclavia dextra or sinistra) – in 3.0% (n = 76), pain, numbness, paresthesia of the upper limb – in 1.6% (n = 41), weakness, collapse – in 1.1% (n = 27), pneumothorax – in 0.2% of patients(n = 4). Positive bacterial cultures from venous blood were detected in 63 patients, with mixed infection in 8 cases (2 or 3 microorganisms). Detailed analysis of the infectious pathogens have demonstrated the prevalence of coagulase‐negative staphylococcus (Staph. epidermidis) – 56.3% (n = 40), At the same time, a relatively large percentage was represented by Staphylococcus aureus – 5.7% (n = 4), Micrococcus spp. – 1.4% (n = 1), Enterococcus spp. – 1.4% (n = 1). Gram‐negative microorganisms were detected in 26.7% (n = 19) of cases: Escherichia coli – 14.1% (n = 10) patients, Enterobacter spp. – 5.6% (n = 4), Enterobacter aerogenes – 1.4% (n = 1), Acinetobacter spp. – 1.4% (n = 1), Pseudomonas aeruginosa – 1.4% (n = 1), Neisseria spp. – 2.8% (n = 2). Causative agents of fungal infections were found for 8.5% of patients (n = 6), including fungi of the genus Candida – 7.1% (C. albicans (n = 4), C. crusei (n = 1), Rhodotorula spp. – 1.4% (n = 1).

Summary/Conclusion:

In patients with HM among catheter‐associated infections, coagulase‐negative staphylococcal infection (Staph. epidermidis) is most prevalent, which is most likely due to contact route of infection.
S1603 FIRST CLINICAL (PHASE 1B/2A) STUDY OF IBERDOMIDE (CC‐220; IBER), A CELMOD, IN COMBINATION WITH DEXAMETHASONE IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA
Authors: Lonial S. , van de Donk N.W. , Popat R. , Zonder J.A. , Minnema M.C. , Larsen J.T. , Nguyen T.V. , Chen M.S. , Bensmaine A. , Biyukov T. , Sonneveld P.
Published: June 2019

Background:

IBER is a novel cereblon E3 ligase modulator (CELMoD) with enhanced tumoricidal and immunostimulatory activities. Preclinically, IBER overcomes immunomodulatory drug (IMiD) resistance and has synergy with daratumumab (DARA), bortezomib (BORT), and dexamethasone (DEX).

Aims:

This phase 1b/2a multicenter, open‐label, dose‐escalation study (NCT02773030) was conducted to evaluate the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety and preliminary efficacy of IBER in combination with DEX, in patients with relapsed/refractory multiple myeloma (RRMM).

Methods:

Eligible patients had RRMM and must have received ≥2 prior regimens including lenalidomide (LEN) and/or pomalidomide (POM), and a proteasome inhibitor (PI). All patients had progressed on or within 60 days of last MM therapy. Escalating doses of IBER were given on days 1–21, in combination with DEX 40 mg (20 mg in patients aged >75 years) on days 1, 8, 15, and 22, of each 28‐day cycle. Dose escalation was reviewed by a dose escalation committee.

Results:

As of January 2019, 58 patients had received IBER + DEX. Median age was 64.5 years (range 33–79), and median number of prior regimens was 5 (2–12). Prior therapies included autologous stem cell transplantation (79%), LEN (100%), POM (69%), PIs (100%), and DARA (66%). IBER dose ranged from 0.3 to 1.2 mg; MTD/RP2D was not reached. Median duration of therapy was 12+ weeks (range 4–109). Grade 3–4 adverse events (AEs) were reported in 41 (72%) patients and were not related to dose. Grade 3–4 neutropenia, thrombocytopenia, neuropathy, and fatigue occurred in 26%, 11%, 2%, and 0% patients, respectively. Three patients discontinued treatment due to AEs. Clinical activity occurred early and was observed across all dose levels (Table 1); 20 of 51 patients remain on treatment (2–27+ cycles).

Summary/Conclusion:

IBER + DEX showed favorable efficacy and safety in heavily pretreated patients with RRMM who failed multiple prior therapies. This study is ongoing, including combinations of IBER with DARA or BORT.

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PB1688 SUCCESSFUL HAPLOIDENTIC BONE MARROW TRANSPLANTATION WITH INOTUZUMAB OZOGAMICIN IN PATIENT WITH RELAPSED AND RESISTANT B CELL ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: Ünal A. , Çelik S. , Güven Z. T. , Eser B. , Kaynar L. , Çetin M.
Published: June 2019

Background:

Although chemotherapeutic(CT) agents that used in the treatment of acute lymphoblastic leukemia(ALL) increase survival, the results are still weak. Long‐term survival with CT's in relapse ALL cases is difficult and the prognosis is very weak. Inotuzumab ozogamicin is an anti‐CD 22 monoclonal antibody and it has the potential to reduce the overall toxicity of intensive regimens for ALL, as well as to possibly increase the number of patients who may achieve a state of minimal residual disease.

Aims:

We aimed to present a case of successful haploidentic bone marrow transplantation in a recurrent B‐ALL patient who was in remission with inotuzumab ozogamicin.

Methods:

Case description: 26‐year‐old male patient was diagnosed with B‐cell ALL in December 2017. After the HOELZER CT protocol was started, maintenance treatment was continued.In the fifth month of treatment,FLAG CT protocol was started cause of recurrence was seen on 5% blast detection in peripheral blood smear. In August 2018, inotuzumab ozogamicin treatment was started and six cures were completed because the patient was not in remission. In September 2018, He had gone Haploidentical bone marrow transplantation from his sibling donor(8/10) with Defibrotid prophylaxis for Veno‐Occlusive Disease(VOD)s. He engrafted succesfully and chimerizm was 99.85% in 30th days of transplantation. He is 60th day of transplantation and in a remission.

Results:

Bone marrow transplantation cannot be performed since the complete response cannot be achieved in patients with relapse and resistant B‐ALL. In these patients, new therapies targeting malignant lymphoblasts are needed. Inotuzumab ozogamicinis a monoclonal antibody drug conjugate that targets CD22 antigen on malignant lymphoblasts.In many studies, it has been shown that Inotuzumab ozogamycin is effective and reliable anti‐tumor activity in adults with recurrent and resistant CD22 positive ALL. However, monoclonal antibody drug conjugates have been shown to be associated with VOD's. For this purpose, we used Defibrotid to protect our patient from VOD.

Summary/Conclusion:

Treatment with combination CT regimens in B‐ALL is suboptimal and long‐term survival is achieved in only 30‐40% of patients. Targeted molecular therapy and new regimens are needed in relapse and resistant patients. At this point, Inotuzumab ozogamycin is an anti‐CD‐22 monoclonal antibody, as in our case, it provides remission in recurrent and resistant B‐ALL patients and allows patients to complete their treatment with an allogeneic transplant from a fully compatible donor.
PB1705 CBC PARAMETERS BASED DERIVED PREDICTIVE FACTOR FOR ACUTE PROMYELOCYTE LEUKEMIA
Authors: Haider R.Z.H. , Buoro S. , Simon‐Lopez R. , De Paula E. , Shamsi T.S.
Published: June 2019

Background:

Acute promyelocytic leukemia (APML) due to coagulopathies drives hematological distress in clinical practices. A targeted and timely offered treatment can be a benefitting tool for patients.

Aims:

Present study was conducted to introduce pre‐microscopic screening of patients with acute promyelocytic leukemia (APML) through research potential parameters generated by routine hematology analyzers during CBC analysis.

Methods:

Blood samples of controls and patients (APML and other hematological neoplasms) were analyzed on Sysmex XN‐1000. Peripheral blood film was examined for morphological diagnosis. CBC parameters and values for intensities of white blood cell's side, forward, and side florescence light scatter were recorded from analyzer software. Statistical and machine learning (unsupervised) tools were used to evaluate the predictive power of routine and research CBC parameters. Novel APML factor was derived from white blood cell and platelet count along mean value of neutrophil side fluorescence light (NE‐SFL) through logistic regression. At proposed cutoff value (‐2.011), APML factor was challenged for prediction of APML among present study cases.

Results:

Values for white blood cell (WBC), platelet, and NE‐SFL were exceptionally discriminative for APML 5.65, 29.5, and 54.4 respectively in comparison to non‐APML 7.96, 219, and 47.00 respectively cases. In combination, WBC and platelet count increased the predictive power of NE‐SFL when utilized in derivation of our proposed “APML factor”: ‐4.5070 + (0.049213 x NE‐SFL) + (‐0.017431 x PLT) + (‐0.0058366 x WBC). This factor gave robust impact in differentiation of APML with high values 0.935 and 0.985 for sensitivity and negative predictive power (NPP) respectively at cutoff of ‐2.011.

Summary/Conclusion:

Our proposed APML factor has strong potential to be incorporate/calculate and examine as part of CBC report for early prediction of APML.
PB1742 AGE, KARYOTYPES AND WHETHER RECEIVING INDUCTION CHEMOTHERAPY ARE INDEPENDENT PROGNOSTIC FACTORS IN ELDERLY PATIENTS WITH AML
Authors: Wang W. , Jiang Z. , Ma J. , Sun H. , Sun L. , Meng X.
Published: June 2019

Background:

Acute myeloid leukemia (AML) is an aggressive disease with an unfavorable prognosis. AML is more common in elderly patients, and the treatments for these patients are limited, particularly for those with poor performance status, comorbidities, and unfavorable cytogenetic abnormalities. There are no universally accepted, standard approaches to treat AML in elderly patients.

Aims:

To analyze the clinical characteristics and prognostic factors of elderly patients with acute myeloid leukemia(AML).

Methods:

A total of 232 AML patients were enrolled in this retrospective study.

The clinical characteristics were collected and analyzed retrospectively. Factors affecting complete remission (CR) were analyzed by using chi square test. Univariate

and multivariate analyses of prognostic factors were performed by using Kaplan‐Meier and Cox hazard regression model respectively.

Results:

195 of 232 patients received induction chemotherapy, among whom 8 patiens died in early phase. 162 patients were able to be evaluated the efficacy, the CR rate after the first circle was 37.0 % (60/162). Overall CR rate was 54.9% (60/162). 37 patiens received palliative treatment, among whom 6 patients died in early phase and none achieved CR. Age between 60‐69 (χ2=4.102, P = 0.043), ECOG score≤2 (χ2=9.917, P = 0.002), NPM1+FLT3‐ITD‐ (χ2=6.423, P = 0.038), favorable karyotypes (χ2=6.033, P = 0.049) were related to a higher CR rate. The median overall survival (OS) was 205 day. Univariate analysis results demonstrated that age≥70 years (χ2=8.7, P = 0.003), white cell count≥100 × 109/L (χ2=4.249, P = 0.039), unfavorable karyotypes (χ2=4.807, P = 0.028), palliative treatment (χ2 = 191.221, P = 0.000) were influence factors on OS. In multivariable analysis, age between 60‐69 (HR = 0.464,95 % CI 0.245∼0.877,P = 0.018), unfavorable karyotypes (HR = 3.618,95 % CI1.491∼6.728,P = 0.003) and receiving induction chemotherapy (HR = 0.076,95 % CI 0.030∼0.194,P = 0.000) were independent prognostic factors for OS in elderly patients with AML.

Summary/Conclusion:

The prognosis of elderly patients with AML is the result of the combined effect of many factors. Age, karyotypes and whether receiving induction chemotherapy are independent prognostic factors in elderly patients with AML.
PB1758 CHILDHOOD ACUTE MYELOID LEUKEMIA IN SOUTHERN TUNISIA: ABOUT 52 CASES
Authors: kassar O. , mallek R. , Fakhfakh Y. , charfi M. , chaari M. , kallel F. , ghorbel M. , frikha I. , belaaj H. , mdhaffar M. , mseddi S. , Elloumi M.
Published: June 2019

Background:

Childhood acute myeloid leukemia (AML) represents 20% of childhood acute leukemia. Despite major improvement in outcome, the prognostic is pejorative compared with childhood acute lymphoblastic leukemia.

Aims:

We report the clinical features and treatment outcome of children de novo AML in southern Tunisia.

Methods:

Our study is retrospective including Children (age ≤ 20 years) affected by de novo AML between January 2005 and June 2018 treated in the department of hematology of CHU Hedi Chaker Sfax. Diagnosis has been established according to FAB classification confirmed by flow cytometry. Secondary leukemia and FAB M3 were excluded. Induction chemotherapy associated cytarabine 200 mg/m2 for 7 days and daunorubicin 60 mg/m2 for 3 days or mitoxantrone 12 mg/m2 for 5 days. After induction, patients with an HLA‐matched sibling donor underwent allogeneic Bone Marrow Transplantation (allo‐BMT) in first complete remission (CR1). Patients without a matched sibling donor received in CR1 three or four courses of consolidation. We evaluated complete remission rate, overall survival (OS) and event‐free survival (EFS). The Kaplan‐Meier method was used to estimate OS and EFS.

Results:

We collected 52 cases of childhood AML, including 28 boys and 24 girls (sex ratio = 1.03). The median age at diagnosis was 12 years (1.5‐20 years). The median initial white blood cell and hemoglobin level were 76 G/L (extreme 0.9 G/L ‐ 900 G/L) and 6.5 g / dL respectively. The median count of platelet was 55000/mm3. Distribution according FAB classification was: 17% of AML0, 21% of AML1, 19% of AML2, 23% of AML4, 6%of AML5 and 2% of AML6, 6% of AML7 and 2% of AMLbipheno. Cytogenetic of bone marrow cells showed chromosomal abnormalities in 58% of cases, only 13 (25%) patients had favorable abnormalities. Thirty‐one patients (60%) achieved complete response after one cure and 34 patients (65 %) after one or two courses of chemotherapy. Failure rate and toxic death were respectively 8% and 27%. Hematopoietic stem cell transplant was indicated in 24 (46%) patients but only 8 underwent the procedure. Nine patients (17.3%) relapsed within 8 months from diagnosis. The 5‐year OS and EFS were 50% and 48% respectively.

Summary/Conclusion:

Our study is characterized by frequent leucocytosis forms and FAB type M2. The CR rate and our EFS and OS rates observed in our series remain lower than in international trials. These can be explained by the frequency of refractory forms and the small number of bone marrow transplantation. Intensification chemotherapy of induction as well as consolidation therapy with allo‐BMT can improve the outcome of our patients.
PB1793 REATMENT OUTCOME FOR PRIMARY CERVIX LARGE B‐CELL LYMPHOMA: A CLINICAL ANALYSIS OF 37 CASES.
Authors: Liu X. , Xia Z. , Liu Y. , Cao J.
Published: June 2019

Background:

Cervical lymphoma is a rare condition and may be difficult to diagnose and treatment. Large B‐cell lymphoma is among the most common sub‐type of Cervical Lymphoma.No standard treatments for patients with primary cervix large B‐cell lymphoma have been introduced currently. Only case reports published in the literature and indicated the R‐CHOP regimens in combination with involved field radiation therapy (RT) are effective. Shanghai Cancer Center is one of the top pathological consultant center in China.

Aims:

We retrospectively analyse the 37 patients with primary cervix large B‐cell lymphoma and outcome after R‐CHOP in combination with RT, explore the treatment outcome by combination chemetherapy in this very rare type of cervix entity.

Methods:

Thirty‐seven untreated primary cervix large B‐cell lymphoma patients received R‐CHOP like regimens. Fourteen of them underwent subsequent RT. Thirteen of them received subsequent salvage chemotherapy.

Results:

Of 37 patients underwent R‐CHOP chemotherapy, only 3 patients received the radical surgery. An overall response rate (ORR) was 78.3% after completion of chemotherapy.The PFS and OS rate at 5 years were 58% and 69%, respectively. For 14 patients who received RT after R‐CHOP, an estimated ORR were 89.2%. For all patients, The PFS reached the platform after 2 years follow up and the OS after 3 years according to the survival curve analysis. The international prognostic index (IPI) score were the only predictor of worse outcome.

Summary/Conclusion:

R‐CHOP regimens plus involved field radiation therapy led high response rate in primary cervix large B‐cell lymphoma. Patients with high IPI had a trend of less satisfied with R‐CHOP regimens plus IFRT. Future prospective and multicenter studies are needed. By the way, we are conducting a gene expression profile between DLBCL‐unspecified and primary cervix large B‐cell lymphoma by NGS in order to get the valuable information to improve the treatment outcome even by using some targeted drugs. The data will be show in the next few months.

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PB1833 PRIMARY CARDIAC LYMPHOMA
Authors: Freue J.M. , Marin Castellanos R. , Silveyra D. , Lalor N. , Scapellato J.L. , Campestri R.
Published: June 2019

Background:

Primary cardiac lymphomas (PCL) are rare, with a fatal course unless diagnosed and treated in time. Non‐neoplastic causes such as infections and thrombi account for most cardiac masses. The most common cardiac tumors are benign, such as myxomas, being sarcomas the most frequent malignancy. Symptoms are inespecific, PCL can present as heart failure, arrythmias, vena cava thrombosis, thromboembolic disease. Patients must examined thoroughly, including echocardiography, CT or MRI and bone marrow biopsy. Final diagnosis will require a biopsy of the cardiac mass. Treatment is with chemotherapies according to lymphoma subtype, usually anthracycline based regimens. If ventricular outflow tract is compromised surgery may be needed due to hemodynamic instability which is associated with a very bad prognosis

Aims:

To describe a case of a patient with PCL

Methods:

A case report

Results:

Case: a 59 years old woman consulted for bilateral lower extremities edema and abdominal distension. She had a previous history of HIV infection diagnosed 10 years ago treated with nevirapine, lamivudine and zidovudine. Last CD4 count was 283/mm3 and viral load undetectable.

Laboratory: Hg 13,5 g/dl, WBC 9400/mm3 (Neutrophil 80%, no atypical cells or blast in blood smear), platelet 344000/mm3, coagulation test, protein electrophoresis, hepatic and renal function were normal, D‐dimer 6 mg/l (normal< 0,5), Hepatitis C and B test were negative, LDH 1200U/l(100‐210)

Abdominal ultrasound showed ascites, liver and spleen were normal. Serum‐Ascites albumin gradient was > 1,1 g/dl (suggestive of transudate).

AngioCT: ascites, thrombosis of iliac, right renal and inferior cava vein (IVC) thrombosis, cardiac mass in both auricles and right ventricle extending to IVC, signs of segmentary pulmonary embolism (PE).

Echocardiogram: atrial mass invading interauricular septum and occupying almost 50% of atrial surface.

Anticoagulation with enoxaparin 1 mg/kg BID was initiated and an angiography guided biopsy was done. Preliminary results were compatible with lymphoma so we added metilprednisolone 500 mg/day for 3 days with no clinical improvement. Chemotherapy was initiated with CHOP + methotrexate.

Bone marrow biopsy showed no lymphoma infiltration and pathology results of the cardiac mass were compatible with pax5, CD10 and TDT positive b cell lymphoblastic lymphoma.

On day 9, despite clinical improvement, she presented cardiac arrest and died. An echocardiogram done than day showed a 50% reduction in the mass size and fragmentation of it. An angio CT was done to rule out PE but was negative.

Summary/Conclusion:

PCL diagnoses is challenging and may have a dismal clinical course. A prompt diagnostic is necessary as soon as possible. We present this case due to the rarity of a solitary cardiac mass as the presentation of lymphoblastic lymphomas.

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PB1853 IMMUNOREGULATORY CYTOKINES (IL1β‐3954 AND IFNγ‐874) GENE POLYMORPHISMS IN NORTH INDIAN PATIENTS AFFECTED BY ACQUIRED APLASTIC ANEMIA.
Authors: Tripathi A. , Shukla S.
Published: June 2019

Background:

The etiopathogenesis of Acquired aplastic anemia is not clear. However immune mediated mechanisms are implicated in the genesis of this disease.

Aims:

The purpose of the study was to evaluate the polymorphisms in cytokine (IL1β‐3954 and IFN‐γ 874) genes in patients with acquired Aplastic Anemia (AA).

Methods:

In this observational case‐control study, 120 cases of AA & 120 healthy controls were taken under the standard criteria of Camitta's et al for AA. Genotyping for IL1β‐3954 and IFN‐γ 874 was performed using polymerase chain reaction and restriction fragment length polymorphism (PCR‐RFLP). Peripheral venous blood was collected in EDTA vial from all participants and DNA was extracted. Primer sequences of IL1β‐3954 and IFNγ‐ 874 genes were used under specific PCR conditions. PCR products were then digested with restriction enzymes at 37 °C for overnight. The digested products were run for gel electrophoresis and gel images were taken using the gel doc.

Results:

The frequency of homozygous (TT) variant genotypes of IL‐1β‐3954 was significantly associated with the higher susceptibility of developing AA when compared with the healthy controls (OR = 2.35, 95% CI = 1.10‐5.00, p = 0.0383). The mutant allele frequency (T) of IFN‐γ 874 showed a significant association with the lower susceptibility of developing AA when compared with the healthy controls (OR = 5.89, 95% CI = 3.97‐8.74, p = 0.0001).

Summary/Conclusion:

These findings suggest that IL‐1β‐3954 and IFN‐γ 874 gene polymorphisms may be implicated in the pathophysiology of Alastic Anemia.
PB1862 WHOLE EXOME SEQUENCING REVEALS XRCC2 MUTATION CAUSING FANCONI ANEMIA
Authors: Alhashem A. , Alabbasi B. , Alfaridi H.
Published: June 2019

Background:

The XRCC2 gene is a member of the RAD51 gene family, which encode proteins involved in homologous recombination repair of DNA damage. The XRCC2 gene acts late in the Fanconi anemia (FA)‐BRCA pathway of DNA repair. Fanconi anemia (FA) is a group of inherited disorder characterized by bone marrow failure, pancytopenia with multiple craniofacial and skeletal involvement.

Aims:

1‐To delinate the XRCC2 gene mutation,how it will present,and it is association with Fanocni anemia.

2‐To show the importance of extensive genetic testing in a high consanguinous population, where autosomal recessive disorders are common.

Methods:

We are reporting here an extremely rare gene, detected by Whole exome sequence(WES) for a 3 years old Saudi girl born at Prince Sultan Medical Military City, with multiple congenital anomalies, bilateral hypoplastic thumb, cafe au lait spots, strabismus, abnormal limb morphology, dysmorphic facial features, short stature.

Results:

Patients had chromosomal breakage study of 100%. Her WES reveled a rare XRCC2 gene, c.643C>T p.(Arg215∗). which creates a premature stop codon.

Summary/Conclusion:

So far the detected variant is the second variant that was reported in the XRRC2 gene and has been associated with the Fanconi anemia of complementation group U (FANCU, OMIM: 617247). It was reported in a Saudi family on 2012. The importance of this communication is to emphasize on the open approach when dealing with a disease with wide possible genes like in FA. Moreover, to consider XRRC2 gene, especially in a Saudi population with high consanguinity and calls for further investigation of the potential contribution of XRCC2 mutations to the overall mutational load of FA.
PB1884 HIGH CXCR3 AND CXCR5 DISTINGUISH IGHVMUT FROM IGHVUNMUT CHRONIC LYMPHOCYTIC LEUKEMIA: EVIDENCE FROM CD5HIGH AND CD5LOW CLONES
Authors: Gabcova G. , Manukyan G. , Papajik T. , Mikulkova Z. , Urbanova R. , Kudelka M. , Smotkova Kraiczova V. , Zehnalova S. , Turcsanyi P. , Kriegova E.
Published: June 2019

Background:

Despite the shared pattern of surface antigens, neoplastic cells in chronic lymphocytic leukemia (CLL) demonstrate heterogeneity in their molecular and functional characteristics. Given the dynamic variability of CD5 expression and its link to the proliferative pool of neoplastic cells, more detailed characterization of CLL cell subpopulations are needed.

Aims:

To further characterize the chemokine receptors (CCR5, CCR7, CCR10, CXCR3, CXCR4, CXCR5) and adhesion molecules (CD54, CD62L, CD49d) on the CD5high and CD5low neoplastic clones in peripheral blood in CLL.

Methods:

Study cohort consisted of CLL patients (n = 60) subgrouped according to the IgHV mutational status (IgHV
mut, n = 24; IgHV
unmut, n = 36). Chemokine receptors and adhesion molecules on CD5high and CD5low cell subpopulations, determined by CD5/CD19 co‐expression, in peripheral blood were assessed by a six‐colour flow cytometry analysis on a BD FACSCanto II (Becton Dickinson). Data were analysed by basic statistics and patient similarity networks.

Results:

CD5high cell subpopulation expressed high levels of CXCR3 (P < 0.001), CXCR5 (P = 0.005), CCR7 (P = 0.013), CCR10 (P = 0.001), CD62L (P = 0.031) compared to CD5low cells expressing high levels of CXCR4 (P < 0.001). When comparing IgHV
mut from IgHV
unmut patients, high‐levels of CXCR3 and CXCR5 on the whole neoplastic population as well as CD5high and CD5low subpopulations were detected in the IgHV
mut patients. Multivariate patient similarity networks confirmed the significance of high CXCR3 levels predominantly on CD5low cells from IgHV
mut patients.

Summary/Conclusion:

Our analysis revealed that CD5high and CD5low neoplastic clones from IgHV
mut and IgHV
unmut differed mainly by the expression of CXCR3. Further characterization of neoplastic cell heterogeneity and role of CXCR3 will advance our understanding of CLL biology and its clinical relevance.

Grants: MZ ČR VES16‐32339A, IGA UP_2019_014, IGA_LF_2019_001, MH CZ–DRO (FNOL, 00098892)
PB1892 REAL WORLD TREATMENT PERSISTENCE OF NEW ZEALAND IBRUTINIB CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS IN A NAMED PATIENT PROGRAM
Authors: Weinkove R. , Doocey R. , Henderson R. , Islam S. , Smith M. , Puig A. , Pateman G. , Acar M. , Amaya‐Chanaga C. , Simpson D.
Published: June 2019

Background:

Named Patient Programs (NPPs) provide access to medicines in response to unsolicited requests by physicians for specific patients before they become commercially available. Janssen New Zealand opened a NPP for ibrutinib for patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) in September 2014. The program closed for new enrolments in April 2018, but enrolled patients have continued to receive treatment as of 7th January 2019.

Aims:

To analyse duration on ibrutinib treatment for patients with relapsed/refractory CLL enrolled in a New Zealand NPP.

Methods:

A retrospective cohort analysis was conducted using data entered by treating physicians when enrolling patients into the NPP via the Janssen Managed Access Portal (MacWeb). At each resupply patients were provided with 3 months’ supply of ibrutinib. Patient time on treatment was estimated using fulfilled resupply requests submitted by physicians. Patients were considered to be on treatment until the date of last ibrutinib resupply, plus one month. A patient was considered discontinued based on physician declaration, or if no ibrutinib had been resupplied for four months or more. All other patients were censored at the reporting date of 7th January 2019. This real‐world estimate of treatment duration was compared to time to treatment discontinuation in the ibrutinib arm of the RESONATE trial, as reported in Hillmen et al. EHA; 2016 (abstract 133196) and Tam et al. EHA; 2018 (abstract 214826). Time on treatment was evaluated using Kaplan‐Meier (KM) curves, and statistical testing was conducted using log‐rank testing.

Results:

112 ibrutinib‐treated patients with CLL were included in the analysis. 59% of the population were male, 37% had 3 or more prior lines of therapy before commencing therapy, and 32% had refractory disease. 73% of patients were on therapy at 12 months (95% CI: 0.64‐0.8) and median time to discontinuation has not been reached at the time of the analysis. 42% of patients were estimated to have discontinued therapy over the 49‐month period. The comparison between patient time on treatment on the New Zealand NPP and the RESONATE trial were statistically not different (HR 1.01; 95% CI: 0.71‐1.44; p = 0.96).

Summary/Conclusion:

This real‐world analysis estimates that patient time on NPP treatment in New Zealand closely tracks time on treatment as observed in the RESONATE trial. While there are limitations to the NPP data as it was based on unmonitored physician declarations, and duration on treatment was estimated from resupply data, these findings suggest that duration of treatment in a New Zealand non‐trial setting is similar to that in the Phase 3 clinical trial.

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PB1939 ACCURACY AND SPEED OF REPORTING MOLECULAR RESPONSE IN PATIENTS ON TYROSINE KINASE INHIBITORS THERAPY WITH GENEXPERT CARTRIDGE‐BASED BCR‐ABL1 QUANTITATION
Authors: Dreisinger M. , Stangler Herodež Š.
Published: June 2019

Background:

Monitoring of minimal residual disease (MRD) in chronic myeloid leukemia (CML) patients who are on tyrosine kinase inhibitors (TKI) is one of the best standardized molecular methods. Guidelines for treating these patients include the evaluation of molecular response (MR) based on % BCR‐ABL1 on the International Scale (IS) in defined time points. Achieving timely MR is necessary for determining the status of the disease and the use of appropriate therapy.

Aims:

The aim of this study was to introduce the GeneXpert cartridge‐based BCR‐ABL1 detection into routine molecular monitoring of CML Slovenian patients from north‐eastern region and compare the MR results with those obtained from a standard laboratory method.

Methods:

BCR‐ABL1 transcript quantification was performed in 40 peripheral blood samples from CML patients at different stages of the disease in two different laboratories. First one used automated GeneXpert BCR‐ABL Ultra Assay (Cepheid, USA) and the second one used standardized laboratory protocol. The results for both analyzes were expressed as % IS and were estimated by MR according to Laboratory recommendations for scoring deep molecular responses following treatment for chronic myeloid leukemia.

Results:

The analysis of the results showed that there were no statistically significant differences in the results expressed in % IS (p = 0, 272). Samples according to the estimated MR were divided into 3 groups (8 MR3 samples, 3 MR4 samples and 27 ≥ MR4.5 samples). 27/40 samples had a completely identical MR with both methods. Furthermore, 11/40 samples had higher MR obtained with GeneXpert, while 0/40 samples had lower MR compared to SP. In 2/40 cases, GeneXpert gave MR5 for sample with SP MR3 and MR4 for sample with SP MR3. None of the results obtained with GeneXpert had any effect on a different clinical decision on treatment with TKI as obtained under the SP. When the major molecular response (MMR) was analyzed, 78% agreement was achieved.

Summary/Conclusion:

GeneXpert BCR‐ABL Ultra Assay provides reproducible results and doesn’t show significant differences compared with the standardized laboratory protocol. From clinical aspect, GeneXpert BCR‐ABL Ultra Assay correctly classified the patients in MR and can be considered as a useful and very fast clinical tool for the molecular follow up of patients on tyrosine kinase inhibitors.
PB1954 DETECTION OF COMPLEX VARIANT T(9;22) CHROMOSOME TRANSLOCATIONS IN NEWLY DIAGNOSED CASES OF CHRONIC MYELOID LEUKAEMIA
Authors: Fareed N. , somroo N.M. , Quraishy M.S. , Rafiq S.
Published: June 2019

Background:

Chronic myeloid leukemia (CML) is a stem cell clonal disease characterized by the acquisition of a fusion protein, BCR‐ABL1 oncogene, which leads to uncontrolled proliferation of myeloid elements in all stages of differentiation. However, a small proportion of patients with CML have simple or complex variants of this translocation, involving various breakpoints in addition to 9q34 and 22q11.

Aims:

Detection of complex variant t(9;22) chromosome translocations in newly diagnosed cases of Chronic Myeloid Leukaemia which help us to choose therapy modalities.

Methods:

This study was conducted for a time period of 05 years from 2012 to 2017 in the department of Oncology/ Hematology of Civil hospital, Karachi. Between April 2012 and April 2017, 88 CML patients were diagnosed in our Department. Informed consent was obtained from the patient in accordance with the Declaration of Helsinki. Diagnosis was done on the morphological basis and BCR‐ABL mutation by PCR/FISH. Conventional cytogenetic analysis was performed on unstimulated 24‐hour culture of a bone marrow (BM) specimen. The cells were cultured and processed by conventional methods, and the chromosomes were stained with trypsin‐Giemsa banding (GTG‐banding).

Results:

A total of 88 patients were Philadelphia‐positive CML, out of which 53(60.2%) were males & 35(39.7%) were females. Mean age was 48 yrs ± 11.43. Out of them, the group of 9 (10.2%) patients with complex cytogenetics were consisted of 5 females and 4 males, ranging in age at diagnosis from 32 to 66 yrs. All the patients were in chronic phase at presentation. Cytogenetic analysis by G‐banding revealed the presence of 9 reciprocal three‐way variant translocations of the classical t(9;22)(q34;q11). The chromosome breakpoints involved in these complex variant translocations were the following: 1p13, 1q21, 1p22, 2q31, 3q21, 3p21, 11q13, 15q24 and Xp11.2

Summary/Conclusion:

In our study 09 patients had complex variants of t(9;22).The presence of these complex variants at diagnosis and during the TKI treatment may announce treatment failure and/ or transformation to advanced stage (accelerated or blast). Early identification of these abnormalities may help in choosing therapy modalities.
PB2033 IMMUNOGLOBULIN REPLACEMENT THERAPY IN ADULT HEMATOLOGICAL PATIENTS: EFFECT ON THE INCIDENCE OF INFECTIOUS COMPLICATIONS
Authors: Gerasimovich O. , Stoma I. , Iskrov I. , Milanovich N. , Lendina I. , Uss A.
Published: June 2019

Background:

The problem of infectious complications in hematology is determined by their high frequency, severity and difficulty of diagnosis. The clinical effect of immunoglobulin replacement therapy in relation to the risk of infectious complications in adult hematological patients currently needs to be assessed and revised.

Aims:

The aim of this prospective study was to evaluate the independent effect of immunoglobulin replacement therapy on the risk of developing infectious complications in hematological patients.

Methods:

The study included 34 adult patients receiving chemotherapy for hematological disease. Intervention groups (immunoglobulin replacement therapy) and the control group were matched by clinical and demographic characteristics. The primary outcome in the analysis was taken as the infection‐free period in the 180‐days survival analysis performed by Kaplan‐Meier with log‐rank test, Cox regression and Cox regression.

Results:

The average age of patients was 57.8 years, with sex distribution: 19 female and 15 male. Hematological diseases were distributed as follows: chronic lymphocytic leukemia ‐ 18, multiple myeloma ‐ 8, acute myeloid leukemia ‐ 2, acute lymphocytic leukemia ‐ 4, myelodysplastic syndrome ‐ 2. Among the included ‐ 15 patients had profound hypogammaglobulinemia (less than 4 g/l). Statistically significant association of immunoglobulin replacement therapy and reduction of the risk of infectious episodes was shown in a 180‐days period (log‐rank test, p = 0.037), Fig 1. The average duration of the period without infectious complications in the replacement group was 164 days (95% CI 147‐180 days), while in the control group it was 148 days (95% CI 124‐171 days). No additional confounding factors, which could cause the differences in the groups were found in the regression analysis (p = 0.035). The number needed to treat (NNT) was 3 patients (p = 0.018).

Summary/Conclusion:

The obtained data show that the use of immunoglobulin replacement therapy is independently associated with a longer period of infection‐free survival in adult hematological patients, what substantially improves the quality of life of such patients. The clinical effect may be assessed within 6 months from the start of immunoglobulin replacement therapy.

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