bluuebunny/crossref_metadata_2025 huggingface dataset:
PB1990 THE CHANGE OF BONE MARROW MICROENVIRONMENT OF SECONDARY POOR GRAFT FUNCTION AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION AND ITS EFFECT ON PROGNOSIS
Authors: Liu S. , Ran C. , Li J. , Peng X. , Zhang X. , Liu Y.
Published: June 2019

Background:

Secondary poor graft functionis a serious life‐threatening complication after allogeneic hematopoietic stem cell transplantation, which pathogenesis, evolution and prognosis are still unclear.

Aims:

To explore the role of adhesion related indicators in secondary poor graft functionafter allogeneic hematopoietic stem cell transplantation

Methods:

In this study, clinical data and post‐transplantation status of 106 patients with hematological tumour who were enrolled in our center and underwent allo‐HSCT from Jan. 1, 2016 to Jan. 31, 2017 was counted.The patients were divided into good graft function (GGF) group and secondary poor graft function (sPGF) group according to the implantation status after transplantation. The differences of age, primary disease, stem cell source, HLA matching, sex matching, ABO blood group matching, degree of bone marrow hyperplasia before transplantation, recurrence rate and mortality between the two groups were compared.29 patients with sPGF after transplantation were selected as the experimental group while 29 patients with GGF were selected as the control group.

Results:

The changes of adhesion related indicators in the two groups were detected.There were no significant differences in age, primary disease, stem cell origin, HLA matching, sex matching, ABO blood group matching and the degree of bone marrow proliferation before transplantation between the two groups (P > 0.05). The infection rate of CMV in sPGF group was significantly higher than that in GGF group, and the remission rate before transplantation in sPGF group was significantly lower than that in GGF group (P < 0.05).Cox regression analysis showed that the survival rate of patients with sPGF after allo‐HSCT was significantly lower than that of patients without sPGF (P < 0.05, HR = 3.598).The expression of CD44, CD29, ICAM‐1 and VCAM‐1 in sPGF group was not significantly different from that in control group (P > 0.05), but the expression of CD105 was higher than that in control group, and the expression of Cx43 was lower than that in control group (P < 0.05).

Summary/Conclusion:

We believe that the survival rate of patients with sPGF after allo‐HSCT will decrease significantly, and the occurrence of sPGF after transplantation may be related to the increase of CD105 expression and the decrease of Cx43 expression in bone marrow stromal cells before transplantation.
PB1995 THE EFFECTS OF ANTITUMOR THERAPY ON BONE REMODELING IN PATIENTS WITH HODGKIN'S LYMPHOMA
Authors: Voytko M. , Pospelova T. , Klimontov V. , Fazullina O.
Published: June 2019

Background:

Cures have been achieved in a significant proportion of patients with Hodgkin lymphoma (HL) for many years. Treatment for HL has been associated with adverse late effects. One of those consequences of antitumor therapy may be a change in bone mineral density (BMD). Hemoblastosis is considered as a strong risk factor for secondary osteoporosis and major low‐energy fractures. The decrease in BMD can be associated with polychemotherapy, including various combinations of cytostatic drugs and glucocorticoids, as well as with hypogonadism caused by toxic effects of radiotherapy and chemotherapy, tumor process, low physical activity and other factors.

Aims:

To assess the bone mineral density (BMD) in patients with HL.

Methods:

The study included 103 patients with HL from the City Hematology Center of Novosibirsk, from 19 to 72 years of age (median 49 years [33;55]). The disease was staged according to the Ann Arbor staging system: 55 patients had early stage disease and 48 patients had advanced stage disease (stage III to IV). All subjects received first‐line regimens (ABVD, BEACOPP‐14, et al.). Eighteen patients with advanced stages and unfavorable prognosis obtained second‐line regimens (DHAP, ESHAP). Radiotherapy was performed in 57 (55,3%) individuals. Complete remission was achieved in 60 of 103 patients (58,2%), and partial remission was recorded in 32 ones (31%). The BMD was assessed by dual‐energy X‐ray absorptiometry with GE Lunar Prodigy densitometer (USA). The assessed variables were BMD and T‐ or Z‐criterion (when appropriate) at the lumbar spine (L1–L4), proximal femur, femoral neck and forearm of a non‐dominant arm. Fracture Risk Assessment Tool (WHO FRAX, web version 3.8, adjusted for Russia) was used to determine the risk of major osteoporotic fractures.

Results:

The decreased BMD was revealed in 47 observed HL subjects (45,6%), 30 of them diagnosed osteoporosis. The decline in BMD was more frequent in patients aged ≥50 years as compared to younger ones (χ2 = 5,75; p = 0,02). More patients with radiotherapy in anamnesis had decreased BMD compared to patients who received chemotherapy only (χ2 = 8,82; p = 0,003) More than half of the patients (60 %) receiving regimens containing glucocorticosteroids had BMD decrease. Based on FRAX assessment, the 10‐year risk of major low‐energy fractures and the hip fractures was expectedly higher in patients with osteoporosis and osteopenia as compared to subjects with normal BMD (p < 0,05). A comparative analysis revealed that patients younger than 50 years old had more often lower values of BMD and Z‐score of the lumbar spine. In turn, the femoral neck was the most frequent localization of osteoporosis in patients older 50 years and postmenopausal women.

Summary/Conclusion:

The study demonstrates high prevalence of decreased BMD in patients with HL. The decrease in BMD is associated with radiotherapy and chemotherapy with glucocorticoids.
PB2031 INVASIVE ASPERGILLOSIS IN ELDERLY ONCOHEMATOLOGICAL PATIENTS
Authors: Shadrivova O. , Desyatik E. , Volkova A. , Popova M. , Uspenskaya O. , Shneyder T. , Melekhina J. , Bogomolova T. , Ignatyeva S. , Zubarovskaya L. , Afanasyev B. , Klimko N.
Published: June 2019

Background:

Invasive aspergillosis (IA) in elderly patients is not well understood.

Aims:

Analysis of underlying diseases, risk factors, etiology, clinical features, treatment and survival rates in elderly patients with IA.

Methods:

Retrospective analysis of the register data in 1998‐2018 yy. We included 646 adultpatients with proven and probable IA. For diagnosis of IA we used criteria EORTS/MSG, 2008.

Results:

In group I we included 137 patients with IA ≥ 60 years old, males – 60%. The control group consisted of 509 patients aged from 18 to 59 years, males – 53%. Oncohematological diseases were less frequent in elderly patients – 77% vs 87%, p = 0,002. In this patients non‐Hodgkin's lymphoma prevailed (35% vs 13%, p <0.05) among underlying diseases, whereas other hematologic diseases were less common: acute lymphoblastic leukemia (6% vs 13%, p < 0.05), Hodgkin's lymphoma (6% vs 13%, p < 0.05). Non‐hematological diseases were more frequent in elderly patients (23% vs 13%, p = 0.002). We identified differences in risk factors between the two groups: prolonged agranulocytosis was detected in 59% vs 75%, (p = 0.0003), lymphocytopenia ‐ 45% vs 60%, (p = 0.002).Significantly smaller numbers of elderly patientswere recipients of allogeneic stem cell transplants (3% vs 26%, p = 0.00001) and received immunosuppressive therapy (17% vs 31%, p = 0.0002). No significant differences were obtained in the localization of the fungal infection, as well as in clinical symptoms and results of galactomannan test. Aspergillusspp. were isolated more often in elderly patients (52% vs 40%, p = 0,01). The main etiological agents wereA. fumigatus (59% vs 45%) and A. niger (25% vs 34%). Mixed fungal infection was found in 9% vs 11% patients. Antifungal therapy was used in most of patients, the main drug used was voriconazole (73% vs 72%). Twelve weeks overall survival rate was 82% vs 79%.

Summary/Conclusion:

Oncohematological diseases were less frequent in elderly patients – 77%.The features of risk factors in elderly patients was less severe immunosuppression: prolonged agranulocytosis – 59%, lymphocytopenia – 45%, immunosuppressive therapy ‐ 17%, allogeneic stem cell transplants – 3%. The overall 12‐week survival in elderly patients with IA was not significantly different (82% vs 79%).
PB2032 BASELINE PREDICTORS INFLUENCING THE PROGNOSIS OF INVASIVE ASPERGILLOSIS IN ADULTS
Authors: Köhler P. , Salmanton Garcia J. , Gräfe S. , Koehler F. , Mellinghoff S. , Seidel D. , Steinbach A. , Cornely O.
Published: June 2019

Please indicate where the abstract has been published before: Journal of Infection.

Background:

Invasive aspergillosis (IA) is a serious hazard to hematological and critical care patients.

Aims:

To understand prognostic variables we analyzed original articles identifying baseline factors that predict treatment outcome in patients with IA.

Methods:

PubMed database was searched for publications since database inception until May 2018. Inclusion criteria were published baseline prognostic factors present at the diagnosis of IA.

Results:

In total, 58 studies from 267 centers reported 7,320 patients with IA, and 40 different predictors. Unfavorable predictors in medical history were kidney (7.4%, 10/136) and liver failure (3.7%, 5/136), ICU admission (3.7%, 5/136), and uncontrolled underlying disease (3.7%, 5/136). Regarding state of immunosuppression, negative outcome predictors were prolonged neutropenia (12.5%, 17/136), corticosteroid treatment (8.1%, 11/136), and graft‐versus‐host disease (3.7%, 5/136). On the pathogen side, relevant predictors were galactomannan positivity (8.1%, 11/136), Aspergillus terreus infection (2.2%, 3/136), and lack of amphotericin B susceptibility (1.5%, 2/136). IA‐specific predictors were disseminated disease (5.1%, 7/136) and CNS involvement (2.9%, 4/136). Imaging results associated with negative outcome were multiple consolidations (2.9%, 4/136), bipulmonary lesions (2.2%, 3/136), and pleural effusion (2.2%, 3/136).

Summary/Conclusion:

At diagnosis of IA, most frequently identified predictors of outcome were neutropenia, corticosteroid use, elevated galactomannan, renal failure, and disseminated disease.
PB2050 USING A FUNCTIONAL SCREEN TO IDENTIFY NOVEL ANTI‐PROLIFERATIVE MIRNAS IN DIFFUSE LARGE B‐CELL LYMPHOMA (DLBCL)
Authors: Sole C. , Goicoechea I. , Lawrie C.H.
Published: June 2019

Background:

Diffuse large B‐cell lymphoma (DLBCL) is the most common B‐cell lymphoma, accounting for around 40% of all newly diagnosed non‐Hodgkin lymphoma (NHL) malignancies worldwide. Thanks to R‐CHOP therapy, the majority of DLBCL patients survive their disease. However, around 15% of patients treated have refractory disease, and of the patients that do respond to therapy, an additional 20‐25% will relapse.

Proliferation is an important hallmark of cancer and in DLBCL has been associated with poor prognostic outcome. Consequently, several studies have focused on targeting molecules responsible for DLBCL proliferation as a novel therapeutic approach. MicroRNAs (miRNAs) are small non‐coding RNA molecules that act as key regulators of many biological and pathological processes including lymphomagenesis. miRNAs have been shown to be involved in many aspects of DLBLCL pathogenesis including initialization and progression of the disease, as well as having prognostic value.

Aims:

Identify miRNAs responsible the sustainment of proliferative signaling in DLBCL with the goal to develop novel anti‐lymphoma therapies.

Methods:

DLBCL cell lines (RIVA, SU‐DHL‐10, SU‐DHL‐4 and Oci‐ly‐10) were infected with a lentiviral library encoding for 698 miRNAs. We used a pooled‐approach using a MOI of 50. An empty vector was used as the control. Stable cell lines were produced by puromycin selection and cells maintained in culture for 4 months in triplicate. Both DNA and RNA were extracted at time 0, 2 months and 4 months post‐infection and the resultant DNA sequenced by NGS (Ion Torrent PGM). Differentially expressed miRNAs were detected by differential expression analysis (P < 0.05). For validation, selected miRNAs were infected individually in cell lines and proliferation rate (CFSE assay) and apoptosis (AnnexinV/TO‐PRO‐3) were determined by flow cytometry.

Results:

More than eighty miRNAs were identified as being differentially expressed between time 0 and time 4 months in each cell and five of these were differentially expressed in all cell lines. We validated five miRNAs by infecting cell lines with individual lentiviral vectors.

Summary/Conclusion:

We have demonstrated that the use of functional miRNA screens is a reliable tool for elucidating the phenotype‐genotype interface of cancers such as DLBCL. From our experiments, we propose that miRNA over‐expression could be used to decrease cell proliferation in DLBCL.
PB2120 THE IMPACT OF DEPTH OF RESPONSE BEFORE AND AFTER AUTOLOGOUS STEM CELL TRANSPLANT FOR MULTIPLE MYELOMA PATIENTS
Authors: Durão S. , Vieira J. , Velosa F. , Neves M. , Infante J. , Alho A. , Espada E. , Martins H. , Valle S. , Lourenço F. , Moreno R. , Alves D. , Costa M. J. , Polo B. , Lopes C. , Martins C. , Lacerda J. Forjaz , Esteves G. , Raposo J.
Published: June 2019

Background:

Over the last decade there has been an improvement on the outcome of multiple myeloma (MM) patients. In patients eligible for high‐dose chemotherapy and autologous stem cell transplant (ASCT), the inclusion of bortezomib in induction chemotherapy (ICT) has significantly delayed disease progression. Several studies have shown that achieving a complete response (CR) after ASCT is a predictive factor for disease control, leading to improved progression‐free survival (PFS) and overall survival (OS).

Aims:

Assessing the impact of depth of response before and after ASCT on PFS in a population of MM patients treated with ICT including bortezomib and identifying predictive/protective factors for disease progression.

Methods

Retrospective study of MM patients admitted for ASCT between January 2015 and December 2017 treated in first line with VCd (bortezomib, cyclophosphamide, and dexamethasone) or VTd (bortezomib, thalidomide and dexamethasone). Demographic (gender, age), clinical and biological variables at diagnosis were collected, as well as response obtained before and at D + 100 after ASCT, and time elapsed between ASCT and disease progression. Statistical analysis was performed using STATA software (V13).

Results:

A total of 53 MM patients in the first line setting were included in this study. 43.4% were male; median age at diagnosis was 60 years old (IQR, 40‐72). Both groups (VCd and VTd) had similar baseline characteristics. Median follow‐up after induction chemotherapy was 20.6 months. PFS of patients who achieved CR or very good partial response (VGPR) post‐induction was 73.7%, versus 60% in patients who achieved partial response (PR) or lower (log‐rank p = 0.07). Looking at different variables that could modify the time between ASCT and disease progression, we observed that ISS stage 3 is an independent predictive factor for disease progression (HR 3.1; p = 0.014), and obtaining CR/VGPR at D + 100 post‐ASCT is an independent protective factor against disease progression (HR 0.2; p = 0.004).

Summary/Conclusion:

Despite the relatively short follow‐up period, in this population of transplant‐eligible MM patients, we have demonstrated that the depth of response after induction chemotherapy (VGPR/CR) is critical for a greater PFS, and that a profound reduction in tumor burden (VGPR/CR) after ASCT allows for prolonged disease control. However, ISS stage 3 is a risk factor for disease progression regardless of the obtained response.
PB2134 THE IMPACT OF COMORBIDITY ON OVERALL SURVIVAL IN MULTIPLE MYELOMA
Authors: Mikhailov E. , Salogub G. , Osipov I. , Melikhova A. , Bessmeltsev S. , Shnalieva N. , Bezrukikh V.
Published: June 2019

Background:

The median age at diagnosis of multiple myeloma (MM) is 66 years. Comorbidity is registered in 40% cases. This can have an impact on overall survival, frequency of complications and duration of hospitalization

Aims:

The aim of this study was to analyze the impact of comorbidity on overall survival in patients with MM.

Methods

The study included 156 patients with newly diagnosed MM. For each patient a comorbidity score was calculated by using Charlson Comorbidity index (CCI), Cumulative Illness Rating Scale (CIRS), Freiburg Comorbidity index (FCI), Kaplan‐Feinstein index (KFI), Satariano Index (SI). The patients with CCI > 2, CIRS > 5, SI > 0, FCI > 1, KFI > 2 score were defined as high risk group, others were considered as the group of standard risk. Primary endpoint was overall survival. The survival analysis including creation of the Kaplan‐Meier survival curves was performed with use of IBM SPSS Statistics 21 The hypothesis was verificated by log‐rank test.

Results:

CIRS, KFI and SI did not show statistically significant difference in all groups. OS was significantly lower in high risk group estimated by CCI (96 vs 65 months, log rank p < 0.05). However, age is also included in calculating of this comorbidity index. Due to median age at diagnosis (more than 60 years) the majority of patients is classified as high risk group CCI based only on age. Karnofsky performance status, glomerular filtration rate <30 ml/min and pulmonary diseases were used for estimation by FCI. OS in high risk group was 43 months in comparison to 86 months in group of standard risk (p < 0.05). 2 patients with FCI = 3 had extremely low OS (less than 2 months).

Summary/Conclusion:

Comorbidity has an impact on OS in patients with MM. According to our analysis, the most valid prognostic instruments turned out to be FCI and CCI. These indices can be used to predict clinical outcomes.

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PB2142 BUSULFAN/CYCLOPHOSPHAMIDE (BU/CY) COMPARED WITH HIGH‐DOSE MELPHALAN (HDMEL) AS CONDITIONING REGIMEN FOR AUTO STEM CELL TRANSPLANTATION OF MULTIPLE MYELOMA
Authors: Fu C. , Zhou S. , Jin S. , Yan L. , Shang J. , Shi X. , Wang J. , Yao Y. , Wu D.
Published: June 2019

Background:

High dose melphalan (HDMEL) represents the standard conditioning regimen before auto stem cell transplantation (ASCT) for multiple myeloma (MM). But melphalan was inconvenient to obtain in mainland China.

Aims:

We compared two groups of MM patients who received HDMEL and busulfan/cyclophosphamide (BU/CY) regiment followed by ASCT.

Methods

105 patients newly diagnosed with MM in our center undergoing ASCT between May 2012 and August 2017 were enrolled. They were divided into two groups according to conditioning regimen (BU/CY vs. HDMEL). In BU/CY group, busulfan [0.6 mg/kg for those with creatinine clearance rate (CCR)≥60 ml/min and 0.5 mg/kg for CCR≥40 ml/min and <60 ml/min] was administered q6 h on days ‐7∼‐5 (7.2 mg/kg and 6.0 mg/kg in total, respectively) and cyclophosphamide (1.8 g/m2 for those CCR≥60 ml/min and 1.5 g/m2 for CCR≥40 ml/min and <60 ml/min) was given once on days ‐4∼‐3. In HDMEL group, melphalan (200 mg/m2) was given one dose on day ‐2.

Results:

At a median follow‐up of 30 months (range 0∼74 months), the average overall survival (OS) and median progression‐free survival (PFS) in BU/CY group were 53.7 months [95% confidence interval (CI) 49.3∼58.1] and 59.0 months (95% CI 48.3∼69.7) respectively, showing no significant difference with that of HDMEL group [average OS: 52.6 month (95% CI 44.5∼60.8) and median PFS: 8.0 months (95% CI 46.9∼69.1) respectively]. No significant difference was found in incidence of pneumonia, fever, mucositis, abnormal liver function, abnormal renal function between BU/CY group and melphalan group. No VOD was observed during the research.

Summary/Conclusion:

BU/CY conditioning regimen for MM before ASCT is not inferior to the HDMEL regimen in the Chinese mainland population. The regimen is effective and the toxicity can be tolerated.
PB2159 CHOLESTEROL LEVELS PROVIDE PROGNOSTIC INFORMATION IN PATIENTS WITH MULTIPLE MYELOMA
Authors: Peipei X.
Published: June 2019

Background:

Hypocholesterolaemia has been reported to be associated with cancer risk and progression.

Aims:

he aim of this retrospective study was to investigate the prognostic value of cholesterol levels in patients with multiple myeloma (MM).

Methods

A total of 153 patients newly diagnosed with MM were retrospectively enrolled. The relationship between cholesterol levels and clinical characteristics was evaluated. The prognostic value of cholesterol levels was explored.

Results:

The levels of low‐density lipoprotein cholesterol (LDL‐c), high‐density lipoprotein cholesterol (HDL‐c) and triglycerides (TC) were significantly lower in MM patients (P < 0.001). What is more, multivariate analyses showed that low TC and LDL‐c levels were independent predictors of a better OS (overall survival; HR = 6.893 and 0.204; CI = 1.135‐41.868 and 0.045‐0.930, P = 0.036 and 0.040) and PFS (progression‐free survival; HR = 7.416 and 0.216; CI = 1.365‐40.290 and 0.047‐0.999, P = 0.020 and 0.049).

Summary/Conclusion:

Serum cholesterol levels in MM patients were low, and TC and LDL‐c levels could be used as prognostic markers for MM patients.
PB2171 THE COMPARISON OF THE RELATIONSHIP BETWEEN POLYNEUROPATHY FREQUENCY AND CLINICAL AND LABORATORY FINDINGS IN MULTIPLE MYELOMA CASES
Authors: Yikilmaz A. Senturk , Akinci S. , Bakanay S. , Dilek I.
Published: June 2019

Background:

Multiple myeloma (MM) patients compose approximately 10% of patients with hematological malignancies. Polyneuropathy (PN) is one of the most important complications related to the disease and treatment.

Aims:

Multiple myeloma (MM) patients compose approximately 10% of patients with hematological malignancies. Polyneuropathy (PN) is one of the most important complications related to the disease and treatment.

Methods

A total of 121 MM cases followed in the Hematology Clinic of Atatürk Training and Research Hospital between 2010‐2018 were included in the study. Electromyography results were evaluated retrospectively and clinical and laboratory findings were compared. Five cases with diabetes mellitus were excluded from the study. Chi‐square method was accepted as statistically significant p <0.05.

Results:

The median age of the patients was 64.5 (min 39 max: 88), and Female/Male ratio was 51/65 (44%/65%). Demographic data of 28 (24.3%) patients with PN and 87 (75.7%) patients without PN were presented in Table 1. Renal function tests were normal in 64 (55.7%) of 87 patients without polyneuropathy (p = 0.005). There were 28 (23%) cases with extramedullary plasmacytoma larger than 1.5 cm which were detected by MR imaging at the time of diagnosis. In cases with extramedullary plasmacytoma, the prevalence of polyneuropathy was higher at the initial diagnosis (p = 0.012).

Summary/Conclusion:

There are publications in the literature showing that PN is associated with perineural and perivascular monoclonal immunoglobulin accumulation in MM. In our cases, there was no correlation between the presence of PN during diagnosis and the immunoglobulin subtype, but it was found to be related to the presence of renal dysfunction and the presence of extramedullary plasmacytoma. And we think that this result is the considerable.

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PB2183 SUPERIORITY OF CYBORD OVER VAD IS MORE EVIDENT IN FIRST THAN IN SECOND LINE TREATMENT OF MULTIPLE MYELOMA
Authors: El Gammal M. , Hassan N. , Fatah M. Abdel
Published: June 2019

Background:

In the era of novel anti‐myeloma agents and monoclonal antibodies (daratumumab) and due to their high cost, earlier low cost regimens (VAD or CyBorD) may be used.

Aims:

to compare outcome of treatment of CyBorD versus VAD regimens in multiple myeloma

Methods

This cohort study included 89 MM patients treated at National Cancer Institute (NCI), Cairo, Egypt from January 2011 to December 2015. All patients were evaluated clinically and laboratory for different responses with either lines of treatment (VAD versus CyBorD), and correlated with different survival parameters; progression free (PFS), disease free (DFS), and overall survival (OS), and clinico‐pathologic factors.

Results:

The median age of patients was 54 years (32‐76), with male predominance (male to female ratio 1.87:1). The most common presenting symptoms were bony pains (44.9%) followed by bony masses (22.5%), fractures (16.9%), pallor (7.9%), neurological symptoms (5.6%) and finally oliguria (2.2%). CyBorD have better overall response rate (≥PR) (p = 0.031), PFS (p = 0.004) and DFS (p= 0.013) as 1st line treatment compared to VAD regimen. Also in previously treated patients CyBorD showed better PFS (p = 0.039) compared to VAD regimen. There was a significant relation between age (p = 0.001& < 0.001) and ASCT (p= 0.001&0.034) with PFS and OS respectively.

Summary/Conclusion:

CyBorD have significant better overall response treatment (≥PR), PFS and DFS in 1st line treatment compared to VAD regimen. While in previously treated patients only PFS benefit for CyBorD over VAD regimen was obtained. Age and ASCT had significant effect on PFS and OS

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PB2188 ANALYSIS OF MINIMAL RESIDUAL DISEASE IN PATIENTS WITH MULTIPLE MYELOMA RECEIVING DARATUMUMAB
Authors: Glazanova T. , Chubukina Z. , Bubnova L. , Karyagina E. , Garifullin A. , Voloshin S. , Bessmeltsev S.
Published: June 2019

Background:

Over the past two decades, with the advent of new drugs, the tactics of treatment of patients with multiple myeloma (MM) has changed significantly; however, the general problem of the effectiveness of MM therapy remains unresolved to date. This disease is characterized by a progressive course and development of resistance to both proteasome inhibitors (bortezomib) and immunomodulatory drugs (lenalidomide), i.e. double refractoriness. Anti‐CD38 monoclonal antibodies are suggested for the treatment of heavily‐pretreated patients, including patients with double refractoriness.

Aims:

To study the dynamics of minimal residual disease (MRD) in patients with MM with double refractoriness receiving daratumumab.

Methods

Seven patients with MM refractory to prior bortezomib and lenalidomide treatment were included in the study from 2017 to 2019. The number of lines of previous therapy was 5 (median = 3). The average age of patients–61 years (48–76 years). Daratumumab was administered to all patients as an intravenous infusion at a dose of 16 mg/kg: weekly at Weeks 1‐8, biweekly at Weeks 9‐24 and from Week 25 till progression. MRD assessment in bone marrow aspirate using multicolor flow cytometry (with a sensitivity of 10−5) was performed every 3 months from the start of treatment. To assess the effectiveness of treatment, generally accepted criteria were used.

Results:

Overall response was 86%. Fifty‐seven % of patients achieved a very good partial response, 29% had a partial response and 14% developed disease progression during therapy. After 3 months of therapy, 6 (86%) patients were MRD‐positive (median 0.072%, range 0.017–0.15%), of these, in 5 patients the monitoring showed a decrease in the number of myeloma cells, while in one patient MRD‐negativity was achieved. One patient (14%) with a very good partial response, after 3 months from the start of therapy, achieved an indicator of MRD‐negativity <0.01% (median ‐ 0.005%), however, after 6 months the MRD status changed to positive.

Summary/Conclusion:

Daratumumab treatment regimen demonstrated a high level of general response. The MRD score reflects the clearance of residual tumor cells and is an important independent prognostic criterion for determining the depth of remission, for stratification by risk groups and disease prognosis.
PB2202 VALIDATION OF THE PRIMERDESIGN® QUANTITATIVE ALLELE SPECIFIC AMPLIFICATION KIT FOR THE DETECTION OF THE JAK2V617F MUTATION
Authors: Vaz D.
Published: June 2019

Background:

Janus Kinase 2 (JAK2) is part of a group of tyrosine kinases which are involved in cellular signalling. A point mutation in codon 617 of the JAK2 gene (JAK2 V617F) causes a ‘gain of function’ effect of this process, stimulating proliferation of the myeloid cell lines, including erythrocytes and platelets, as well as causing myelofibrosis in the bone marrow. Testing for this specific mutation using an allele‐specific PCR kit at our facility (NHLS‐TAD), Pretoria] should provide quick and reliable results to investigate suspected myeloproliferative neoplasms. As part of method comparison, 15 specimens known to be positive for the JAK2V617F mutation and 19 specimens known to be JAK2 negative, as previously assessed using PCR with melting curve analysis at Charlotte Maxeke Johannesburg Academic Hospital, will be analysed using the Primerdesign Quasa test kit on the BioRad CFX 96 platform. Results of the two PCR tests will be compared to evaluate accuracy of the kit.

Aims:

To validate the Primerdesign® quantitative allele specific amplification (Quasa) kit for detection of the JAK2V617F mutation in DNA extracted from whole blood samples.

Methods:

Patients’ samples, previously tested at the National Health Laboratory Service laboratory, Charlotte Maxeke Johannesburg Academic Hospital, will be used. These comprise both whole blood collected in EDTA as well as genomic DNA. 15 specimens known to be positive for the JAK2V617F mutation as well as 19 JAK2 negative specimens will be analysed as part of method comparison. We have chosen a sample size of 34 due to the substantial cost of each kit and we are limited due to financial constraints. The WHO international reference panel for genomic JAK2V617F with proposed percentages of 0, 0.03, 1, 10.8, 29.6, 89.5 and 100% will be used for quantitative analysis of the kit. In addition, we will be analysing a diluted JAK2V617F WHO sample to confirm the manufacturer's claim of an analytical sensitivity of 0.1%. Specimens already analysed will be re‐tested using the Primerdesign® quasa kit on the CFX96 real‐time PCR platform (Bio Rad).

Results:

There is a 95% concordance between the results obtained from the index test (Primerdesign kit) when compared to the test of reference (LightCycler). Precision includes repeatability and reproducibility, both of which were shown in this study. We were able to detect 0.1% mutant DNA in background wild type DNA as claimed by the manufacturer. Therefore the analytical sensitivity was at 0.1%. The ability of the test to not detect the mutation in a known negative sample was at 100% concordance. Therefore analytical specificity was 100%

Summary/Conclusion:

The Primerdesign allele specific kit has the capability of being able to produce qualitative as well as quantitative results based on the manufacturer's instructions. Being able to provide this diagnostic test in our department will decrease turn‐around time and improve patient care.
PB2203 IMPROVEMENT OF THE HEMATOLOGIC TOXICITIES OF RUXOLITINIB IN PATIENTS WITH MPN‐ASSOCIATED MYELOFIBROSIS USING A COMBINATION OF THALIDOMIDE, STANOZOLOL AND PREDNISONE
Authors: Duan M. , zhou D.
Published: June 2019

Background:

Anemia and thrombocytopenia are the most frequently reported adverse events of ruxolitinib in patients with MPN‐associated myelofibrosis (MPN‐MF). Although thalidomide, androgens and prednisone have previously demonstrated improvements in myelofibrosis‐associated anemia, it is unclear whether these drugs are effective in patients taking ruxolitinib.

Aims:

To evaluate the efficacy and tolerability of combination therapy with low dose thalidomide, stanozolol and prednisone (TSP) in patients with IPSS intermediate‐2 or high‐risk myelofibrosis (MF) who received ruxolitinib treatment.

Methods:

Sixty‐five patients with MPN‐MF who took ruxolitinib were enrolled in this retrospective study, of which 46 patients also took TSP while 19 did not take TSP (TSP and non‐TSP groups).

Results:

Within the first 24 weeks, the proportion of patients with anemia and platelet count ≥50 × 109/L were 45.7% and 67.4% in the TSP group as compared to 0% and 10.5% in the non‐TSP group (p < 0.001). The mean hemoglobin level in the non‐TSP group reached the nadir after approximately 12–16 weeks of therapy, but gradually increased in the TSP group.

Summary/Conclusion:

In summary, TSP regime can improve anemia and thrombocytopenia during ruxolitinib treatment in patients with MPN‐MF, and the associated adverse events were manageable.

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PB2232 THE NATURAL ANTICOAGULANTS IN PATIENTS WITH PHILADELPHIA‐NEGATIVE MYELOPROLIFERATIVE NEOPLASMS
Authors: Efremova E. , Korsakova N. , Matvienko O. , Fominykh M. , Silina N. , Golovina O. , Papayan L. , Martynkevich I. , Samorodova A. , Polushkina L. , Voloshin S. , Shuvaev V.
Published: June 2019

Background:

Myeloproliferative neoplasms (MPNs) are characterized by an increased frequency of thrombotic complications. Patients with MPNs show little or no abnormalities in traditional coagulation tests. Chronic inflammation associated with pathological secretion of several inflammatory cytokines leads to activation of endothelial cells and imbalance between coagulation and anticoagulation systems.

Aims:

To estimate the natural anticoagulants activity and activated protein C resistance in MPNs patients.

Methods:

The study included 99 MPNs patients (aged 25 – 86 years, median = 55) and 43 healthy controls (aged 30‐73 years, median = 46). There were 65 female and 34 male in the study group. 75 (76%) patients were JAK2V617F positive, 24 (24%) were JAK2V617F negative. Antithrombin (AT), protein C (PC) activities and free protein S level (PS) estimation was performed by standard techniques. Thrombin generation was assessed by calibrated automated thrombinography (CAT) according to Hemker et al. Measurement was conducted in platelet poor plasma with or without thrombomodulin (TM). Such parameters as endogenous thrombin potential (ETP, nM∗min) and peak thrombin (Peak, nM) were evaluated. ETP and Peak sensitivity for TM were calculated as percent of these parameters decrease after TM adding to assay (S ETP, % and S Peak, % respectively). STATISTICA 6.0 package was used for data analysis. Parameter results were presented as median (Me) with 95% confidence intervals (CI), p<0.05 was considered statistically significant.

Results:

Protein C and protein S activity, Peak and ETP decrease were lower in patients with MPN than controls. Patients with Jak2V617F‐ had a tendency to lower sensitivity for TM in comparison with Jak2V617F+ patients. This fact could have a significant role in thrombotic complication development.

Summary/Conclusion

: Our results showed presence of activated protein C resistance probably caused by anticoagulant protein C system dysfunction. Jak2V617F influence on hemostatic parameters demands further investigations.

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PB2240 EPIDEMIOLOGICAL DATA ON MYELOFIBROSIS IN ALBANIAN POPULATION (1999‐2018)
Authors: Çalliku E. , Perolla A. , Pulluqi P. , Caja T. , Cili A. , Ivanaj A.
Published: June 2019

Background:

Worldwide published epidemiological data on primary and secondary myelofibrosis (MF) are scarce, and multiple sources are needed to assess the disease burden in each country, in our country we have a lack of epidemiological data on MPD and MF.

Aims:

The aim of our study is to evaluate the annual incidence of Myelofibrosis in the Albanian population during the period of time from 1999‐2018.

Methods:

In our study the data were collected from the registries in our Service of Hematology and from the registries in the Department of Statistics, UHC “Mother Teresa” and were analyzed with SPSS 22.0. We have analyzed the data of all patients, age > 18 years, diagnosed with Myelofibrosis and hospitalized in the UHC “Mother Teresa” and in our Service of Hematology from 1999 to 2018.

Results:

During the interval 1999‐2018 in our hospital are diagnosed 108[100%] patients with MF, 54 pts (50%) males, and 54 pts (50%) female. The annual incidence of MF in Albania results around 0,22 new cases / 100,000 habitants per year. The median incidence of MF is about 5,7 new cases per year with a peak in 2013 (13 new cases) and an increase with respectively 10 new cases in 2017 and 15 new cases in 2018.

The median age at the moment of the diagnosis resulted in 62,5 years old (interval range 25‐83 years old)

Almost all the patients were on advanced stages of MF at the moment of the diagnosis (95%).

Actually, 49 patients are on treatment with Ruxolitinib since 2015.

Summary/Conclusion:

A careful study, using standardized definitions of MF and complete assessment of patients including both primary and secondary MFs, should be performed to estimate the population aimed to receive novel era treatments for these neoplasms
PB2278 PRETREATMENT SERUM 25(OH) VITAMIN D AS PREDICTOR OF EVENT‐ FREE SURVIVAL IN LYMPHOID MALIGNANCIES
Authors: Djurasinovic V. , Mihaljevic B. , Vukovic V. , Antic D. , Tomic K. , Otasevic V.
Published: June 2019

Background:

Vitamin D was investigated as a prective factor in lymphoid malignancies recently.

Aims:

Assessment of 25(OH) vitamin D status in lymphoid malignacies before active treatment and its influence on event‐free survival (EFS).

Methods:

Study included 153 patients, median age 58(18‐84) years with diagnose: diffuse large B cell lymphoma‐70, Hodgkin lymphoma‐22, chronic lymphocitic leukemia‐21, follicular lymphoma‐20 and multiple myeloma‐20, who had pretreatment 25(OH) vitamin D level. Comorbidities were assessed by Cumulative comorbidity index (CIRS). Patients were treated with immunochemotherapy and followed for event‐free survival for median 38(2‐53) months.Event was defined as progression or death.

Results:

Pretreatment serum 25(OH) vitamin D was 34,4 ± 13,6 nmol/l, without significant difference between lymphoma subgroups (ANOVA p = 0,069). Multivariate Cox regression for EFS showed 25(OH)D<25nmol/l (HR 2,732, 95%CI 1,37‐5,44), elevated LDH (HR 3,79, 95%CI 1,87‐7,66) and CIRS > 3 (HR 2,88, 95%CI 1,43‐5,78) as significant parameters for EFS.

Summary/Conclusion:

Average pretreatment 25(OH)D level in lymphoid malignancies is low. Severe deficiency, 25(OH)D <25nmol/l, is strong predictor of EFS in analysed group of patients.
PB2287 REFERENCE INTERVALS OF BLOOD COUNT IN HEALTHY FULL‐TERM PREGNANT GREEK WOMEN
Authors: Karantani K. , Petassis G. , Tsioni K. , Issa M. , Tsamis E. , Vagdatli E.
Published: June 2019

Background:

Since blood count reference intervals are generally based on samples collected from non pregnant women, these should not be used for the evaluation of pregnant women.

Aims:

The aim of this study was to determine White Blood Cells (WBC), Neutrophils (NEU) and Lymphocytes (LY) reference ranges in healthy Greek full‐term pregnant women and to evaluate them before and after delivery.

Methods:

Blood samples from 278 healthy pregnant women, before and after labour were collected using EDTA anticoagulated tubes. WBC, NEU and LY were determined in COULTER LH780 analyzer pre and one or two days post partum. 5% of the upper and lower results concerning WBC, NEU and LY were excluded. A normality test was performed using SPSS 21 statistical software and median, minimum and maximum ranges were calculated.

Results:

The WBC, NEU and LY mean, median, maximum and minimum values in healthy prepartum women are showed in Table I. Out of 278 pregnant women, only in 112 (40,3%), there was a statistically significant (p = 0.001) decrease in WBC post partum with a simultaneous fall of NEU in 84,8% of them. Furthermore, there was a post partum NEU decrease, only in 129 (46,4%) out of them, albeit not statistically significant (p = 0.283), whereas there was a LY significant fall (p = 0.004) in 114 (41,64%) of them.

Summary/Conclusion:

WBC and NEU in healthy full term pregnant women prepartum are elevated, while LY are within normal range.40,3% reduce WBC post partum. Nevertheless, in an excessive number women post partum develop elevated WBC due to possible infection.

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PB2358 THE IMPACT OF THE NUMBER OF CD34 + CELLS TRANSPLANTED IN ENGRAFTMENT AFTER AUTOLOGOUS TRANSPLANTATION OF HEMATOPOIETIC PROGENITORS
Authors: Luís D. Andrade , Guedes C. , Roque A. , Esesumaga A. , Borges C. , Geraldes C. , Tomaz J.
Published: June 2019

Background:

Despite the emergence of new therapeutic options, autologous hematopoietic stem‐cell transplantation (AHCT) is still one of the pillars in the treatment of patients with multiple myeloma (MM), especially in younger and fit patients. However, the ideal number of transplanted CD34 + cells to maximize post‐transplant results is still under discussion.

Aims:

Verify the corelation between the number of cell CD34+ infused and the outcomes in neutrophils and platelets recovery and transfusional requirements.

Methods:

Prospective analysis of 243 autologous transplants in patients with multiple myeloma for 10 years from January 2007 to December 2017,in a single institution.

For this study, where analysed: the myeloma subtype, the age of diagnosis, the time from diagnosis to transplantation, the conditioning used, the number of days of hospitalization, number of cells infused, the number of days of engraftment, number of days with neutrophils< 0,5 × 109/L, number of days with platelets< 20 × 109, number of transfused platelets pools, number of transfused red blood cells (RBC).

The statistical treatment of the data was done in SPSS version 24.

Results:

In this sample 217 patients were analysed, of whom 79 were females (36,4%) and 138 were males (64%). The medium age of diagnosis was 54.28 years (27 – 77 years) and of transplantation was 58.42 years (28 – 72 years). The most frequent subtype of MM was IgG kappa(45,7%), IgA kappaand IgG lambda(both with 13,2%). The median time from diagnosis to transplant was 533 days. The conditioning regimen used in the majority of the patients was melphalan 200 (97%), and the mean time of hospitalization was 19 days (12 – 77). The number of cells CD34+infused ranged from 1.40 to 13 × 106cells/kg, with a average of 3.49 cells/kg.

In this study, no correlation was verified between the number of cells CD34+infused and the number of days with neutrophils< 0,5 × 109/Lor with the transfusion need for RBC. The average number of days of engraftment was 13 days (9 – 28), and there is also no correlation between the number of cells CD34+infused. However, there is an inversely proportional and statistically significant correlation (p < 0.01 and p < 0.05, respectively) related to the number of days with platelets< 20 × 109/L as well as to the number of transfused platelets pools.

Summary/Conclusion:

An increased number of transplanted CD34+cells was shown to have a significant impact in time until recovery of the number of platelets, and was associated with lower transfusion dependencepost‐AHCT. The remaining variables evaluated did not show to be dependent on the number of transplanted cells.
PB2363 AUTOLOGOUS STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA: A SINGLE INSTITUTE OUTCOME ANALYSIS
Authors: Keat T. Sui , Soon T. Ching , Sim G. Ai , Keat C. Teng , Kien C. Su
Published: June 2019

Background:

High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is now considerd as standard therapy for young patients (< 65 years) with multiple myeloma (MM).

Aims:

Although myeloma is the 3rd commonest hematological malignancy, only a few centres in Malaysia offer ASCT service for this group of patients. We hereby, share our 9 year's experience in Penang General Hospital.

Methods:

Clinical data of patients with MM who were transplanted in Penang General Hospital between 2008 to 2017 were collected retrospectively and analysed using SPSS IBM version 22.0. The patients were followed up from the time of transplant until 28 February 2018. The variables assesed included demographics, MM subtypes, remission status, induction chemotherapy pre‐transplant and maintenance therapy post‐transplant.

Results:

A total of 41 patients (18 males, 23 females) were evaluated. The median age at transplant was 54 years (ranged 33‐65 years). There were 19 Malays (46.3%), 15 Chinese (36.6%) and 7 Indian patients (17.1%). 73% had IgG Kappa subtype. 41.5% presented with ISS II, 34.1% ISS III and 24.4% ISS I. 61% of patients were transplanted with at least a very good partial response (VGPR) compared with 39% with partial response (PR). Majority of patients (75%) received Bortezomib based induction therapy prior to transplant. 58% patients received maintenance treatment post‐ASCT. The median follow‐up was 35 months (range 3‐103 months). The 5 years overall survival (OS) and progression‐free survival (PFS) was 70% and 44.3% respectively. There was no transplant related mortality. Median PFS of patients with ISS III was only 11 months compared with 53 months for ISS I‐II (p < 0.001). Patients who received maintenance had longer PFS (65 months versus 12 months, p = 0.032). Multivariate analysis revelaed ISS III as an independent risk factor for survival in our cohort (PFS hazard ratio (HR), 4.76;95% CI 1.81 to 12.49;p = 0.002). Other variables evaluated did not affect survival.

Summary/Conclusion:

ASCT improves survival in patients with multiple myeloma and is safe in patients below 65 years. ISS III is an independent risk factor of PFS.
PB2371 CAN NELARABINE RESCUE THE GRAFT AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN T‐ALL ?
Authors: Yuksel M. Kurt , Seval G. Cengiz , Bozdag S. Civriz , Toprak S. K. , Topcuoglu P. , Arslan O. , Muhit O. , Demirer T. , Akan H. , Beksac M. , İlhan O. , Gurman G.
Published: June 2019

Background:

Adult ALL is a rare disease, T‐ALL accounts for nearly %20 of all ALL and T‐ALL is more common in adults than children. The use of pediatric intensive chemotherapy regimens in AYAs and nelarabine for relapsed and refractory diseases has improved outcomes. Still, allogeneic SCT remains an important component of treatment. Nevertheless relapse is inevitable.

Aims:

Aim of this study is to evaluate the effect of nelarabine as salvage therapy after HSCT, in terms of disease control, GVHD, PFS and OS.

Methods:

Between 2014‐2018 Nine (F/M = 1/8; median age = 28 years (21‐45)) patients,from one center are evaluated retrospectively. None of them received nelarabine, before HSCT. Transplantation characteristics are given in table 1. Patients were treated at the time of relapse with nelarabine alone 1.5 g/M2/day on days 1, 3, 5 every 28 days.

Results:

Among the 9 patients 67% achieved hematologic remission during 8.2 months (range; 2.9‐19.2 mos) follow‐up. The features of nelarabine based salvage therapy are shown in table 2. The main toxicity was neurological and involved 22% of patients. At 1 year, disease‐ free and overall survival rates were 66.7% and 50% respectively (Figure 1). Only one patient (11%) received DLI and MRD was lost. On the other hand patients who had MRD (4 (44%)) and received nelarabine had a stable MRD disease those did not transform to overt leukemia.

Summary/Conclusion:

The OS at 1 year for salvage treatment with nelarabine at first and secondary relapse is 28%, which is lower than nelarabin usage after HSCT (50%). There is no data about interaction between immune reconstitution, relapse prevention and nelarabine after HSCT. Nelarabine is a well‐tolerated drug with minimal toxicity and can be considered for maintenance therapy post HSCT in both MRD positive, bulky and CNS disease. Even though it does not show graft versus tumor effect, it can just prevent T‐ALL transform to an aggressive leukemia.

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