bluuebunny/crossref_metadata_2025 huggingface dataset:
PB2044 DIAGNOSIS OF IRON DEFICIENCY ANAEMIA AND PARENTERAL IRON THERAPY: CLINICAL AUDIT IN A DISTRICT GENERAL HOSPITAL
Authors: Lovato S. , Ali H. , Dahotia B. , Bhatkal B.
Published: June 2019

Background:

Iron deficiency anaemia is the most common cause of anaemia. Parenteral iron therapy in the UK has to be administered in hospital settings as it comes with risk of allergic reactions and anaphylaxis. Clear procedures should be established in each hospital to ensure that parenteral iron therapy is prescribed according to the national guidelines ans audited regularly.

Aims:

The aim of this audit was to estabilish if if the diagnosis of iron deficiency was performed according to the guidelines and if patients were adequately monitored after receiving parenteral iron.

Methods:

Pharmacy provided the list of IV iron prescriptions issued in a period of 12 months. A clinical audit was performed to understand if patients had a documented diagnosis of iron deficiency (low haemoglobin, low ferritin or low transferrin saturation according to the local laboratory ranges); if there was a follow up blood test including the same parameters and if patients who were still iron deficient were prescribed further iron.

Results:

A total of 233 prescription for 227 patients were analysed. Of those 99% had a blood test previous to the iron infusion (99% had full blood count, 94% had ferritin level, 63% had transferrin saturation). Only 80% of patients had confirmed iron deficiency, in 2 % of the patients there was no iron deficiency and in 1 patient there were laboratory signs of iron overload, in the remaining 18% iron status was incomplete as transferrin saturation was not performed.

Follow up was missing in 16% of the cases, in 66% of the patients was done between 2 weeks and three monts, in 20% of the cases after that. All the patients had full blood count, only two thirds had ferritin level done and less than a quarter had transferrin level done. Thirty nine patients (17% o) were found to be still iron deficient but only a fifth of them received further iron therapy. Only 10% had normal iron studies, in the remaining cases iron status was not evaluable.

Summary/Conclusion:

Several issues were identified that will require improvement. First of all we found that some of the prescriptions were unnecessary (2%) or controindicated (0.5%). In a fifth of the cases as iron studies were incomplete, was not possible to establish of the therapy given was appropriate. The main problem was lack of follow up or follow up with incomplete iron studies that made impossible to interpret the iron status in tre quarter of the patients, and missed iron therapy in five out of six patient with documented iron deficiency. Resolving these problem, as they are not isolated to a single department, will be a challenge. Solutions should be found to ensure that there are no inappropriate parenteral iron prescriptions and that patients are monitored adequately and given further therapy when required. Establishing an iron deficiency service to monitor patients could be one of these solutions, but it will require major institution re‐organisation.

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PB2058 THE PROGNOSTIC ROLE OF MYOCYTE‐SPECIFIC ENHANCER FACTOR 2 C (MEF2 C) IN PATIENTS WITH DIFFUSE LARGE B‐CELL LYMPHOMAS (DLBCL)
Authors: Anastasiou M. , Tsakiraki Z. , Spathis A. , Bouchla A. , Papageorgiou S. , Panayiotides I. , Pappa V. , Foukas P.
Published: June 2019

Background:

DLBCL is the most common subtype of non‐Hodgkin's lymphomas. However, the pathogenesis of DLBCL is not fully understood. Transcription factors or signaling pathways involved in normal B cell development and function might represent future therapeutic targets. Such a transcription factor is MEF2 C contributing to B cell activation and germinal center formation.

Aims:

This study aims at investigating the role of MEF2 C as prognostic biomarker in DLBCL.

Methods

82 patients with DLBCL were enrolled in our study. We assessed the expression of MEF2 C by performing immunohistochemistry (IHC) on paraffin slides of 62 tissue blocks and results were evaluated by using the H‐score semiquantitative approach, with a range from 0 to 300. Additionally, we analyzed clinical [sex, age, stage of DLBCL, performance status, extranodal sites, B symptoms, International Prognostic Index (IPI), age‐adjusted IPI, revised‐IPI, National Comprehensive Cancer Network (NCCN)‐IPI], laboratory [lactate dehydrogenase (LDH), hemoglobin (Hb), white blood cells (WBC), neutrophils, lymphocytes, monocytes, platelets and beta‐2‐microglobulin] and pathologic characteristics (CD10, BCL6, MUM‐1, Ki‐67) of patients in relation to overall (OS) and disease free survival (DFS).

Results:

Mean and median value of MEF2 C H‐score was 120 ± 58. We observed a statistical significant correlation with age (p= 0.021) and a tendency to correlate with LDH (p = 0.18). The expression of MEF2 C was not associated with other clinical or laboratory values. MEF2 C positivity >80% was correlated with borderline inferior OS (p = 0.083). Among patients, who survived more than 12 months after initial diagnosis, those with MEF2 C H score <120 had a significant better OS comparing with those with MEF2 C H score >120 (p = 0.009).

Summary/Conclusion:

High IHC expression of MEF2 C showed a negative prognostic influence in patients with OS more than 12 months after initial diagnosis. However, these results should be confirmed in larger groups of DLBCL patients and the underlying oncogenic mechanism of MEF2 C in DLBCL should be further explored.
PB2068 THE CASTLEMAN DISEASE: HISTOLOGICAL VARIANTS, POEMS‐SYNDROME AND PRODUCTIVE PLASMA CELL VASCULITIS
Authors: Mihailov A. , Bessmeltsev S. , Rugal V. , Semenova N. , Khmelnitskaya N.
Published: June 2019

Background:

The Castleman disease (CD) is a rare, little‐studied disease characterized by lymphadenopathy with follicles hyperplasia and active neoangiogenesis. Occurs in the form of two histological variants: plasma cell and hyaline‐vascular. The total vasculitis in the vessels of internal organs, previously not noted by researchers, was revealed in the analysis of 2 sectional cases of CD.

Aims:

To study the state of microcirculatory vessels in patients with plasma cell and hyaline‐vascular type of CD in sections of biopsied lymph nodes.

Methods

Sections of biopsied lymph nodes were used. It was used hematoxylin‐eosin and reaction to antibodies to CD138 to identify plasma cells. In all patients with plasma cell variant cells were painted with antibodies to HSV‐8. Vessels estimated in perinodular tissue of capsule and fat. We examined 15 patients with CD. According to histology and CD138 content, the plasma cell variant was diagnosed in 8 patients, 7 men and 1 woman aged from 40 to 70 years. In 5 patients approved POEMS syndrome by the presence of M‐protein, disorders of neuro‐muscular conduction according to the electro‐neuromyography, and other symptoms. In 7 patients was diagnosed hyaline vascular type of CD, including 5 women and 2 men aged from 30 to 60 years.

Results:

In 1 patient with plasma cell variant of CD revealed HSV8 reaction with intranuclear staining antibodies. Vasculitis in the form of vascular walls thickening of the microcirculatory bloodstream with a decrease or obliteration of their lumen, wall fibrosis and plasma cell infiltration was found in all 15 patients. The most pronounced changes in the form of fibrosis, complete vascular obliteration and massive perivascular infiltration CD138+ cells by type of massive colonies of hundreds of cells were found in patients with the POEMS‐ syndrome. They also noted the location of single CD138 + cells inside the intima of the sclerosal vessels. Fibroplastic vascular changes in patients with POEMS‐syndrome were weirdly shaped in the form of “mood masks”. It coincided with massive osteosclerotic changes of the vertebrae on radiographs. Massive development of fibrosis corresponds to the POEMS pathogenesis. All patients with its presence later died.

Summary/Conclusion:

The Castleman disease, regardless of the histological variant, includes in its morphological pattern productive plasma cell vasculitis, most pronounced in the plasma‐cell variant with POEMS‐ syndrome.
PB2102 A SAME DAY ASSAY USING CYTOCHROME C RELEASE DETERMINES SENSITIVITY TO COOPERATIVE BCL‐2 AND MCL‐1 TARGETING IN MULTIPLE MYELOMA CELL LINES AND PRIMARY SAMPLES
Authors: Grundy M. , Cull J. , Al‐Kaisi F. , Williams C. , Smith D. , Seedhouse C.
Published: June 2019

Background:

Multiple myeloma is an incurable haematological malignancy with remarkable clonal and genetic heterogeneity. Although both MCL‐1 and BCL‐2 are necessary for myeloma survival, most myelomas are dependent on MCL‐1 for survival such that BCL‐2 inhibition alone only yields significant cytotoxicty in a minority and cooperative inhibition of both proteins is required. Knowing which patients will respond can be challenging since cytotoxicty assessment of primary patient samples is significantly hampered by the lack of longevity of those cells in culture ex vivo.

Aims:

We aimed to study whether a short term flow cytometric assay could be used to determine cytotoxicity in myeloma cell lines and primary samples after cooperative inhibition of BCL‐2 and MCL‐1 by the BH3 mimetics (venetoclax and S63845).

Methods

Myeloma cell lines and patient samples were treated with venetoclax and S63845 alone and in combinations. Sub‐toxic doses of drugs were determined for each cell line. Samples were fixed after 4 hours drug incubation thus precluding the need to keep those cells alive in culture for prolonged periods and then assayed for cytochrome c release using flow cytometry. The Bliss independence model was used to demonstrate synergy.

Results:

The cytochrome C release assay demonstrated that the combination of venetoclax and S63845 was synergistic as compared to controls and single agent treatment in all six cell lines tested (Combination index values 7.8‐80). All three cyclin D2 translocated cell lines were particularly sensitive to the combination and synergy was p53 independent. Furthermore, the same day assay was used on CD138‐selected primary myeloma cells also demonstrating effective cooperative targeting in patient samples.

Summary/Conclusion:

The attractiveness in this assay lies in its ability as a predictor of apoptotic response to chemotherapy and molecular targeting agents providing rapid results. Here, we have demonstrated for the first time in myeloma that using the cytochrome C release assay we can quickly predict apoptosis in cell lines. Importantly we are now demonstrating that this assay can also be used in primary samples. This can set the steps for an individualised assay to determine patient responses to targeted molecular therapies.
PB2145 POMALIDOMIDE AND DEXAMETHASONE IN RELAPSING POEMS SYNDROME: A FRENCH REPORT OF 5 CASES
Authors: Golfier C. , Chaubard S. , Sciortino D. , Salles G. , Viel S. , Garnier L. , Lazareth A. , Karlin L. , Jaccard A.
Published: June 2019

Background:

Significant improvements have been made in the management of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammapathy and skin changes) syndrome, but patients (pts) still experience relapses or refractoriness. Immunomodulatory drugs are effective agents in the treatment of plasma cells dyscrasias. Lenalidomide has shown interesting activity in POEMS syndrome, but no data on pomalidomide have been published so far.

Aims:

We report the use of pomalidomide and dexamethasone in five patients with relapsing POEMS syndrome after lenalidomide regimen.

Methods

Demographics: 5 patients (3 men), median age 74 years old (range, 67–77), median of 2,6 previous lines received (range, 2–4). All patients had received lenalidomide as previous therapy.

Results:

Hematological overall response rate (ORR) was 3/5 (60%): all 3‐responding patients experienced complete response (CR) according to local evaluation based on IMWG criteria, leading to clinical improvement of neuropathy in all of them, endocrinopathy and peripheral edema (2 of 2 pts). Other clinical responses concerned resolution of papilledema (2 of 2 pts) and improvement of pulmonary hypertension (1 of 1 pt). Noteworthy, serum Vascular Endothelial Growth Factor (sVEGF) level normalized after only one cycle of treatment in those 3‐responding patients (figure 1). No emergent toxicity was observed. As expected, adverse events were mainly hematological but of mild intensity and easily manageable. At this time, the 3‐responding patients are alive, including 2 without relapse after 11 months of follow‐up for both of them. The 2 other patients died, one of them from rapidly progressing disease, the other from heart disease not related to POEMS.

Summary/Conclusion:

In conclusion, pomalidomide and dexamethasone appears to be a safe and effective option in relapsing POEMS syndrome after lenalidomide regimen, demonstrating rapid and durable responses.

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PB2151 HEPATITIS B VIRUS INFECTION MIGHT CONTRIBUTE TO MULTIPLE MYELOMA PROGRESSION THROUGH 1Q21 AMPLIFICATION
Authors: Peipei X.
Published: June 2019

Background:

Hepatitis B virus (HBV) is not only a hepatotropic virus but also a lymphotropic virus. The association between HBV and hematologic malignancies has also been described, but the correlation between HBV infection and multiple myeloma (MM) has remained controversial.

Aims:

This study aimed to assess the prevalence of HBV infection in patients with MM and investigate their characteristics and prognostic significance.

Methods

The clinical data of 165 patients with MM receiving at least four cycles of chemotherapy from April 2008 to February 2017 in Nanjing Drum Tower Hospital were collected. HBV markers were determined by an enzyme‐linked immunosorbent assay.

Results:

The rates of an acute or chronic HBV infection and resolved HBV infection in patients with MM were 12.12% and 26.06%, respectively. The gain of 1q21 was statistically significant in HBV‐positive and HBV‐negative patients (54% vs. 38.2%, P = 0.048), and the level of alanine transaminase (ALT) in HBV‐infected patients was significantly higher than that of the non‐infected group (63.29 vs. 24.66 U/L, P = 0.043). Lactate dehydrogenase, serum creatinine, and serum calcium levels were found as significant risk factors of overall survival. The progression‐free survival (PFS) of HBV‐positive patients was shorter than that of HBV‐negative patients (18.97 vs. 29.67 months P = 0.006), and HBV positive was considered an independent prognostic factor of PFS.

Summary/Conclusion:

HBV infection might contribute to MM progression through 1q21 amplification, and HBV markers should be closely monitored in patients with MM.
PB2154 TIME TO FIRST PLATEAU AS A PROGNOSTIC PREDICTOR IN MULTIPLE MYELOMA
Authors: Kirkizlar O. , Umit E. , Baysal M. , Bas V. , Gulsaran S. , Demirci U. , Demir A. M.
Published: June 2019

Background:

As novel treatments emerge, prognostic assessment has become the backbone of patients with multiple myeloma (MM). Depth and duration of response have been associated with survival and recently, evaluation residual disease status has been related with both progression free and overall survival.

Aims:

We aimed investigated the relation with time to plateau, which has been proposed by MayoClinic with survival in our patient group.

Methods

Data of 105 patients with MM, diagnosed and treated at our clinic between 2015 and 2018 were enrolled in a retrospective manner. All patients received bortezomib‐cyclophosphamide and dexametazone as first line therapy. Time to plateau was defined as best response date to the first line therapy.

Results:

Mean age was 65,86 years (28‐93). 49 patients were female (46,7%) while 56 were male (53,3). 29 patients had IgA disease while 74 were Ig G and 2 were light chain MM. 68 patients had International Scoring System (ISS) III disease (64,8%) while 27 had ISS II (25,7%) and 10 had ISS I disease (9,5%). Mean time to plateau was 6,74 months (4‐15) while mean overall survival was 44,87 months (8‐145). As all patients who were physically fit and <70 years of age have moved to autologous stem cell transplantation, we could not evaluate a duration of initial response.

Patients who required less than 6 months (65 patients) to reach a plateau status had a mean survival of 47,51 months while patients requiring 6‐12 months had 41.23 months and patients who needed more than 12 months had a mean survival of 36 months.

Summary/Conclusion:

Despite the observation of MayoClinic, we did not observe a relation with slow responders and prolonged survival. On the contrary, we observed that patients who respond to first line therapy had a longer survival, probably related with more chemosensitive disease.
PB2174 EPIDEMIOLOGY OF MULTIPLE MYELOMA (MM) IN MOSCOW (RUSSIA)
Authors: Ptushkin V. , Vinogradova O. , Chernikov M. , Kochkareva Y. , Zherebtsova V. , Kobzev Y. , Markova E. , Shikhbabaeva D.
Published: June 2019

Background:

The incidence of MM varies greatly between countries, but since 1990 it has increased steadily. Despite improvements in the care of patients with MM, these advances have largely delivered better outcomes to patients in high‐income countries. Moscow is a big city (12.6 million inhabitants in 2018) with relatively identical protocols for the diagnosis, staging and treatment of MM.

Aims:

To evaluate the incidence and mortality of MM depending on age, gender and year of observation in Moscow in 2009–2019.

Methods

Data of 3,942 MM patients (pts) who reside in Moscow and were treated at Moscow City Hematology Center (Botkin Hospital) have been studied. It was collected from out‐ and in‐patient clinical records and state registries. The period from 2009 through 2019 was analyzed. The median follow up of patients since the diagnosis of MM was 34 (1 ‐ 423) months.

Results:

Among the registered 3,942 patients with MM, 1,707 were men (43%) and 2,241 women (57%). The median age at diagnosis was 65 (23–93) years. For men, it was 63 (23–93), for women ‐ 66 (29–92) years. Most of the patients were older than 65 ‐ 2047 (51.9%). Over the 10‐year period, the median age at diagnosis has increased by 3 years ‐ from 64 to 67 years.

The average annual MM incidence recorded for 10 years increased by 60.52% ‐ from 1.9 to 3.05 per 100,000 population. However, such increase in the incidence was observed only for a cohort of patients older than 50 years, achieving a peak in the age range of 60 ‐ 69 years. Prevalence rate (PR) of MM has grown from 8.0 per 100,000 population in 2009 to 15.2 in 2018, mostly due to improved therapy outcomes. 2‐year overall survival was 76%, 5‐year ‐ 49%, and 10‐year ‐27%. Median overall survival of pts younger than 65 years of age at diagnosis was 79 months, 65 and older–48 months.

Summary/Conclusion:

Significant changes in MM epidemiology in the City of Moscow were observed. In the last 10 years, the incidence has increased mostly due to the increase of life expectancy, whereas improved MM diagnostics and treatment resulted in substantial increase in OS. In turn, this have caused MM PR increase, and this trend will most likely continue in the future.
PB2234 MUTATIONAL SIGNATURES AFFECT THE PHENOTYPIC PRESENTATION OF DISEASE SUBTYPES IN MPN PATIENTS FROM BOSNIA AND HERZEGOVINA
Authors: Islamagic E. , Kurtovic S. , Komic H. , Dizdarevic‐Rekic A. , Burekovic A. , Uzunovic A. , Kurtovic‐Kozaric A.
Published: June 2019

Background: Philadelphia‐negative myeloproliferative neoplasms (MPNs), including PV, ET, PMF, and MPN‐U are a group of clonal myeloid disorders characterized by myeloproliferation without dysplasia. WHO 2016 revision lists the presence of driver mutations as one of several major criteria in the diagnosis of MPN patients. MPN subtypes have overlapping clinical symptoms and a common molecular basis.

Aims:

The aim of this study was to evaluate disease phenotypes and evolution in regards to the detected JAK2, CALR and MPL mutations in the population of MPN patients in Bosnia and Herzegovina. Also, we compared hematologic and clinical features of ET patients carrying either JAK2 or CALR mutations with JAK2 positive PV patients in order to determine the correlation of clinical features and disease evolution.

Methods:

A cohort of 138 patients diagnosed with MPN and treated at Clinical Center of the University of Sarajevo and Cantonal Hospital Zenica, in the period from January 2000 to June 2018 were included in this retrospective study. Analyzed patients were subcategorized according to BCR‐ABL negative MPN subtypes: ET (n = 41), PV (n = 56), PMF (n = 10), and MPN‐U (n = 31). Patients characteristics included full blood count, bone marrow characteristics, hepato/splenomegaly, overall survival as well as mutational status of JAK2, CALR, and MPL genes. Comparisons of quantitative variables between groups of patients were carried out by one‐way ANOVA. Correlation between numerical variables was tested by the Spearman's coefficient. Survival probabilities were estimated with the Kaplan‐Meier method and compared using the log‐rank test. Data were analyzed using IBM SPSS v.21.

Results:

In the present work, we compared hematologic and clinical features of patients with JAK2‐mutated ET with those of patients with CALR‐mutated ET and related the findings to features observed in patients with PV. Median follow‐up was 33 months (50, 45.5, 69 and 20 months for PV, ET, PMF and MPN‐U subtypes, respectively). We found that JAK2
V617F+ patients had higher values for RBC, Hb and Hct compared to CALR+ patients (p<0.05). MPL+ patients had higher values for Plt compared to JAK2
V617F+ patients (p<0.05). The mutant allele burden in JAK2
V617F+ PV and ET patients was directly correlated with hematological parameters (ρ = 0.36, ρ = 0.14, and ρ = 0.21 for Hb, RBC, and Hct, respectively) and inversely correlated with Plt count (ρ = −0.12). JAK2
V617F+ patients had worse survival compared to CALR+ and MPL+ patients, eventhough significant differences were not found (p > 0.05).

Summary/Conclusion:

Mutant allele burden is a determinant of the clinical phenotypic features in JAK2
V617F MPN patients. Mutational profile define clinical course and outcomes in MPN subtypes.
PB2293 PEGFILGRASTIM VERSUS FILGRASTIM IN THE MANAGEMENT OF THERAPY‐RELATED NEUTROPENIA IN RELAPSED AND REFRACTORY MULTIPLE MYELOMA IN TREATMENT WITH POMALIDOMIDE‐DEXAMETHASONE
Authors: Cerchione C. , Martinelli G. , Nappi D. , Pareto A. E. , Pane F. , Catalano L.
Published: June 2019

Background:

Pegfilgrastim is a pegylated long‐acting recombinant form of G‐CSF that extends the half‐life and allows for once‐per‐cycle dosing, requiring less frequent dosing than nonpegylated G‐CSF.

Aims:

The objective of this study was to compare the efficacy and safety of pegfilgrastim in patients affected by heavily pretreated MM, treated with pomalidomide‐dexamethasone, in order to determine whether a single subcutaneous injection of pegfilgrastim is as effective as daily injections of standard filgrastim, in terms of haematological toxicity, febrile neutropenic episodes, antibiotic usage and hospedalization duration.

Methods:

We enrolled 33 patients (19 male and 14 female) median age at diagnosis 69 years (r. 52‐84), and median age at start of treatment 76 years (r.56‐90) treated with several lines of treatments (median 7, r. 2‐11), every refractory to all the drugs previously received, received Pomalidomide‐Dexamethasone (Pomalidomide 4 mg for 21 days, Dexamethasone 40 mg days 1,8,15,22, pegfilgrastim day +8) every 28 days, until progression.

Results:

Since first course, received in domestic setting, with a very good compliance, patients performed blood counts once weekly and received, from day +8 to day +19 (“day + 1” when the protocol starts), prophylactic oral chinolonic antibiotics and anti‐fungal drugs. During neutropenia after first cycle, Filgrastim (5 μgr/kg/day for 3 days) was given if neutrophils count was <1500 × 10^9 cells/L. Median number of filgrastim administrations was 4.8 (r. 3‐6); nadir neutropenia was registered after a median of 10.7 days (r. 7‐14); median of nadir neutrophil count was 1.17 × 10^9 cells/L (range 0.3 – 1.5 × 10^9 cells/L), with maximum duration of 14 days. From the second course, all patients switched to prophylaxis with pegfilgrastim (6 mg), injected subcutaneously with a single administration on day +3 independently from the neutrophil count at that time. During pegfilgrastim, neutropenia was never longer than 8 days, with a consequent reduction of neutropenia‐related infections. Median nadir neutrophil count, evaluated for every patients for at least three courses of therapy (r. 3‐6) registered at day +11, was 1.39 (range 0.9‐2.2 × 10^9 cells/L). Only 4 patients needed a supplement of 3 administrations of filgrastim. Pegfilgrastim was well tolerated in all patients: main side effects in our patients were mild fever and bone pain (21.2%).

Summary/Conclusion:

In conclusions, in patients affected by heavily pretreated MM treated with pomalidomide‐dexamethasone, pegfilgrastim seems to reduce the incidence of severe neutropenia and infections and may increase the possibility to maintain the scheduled time of treatment.
PB2296 SURVEILLANCE BREAST SCREENING PROGRAMS FOR PATIENTS WHO UNDERWENT CHEST RADIATION THERAPY (LYMPHOMA SURVIVORS)
Authors: Moschetta M. , Telegrafo M. , Troiano N. , Perrone T. , Bambace S. , Piombino M. , Specchia G. , Gaudio F.
Published: June 2019

Background:

Women who underwent chest radiation therapy (CRT) during pediatric/young‐adult age have an increased breast cancer (BC) risk. The cumulative BC incidence in women who underwent CRT is 13‐20%, higher than the incidence observed in the young female general population. BC is diagnosed on average about 15 years after CRT at about 40 years of age, compared with about 61 years in the non‐exposed female general population.

Aims:

From January 2018 to December 2018, a group of consecutive 46 patients (45 females, 1 male), aged between 23 and 62 (mean 44), who underwent CRT at least in the previous 8 years, underwent breast clinical, ultrasound (US) and mammographic examinations.

Methods:

Breast density at US was evaluated according to the BIRADS lexicon (homogeneous‐fat; homogeneous‐fibroglandular; heterogeneous) and compared with a control group of healthy patients (n = 46) with similar demographic features. Any statistical significant difference was searched by t‐student test for unpaired samples. The incidence of breast cancer in the examined series was assessed.

Results:

Among the examined series, 10/46 (22%) patients with homogeneous, 20/46 (43%) with fibroglandular and 16/46 (35%) with heterogeneous density were found. In the control group, 8/46 (17%) patients with homogeneous, 21/46 (46%) with fibroglandular and 17/46 (37%) with heterogeneous density were found. No significant difference occurred among the two groups of patients (p > 0.05). 4/46 (3 females, 1 male) patients were affected by breast cancer (invasive ductal carcinoma, n = 3; ductal carcinoma in situ, n = 1) with a 9% incidence.

Summary/Conclusion:

A surveillance breast imaging protocol should be strongly recommended to patients with a previous CRT. Breast cancer incidence seems to be higher compared with general population. No significant effect on US breast density seems to exist in CRT patients. Future research should be directed at examining the underlying cancer biology and etiology of treatment induced cancers, as well as inherent and treatment‐induced genetic susceptibility of HL survivors.
PB2303 SPECTRAL‐DOMAIN OPTICAL COHERENCE TOMOGRAPHY IN ASYMPTOMATIC CHILDHOOD SICKLE CELL PATIENTS
Authors: Yilmaz K. , Öncül H. , Uzel H. , Öncel K. , Soker M. , Soker S. , Yilmaz E. D.
Published: June 2019

Background:

Sickle cell disease results in localized ischemia and sometimes infarction of local tissues in the area of vascular sickling of erythrocytes.This process can result in a variety of ocular abnormalities; all structures can be affected, ranging from orbital tissues to the retina. Macular thinning has been described in patients with sickle cell disease.

Aims:

The aim of this study was to investigate the effect of asymptomatic childhood sickle cell anemia on choroidal, macular and retinal nerve fiber layer thickness (RNFL) by spectral‐domain optical coherence tomography(SD‐OCT).

Methods:

Twenty sickle cell patients (40 eyes) without ocular diseases and 30 healthy control patients (60 eyes) underwent SD‐OCT. We used SD‐OCT to take all measurements of ocular thickness, as well as measured intraocular pressure, axial length, and central corneal thickness. We later analyzed correlations of hemoglobin S levels and number of crises with ocular parameters.

Results:

A statistically significant difference emerged between patients with sickle cell anemia and the healthy controls in terms of mean values of subfoveal and temporal choroidal thickness (p = 0.004 and p = 0.042, respectively). There was no statistically significant difference between the two groups in central and paracentral macular thickness. In addition, there was no statistically significant difference between the two groups in the thickness of the retinal nerve fiber layer.There was no statistically significant difference correlation analyses between the hemoglobin S level and the study parameters. Correlation analysis of the number of crisis and working parameters revealed a negative correlation with subfoveal choroidal thickness and superonasal quadrant RNFL thickness (p = 0.036 and p = 0.002, respectively)

Summary/Conclusion:

Manual segmentation of SD‐OCT images revealed quantitative and qualitative changes in asymptomatic sickle cell patients.Further studies are required in a larger number of patients to detect a possible association between the retinal thinning seen on SD‐OCT images and peripheral retina ischemia.
PB2307 SICKLE CELL DISEASE PATIENTS HAVE NORMAL NEUTROPHIL OXIDATIVE BURST RESPONSE
Authors: El‐Samahi M. , Makkeyah S. , Hamza M. , Abouelnour A.
Published: June 2019

Background:

Bacterial infections are a frequent cause of acute morbidity and sometimes mortality in sickle cell disease (SCD). Splenic dysfunction alone does not explain the susceptibility to specific organisms e.g., Staphylococcus aureus and Klebsiella as shown in some studies; suggesting that the splenic dysfunction is not the only explanation and that neutrophil dysfunction may be present. Neutrophils destroy microbes by producing a burst of reactive oxygen species (ROS) (respiratory burst) in response to bacterial components, as well as to phorbol‐myristate‐acetate (PMA). Some studies have shown that the state of chronic hemolysis in SCD impairs the ability to develop neutrophils to mount a bactericidal oxidative burst, and hence increasing susceptibility to bacterial infections.

Aims:

to assess the neutrophil oxidative burst in SCD patients and explore the relation to markers of hemolysis.

Methods:

Twenty‐seven hydroxyurea naïve children and adolescents with SCD (mean age 11.1 ± 3.9 years) were enrolled from Pediatric Hematology Clinic at Ain Shams University Children's Hospital. They were compared to 26 age‐ and sex‐matched healthy controls. Patients were studied stressing on transfusion history, chelation therapy, serum ferritin, hematological profile, markers of hemolysis and serum haptoglobin. Neutrophil oxidative burst assay was performed using DHR based flow cytometry.

Results:

Eleven (40%) out of the 27 patients had HBSS while 16 (60%) patients were sickle thalassemias. Six patients (22.2%) were splenectomized. Severe vaso‐occlusive crisis and acute chest syndrome were found in 22.2% and 18.5% of patients, respectively. Four (14.8%) patients had evidence of stroke. Bone fractures and avascular necrosis were found in 5.5% and 11.1 % of patients, respectively. Most of the studied patients were on chelation therapy, either as monotherapy or combined chelation (37% each). White blood cell count and reticulocytic count were significantly higher in SCD patients as compared to healthy controls (P = 0.03 and <0.01 respectively). All subjects, whether SCD or controls showed a normal neutrophil oxidative burst response to PMA‐stimulation. Unstimulated and PMA stimulated rhodamine fluorescence were comparable in SCD patients and controls, indicating normal basal production of reactive oxygen species, and normal oxidative burst in SCD patients (P = 0.09). We did not demonstrate any correlation between markers of hemolysis including reticulocytic count, indirect bilirubin, LDH, serum haptoglobin and DHR response in the SCD group.

Summary/Conclusion:

Neutrophils in SCD patients can mount a normal oxidative burst in response to PMA stimulation. This data excludes the role of impaired neutrophil oxidative burst as a risk for bacterial infections in SCD.
PB2309 INCIDENCE OF ALLOIMMUNIZATION IN SICKLE CELL DISEASE: EXPERIENCE OF A CENTER IN LISBON
Authors: Dutra R. , Araújo E. , Dias M. , Marco J.
Published: June 2019

Background:

Nowadays, red blood cell (RBC) transfusion is an indispensable option for the treatment and prevention of chronic complications of sickle cell disease (SCD). In SCD patients it has been reported at a rate of 18–76% of alloimmunization after transfusion. It has also been suggested, that transfusion is related to the formation of RBC autoantibodies, especially in patients with hemoglobinopathies. Interestingly, some authors correlate higher susceptibility to allo and autoimmunization in patients without the spleen. That could be one of the explanations why SCD patients have a higher incidence of RBC immunization.

Aims:

To determinate the rate of alloimmunization among the transfused SCD patients residing in Lisbon. The other objectives were to clarify among the same study population the incidence of positive direct antiglobulin (DAT) test and spleen absence and correlate both with alloimmunization.

Methods:

The subjects for the study were selected from the adult patients (≥18 years of age) of a tertiary hospital in Lisbon, between 01‐01‐2017 and 20‐02‐2018, that were transfused at least one time and monitored for the presence of irregular antibodies. A total of 61 patients met the inclusion criteria. Most of the routine immunohematological tests, i.e. blood group typing, indirect antiglobulin test (IAT) and DAT, were done using a microtube gel technique. Moreover, clinical assessment of the spleen status (absence or presence) were obtained from imagiological data.

Results:

In our study, we obtained a rate of alloimmunization of 21,3% (N = 13). 40% of the transfused SCD (N = 22) have in DAT positive and 50% of those/these have alloantibodies. We found in our population a significant association between positive DAT with alloimmunization (p < 0.001). In 58 patients we succeed in obtaining their spleen status and among those without a spleen (N = 36) 25% became alloimmunized.

Summary/Conclusion:

In our study, the risk of alloimmunization was higher in patients who received more than 20 red blood cell units. Our alloimmunization rate is in agreement with the literature as well as the significant association of DAT with alloimmunization. Interestingly, 50% of those patients with DAT positive also have alloantibodies, supporting the idea that those patients develop autoantibodies due to transfusion therapy. This fact advocates some plausibility in screening for autoantibodies at regular intervals prior to each transfusion. There was no significant correlation between the presence or absence of a spleen and alloimmunization (p = 0.7475). In conclusion, this study is one of the few to approach the rate of alloimmunization in SCD patients. Therefore, it is necessary to have further studies in Portugal in order to study and to understand our heterogeneous SCD population.
PB2320 PHASE II STUDY OF IMATINIB MESYLATE PLUS MYCOPHENOLATE MOFETIL FOR PEDIATRIC STEROID‐REFRACTORY SCLEROTIC/FIBROTIC TYPE CHRONIC GRAFT‐VERSUS‐HOST DISEASE
Authors: Kang H. J. , Choi J. Y. , Kim H. , Baek H. J. , Kook H. , Lee J. M. , An H. Y. , Hong K. T. , Shin H. Y.
Published: June 2019

Background:

Chronic graft‐versus‐host disease (cGVHD) is the most common late complication following allogeneic stem cell transplantation. Sclerotic/fibrotic cGVHD is one of the severe type, and often refractory to standard and secondary therapy.

Aims:

In this study, we evaluated the efficacy and safety of imatinib mesylate and mycophenolate mofetil (MMF).

Methods:

In non‐randomized, open‐label, single‐arm, multi‐center, prospective phase II study, we enrolled patients with steroid‐refractory sclerotic/fibrotic type cGVHD. Participants were treated with MMF at a dose of 15‐20 mg/kg (maximum 1 g) bid and imatinib mesylate at the initial dose of 260 mg/m2/day (maximum 400 mg) in combination with previous cGVHD treatment. The primary endpoints was overall (complete and partial) response rate at 1 year. Secondary endpoints included safety, quality of life, discontinuation of steroid and overall survival (OS) rate.

Results:

A total of 13 patients were enrolled between October 2013 and July 2017. The median age was 10.4 years (range 5.0‐20.1 years). Five of the 13 patients had previously experienced acute GVHD. The diagnoses were acute lymphoblastic leukemia in 5, acute myeloid leukemia in 3, chronic granulomatous disease in 3, neuroblastoma in 1 and hemophagocytic lymphohistiocytosis in 1 patient. Nine of the 13 patients achieved partial response (PR), 2 showed stable diseases (SD), and 1 died of pulmonary infection and progression of chronic lung GVHD. The remaining 1 patient died of primary disease progression. The overall response rate was 69.2 %. Nine of the 13 patients were able to reduce or discontinue steroids. Among 13 patients, 6 patients showed improvements in Lee cGVHD symptom scale score to assess quality of life. Common adverse events included grade 1‐2 liver enzyme, creatinine elevations and fever. The 2‐ and 5‐year OS rate was 76.9% and 67.3%, respectively.

Summary/Conclusion:

Although limited by a small sample size, Gleevec plus MMF for cGVHD showed promising results with acceptable toxicity.
PB2329 THE IMPACT OF VITAMIN D LEVELS ON PERIPHERAL STEM CELL MOBILIZATION IN ALLOGENEIC HEMATOPOIETIC STEM CELL DONORS
Authors: Hocaoğlu E. , Yegin Z. A. , Can F. , Özkurt Z. N. , Yağcı M.
Published: June 2019

Background:

Vitamin D is a steroid hormone which has an essential role in many physiological conditions including bone metabolism, immune regulation and hematopoiesis. Vitamin D was indicated to have a favourable impact on hematopoietic stem cell (HSC) production in in‐vitro studies. Additionally, animal experiments designated a potential for vitamin D receptor in HSC mobilization. Despite these advances, the possible role of vitamin D in peripheral HSC mobilization remains to be defined.

Aims:

The aim of this study was to evaluate the impact of pre‐mobilization serum vitamin D levels on peripheral HSC mobilization in allogeneic donors.

Methods:

We investigated the impact of pre‐mobilization serum vitamin D levels of 112 allogeneic donors [median age: 39(18‐69) years; male/female: 62/50] on peripheral HSC mobilization. All donors had received granulocyte colony stimulating factor (G‐CSF) at a dose of 10 mcg/kg/day for 4 days. First HSC apheresis was performed on the fourth day of G‐CSF. Serum 25‐hydroxy vitamin D levels were measured with immunoassay method before G‐CSF administration.

Results:

Median vitamin D level was found to be 15.8(3‐63.2) μg/L in the study population. On the first apheresis day, median peripheral and product CD34(+) cell counts were 36.5(7‐206) × 106/kg and 5.3(0.5‐22.8) × 106/kg respectively. Median vitamin D levels were significantly lower in donors with low peripheral CD34(+) cell count which was defined as <20 × 106/kg, compared to donors with CD34 level≥20 × 106/kg [13.5(7‐27.4) μg/L vs 17(3‐63.2) μg/L; p = 0.035] (Figure 1). When we divide the study group into two subgroups based on median vitamin D levels, peripheral CD34(+) cell counts were found to be significantly lower in low‐vitamin D group compared to high‐vitamin D group [35(7‐135) × 106 vs 41.4(10‐206) × 106; p = 0.038]. Any significant association was not observed between vitamin D levels and product CD34(+) cell counts. In logistic regression analysis, serum vitamin D level was considered to be correlated with peripheral CD34(+) cell count [p = 0.042; SE: 0.034; 95% Cl Exp(B): 1.003‐1.145].

Summary/Conclusion:

Mobilization failure still remains to be a critical issue for HSC transplantation. In this study, the significant association between vitamin D levels and peripheral CD34(+) cell counts, lacking a similar correlation with product CD34(+) cell counts, requires further evaluation with larger study populations and more standardized procedures including product processing and collection. In these circumstances, the possible role of vitamin D in HSC mobilization deserves further consideration as vitamin D replacement before mobilization would be an easy, safe and cost‐effective approach to improve mobilization success.

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PB2352 PROPHYLACTIC PROSTAGLANDIN E1 PREVENT SINUSOIDAL OBSTRUCTION SYNDROME/VENO‐OCCLUSIVE DISEASE OF THE LIVER AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Lim S.‐N. , Ko S. , Park S. , Sohn B.
Published: June 2019

Background:

Prostglandin E1 (PGE1) was used to prevent sinusoidal obstruction/veno‐occlusive disease (SOS/VOD) of the liver after allogeneic hematopoietic stem cell transplantation (HSCT) for hematologic malignancies.

Aims:

We evaluated retrospectively that prophylactic using of prostaglandin E1 prevent SOS/VOD of the liver in patients received allogeneic hematopoietic stem cell transplantation.

Methods:

It was given in continuous intravenous infusion from day ‐8 to day 14 after allogeneic HSCT at a dose of 0.3 micrograms/kg/hour. The patients were studied according to the risk factors for SOS/VOD: diagnosis, intensification of the conditioning and previous liver abnormalities. The diagnosis of SOS/VOD was made on revised diagnosis and severity criteria for SOS/VOD in new classification from the European society for blood and marrow transplantation. Seventy‐eight patients underwent allogeneic HSCT between September 2010 and November 2017 and 71 were treated by PEG1 and seven did not receive it.

Results:

The median age of included patients was 45‐year‐old (range, 18‐64 year‐old) and the male was 36 patients (46%). The actual incidence of SOS/VOD was 1.3% (one patient) in the PGE1 group and 14.3% (one patient) in the non PGE1 group (P < 0.001). SOS/VOD developed in two of 78 patients (2.6%) with diagnosis day 7 and day 11 after hematopoietic stem cell infusion. of two patients, one had moderate SOS/VOD and one had severe SOS/VOD as new EBMT criteria for severity grading. Two patients who were diagnosed in SOS/VOD were in acute leukemia. Survival at day +100 for

Summary/Conclusion:

The prophylactic PGE1 treatment may decrease the incidence of SOS/VOD in patients by allogeneic hematopoietic stem cell transplantation.
PB2365 CELL DOSE AND HEMATOLOGIC RECOVERY AFTER AUTOLOGOUS STEM CELL TRANSPLANTATION FOR MULTIPLE MYELOMA
Authors: Tonev I. , Simeonov S. , Mitkov I. , Ilieva M. , Petrov Y. , Ganeva P. , Arnaudov G. , Spassov B. , Mincheff M.
Published: June 2019

Background:

The relation between the dose of the infused hematopoietic stem cells and the time of hematologic recovery after autologous transplantation has been investigated in different types of patients.

Aims:

We assessed the strength of this relation in patients with multiple myeloma, transplanted in our center.

Methods:

We analyzed the relation between different factors and the hematologic recovery in 277 transplantations performed on 249 patients (138 male and 111 female) with multiple myeloma, who underwent autologous transplants between 2005 and 2018. Twenty eight of them had second (tandem or not tandem) transplantation.

The conditioning regimen consisted of Melphalan for most of the patients. The average age at the time of transplantation was 55 years (35 ‐ 71). Patients were transplanted with an average cell dose of 2,95 × 106/kg (1,30 – 9,20 × 106/kg) for the first transplantation and 2,36 × 106/kg (1,64 – 3,19 × 106/kg) for the second one (every patient received the same cell dose as for the first) with average cell viability 95,34 % (70 – 99%), with little difference between first and second transplantation.

Results:

The average time for hematological recovery was 11,60 (between 9 and 19) days for the neutrophils, and 12.11 (between 9 and 20) days for the platelets.

We found no correlation between the cell dose and the hematological recovery. There was no difference in the hematopoietic recovery between the first and the second transplantation in the patients, who underwent tandem or two transplantations.

Summary/Conclusion:

Recovery time is considered by some to be a function of the effective stem cell number. We did not find such correlation, probably because in the analyzed group all the patients, except four of them, received a dose greater than 2 × 106/kg cell, which is accepted as a safe dose for autologous stem cell transplantation.
PB2366 LOW DOSE CYCLOPHOSPHAMIDE CONDITIONING REGIMEN IN HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION IS WORTH EXPLORING IN THE TREATMENT OF ACQUIRED APLASTIC ANEMIA
Authors: Cui S. , Kong F. , Fang Y. , Cui X. , Wang Y. , Wang J. , Liu K. , Ding S. , Shen M. , Xu R.
Published: June 2019

Background:

In recent years, haploid hematopoietic stem cell transplantation has made great progress in the treatment of acquired aplastic anemia, but the incidence of transplant related complications and transplant related mortality are still high, and the conditioning reginem needs to be further optimized.

Aims:

To investigate the safety and efficacy of haploidentical hematopoietic stem cell transplantation with different intensity conditioning regimen in the treatment of aplastic anemia (AA).

Methods:

27 AA patients who underwent haploidentical transplantation in Affiliated Hospital of Shandong University of Traditional Chinese Medicine from July 2017 to July 2018 were enrolled. All patients received bone marrow plus peripheral blood stem cells.According to the dosage of cyclophosphamide in the conditioning regimen, 26 patients excluding one other conditioning regimens were divided into high‐dosage group (regimen 1, 16 cases) and low‐dosage group (regimen 2, 10 cases). The data of Engraftment, graft‐vs‐host disease (GVHD), hematopoietic reconstitution, relapse, infection, overall survival (OS) were analyzed. The comparison between the two groups was tested by χ(2) test.

Results:

ALL patients achieved primary engraftment. The activation rate of CMV and EBV was 63 % (17/27). Post‐transplant lymphocyte disease (PTLD) in 0 case. The cumulative incidences of acute GVHD grade I‐IV and chronic GVHD were 22.2% (6/27) and 18.5% (5/27) respectively and the incidence of extensive chronic GVHD was 0%. The median follow‐up time was 6.5 (0.5‐12.5) months, the OS was 96.3% (26/27). All survived patients were no longer dependent on blood transfusion and none of them had recurrence. Comparing the rates of overall survival(94%(15/16) vs.100%(10/10)) and rates of chronic GVHD(18.8%(3/16) vs. 20%(2/10)) in regimen 1 and regimen 2 group, there were no significant difference (P > 0.05). Significant difference was found at the incidence of I‐IV acute GVHD (12.5% (2/16) vs. 30% (3/10),P < 0.05).

Summary/Conclusion:

Haploidentical hematopoietic stem cell transplantation is effective and safe in the treatment of acquired aplastic anemia. It is suitable for patients who are not eligible for matched donor transplantation. Application of low dose cyclophosphamide preconditioning in haploid transplantation is worth exploring.