bluuebunny/crossref_metadata_2025_split huggingface dataset:
PB2093 CLINICAL, PARACLINICAL CHARACTERISTICS AND OUTCOME IN ALGERIAN MYELODYSPLASTIC SYNDROMES: A SINGLE CENTER EXPERIENCE
Authors: Talbi T. F. , abbadi M. R. , menouer S. , belakhel S. , djouadi K. , ardjoun F. Z. 
Published: June 2019

Background:Myelodysplastic syndromes refer to a heterogeneous group of clonal diseases affecting the hematopoietic stem cell resulting in qualitative and quantitative abnormalities of the three myeloid lineages. The overall incidence is 03‐05/105 hbts/year without ethnic difference; it increases with age (03‐15/105 hbts/year between 50‐70 years and 15‐50/105 hbts/year> 70 years).Aims:we analyzed the characteristics of our patients and we investigated the impact of prognostic factors and parculier comorbidities on their futureMethodsa single‐center descriptive retrospective study, including all MDS diagnosed in the hematology department of military hospital over a 21‐year period (1994‐2014) from patient records. The diagnosis is retained on blood and bone marrow cytology and Perls staining (the karyotype was carried out in a few cases) after exclusion of a vitamin deficiency (ferritin, folate, vitamin B12: dosage or therapeutic test), or associated pathology (thyroid, lever, inflammatory or haemolytic). We have classified our patients according to the WHO classification (2016).Results:n = 85 evaluable pts: the clinical, biological and cytological characteristics of patients are summarized in the following table I, the observed comorbidities: cardiovascular d (40%), diabetes (30%), and respiratory insufficiency (29%): more frequent (HR = 1.65, 95% CI = 0.65‐ 3, 66) in men/women and more severe (≥3 points: 12 patients): HR: 4.5: 95% CI: 1, 88‐5) P = 0.012. Patients 65 years and older have a high prevalence of comorbidities (vs young): HCT‐CI score: HR = 0, 19 (95% CI: 0, 023‐0, 89): p = 0.01, with a very negative impact on survival (p = 0.001).Summary/Conclusion:the presentation of MDS in our series is similar to that of national and international series with a particularly poor prognosis since this pathology preferentially affects the elderly, with in most cases associated defects making the management very difficult. Immunomodulatory agents could improve the evolution of these patients.image
PB2113 IMPACT OF CLONAL HETEROGENEITY IN COMPLEX KARYOTYPES OF MULTIPLE MYELOMA PATIENTS WITH FIRST LINE BORTEZOMIB‐BASED THERAPY: A SINGLE‐INSTITUTION EXPERIENCE IN BULGARIA
Authors: Angelova S. , Ignatova K. , Ganeva P. , Lozenov S. , Jagurinoski M. , Balatzenko G. , Spassov B. 
Published: June 2019

Background:Multiple myeloma (MM) is genetically heterogeneous with varied clinical outcomes, primarily due to the coexistence of diverse numerical and structural cytogenetic abnormalities (CA). The data about prognostic significance of clonal evolution and cumulative effect of multiple high‐risk (HR) CA in complex karyotypes (CK) of MM patience (pts) is controversially.Aims:1) to make cytogenetics profiling of CK in our MM pts with first line bortezomib‐based therapy (BBT); 2) to find relationship between clonal heterogeneity in CK and therapeutic response and OS of our MM pts.MethodsWe examined the cytogenetic features in 78 pts with newly diagnosed MM using conventional cytogenetics and molecular‐genetics (for t(4;14)/MMSET‐IgH) analysis for 5 years (2014‐2018) in SBALHZ–Sofia, Bulgaria. The followed CA were considered as clinically relevant: hyperdiploidy, hypodiploidy, gap 1q, ‐13/13q‐, ‐17/17p‐, t(4;14), t(11;14). OS was calculated using Kaplan‐Meier estimates.Results:The CK was occurred in about 38% (30/78) of our pts: in 77% (23/30) with hyperdiploidy and in 23% (7/30) without it. The features of clonal evolution (2 or more aberrant cell clones) were defined in 57% (17/30) CK and predominantly were connected with hyperdiploidy (15/17). The coexistence of 2 or more adverse prognostic CA was defined in 60% (18/30) CK. The proportion of pts with normal karyotype (NK) who achieved CR and VGPR was two and half times more than in pts with CK (16,7% vs 41,7%). The autologous stem cell transplantation (ASCT) was applied at 26,7% (8/30) pts with CK and 31% (15/48) pts with NK. We have not found a statistically significant difference in the OS of our pts with signs of clonal evolution or multiple HR CA in CK compared to other CK pts. Although the mean OS of pts with HR CA or clonal heterogeneity in CK without ASCT was lower than OS of CK pts treated with ASCT, the difference in OS wasn’t statistically significant (19.0 mths vs 25.2 mths, p = 0.419). Only groups that stratified according to Mayo Stratification of Myeloma (with HR CA, intermediate‐risk CA and standard‐risk CA) had a statistically significant OS difference (p < 0,006).Summary/Conclusion:We have not found cumulative adverse effect of multiple HR CA or signs of clonal evolution in CK on OS of our MM pts.
PB2114 NEUTROPHILIC LEUKEMOID REACTION ASSOCIATED WITH SMOLDERING MULTIPLE MYELOMA
Authors: Martínez‐Cordero H. , Valdes‐Cespedes J. , Enciso‐Olivera L. , Alfaro‐Acosta L. , Otero D. , Spirko P. , Patiño‐Escobar B. 
Published: June 2019

Background:Chronic neutrophilic leukemia is a rare chronic myeloproliferative neoplasm characterized by splenomegaly, sustained neutrophilia, elevated B12 levels, and negative BCR/ABL translocation. It can be confused with leukemoid reactions in the context of plasma cell neoplasms.Aims:To describe the clinical case of a female patient with neutrophilic leukemoid reaction in the context of latent IgA multiple myeloma treated at the National Cancer Institute of Colombia.MethodsClinical case reportResults:We present a 67‐year‐old woman with a history of type 2 diabetes mellitus and rosacea with headache, epistaxis, fatigue, intermittent chest pain, hyperleukocytosis in the hemograma and qualitative negative PCR BCR ABL in peripheral blood. She received treatment with hydroxyurea since January 2016 extra institutionally. Upon admission to our institution a complete bone marrow study was requested confirming the BCR ABL negativity by cytogenetics and JAK2 V617F negative mutational state, however the myelogram showed infiltration by plasma cell disorder with dohle bodies and moderate megaloblastic changes in the myeloid and erythroid series. Bone marrow biopsy was hypercellular with 30% infiltration by abnormal plasma cells. The immunophenotype of the plasmacytic population in flow cytometry revealed a positive population for CD38/CD138/CD56/B2‐m and negative CD19/CD45 with lambda restriction. Protein electrophoresis showed a monoclonal peak in the beta region, immunofixation was positive for lambda IgA, high IgA levels with a value of 3874 mg/dL. No monoclonal component was detected in the urine, including immunofixation. The free light chains in serum showed a monoclonal lambda of 116.52 mg/L, Kappa 11.01 mg/L with a ratio of 10.5. No CRAB component was shown including PET CT without bone or extramedullary lesions. Despite treatment with hydroxyurea, hyperleukocytosis persisted with 47330 cels/ul with neutrophilia (44060/uL). Finally, smoldering IgA lambda high risk multiple myeloma diagnosis was made. She started treatment with lenalidomide and dexamethasone attaining partial response after two cycles and progresive resolution of leukemoid reaction.Summary/Conclusion:The neutrophilic leukemoid reaction or a similar clinical picture should alert to the existence of a plasma cell neoplasm. The associated morphological characteristics are usually the toxic granulations and Dohle bodies like in our patient. It is not clear if neutrophilia becomes a factor of poor prognosis in smoldering multiple myeloma, for this reason the risk should be stratified according to existing guidelines. There are still controversies about the need for treatment even in higk risk patients. The fact of being IgA, having a peak greater than 3 grams in SPEP, the ratio of light chains greater than 8 were the high‐risk characteristics seen in our patient that they defined in management.image
PB2115 NRF1‐DEPENDENT PATHWAY: SALVAGE PATHWAY AFTER THE PROTEASOME INHIBITION IN MULTIPLE MYELOMA AND MANTLE CELL LYMPHOMA?
Authors: Fassmannová D. , Sedlák F. , Šašková K. Grantz 
Published: June 2019

Background:Proteasome inhibitors (PI) are compounds with anti‐neoplastic effect in various hematological cancers. Bortezomib, the first FDA approved PI compound, represents the backbone therapy in case of multiple myeloma (in the first line therapy and in relapse) and has proven efficacy in mantle cell lymphoma. However, the resistance to proteasome inhibitor treatment often occurs and limits the possibility of subsequent therapy. The mechanism of resistance to PI is not fully understood. Usually, it is associated with high expression of proteasome subunits or, in some cases, could be caused by mutations in proteasome subunits that hinder the binding site of the inhibitor. One of the homeostasis pathways that regulates the synthesis of proteasome subunits is the nuclear factor erythroid‐derived 2 related factor 1 (Nrf1)‐dependent pathway. Nrf1 is a transcription factor responsible for the regulation of the genes involved in protecting cells from oxidative stress and regulating proteasomal activity. In normal conditions, it is embedded in the membrane of endoplasmatic reticulum, retrotranslocated by VCP/p97 complex to cytosol, deglycosylated and processed by proteasome. However, when proteasome is inhibited, Nrf1 is cleaved by DDI2 protease, becomes active and acts as a transcription factor in the nucleus where it upregulates the synthesis of the proteasome.Aims:Evaluation of the roles of individual factors of Nrf1‐dependent pathway under the PI treatment of hematologic neoplasias.MethodsThe cell lines with various sensitivity to PI generated from various hematologic neoplasias (mainly multiple myeloma, mantle cell lymphoma) were treated by several PIs and the levels and forms of the components in the Nrf1‐dependent pathway were measured.Results:The presence of the Nrf1‐dependent pathway components in hematologic neoplasia was confirmed. The PI treatment in the majority of cell lines led to the increase of the levels of the activated form of Nrf1 while the DDI2 levels did not significantly change.Summary/Conclusion:The activation of the Nrf1‐dependent pathway responsible for the proteasomal units expression after the PI treatment in hematologic neoplasia derived cells suggests that the inhibition of this pathway can improve the sensitivity to PI and might potentially open up new approaches to the PI refractory disease therapy.
PB2129 PRETREATMENT D‐DIMER LEVELS PROVIDE PROGNOSTIC INFORMATION IN PATIENTS WITH MULTIPLE MYELOMA
Authors: Peipei X. 
Published: June 2019

Background:High D‐dimer levels are associated with poor overall survival in patients with general cancer.Aims:This retrospective study aimed to investigate the prognostic value of D‐dimer levels in patients with multiple myeloma (MM).MethodsA total of 214 patients newly diagnosed with MM were retrospectively enrolled. The correlation between pre‐treatment plasma D‐dimer levels and clinical factors was evaluated. The cut‐off value of D‐dimer for predicting survival was set as 0.8 μg/ml based on receiver operating curve analysis. Patients with a D‐dimer level ≥ 0.8 mg/ml had more adverse clinical features, including advanced R‐ISS stage, higher International Myeloma Working Group risk stratification, more abnormal chromosome, and increased serum creatinine level. The prognostic value of d‐dimer levels was explored.Results:Patients with a D‐dimer level ≥ 0.8 mg/ml showed poor overall survival (OS) and progression‐free survival (PFS). Multivariate analyses revealed that the D‐dimer levels were independent predictors of OS and PFS (hazard ratio = 10.15 and 0.27, 95% confidence interval = 4.86–21.19 and 0.18–0.42, P < 0.001 and P < 0.001).Summary/Conclusion:In conclusion, D‐dimer levels might be considered as a simple and effective prognostic marker in patients with MM.
PB2133 IMPACT OF THE PRE‐TRANSPLANT INDUCTION (PTI) DURATION ON THE SURVIVAL OF PATIENTS WITH MULTIPLE MYELOMA (MM)
Authors: Pereira S. , Sarmento L. M. , Fernandes M. Leal , Brito R. , Monteiro A. , Ferreira G. , Costa F. , de Sousa A. Botelho 
Published: June 2019

Background:The first‐line strategy consensually accepted as the most effective in MM is a triplet PTI followed by autologous hematopoietic progenitor transplantation (AHPT). The proportion of patients eligible for AHPT has been steadily increasing as its safety and efficacy are documented in older patients. In this context, the duration of PTI gains relevance in real life: the standard recommendation of 3‐4 cycles is defined based on the unproven statement that a longer PTI may have negative effects on patient outcome, a conviction recently denied by the evidence published by Chakraborty et. al. (2018). Additionally, the possibility of prolonging PTI, although potentially associated with undesirable toxicity, may be beneficial in improving response depth prior to AHPT and sustain the response until transplantation is possible according to the transplantation center schedule.Aims:Evaluate the impact of PTI duration on the 3 month (mo)‐CR rate post‐AHPT, on median progression‐free survival (mPFS) and overall survival (OS) in MM patients transplanted at our center over a 12‐year period.MethodsData from 273 MM patients consecutively transplanted after PTI between September 2005 and March 2018 was collected. 104 patients were excluded from the analysis: 75 due to > 12 mo interval from PTI beginning to AHTP, 10 due to > 1 PTI line prior to AHPT and 19 due to missing data.Results:We analyzed 169 patients, median age 61 (30‐73), comparing those treated with PTI up to 4c (n = 70) with those subjected to > 4c (n = 99). The proportion of patients with unfavorable ISS, high‐risk cytogenetics, or that received doublet PTI did not differ among the groups. With a median follow‐up of 40mo, the 3mo CR rate post‐AHPT was similar between the 2 groups (41 vs 51%, p = 0.2) as were the mPFS (37 vs 33mo, p = 0.3) and the 5y OS (68 vs 59%, p = 0.1). We also explored the influence of PTI duration in particular subpopulations: high‐risk cytogenetics; VGPR pre‐AHPT; or treated with doublet PTI (vs triplet). No significant differences were found, except for the mPFS in the subgroup treated with VCD (NA vs 27mo, p = 0.02).Summary/Conclusion:Our results suggest that a prolonged PTI beyond 4c does not improve post‐AHPT outcomes. These findings are similar to those of the Mayo Clinic study. Nevertheless, the conclusion we find most relevant is that a prolonged PTI, which may be required to deepen pre‐AHPT response or to sustain response up to transplantation, is not more deleterious in terms of PFS and OS.
PB2140 IMPACT OF EXTRAMEDULLARY DISEASE IN THE OUTCOMES OF MEXICAN PATIENTS WITH MULTIPLE MYELOMA
Authors: Vargas‐Serafin C. , Rangel‐Patino J. , Perez‐Samano D. , Acosta‐Medina A. , Ordonez‐Perez I. , Bourlon C. 
Published: June 2019

Background:Extramedullary myeloma (EMM) is the synchronous presence of clonal plasma cells (CPC) at bone marrow and distant sites. Its frequency is reported among 6‐20% of multiple myeloma (MM) patients and manifest as bone‐dependent plasmocitoma (BP) or tissue‐dependent plasmocitoma (TP). Previous reports state a more aggressive clinical course, whether at diagnosis or relapse. There is no data regarding the clinical course and prognosis in Mexican patients with EMM.Aims:To analyze and describe the impact of EMM on overall survival (OS) and progression free survival (PFS) of Mexican patients diagnosed and treated at monoclonal gammapathies clinic of our institution.MethodsRetrospective analysis including >18 year‐old patients with MM diagnosis according to IMWG criteria. EMM was defined as presence of CPC corroborated by immunohistochemistry in BP or TP or demonstration of a synchronous tumor by imaging method and no accessible to biopsy.Results:A total of 199 patients were included. Sixty‐three patients had EMM (31.8%), 45 cases (71.4%) presented at diagnosis and 18 (28.6%) at progression. Forty‐eight cases (76.2%) were diagnosed by biopsy and 15 (23.8%) by imaging. Fifty‐four percent (n = 34) cases presented BP and 46% (n = 29) TP. Most frequently involved sites were abdomen (34.5%), thorax (27.6%) and lymph nodes (13.8%) in TP and spine (50%), chest wall (26.3%) and head/neck (13.2%) in BP. EMM was associated with lower comorbidity rate and higher renal failure. Population characteristics are shown in Table 1. Mean PFS and OS was 22.9 and 43.7 months, respectively. EMM at any time of disease resulted on lower PFS and OS (p = 0.03, p = 0.04), while TP showed lower OS (p < 0.01). A higher ECOG PS and lower deep response was associated with worse PFS (HR 1.05‐2.60 (p = 0.03) and HR 0.20‐0.38 (p < 0.01), respectively) while ISS and lower deep response resulted on worse OS (HR 1.0‐2.2 (p = 0.02) and HR 0.37‐0.73 (p < 0.01)) at multivariate regression.Summary/Conclusion:A higher EMM rate was found in the studied population. EMM was associated to higher renal failure and low incidence of comorbidities, as shorter PFS and OS, particularly in TP. Identification of this high risk myeloma population allows an attempt for more intensive treatment with intention to improve prognosis.image
PB2180 EXPERIENCE VRD‐PACE‐LIKE REGIMEN IN PATIENTS WITH PRIMARY REFRACTORY MYELOMA FOR PERIPHERAL STEM CELL MOBILIZATION
Authors: Nakastoev I. , Ryzhko V. , Novikova A. , Balzhanova Y. , Grachev A. , Abramova T. , Samtcova M. , Vasilchenkova P. , Danilina A. , Kanaeva M. , Gribanova E. 
Published: June 2019

Background:High‐dose chemotherapy followed by autologous stem‐cell transplant (ASCT) is the current treatment in patients with multiple myeloma (MM). To obtain the effect of ASCT it is necessary to achieve a response to induction therapy. Lenalidomide‐based regimens as the second‐line therapy failed peripheral blood mobilization of CD34+ cells and increase the risk of its inadequate collection. Thus, intensive chemotherapy regimens as VRD‐PACE and its modifications are used to enhance treatment response and effective mobilization.Aims:To estimate safety and efficacy of VRD‐PACE‐like regimens for peripheral stem cell mobilization.MethodsA total of 7 patients with primary refractory multiple myeloma were enrolled in the study. All patients received VRD‐PACE‐like regimens in conventional doses followed by granulocyte colony‐stimulating factor (G‐CSF 10 μg/kg/day) started after reducing leukocytes count ≤ 1.0 × 109/L. As mobilizing regimen in 3 patients was administred VRD‐PACE, 3–RD‐PACE and 1–KRD‐PACE.Results:A total of 7 patients with primary refractory myeloma were enrolled in the study. The median age was 51 (range 40–56 years), of them 3 were men. These patients didn’t receive suboptimal response to bortezomib‐based regimens. Therefore, administration of second‐line therapy was required. Patients received in average 6 cycles of chemotherapy (6–10) and three lines of therapy. At initiation treatment with VRD‐PACE only 1 patient had very good partial response (VGPR), 3–partial response (PR), 3–disease progression. One patient with VGPR had adverse cytogenetic abnormalities and for this reason was treated with VRD‐PACE. All patients who received VRD‐PACE‐like regimens achieved decline of serum monoclonal protein, of them 2 obtained VGPR. Mobilization failure was in 2 patients due to inadequate collection of CD34+ cells. Before mobilization each of these patients received only 2 lenalidomide‐based cycles. Afterwards, high‐dose cyclophosphamide‐based mobilization was performed and sufficient amount of CD34+ cells was received. In the others 5 patients CD34+ cells were collected enough for tandem ASCT (6–12.4 × 106/kg). VRD‐PACE‐like regimens were not associated with severe complications. Only 1 patient was diagnosed with parietal thrombosis of the common femoral vein and 1 patient had Herpes labialis. One patient needed packed red cell and platelet transfusion.Summary/Conclusion:VRD‐PACE‐like regimens are an effective option for treatment of refractory/relapse MM. We concluded that VRD‐PACE‐like regimens are well‐tolerated and effective option for mobilization of CD34+ cells in patients with suboptimal treatment response or aggressive MM.image
PB2199 MESENCHYMAL STEM CELLS IN PH‐NEGATIVE MYELOPROLIFERATIVE NEOPLASMS: IDLE OBSERVERS OR PART OF THE DISEASE?
Authors: Santoro M. , Di Stefano A. B. , Di Piazza F. , Re J. Lo , Accurso V. , Mancuso S. , Russo A. , Cordova A. , Siragusa S. 
Published: June 2019

Background:Pathogenesis in Philadelphia‐negative Myeloproliferative Neoplasms (MPNs) is surely linked to genomic alterations in Hematopoietic Stem Cells (HSCs), most of all on genes which can carry mutations referred to as driver mutations: JAK2, CALR and MPL. Inflammation, neoangiogenesis and fibrosis are part of the clinical and biological picture of MPNs. Recent studies have hypotized a possible HSC‐independent, active role of the Mesenchymal Stem Cells (MSCs) in the pathogenesis of these diseases.Aims:Our aim is to characterize the molecular profile of bone marrow MSCs (BM‐MSCs) of patients with diagnosis of MPNs to explore their possible contribution in the pathogenesis of the disease. In particular, we focused on the study of specific miRNA and mRNA already known in literature to be involved in processes of inflammation, neoangiogenesis and fibrosis in MPNs.MethodsPrimary cultures of BM‐MSCs were obtained from bone marrow samples of patients with diagnosis of MPNs. Genic expression profile was evaluated with Real‐Time Polymerase Chain Reaction compared to mesenchymal human healthy cell line.Results:We found that some markers known to be involved in angiogenesis, as miR221, miR20a, HIF‐1a and VEGF, are upregulated in BM‐MSCs of MPNs patients. Regarding bone marrow fibrosis, expression analysis of THSB1, TGF‐beta mRNAs and miR21 in BM‐MSCs highlighted sensible upregulation in all samples, strongly suggesting a possible role of the MSCs in the mediation or induction of the fibrosis process in the bone marrow, in these diseases.Summary/Conclusion:Our data suggest a possible role of the BM‐MSCs in fibrosis and neoangiogenesis in MPNs. In subgroup analysis, no significant differences were found between specific diseases (polychythemia vera, essential thrombocytemia, myelfibrosis and MPN‐unclassifiable). Being driver mutations not enough to explain different clinical and histological presentations, it maybe that the study of the pathological MSCs will help comprehend the complex machine of pathogenesis in MPNs and possibly find new targets to develop drugs that may change the natural history of these diseases.