bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of Circulating Plasma Cells in Multiple Myeloma with Extramedullary Plasmacytoma
Authors: Wang Jing , Geng Shuang , Zhong Yuping , Chen Mingyi , Wang Wenming , Pang Yuhong , Zhang Jiajia , Liu Yuanyuan , Huang Yanyi , Jing Hongmei 
Published: October 2019

Abstract
Objective: To detect the circulating plasma cells (cPCs) in patients of multiple myeloma (MM) with or withoutextramedullary plasmacytoma (EMP).
Methods: The 21 patients of MM samples were collected from April 2014 to April 2015. There were 12 males, 9 females, with a median age of 60 (49 to 76 years old). Peripheral blood and bone marrow were examined before treatment or after EMP. Multi parameter flow cytometry (MFC) was used to analyze abnormal plasma cells (tumor cells) in samples of bone marrow and CD138 MACS positive sorting peripheral blood. The antibodies used in the flow cytometry were CD38-APC, CD138-PE, CD81-PE-Cy7, CD45-PacBlue, CD19-Percp-Cy5.5, CD56-mCherry-PE-ef610, CD117-AmCyan, CD16, Zombie-APC-Cy7.
Results: In these 21 patients, he ratio of sex is 1.33:1, the median age is 60 (49-76). The immunoglobin type is as follows: IgG κ 7 cases, IgG λ 5 cases, IgG 2 cases, IgA κ 3 cases, IgA λ 2 cases, λ light chain 1 cases. The morphology of bone marrow aspiration showed more than 15% plasma cells and abnormal plasma cells can be seen in bone marrow in cytometry. 9 of 21 patients diagnosed MM with EMP, 2 of them find EMP when initial diagnosis and 7 of them find EMP in the course of disease (6 months to 8 years). The sites of the EMP included head, jaw, chest wall, side of the rib, the soft tissue of the sacral region and the vertebral body and all patients had bone involvement. In 17 patients with complete clinical data, bone marrow and peripheral blood specimens, the cPCs negative rate was 87.5%(7/8) in EMP negative patients, while the cPCs positive rate was 66.7% (6/9) in EMP positive patients, the difference among groups was statistically significant (chi square values: 5.13, p = 0.024).
Conclusion: MFC has been widely used in diagnosis and minimal residual disease surveillance of MM, here we established the detection method of cPCs in MM patients, and it is valuable for clinical diagnosis and prognosis judgment.

Disclosures
No relevant conflicts of interest to declare.
The Majority of Myeloma Patients Are Vitamin D Deficient, Unrelated to Survival or Cytogenetics
Authors: Hudzik Samantha , Snoad Beau , Mousa Luay , Sborov Douglas W , Williams Nita , Jones Desiree , Hofmeister Craig C 
Published: October 2019

Abstract

Introduction: Since a link between solar radiation, vitamin D production, and decreased colon cancer mortality was established in 1980, there has been increasing interest in vitamin D and cancer, suggesting that higher vitamin D levels improve overall survival, specifically in breast and colorectal cancer (Maalmi H et al, Eur J Canc, May-2014, PMID 24582912), but also in follicular lymphoma (Kelly JL, J Clin Onc, 1-May-2015, PMID 25823738). In myeloma, largest published series is from the Mayo Clinic reporting on 148 newly diagnosed MM patients for which no survival association was found, but there were associations between low 25-OH-Vit D (<20 ng/mL) and higher serum CRP, serum creatinine, and ISS stage (Ng AC, Am J. Heme, Jul-2009, PMID 19415724); we wanted to expand on their trailblazing analysis. Cytogenetically high risk myeloma characterized by the amplification of 1q21 is associated with increased serum levels of soluble IL-6 receptor (sIL-6r) (Stephens OW, Blood, 2012, PMID 22072558) which may be associated with other markers of inflammation, e.g. CRP, creatinine, and b2microglobulin.
Methods: The Buckeye Myeloma Registry (OSU 10115) opened in 2011 to enroll any patient with a plasma cell dyscrasia. Serum total 25-OH-Vitamin D was measured at the time of the initial clinic visit to the myeloma group at Ohio State.
Results: Of a total of 843 patients, 115 (13.6%), 53 (6.3%) with SMM, and 675 (80.1%) with MM. In the 675 MM patients, the median age was 64 y.o. (range 28-95), 14.5% African-American and the remainder Caucasian, with 28.6% ISS stage 1, 48.7% ISS stage 2, 21.9% ISS stage 3, and 24.5% unknown. At diagnosis for the MM patients, 67% presented with lytic bone disease.
Out of 675 MM patients, there were 52 (7.7%) patients with < 10 ng/mL 25-OH-Vit D, 394 (51%) with low vit D (10-30 ng/mL), and 229 (39%) for 25-OH-Vit D 30-100 ng/mL. There was no correlation between 25-OH-Vit D and BMI or creatinine, but there was a strong correlation with race (r=0.18, p<0.000026).
Among the MM patients, log-rank [Mantel-Cox] analysis of overall survival with serum 25-OH-Vit D including all groups demonstrated no significant differences (p=0.9725) with only 101 events. There was no correlation between 25-OH-Vit D and the presence on CD138-selected FISH of 1q21 amplification (p=0.196), 17p (p53) deletion (p=0.68), or 13q deletion (p=0.812).
Conclusion: The majority of myeloma patients are vitamin D deficient, but this was not associated with worsened overall survival or with high risk cytogenetics. Cox proportional hazards analyses of survival adjusted for significant univariate covariates will be presented at the meeting. Correlations with presence or absence of diffuse lytic bone disease, severity of renal insufficiency, and race will also be presented at the meeting.

Disclosures
No relevant conflicts of interest to declare.
Re-Challenging with Anti-CD38 Monotherapy in Triple-Refractory Multiple Myeloma Patients Is a Feasible and Safe Approach
Authors: Lund Johan , Alici Evren , Chrobok Michael , Gruber Astrid , Ahmadi Tahamtan , Khan Imran , Nahi Hareth 
Published: October 2019

Abstract
Multiple Myeloma patients refractory to both proteasome inhibitors and immuno-modulatory drugs have poor prognoses, with median overall survival estimates of 9. We present data from two patients with MM in disease progression on ongoing treatment; both had received Daratumumab (Dara) as monotherapy earlier and were re-challenged with Dara on relapse.
Bone Marrow and blood samples were collected before start of treatment and the later before administration of each dose. Detailed analyses of circulating cell populations were performed.
We demonstrate that Dara had durable single-agent activity on re-treatment in both patients while both patients had no effective treatment options. As expected, we show that following initial Dara treatment, MM cells at relapse retained high levels of CD38 expression. Dara treatment depletes circulating NK cells almost immediately after the start of the treatment. Furthermore, both NK cells and CD8+ populations were partially increased at treatment interruption. Anti-inflammatory myelomonocytic cells showed a sharp decrease at the same time.
These data strongly suggest that continuous treatment with Dara decreases ADCC mediated antitumor activity using two independent mechanisms, which can both be recovered by a short treatment interruption. In line with this, maintenance treatment should include an intermittent treatment regime with appropriate time for recovery.
Figure 1. Figure 1.

Disclosures
Off Label Use: In this study Daratumumab was used in a compassionate use program provided by Janssen.. Ahmadi:Janssen: Employment. Khan:Janssen: Employment. Nahi:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
Clinical Analysis of Thromboembolism Associated with Lenalidomide-Based Regimens for Multiple Myeloma Patients
Authors: Qu Xiaoyan , Gu Yan , Li Jianyong , Chen Lijuan 
Published: October 2019

Abstract
Objective: To investigate and analyze the incidence, risk factors, prophylaxis and treatment of thromboembolism associated with lenalidomide-based regimens for multiple myeloma (MM) patients.
Methods: 22 newly diagnosed / relapsed MM patients received lenalidomide-based regimes from May 2013 to May 2015 in our department. All diagnosis of thromboembolism were based on objective clinical symptoms, and confirmed by imaging (lower extremity vascular ultrasound, chest CT angiography (CTA), and two-dimensional echocardiography). Investigatethe incidence of thethromboembolism, and analyze the prophylaxis and treatment for the thromboembolism according to risk factors such as patients' characteristics, disease status, and therapy regimes.
Results: Aspirin was used as thromboprophylaxis in 16 patients, low molecular weight heparin (LMWH) in 2 patients, and warfarin in 1 patient, while 3 patients received no thromboprophylaxis. There were 4 cases were diagnosedas thromboembolism with the incident of 18.2%. Threeof them were deep vein thrombosis (DVT), while 1 patient was combined withpulmonary embolism (PE), andthe rest one was found thromboembolism in the left atria. The chemotherapy regimes were lenalidomide plus dexamethasone (≤40mg qw). Other risk factors include: old age, male, immobility, central venous catheter (CVC), surgical history, hypertension, cardiovascularevent, IgG/IgA and light chain type, newly diagnosis, and erythropoietin (EPO). The management of thromboembolism included LMWH, warfarin, venous filter placement, adjustment of chemotherapy regimes and maintenance therapy of antithromboembolism. All the 4 patients were well managedat the last follow-up.
Conclusion: Thromboembolism was one of the most common non-hematologic adverse events of lenalidomide-based therapy. Aspirin was an effective option for thromboprophylaxis. More cases will be observed for longer time to optimize further evaluations forantithromboticprophylaxes, which include risk stratification-based prophylacticstrategies, new predictors and specific assessment of all thromboprophylaxis options.

Disclosures
No relevant conflicts of interest to declare.
Fetal Liver-Derived Stem Cells Ameliorate Immune Functions in Leptin Receptor-Deficient Mice
Authors: Li Ming , Adachi Yasushi , Ikehara Susumu 
Published: October 2019

Abstract
Fetal liver (FL) contains hepatic stem cells, hematopietic stem cells, and mesenchymal stem cells, as well as pluripotent stem cells and very small embryonic-like stem cells. FL has thus been available as a source of stem cells for regenerative medicine. Our previous report suggested that combining FL cell transplantation with the transplantation of fetal thymus prevented tumor growth in tumor-bearing mice. Moreover, in animal models, intra bone marrow-bone marrow transplantation (IBM-BMT) has proven to be the best approach for allogenic BMT. We here propose that transplanting FL cells by IBM-BMT can improve immune functions in leptin receptor-deficient (db/db) mice. FL cells were collected from FLs of C57BL/6 mice at 16 days post coitum, and then transplanted by IBM-BMT to leptin receptor deficent mice, an animal model of type 2 diabetes with obesity. Our results showed that the body weight was significantly lowered in the treated db/db mice than in the sham-treated db/db mice. The plasma IL-6 level significantly decreased and adiponectin level significantly increased after the transplantation of FL cells. Blood glucose levels also significantly decreased although not to within the normal range. This is the first report that the transplantation of FL cells may improve immune function, resulting in increased adiponectin levels, and decreased body weight in db/db mice.

Disclosures
No relevant conflicts of interest to declare.
Personalized Prophylaxis with Human-Cl Recombinant FVIII in HA Patients
Authors: Klamroth Robert , Lissitchkov Toshko , Rusen Luminita , Walter Olaf , Bichler Johann , Pasi K John , Tiede Andreas , Knaub Sigurd 
Published: October 2019

Abstract
Background
Prophylactic therapy aims to maintain sufficient factor VIII (FVIII) plasma levels to prevent bleeding. FVIII plasma trough level and time spent above a certain threshold are mainly determined by the half-life of the FVIII concentrate and the injection interval.
Aims
A clinical study was conducted to investigate the efficacy of individually PK-tailored prophylaxis with Human-cl rhFVIII.
Methods
This prospective, open-label, multicenter phase 3b study included previously treated immunocompetent adult patients with severe hemophilia A without past or present inhibitors. Each patient started with a PK evaluation (single dose of 60 ± 5 IU/kg) followed by 1-3 months of routine prophylaxis (i.e. 30-40 IU/kg every other day or 3 times per week, Phase I) until individual PK data was analyzed. It was calculated, which dose and injection interval would theoretically result in a trough FVIII level of ≥1%. Then, prophylaxis was continued for 6 months using the individually recommended treatment scheme (Phase II).
Results
The study enrolled 66 patents from 20 centers across 8 countries. The majority of patients (62.1%) had been treated on-demand only before study entry. Their median annualized bleeding rate (ABR) was 41. Key outcomes of the personalized prophylaxis are: The prophylactic injection interval was extended from usually 3 times per week in Phase-I to twice per week or less in 58% of patients.The median dosing interval was 3.5 days.73% of patients did not experience any bleeding episode.The mean ABR in phase-II was 1.45 (3.16 in Phase-I).The median weekly prophylactic dose decreased by nearly 10% compared to Phase-I.There were no inhibitors and related serious adverse events.
Conclusion
The data suggest that personalized prophylaxis with Human-cl rhFVIII results in a more convenient treatment for more than half of the patients with lower factor consumption and a lower ABR while remaining safe and efficacious.

Disclosures
Klamroth: Biogen and SOBI: Honoraria, Speakers Bureau; Bayer, Baxter, CSL Behring, Pfizer, Novo Nordisk, and Octapharma: Honoraria, Research Funding, Speakers Bureau. Rusen:Octapharma: Other: Investigator. Walter:Octapharma: Employment. Bichler:Octapharma AG: Employment. Pasi:Biogen, Octapharma, Genzyme, and Pfizer: Consultancy, Honoraria; Octapharma: Research Funding. Tiede:Octapharma: Other: Investigator, Speakers Bureau; Leo Pharma: Consultancy, Honoraria; SOBI: Consultancy, Honoraria; Boehringer Ingelheim: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novo Nordisk: Consultancy, Honoraria, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; Biogen Idec: Consultancy, Honoraria; Biotest: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Investigator, Research Funding; Baxter: Consultancy, Honoraria, Research Funding; Coachrom: Research Funding. Knaub:Octapharma: Employment.
Prolonged Survival in Philadelphia Positive Acute Lymphoblastic Leukemia Treated with Autologus Stem Cell Transplantation in the Inhibitor Tyrosine Kinase Era : A Retrospective Study
Authors: Favennec Camille , Chretien Marie-Lorraine , Legouge Caroline , Bastie Jean-Noel M. , Caillot Denis 
Published: October 2019

Abstract
With tyrosine kinase inhibitors (TKI) containing regimen and without allogenic stem cell transplantation (SCT), some studies showed prolonged survival in Philadelphia positive (Ph+) acute lymphoblastic leukemia (ALL), questioning the place of the allogenic SCT in the TKI era. We retrospectively reported the outcome of 39 patients with ALL Ph+ cured at the Bocage hospital, Dijon, France. The complete remission rate (CR) after induction was 100%, 1 patient died during consolidations. Two patients received an allogenic SCT and died of treatment related toxicity. Thirty six patients were referred to an autologus SCT strategy, in case of collection failure (7 patients) they received prolonged chemotherapy, for all TKI was given until progression or death. In this group the 5 years probability of overall survival and progression free survival are 60% and 53% respectively. Twenty two patients are alive in CR, 13 relapsed, 1 died in CR. Older age and high white blood count at diagnosis are bad prognostic factors. There were no correlation between minimal residual disease and prognosis. Our study showed prolonged survival is possible without allogenic SCT, in the TKI era. Autologus SCT is easily accessible and is associated with a very low mortality. These results should be confirmed by prospective studies including a larger number of patients.

Disclosures
No relevant conflicts of interest to declare.
Local Experience with Autologous Stem Cell Transplant in Multiple Myeloma at a Public Institution (Instituto Nacional de Cancerologia)
Authors: Cervera Eduardo , Torres Jorge Carlos , Zapata Nidia P. , Labardini Juan Rafael , Espinoza Jose Ramiro , Vieyra Magnolia , Sosa Antonio , Lozano Valentin , Candelaria Myrna , Meneses Abelardo 
Published: October 2019

Abstract
Introduction.
Autologous stem cell transplant is considered the standard of care in young (<70) fit patients with Multiple Myeloma. We know that intensive chemotherapy or stem cell transplant do not produce a cure, but it does prolong event free survival and overall survival.
The aim of this study is to report 15 years of experience in stem cell transplant at the Multiple Myeloma (MM) clinic at Instituto Nacional de Cancerologia (INCan).
This is a retrospective, observational trial, we reviewed clinical and electronic files of patients that received an autologous stem cell transplant between January 1st of 2005 and March 1 2015. We assessed clinical status, demographic variables, disease status and clinical outcome of the patients that were included in the study.
48 patients were included into the study, 25 males and 23 females, we grouped the patients according to age, <35 years (2 patients), <50 years (14 patients), 50-65 years (31 patients), >65 years (1 patient).
34 patients had a normal karyotype, 4 had 13q14, 2 had MLL deletion and 8 did not had a karyotype performed. According to the M component we had 6 IgA patients, 32 IgG, 1 IgM, 1 Kappa, 5 lambda, 2 non secretory and 1 combined.
According to ISS, 34 patients were assigned a ISS of 1, 10 a SS of 2, and 4 a ISS of 3. The majority of our patients were transplanted within the first line of treatment, 2 within the second line and none with more than 2 lines of treatment.
20 patients that received thalidomide plus dexamethasone achieved complete remission prior to transplant. 14 patients received thalidomide plus dexamethasone achieved very good partial response. 4 patients that received bortezomib plus thalidomide or dexamethasone achieved complete remission prior to transplant. 4 patients received bortezomib plus thalidomide or dexamethasone achieved very good partial response prior to transplant. 3 patients that received two lines of treatment achieved complete remission prior to transplant. 3 patients achieved very good partial response prior to transplant and received more than two lines of treatment.
Time from diagnosis to transplant had a mean time of 17.4 months, with 6-12 months as the most prevalent group with 20 patients, followed with 13 patients in the 12-24 months window. 17 tandem transplants were performed.
From the 25 patients that received a ASCT and were in CR, 19 maintained that response, from the 23 patients that achieved VGPR 20 maintained that response, 1 achieved partial response (PR), 4 had stable disease, and 4 had progression of the disease.
We are looking forward to presenting the full data of our analysis. Since our casuistry does not differ from the international reports.

Disclosures
No relevant conflicts of interest to declare.
Haploidentical Donor Transplantation Is Not Inferior to Identical Sibling Donor for Patients with Chronic Myeloid Leukemia in Blast Crisis
Authors: Ma Yanru , Xu Lanping , Huang Xiaojun 
Published: October 2019

Abstract
Objectives: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for patients with chronic myeloid leukemia (CML) in blast crisis (BC). Haploidentical donors (HID) are immediately available for almost all of them. We compare the outcomes of HID transplantation with those of matched related donor (MRD) transplantation in cohort study.
Methods: We studied 90 T-replete HID (n=67) and MRD (n=23) HSCT for CML-BC patients in our center from Jan 1st, 2001 to September 30, 2013. After transplantation, patients received tapering immunosupressant or TKI or donor lymphocyte infusion (DLI) or combined therapy as intervention based on BCR-ABL levels.
Results: Of the 86 engrafted patients, 30 received intervention after transplantation. The 1-year cumulative incidence of intervention in HID transplants was significantly lower than in MRD transplants, 24.7% vs. 56.5% (P=.002). At 3 years, overall survival (OS) was similar (60.0% vs. 53.3%), 3-year event-free survival (EFS) higher (35.8% vs. 13.0%; P=.002) in HID transplants. Three-year incidences of transplant related mortality (TRM) and relapse did not significantly differ.
Conclusions: HID transplantation achieves comparable OS with less post-transplant intervention, which is not inferior to MRD in CML-BC patients, and might be regular donors for those who need urgent transplantation.

Disclosures
No relevant conflicts of interest to declare.
Allogeneic Stem Cell Transplantation in a Pediatric Patient with Whim Syndrome
Authors: Bhar Saleh , Yassine Khaled , Martinez Caridad , Sasa Ghadir S. , Naik Swati , Mahoney Donald , Allen Carl , Ahmed Nabil , Hegde Meenakshi G. , Heslop Helen E. , Gottschalk Stephen , Krance Robert A. , Leung Kathryn S. 
Published: October 2019

Abstract
WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis) is a rare autosomal dominant immunodeficiency disorder that is caused by a gain in function in cysteine-X-cysteine chemokine receptor 4 (CXCR4) gene. Affected individuals have recurrent infections of the respiratory tract and soft tissues, and marked susceptibility to warts caused by human papilloma viruses (HPV). Patients have an increased risk of malignancy (lymphoma) and HPV-associated cancers. The optimal therapy for WHIM syndrome has not been defined and treatment has been with supportive care using intravenous immunoglobulin (IVIG) and granulocyte colony stimulating factor (G-CSF). New CXCR4 antagonist therapies are still in either phase I trials (plerixafor) or considered experimental (Chlacone-4).
A successful umbilical cord blood transplant has been reported by Kriven et al. Here we describe a successful matched unrelated allogeneic stem cell transplant (SCT) in a girl with WHIM syndrome caused by a known mutation in the CXCR4 gene.
This patient was diagnosed at birth with familial congenital neutropenia as findings were similar to those for the patient's mother and maternal grandmother. A complete blood count showed pancytopenia (WBC= 1.03 x103/µL, hemoglobin= 9.2 g/dL, platelet count= 74,000/µL, ANC= 70). Despite G-CSF and IVIG therapy, the patient had recurrent infections with sinusitis and pneumonia, along with progressive organomegaly with progressive pancytopenia.
At the age of 4, the patient underwent matched unrelated SCT with a fully ablative regimen [busulfan 0.8 mg/kg/dose for 16 doses (days -9, -8, -7, and -6), cyclophosphamide 50 mg/kg/dose for 4 doses (days -5, -4, -3, and -2) and alemtuzumab 5 mg/day (weight-based dosage) for 3 doses (days -5, -4, and -3)]. Tacrolimus and mini methotrexate (on days +1, +3, +6 and +11) were given for GVHD prophylaxis. Neutrophil and platelet engraftment occurred on days + 21 and + 45, respectively. The patient is 100% donor chimeric. Post-transplant course has been complicated by grade II skin GVHD treated successfully with oral and topical steroids. The patient also developed adenovirus, BK virus and HHV-6 viral reactivations but without disease. The patient is now approximately 2 years post SCT with durable engraftment, normal humoral immune reconstitution and no chronic GVHD.
Thus, stem cell transplant following myeloablative conditioning can be accomplished for patients with WHIM syndrome. Furthermore, transplantation performed at the patient's young age likely prevented complications of recurrent infections and warts.

Disclosures
Allen: NovImmune: Consultancy, Other: unpaid; Roche: Consultancy, Other: unpaid. Heslop:Cell Medica: Other: Licensing Agreement; Celgene: Other: Collaborative research agreement.