bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-Transplantation of Mesenchymal Stem Cells Further Improves the Prognosis of Allo-HSCT in the Treatment of High Risk and Refractory/Relapse Hematologic Malignancies: A Single-Center Retrospective Study of 175 Patients
Authors: Ren Jinhua , Luo Xiaofeng , Chen Minmin , Xiao Min , Li Qian , Lin Kangni , Zheng Zhihong , Chen Zhizhe , Hu Jianda , Yang Ting 
Published: November 2019

BACKGROUD:
Mesenchymal stem cells (MSCs) are known to have immunomodulatory, anti-inflammatory and pro-angiogenic properties and thus have the potential to improve the likelihood of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of hematologic malignancies.
OBJECTIVE:
To explore the efficacy and safety of allo-HSCT by co-transplantation with MSCs in hematologic malignancies patients.
METHODS:
We conducted a single-center retrospective study to comparing the incidence and severity of acute GVHD, recurrence rate and overall survival (OS) of high risk and refractory/relapse hematologic malignancies patients undergoing allo-HSCT with or without co-injection of MSCs. A total of 175 patients (113males/62 females) at Fujian Medical University Union Hospital from January 2016 to June 2019 were analyzed. The median age of the patients is 22 (range 1-65 years). Patients received salvaged conditioning regimens FA5-BuCy as previous reported for high risk and refractory/relapse hematologic malignancies, registered on http://ClinicalTrials.gov (NCT02328950), among whom 31(17.7%)were MSD-HSCT, 21(12%) MUD-HSCT and 123(70.3%)haplo-HSCT. All patients received ATG, cyclosporine A with short course methotrexate for prevention of GVHD. 85 patients transplanted with donor HSCs only, and 90 patients transplanted with HSCs and MSCs .MSCs infusion dose was 1-2×106/kg, at -1~+1 days following HSCs infusion.
RESULTS:
The two groups were well matched demographically. All patients achieved successful engraftment within one month post-HSCT. There was no difference in time to leukocyte and platelet engraftment in the two groups. The incidence of aGVHD (36.5 % versus 26.7 %, P =0.163) was similar in the HSC versus MSC groups. With a median follow-up time of 373 days (range:29-1265days), the 2-yr OS was much better in MSC co-injection groups (77.6% versus 48.4%, P =0.005). Moreover, there was no significant difference in the 2-yr cumulative recurrence rate between the two groups (25.1% vs 16.2%, P = 0.4).
CONCLUSION:
FA5-BUCY as an intensive conditioning regimen facilitates the outcome of advanced diseases with allo-HSCT, and co-transplantation with MSCs could further improve the survival of hematologic malignancies patients who did not reach remission.

Disclosures
No relevant conflicts of interest to declare.
A Phase 1, Open-Label, Multi-Center Study of Alteminostat (CKD-581) in Combination with Lenalidomide and Dexamethasone in Patients with Previously Treated Multiple Myeloma (MM)
Authors: Min Chang Ki , Kim Kihyun , Kim Seok Jin , Yoon Dok Hyun , Park Sung-Soo , Han Seunghoon 
Published: November 2019

Background
Alteminostat (CKD-581), a novel hydroxamate-based pan-HDAC inhibitor, increases acetylation of histones and other proteins involved in multiple oncogenic pathways. It modulates gene expression involved in cell-cycle regulation, differentiation, and apoptosis. Altemonstat in combination with lenalidomide and dexamethasone demonstrated promising anti-cancer efficacy both in vitro and in vivo studies, including xenograft models of multiple myeloma (MM). In addition, it was well tolerated in patients with lymphoma and MM refractory to standard therapy. On the basis of this background, we conducted a phase I dose-finding study of alteminostat in combination with lenalidomide and dexamethasone in relapsed MM patients.
Methods
Subjects with MM who had relapsed after at least one prior treatment were infused alteminostat iv (90, 120, or 160 mg/m2, level 1-3, respectively once weekly for 3 weeks out of a 4-week cycle in a standard 3+3 dose-escalation, phase 1 design, combined with lenalidomide 25 mg on day 1-21 and dexamethasone 40 mg on day 1, 8, 15, 22 in a 28-day cycle
Results
As of July 11th, 2019 the study has enrolled 10 patients with relapsed MM to Level 3. The median age was 56 (range 46-64), and the median number of previous regimens received was 2.5 (range 1~8). Based on the data cut off day, no dose-limiting toxicities were identified. 2 patients were in progress on the maximum planned dose of 160 mg/m2. The most common (>20% of subjects) drug-related adverse events (AEs) were thromobcytopenia (80%), neutropenia (60%), anemia (50%), muscle spasms (50%), fatigue (30%), upper abdominal pain (30%), and constipation (30%). Serious adverse drug reaction was not reported. AEs related with cardiac disorder have not been observed. The most common ≥Grade 3 hematologic AEs were neutropenia (70%), thromobcytopenia (60%), and anemia (60%). The most common ≥Grade 3 non-hematologic AEs are pneumonia (40%). One patient at dose level 2 died from pulmonary embolism after pneumonia. Two of ten patients had exposed to lenalidomide before participating in this clinical trial. The median cycle was 3 in level 1, 4 in level 2 and 2 in level 3, while level 3 is still in progress. The overall response rate, defined as achieving more than partial response (PR), for all patients was 70%, including 10% stringent complete response (sCR), 10% CR, 20% very good PR and 30% PR. The median duration of response was 236 days and median progression-free survival was 232 days.
Conclusions
Alteminostat, a novel hydroxamate-based pan-HDAC inhibitor, can be combined safely with lenalidomide and dexamethasone, demonstrating significant clinical activity in subjects with MM. Enrollment is ongoing and full phase 1 will be updated and presented.

Disclosures
No relevant conflicts of interest to declare.
The Appropriateness of Fresh Frozen Plasma (FFP) Administration in Three Community Teaching Hospitals
Authors: Shikdar Sufana , Agrawal Kavita , Ghionni Nicholas , Hommadov Kakageldi , Abdollahi Shahrzad , Micaily Ida , Green Eric 
Published: November 2019

Objective: Although Fresh Frozen Plasma (FFP) is indicated in critically ill patients, there are growing concerns about it's cost effectiveness and adverse effects in instances that do not conform to evidence-based indications. Despite a range of adverse reaction with the inappropriate usage of FFP, its usage has significantly increased over the last decade. We previously evaluated the overuse of FFP in our community teaching hospital in 2010-2011 and 2016-2017. The interventions to reduce the inappropriate FFP transfusion were implemented after the results from 2016-2017. The present multicenter study is a post-interventional study that describes practices regarding administration of FFP in three community teaching hospitals between 2017-2018.
Methods: A retrospective chart review of patients who received FFP transfusion in three community teaching hospitals between 2017-2018 were included in our study. Criteria were established to evaluate the appropriateness of FFP. Descriptive statistics were utilized to compare the appropriateness of FFP transfusion among the participating hospitals.
Results: Overall, 306 participants were evaluated where 25% of the participants (77 out of 306) received inappropriate FFP transfusions. The most common rationale for inappropriate FFP transfusions were bleeding with INR less than 1.5 followed by INR over 1.5 (without any evidence of active bleeding).Based on our study criteria, the proportion of inappropriate FFP transfused out of the total FFP transfused decreased from 49% in the study period 2016-2017 to 25% in the study period 2017-2018. 15% of the study population received inappropriate FFP transfusion for bleeding in 2017-2018 compared to 42% in 2016-2017.
Conclusion: Our study showed a reduction in inappropriate FFP transfusions in 2017-2018 compared to 2016-2017. This can be attributed to the interventions implemented after obtaining study results from 2016-2017. The interventions included creating fliers educating about lack of effectiveness of FFP to reduce INR below 1.6 and arranging educational talks from transfusion committee about the evidence-based usage of FFP transfusion. Such interventions are essential to reduce healthcare expenditure and transfusion related adverse events.

Disclosures
No relevant conflicts of interest to declare.
An Electronic Health Record Facilitates a Safer and More Efficient Rural Outreach Haematology/Oncology Service
Authors: Cashman Helen , Hamad Nada , Moore John , Milliken Sam , Lavee Orly , Withers Barbara , Mayson Eleni , Kliman David , Kesby Janet , Bell Jenny , Vachalec Sue 
Published: November 2019

Background: Rural Australian oncology patients are known to have inferior mortality rates compared to metropolitan patients, possibly related to access to appropriate healthcare services and treatments. Replacement of paper-based chemotherapy charting with electronic systems improves the safety of chemotherapy administration through reduced prescribing and administrative errors.
Aims: To integrate the electronic healthcare delivery systems at a metropolitan hospital and a rural outreach haematology clinic to facilitate streamlined and safe rural outpatient care.
Method: The MOSAIQ v2.64 [Elekta] system utilized at St Vincent's Hospital, Sydney, was introduced at a linked rural outreach haematology clinic in Griffith, a city in the Riverina region of New South Wales. MOSAIQ is a comprehensive practice management system incorporating all relevant patient results and notes along with administrative capabilities. The two systems were consolidated into one with patient information accessible from both sites.
Results: The electronic systems were successfully linked between the two sites in October 2017. As of November 2018 there were 497 patients registered with the service with the breakdown of diagnoses shown in Figure 1, with lymphoma found to be the most common haematological diagnosis. Tracking of service activity over time including clinic appointments and patient numbers is now possible, with increases in both seen since implementation. Nine chemotherapy regimen types encompassing 2174 overall treatments were delivered at the service over the fifteen months since implementation, the most common being R-CHOP [Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] followed by azacitidine. The linked system has improved streamlined care during patient transitions between the two hospitals with enhanced continuity of documentation and management. Chemotherapy prescribing has transitioned to electronic at the Griffith site and is guided by inbuilt, pharmacist-reviewed protocols allowing for safer and flexible prescribing remotely which has standardized management of haematology patients across both hospitals.
Conclusion: Our study provides a novel example of the successful implementation of a centralised electronic healthcare record and chemotherapy prescribing system in a haematology setting shared between a metropolitan service and a rural outreach hospital clinic. This has positive implications for the safety and efficiency of healthcare delivery at the rural site applicable to all linked rural clinics, as well as allowing data collection to assist future planning of the service.

Disclosures
No relevant conflicts of interest to declare.
Managing Multiple Myeloma with Second and Later Lines of Therapy: A Challenge in Developing Countries
Authors: Pydi Venkateswar Rao , Bala Stalin Chowdary , Gundeti Sadashivudu 
Published: November 2019

Introduction:
Multiple myeloma is characterised by abnormal plasma cell proliferation leading to anaemia, hypercalcemia, skeletal lytic lesions and renal failure. Though myeloma is incurable, novel agents have improved the outcomes. Despite the availability of multiple new agents which lead to improvement in survival, majority of patients are still unable to receive second and further lines of therapy. The present study was designed to analyse the outcomes of patients who received 2nd line and later lines of therapy.
Materials and methods:
Data of all patients diagnosed with multiple myeloma from 2013-2018 was retrieved. Clinical, haematological, other significant lab parameters, treatment details were noted. For patients who progressed on 1st line therapy and those who had responses of less than PR, 2nd line therapy was started. PFS 2 was calculated from start of 2nd line therapy till progression. Survival probabilities were estimated by Kaplan-Meier method and compared by log rank test. SPSS 25 software was used for statistical analysis.
Results:
A total of 258 patients were diagnosed between 2013 and 2018. The median age at presentation was 56 years (range, 28-84 years). Male to female ratio was 2.03:1. Of these 258 patients, 191(74%) patients took planned therapy and 172(66%) patients had at least one response evaluation. Of these, only 81(47%) patients were able to receive 2nd line therapy. Five patients died during therapy, 16 patients did not complete planned therapy and 58(33%) patients had response evaluation. Seventy five percent of patients received triplet chemotherapy. MPT and VRD were the most commonly used regimens. Median number of cycles before response evaluation was 4 cycles. Of these 81 patients, 14(17.2%) patients underwent autologous stem cell transplantation. The baseline characteristics and outcomes were shown in Table 1. Twenty (34%) patients received 3rd line and further lines of therapy. Of these 20 patients, best response was VGPR, seen in 50% percent of patients. The median progression free survival (PFS2) was 15 months (range1-59 months). At a median follow up of 18 months, 2-year PFS was 61.6%. The 2-year OS of all patients and those who receive 2nd and later lines were 76% and 84% respectively.
Conclusion:
Only 30% of patients received second line and one tenth of all patients were able to receive third and later lines of therapy. Majority of the patients who received second and later lines of therapy had ≥ VGPR. Overall survival was higher in patients who received further therapy at progression. Outcomes in multiple myeloma can be improved by optimal sequencing of available drugs. Treatment discontinuity is major caveat in management of myeloma in real-world scenario and overcoming this challenge might improve survivals.

Disclosures
No relevant conflicts of interest to declare.
Cerebral Thrombosis As an Initial Presentation of Pediatric Acute Promyelocytic Leukemia
Authors: Aytac Selin , Coskun Cagrı , Aksu Tekin , Kuskonmaz Baris 
Published: November 2019

Disseminated intravascular coagulopathy and bleeding are common manifestations of acute promyelocytic leukemia(APL) which are both associated with significant mortality and morbidity. However APL related thrombosis is very rare and majority of the reported cases are adults in the literature. In the past 14 years, 14 cases with APL were found in our hospital database.There were 6 female and 8 male children with a mean age of 10.7±4.6 years (2-17y). Here, we report two pediatric APL case who presented with cerebral thrombosis at the initial presentation. 8/14(57%) had disseminated intravascular coagulation at the initial presentation and one patient had intracardiac and cerebral sinovenous thrombosis during the induction period.
Case 1:A 13-year-old boy was admitted to our hospital with a complaint of headache for two days. His physical examination revealed a papilledema and cranial MRI did show sinovenous thrombosis. At the time of the evaluation his WBC count was found to be low and there were myeloid blasts on his peripheral smear,bone marrow aspiration was done and diagnosed as translocation t(15;17)positive APL. He remain in remission more than 4 years without any event however deceased after relapse.
Case 2: A 8-year-old boy was admitted to our hospital with a complaint of right hemiparesis, there was a thrombotic occlusion of the left middle cerebral artery associated cerebral infarct on his MRI.His WBC was 5.9x109/l with 76% blasts and bone marrow aspiration and flow-cytometry were both compatible with APL. Patient died after 2 weeks of admission because of thrombosis and bleeding.
The incidence of APL related thrombosis was 4.5 and 5.6% in two large adult cohorts. Both arterial and venous thrombosis may ocur in patients with APL. To the best of our knowledge there were limited number of pediatric APL case reports in the literature who presented with thrombosis. In our small group of pediatric APL patients 14% presented with thrombosis and the total number of thrombotic events were found to be 28% during the follow up.

Disclosures
No relevant conflicts of interest to declare.
Rebound Thrombocytosis after Induction Chemotherapy Is a Strong Biomarker for Favorable Outcome in AML Patients
Authors: Pabst Thomas , Schnell Bianca R , Bacher Ulrike , Jeker Barbara , Banz Yara , Novak Urban , Seipel Katja - 
Published: November 2019

Background: Whereas the molecular events underlying acute myeloid leukemia (AML) are increasingly identified, dynamics of hematologic suppression and recovery following induction chemotherapy remain enigmatic. In addition, thrombocytopenia at diagnosis is related to deregulated cytokine expression in specific leukemia subtypes rather than on the degree of bone marrow infiltration per se. Similarly, recovery of platelets after the first induction cycle among individual patients can vary from incomplete to excess recovery even if morphologic remission is achieved. In particular, excess platelet rebound (EPR) with values exceeding 500 G/L can be observed in some patients. However, this clinical observation of EPR is poorly understood so far, and its prognostic relevance is unknown.
Methods: We analyzed platelet recovery after the first induction cycle in 291 consecutive AML patients receiving at least one cycle of intensive "3+7" based induction treatment. We defined excess platelet rebound (EPR) as a platelet increase above 500 G/L during hematologic recovery after the first induction cycle.
Results: We observed EPR in 120 (41.2%) patients. EPR+ patients had lower platelets at diagnosis, higher marrow infiltration, more frequently NPM1 mutations, and were associated with ELN favorable risk. Absence of EPR correlated with complex karyotypes, ELN intermediate-I and adverse risk, and therapy-related AML. Overall survival was better in EPR+ patients than EPR- (median 125 versus 41 months; P=0.04), as was disease-free survival (Figure 1). By multivariate analysis, achievement of EPR+ was an independent parameter associated with favorable survival. Plasma thrombopoietin (TPO) levels at diagnosis indicated EPR+ (p<0.0001), while GATA-1, GATA-2 and MPL mRNA expression did not differ between EPR+ and EPR- patients. Finally, transcription factors blocking early megakaryopoiesis were upregulated in EPR- patients, while NFE2 involved in late megakaryocyte differentiation was increased in EPR+ patients.
Conclusion: This study suggests that excess platelet rebound (EPR+) defined as platelets exceeding 500 G/L is a common event identified in AML patients after the first induction cycle. EPR+ was predominantly observed in ELN favorable risk AML, and it was associated with significantly better overall and disease-free survival as compared to EPR- patients. In addition, achievement of EPR+ represented an independent prognostic parameter for improved survival in a multivariate analysis, and may contribute to prognostic assessment in AML patients undergoing intensive treatment with intention to cure.

Disclosures
No relevant conflicts of interest to declare.
Serum microRNA Prognostic Model and Underlying Immune Alterations in Diffuse Large B Cell Lymphoma
Authors: Rui Sun , Zhao Weili 
Published: November 2019

Serum microRNA prognostic model and underlying immune alterations in diffuse large B cell lymphoma
Abstract
Background: MicroRNAs (miRs) have been investigated as prognostic biomarkers and therapeutic targets in diffuse large B-cell lymphoma (DLBCL). Translating these findings into clinical approaches should be validated by independent patient cohorts and a better understanding of underlying biology mechanism remains great interests.
Methods: MiRNA microarray was performed on serum samples of 20 DLBCL patients at diagnosis, remission and at relapse. Subsequent real-time PCR validation of 504 newly diagnosed DLBCL patients was used to generate a serum prognostic model in predicting clinical outcomes. The mechanism of action of miR signature on tumor progression was further analyzed by whole exome sequencing and RNA sequencing.
Results: Four serum miRs (miR-21, miR-155, miR-130b and miR-28) were identified to predict relapse in a training cohort of 225 DLBCL patients and validated in a validation cohort of 279 DLBCL patients. Multivariate Cox regression models indicated that when the International Prognostic Index was controlled, this serum miR prognostic model was an independent prognostic factor in DLBCL. Moreover, mutations of transcription factors (TFs) were significantly correlated with these four miRs. Twenty lymphoma-associated TFs regulated at least one miR by transmiR v2.0 database and different genetic mutation burden was present between low-index and high-index of the model. Furthermore, RNA sequencing data manifested that the four-miR signature correlated with immune status of the DLBCL patients.
Conclusions: An easy-to-use miR prognostic model was utilized to predict disease relapse and prognosis of DLBCL patients. The tumor-specific mutation burden and immune dysregulation potentially contribute to tumor progression in DLBCL.
Key words: MicroRNAs, Diffuse Large B-cell Lymphoma, Prognosis, Signaling pathways.

Disclosures
No relevant conflicts of interest to declare.