bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progressive Increase Of Thymoglobulin Severe Infusion Reactions Used In The Conditioning Regimen Of Allogeneic Stem Cell Transplantation. Comparative Study Between 2004 and 2012
Authors: Yanez Lucrecia , Pereira Brenda López , Bermudez Arancha , Insunza Andres , Richard Carlos , Ruiz Mario Gonzalez , Cuaresma Esmeralda , Conde Eulogio 
Published: October 2019

Abstract

Introduction
Thymoglobulin (ATG) infusion-related reactions in stem cell transplant (SCT) recipients are frequent. Minor reactions as fever and chills are the most usually observed. Severe and potentially life-threatening reactions are rare (>1/10.000 and <1/1000) and are associated with hypotension, oligoanuria, respiratory and heart impairment,

Objective
To analyze the adverse events observed during ATG infusion in patients undergoing SCT and treated with ATG for GVHD prophylaxis. The emergence of fever, chills, rash, pruritus, gastrointestinal symptoms, cephalea, peripheral edema, hypotension, oligoanuria, pulmonary edema, dyspnea, chest pain, arrhythmia and death during ATG infusion were collected. Premedication with corticosteroids, acetaminophen and antihistaminics, and the needs of additional treatment, oxygen support, diuretics and treatment discontinuations or switch were also analyzed.

Patients and Results
Sixty-five patients received ATG since 2004 to June 2012. Patients were grouped into three periods: first (2004-2006, 13 patients), second (2007-2009, 25 patients) and third (2010-2012, 27 patients). In all periods total median dose of ATG was 7.5 mg/kg. Fourty-nine patients (75%) developed infusion-associated reaction, being higher into the third period (46%, 72%, 93%, p< 0.01). The incidence of minor reactions as fever (90%), chills (57%), and skin reaction (35%) was similar in the three periods. Moderate reactions as peripheral edema (0%, 11%, 61%, p <0.001) and gastrointestinal symptoms (0%, 13%, 52%, p <0.002) were higher into the third period. Fifteen patients (31%) developed serious reactions and the majority accounted into the last period (29%, 11%, 48%, p=0.04). Dyspnea (25%) and pulmonary edema accounted for 9% of patients and both were higher into the third period (14%, 6%, 44%, p= 0.02) and (0%, 0%,26%, p=0.02). Although we did not reach statistical differences (p = 0.09) there were more cases of hypothension (0%, 6%, 26%) and oligoanuria (0%, 0%, 17%) in the last period. One patient developed chest pain associated with arrhythmia in the third period. None patient died during or shortly after ATG infusion. The needs of additional treatment, specially steroids (29%, 33%, 64%, p=0.09), oxygen (0%, 0%, 57%, p = 0.002) and diuretics (0%,0%,83%, p =0.001) were mostly used in the last period.

Conclusion
Since 2010, the incidence of moderate and severe ATG infusion-associated reactions in patients undergoing SCT is significantly more frequent than previously and in our opinion these facts may be confirmed in other studies.

Disclosures:
No relevant conflicts of interest to declare.
Risk Factor Analysis Of Idiopathic Pneumonia Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation In Children
Authors: Sano Hirozumi , Kobayashi Ryoji , Iguchi Akihiro , Suzuki Daisuke , Kishimoto Kenji , Yasuda Kazue , Kobayashi Kunihiko 
Published: October 2019

Abstract
Idiopathic pneumonia syndrome (IPS) is a critical complication following allogeneic hematopoietic stem cell transplantation (HSCT); however, few reports have analyzed the risk factors for IPS in children. A total of 210 consecutive pediatric patients, including 131 boys and 79 girls, with various hematologic malignancies, aplastic anemia, or solid tumors who underwent allogeneic HSCT were analyzed to clarify the incidence and risk factors for IPS. Patient and transplantation characteristics after allogeneic HSCT were compared between patients with and without IPS. Cumulative incidence rates of IPS 120 days after allogeneic HSCT were 6.7% (14/210). Of 14 patients with IPS, 11 (78.6%) died after developing IPS. The presence of prior HSCT was more frequent in patients with IPS (IPS group) than in those without (non-IPS group) (35.7 vs 12.8%, respectively, P=0.018). The IPS group contained more patients with acute GVHD (grade II-IV) than the non-IPS group (50.0 vs 18.9%, respectively, P=0.006). The association of these two factors with IPS was further confirmed by multivariate analysis. We should be aware of these risk factors in patients who have undergone allogeneic HSCT. The rapid progression to respiratory failure and high mortality rate following the onset of IPS, despite advances in supportive care, require the development of new preventive measures and treatment modalities. Further preclinical and clinical studies are required to understand the pathogenesis of IPS and improve the prognosis of HSCT recipients.

Disclosures:
No relevant conflicts of interest to declare.
Immune Reconstitution In Fanconi Anemia Patients Following Allogeneic Bone Marrow Transplantation
Authors: Beltrame Miriam P , Malvezzi Mariester , Carmem Bonfim , Covas Dimas T , Orfao Alberto , Pasquini Ricardo 
Published: October 2019

Abstract

Background
Fanconi anemia is an autosomal recessive or X-linked genetic disorder characterized by bone marrow (BM) failure/aplasia. Failure of hematopoiesis results in depletion of the BM stem cell reservoir, which leads to severe anemia, neutropenia and thrombocytopenia, frequently requiring therapeutic interventions including hematopoietic stem cell transplantation (HSCT). Successful BMT requires reconstitution of normal immunity.

Methods
In the present study, we performed a detailed analysis of the distribution of peripheral blood subsets of T, B and NK lymphocytes in 23 patients with Fanconi anemia before and after BM transplantation (at days D+30, D+60 and D+100, D+180 D+270 and D+360). In parallel, we also compared the patients groups who received related and unrelated bone marrow, pre and one year after BMT.

Results
After transplantation, we found different kinetics of recovery for the distinct major lymphocyte subsets. NK cells were the first to recover, followed by cytotoxic CD8+ T-cells and B-cells, and finally also the CD4+ T-helper cells. Early recovery was at the expenses of memory cells which would therefore be potentially derived from the graft whereas, recent thymic emigrant (CD31+ CD45RA+) and naive CD4+ or CD8+ T-cells, rose only 6 months after HSCT, in the presence of immunosuppressive graft-vs-host disease (GVHD) prophylactic agents. While only slight differences were observed in the early recovery of cytotoxic CD8+ T-cells among cases receiving a graft from related vs. unrelated donors, cases suffering from GVHD displayed more marked differences vsother patients.

Conclusions
Overall, our results support the utility of post-transplant monitoring of peripheral blood lymphoid subsets, for improved monitoring and follow-up of Fanconi anemia patients undergoing BMT.

Disclosures:
No relevant conflicts of interest to declare.
Second Autologous Stem Cell Transplant As Salvage Therapy For Multiple Myeloma
Authors: Elemary Mohamed , Emara Mohamed , Sharma Ankur , Sarker Sabuj , Sabry Waleed , Stakiw Julie 
Published: October 2019

Abstract

Introduction
Therapeutic options for patients with multiple myeloma whose disease has relapsed after a prior autologous
SCT include novel agents, traditional chemotherapy or a second transplant, with no clear standard of care. Limited data are available regarding the value of salvage therapy with a second autologous SCT in patients who relapse after the first one, and the factors that determine the outcome of the second SCT.
We retrospectively reviewed our experience at Saskatoon Cancer Center with salvage autologous SCT for relapsed multiple myeloma.

Methods
Thirty three patients had received a salvage auto-SCT at our institution between February 2000 to February 2012.
Median age at second SCT was 60 years (range; 46-71), Median time to relapse after the first SCT was 32 months (range; 3-80). Median interval between the first and second transplant was 34 months (range; 4-85).
Re-induction therapy prior to second transplant contained combination with novel therapies (Bortezomib , lenalidomide or Thalidomide) in Thirteen patients ( 40 %) and the rest received conventional combination chemotherapies.
Median line of therapies before the second SCT was 1 (range 0-3) with 23 patients (70%) received less than 2 lines and 30% received more than 2 lines.

Results
Responses to second autologous SCT at day 100 showed CR in 21%, VGPR 30 %, PR 42% with ORR 93 %.
Non relapse mortality at day 100 after second transplant was 3 % (no= 1)
With a median follow up time of 24 months (range 1-99) from the salvage SCT, the median PFS was 27 months
(range 1-89) and the median overall survival (OS) was 36 months ( range 1-99)
Eleven patients had TTP inversion (PFS longer after the second transplant) with a median increase of 18 months , of note only two of them received novel agents for salvage, but 70 % required less than two lines prior to salvage SCT.
In univariate analysis, patients who had received < 2 lines of therapy prior to salvage SCT (23/33) had significantly higher median TTP of 31 and OS of 52 months, compared to 19 and 33 months for patients who had received ≥2 lines of therapy (10/33). (P = 0.04)
Patients who had relapsed more than 2 years post 1st SCT (18/33) had a significantly higher median TTP and OS of 27 and 39 months respectively compared to 22 and 24 months patients who had relapsed less or equal to 2 years (15/33) (P= 0.04)
In multivariate analysis, only response to salvage SCT > PR had an impact on TTP and OS; however it was not statistically significant.

Conclusion
Second salvage auto-SCT generally is safe and effective in patients with relapsed multiple myeloma. Patients with ≥2 prior lines of therapy and a TTP after initial transplant of ≤24 months are unlikely to benefit significantly. Salvage auto-SCT should therefore be considered for appropriate patients with relapsed multiple myeloma.

Disclosures:
No relevant conflicts of interest to declare.
Comparison Of Allogeneic Hematopoietic Cell Transplantation Versus Chemotherapy In Patients With Acute Myeloid Leukemia In First Remission
Authors: Lai Xiaoyu , Zhu Mingyu , Luo Yi , Tan Yamin , Zheng Weiyan , Zhu Yuanyuan , Shi Jimin , Huang He 
Published: October 2019

Abstract

Objective
To compare the effiency and safety of allogeneic hematopoietic stem cell transplantation versus chemotherapy in patients with acute myeloid leukemia in first remission

Methods
Clinical data of 225 patients who were diagnosed AML between Jan 1st 2006 to Dec 31 2011,getting CR1 after chemotherapy,of which 77 patients received allogeneic stem cell transplantation after CR1(SCT group) and 148 patients still received chemotherapy(CTx group).Follow up to Dec 31 2012,we evaluate the RFS and OS between SCT and CTx group

Results
Median follow up timeFSCT 34.00 monthsGCTx 25.50 months.The median CR period(months): SCT 33.00 vs CTx 22.50(p<0.01)G 3y OS: SCT 75.8% vs CTx 55.8%(p<0.001),both in intermediate and unfavourable karyotype group, SCT is better than CTx with statistical significance. 3y RFS: SCT 72.7% vs CTx 44.8%(p<0.001),both in intermediate and unfavourable karyotype group, SCT is better than CTx with statistical significance. Among the 148 patients in CTx group,79 died by the end of the follow up time,of which 31 died of TRM.In the SCT group, the TRM rate was 11/18,the TRM rate has no statistical significance between the two groups.

Conclusions
Allogeneic hematopoietic stem cell transplantation is safe and effective for AML-CR1 patients who are categorized into the intermediate or unfavourable group according to the SWOG criteria.

Disclosures:
No relevant conflicts of interest to declare.
Pre-Transplantation Assessment Of Mortality (PAM) Score Is a Poor Predictor For Survival In The Highest Risk Group When Used In T Cell Depleted Myeloablative Allogeneic Transplants
Authors: Kishore Bhuvan , Wiseman Daniel , Nikolousis Emmanouil , Lovell Richard , Milligan Donald , Holder Kathy , Bratby Lynn , Murthy Vidhya , Paneesha Shankaranarayana 
Published: October 2019

Abstract

Introduction
PAM score is a simple tool for predicting mortality risk in patients undergoing allogeneic bone marrow transplantation. Originally developed and validated at Fred Hutchinson Cancer Research Center, Seattle, this has recently been validated in 276 patients from Japan. We retrospectively evaluated this in our cohort of T deplete myeloablative allogeneic transplants as there are no published studies validating PAM score in T deplete myeloablative setting.

Results
After a median follow up of 63 months 51% of the patients are alive. The predicted mortality for category 2, 3 and 4 patients via PAM score was 28%, 48% and 28% respectively. This was concordant with the predicted mortality at 2yrs for category 2 and 3. Category 4 was not concordant (Chi-square test, P=0.0035).

Disclosures:
Milligan: Celgene: unrestricted educational grant Other.
Abnormal Expression Of Shelterin Is Associated With Short Telomere and Immune Disorder In Severe Aplastic Anemia
Authors: Shao Zonghong , Wang Ting , Fu Rong 
Published: October 2019

Abstract

Objective
To identify changes in telomere length and gene expression of shelterin (which is composed of six core components: TRF1, TRF2, POT1, TIN2, TPP1 and RAP1) in severe aplastic anemia(SAA). Looking for the reason why telomere getting short in SAA patients and the pathway that abnormal telomeres cause AA.

Methods
15 controls and 27 cases of SAA were enrolled in this study. There were 9 untreated and 18 recovering patients. Peripheral white blood cells(PWBCs)’ telomere length was tested by southern blot and gene expression of shelterin were detected by RT-PCR. Bone marrow mononuclear cells (BMMNC) from controls were cultured in different culture medium which were fetal calf serum only , SAA serum only, fetal calf serum containing TNF-α and fetal calf serum containing IFN-γ respectively. The apoptosis of these cells were detected by flowcytometry. The mRNA expression of POT1 were tested by RT-PCR , all the protein below including ATR, phosphorylated ATR, and phosphorylated ATM/ATR substrate were detected by western blot.

Results
Telomeres length of PWBCs were found significantly shorter in SAA untreated group (4.89±1.66)kb and recovering group (7.04± 1.47 )kb than control group (11.65±5.55)kb (P<0.05). Telomeres Length of PWBCs turned shortening in accordance with TH/S (CD4+Tcells/CD8+Tcells ratio) decreasing (r=0.593, p=0.007). The mRNA expression of POT1 decreased in SAA untreated group( 0.29(0.09-0.58)) than in recovering group( 0.78(0.22-2.69)) and controls (1.88(0.93-3.81)), (P<0.05). No differences about mRNA expression of TRF1、TRF2、TIN2、TPP1 and RAP1 were found among SAA untreated group, recovering group and controls in PWBCs. Undoubtedly, cells that cultured in SAA serum got more apoptosis(13.88±4.55) than that cultured in fetal calf serum(9.85±2.67)(P<0.05). The mRNA expression of POT1 was significantly declined in cells that from SAA patient uncultured group (0.45±0.29) , normal BMMNCs cultured by AA serum group (0.59±0.49) and IFN-γ group (0.40±0.35) than the cells cultured only by fetal calf serum group (1.19±0.62). ATR, phosphorylated ATR, and phosphorylated ATM/ATR substrate were found significantly increase in cells from AA serum group , TNF-α group and IFN-γ group than fetal calf serum group.

Conclusion
SAA patients have short PWBCs’ telomeres length which was in accordance with TH/S.TNF-α and IFN-γ which were found at high concentration in SAA decades before may be the effective component that can trigger apoptosis through POT1 and the pathway of ATM/ATR and eventually lead to SAA.

Disclosures:
No relevant conflicts of interest to declare.
Identification of MLL-Fusion/Myc⊣miR-26a/Mir-29a⊣Tet1 Signaling Circuit in MLL-Rearranged Leukemia
Authors: Huang Hao , Jiang Xi , Wang Jinhua , Li Yuanyuan , Chen Ping , Arnovitz Stephen , Li Shenglai , Wang Yungui , Weng Hengyou , Neilly Mary Elizabeth , Li Zejuan , Chen Jianjun 
Published: October 2019

Abstract
Approximately 10% of human acute leukemias are involved in chromosomal translocations between the mixed lineage leukemia (MLL) gene and over 50 partner genes. MLL-rearranged leukemias occur preferentially in infant and young children and are often associated with poor outcome. MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs which repress gene expression and mRNA stability by base pairing with target mRNAs usually at the 3’-untranslated regions (UTRs). The ten-eleven translocation 1 (TET1), the founding member of the TET family of enzymes (TET1/2/3) that convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), was first identified in MLL-rearranged leukemia. But its definitive role in leukemia was unclear until our recent report published in PNAS (Huang H. et al. 2013). In contrast to the frequent repression and tumor-suppressor roles of the three TET genes observed in various cancers, we showed that TET1 is a direct target of MLL-fusion proteins and significantly up-regulated in MLL-rearranged leukemia, leading to a global increase of 5hmC level. Furthermore, Tet1 plays an indispensable oncogenic role in MLL-rearranged leukemia, through coordination with MLL-fusion proteins in regulating their critical co-targets including Hoxa/Meis1/Pbx3 genes. However, whether TET1 is also post-transcriptionally regulated by miRNAs in hematopoietic cells remains unknown. In the present report, through genome-wide miRNA expression profiling assays, we found that miR-26a and miR-29a were expressed at a significantly lower level in MLL-rearranged AML than in normal controls. The down-regulation of miR-26a and miR-29a is, at least in part, attributed to the transcriptional repression mediated by MLL-fusion proteins and MYC. Interestingly, both miR-26a and miR-29a target TET1 directly at the post-transcriptional level. More importantly, we showed that miR-26a or miR-29a significantly inhibited MLL-fusion-mediated cell transformation in vitro and leukemogenesis in vivo down regulating expression of Tet1 and its downstream target genes. Thus, our data suggest that the transcriptional repression of miR-26a and miR-29a is required for the aberrant overexpression and potent oncogenic role of TET1 in MLL-rearranged leukemia, and that miR-26a and miR-29a play important tumor-suppressor role in leukemogenesis.
Taken together, our data reveals a previously unappreciated signaling pathway involving the MLL-fusion/Myc⊣miR-26a/miR-29a⊣Tet1 circuit in MLL-rearranged leukemia. Our data not only provides novel insight into our understanding of the complex molecular mechanisms underlying the pathogenesis of MLL-rearranged leukemia, but also may lead to the development of novel, more effective therapeutic strategies to treat this type of dismal disease.

Disclosures
No relevant conflicts of interest to declare.
Recently Improved Results of Hematopoietic Cell Transplantation in Thalassemia Patients in Asia
Authors: Li Chunfu , Lee Vincent , Ha Shau Yin , Lin Hai Peng , Lee Anselm , Luo Chengjuan , Tan Poh-Lin , Tan Poh-Lin , Li Qi 
Published: October 2019

Abstract
Objective
Hematopoietic cell transplantation (HSCT) is not widely used for patients with b-thalassemia major (TM) so far because of transplant toxicities. Furthermore the tangible outcomes of contemporary HSCTs in Asia are unknown.
Methods
A newly founded consortium named the Viva-Asia BMT Group collected HSCT data retrospectively and investigated whether TM-HSCT outcomes had improved in recent years in Asia and whether an upper age limit can be determined for safe transplantation.
Results
From 1991 to 2012, 422 TM-HSCTs were performed among the 8 Asian centers; half (n=209) were before January 2009 (early cohort) and the other half (n=213) were performed thereafter (recent cohort). All major outcomes including overall survival (OS), TM-free survival (TFS), incidences of graft rejection (GR) and transplant-related mortality (TRM) improved significantly in the recent cohort (OS 93.4%, TFS 88.6%, GR 4.4% and TRM 6.6%) when compared with the earlier cohort (OS 84%, TFS 68.1%, GR 17.1% and TRM 16%). In the recent cohort, favorable OS, TFS, GR and TRM were observed with unrelated donors (n=168, 92.8%, 87.8%, 4.2% and 7.2%, respectively), with one-antigen mismatched parental donors (n=26,100%, 100%, 0% and 0%, respectively), and in patients younger than 10 years (n=173, 96%, 90.8%, 4.7% and 4.0%, respectively). TFS with unrelated cord blood (35.3%) was poor.
Conclusion
The excellent outcomes of contemporary TM-HSCT in general suggest that transplantation is a viable option for many Asian patients, particularly those younger than 10 years from areas with limited resources for chronic transfusion and iron chelation.
Figure 1A OS, TFS, GR and TRM in (A) the total 422 patients, (B) the recent cohort, and (C) the earlier cohort. Abbreviations: GR, graft rejection; OS, overall survival; TFS, thalassemia major-free survival; TRM, transplant-related mortality. Figure 1A. OS, TFS, GR and TRM in (A) the total 422 patients, (B) the recent cohort, and (C) the earlier cohort. Abbreviations: GR, graft rejection; OS, overall survival; TFS, thalassemia major-free survival; TRM, transplant-related mortality.
Figure 1B Figure 1B.
Figure 1C Figure 1C.

Disclosures
No relevant conflicts of interest to declare.
P-Selectin Expression and Platelet Function Are Developmentally Regulated
Authors: Stolla Massiel Chavez , Leyens Kathryn , Catherman Seana C , McGrath Kathleen E , Palis James 
Published: October 2019

Abstract
Platelets have numerous well-defined roles during adult hemostasis, however little is known about whether these functions are developmentally regulated. In the adult, P-selectin is constitutively expressed in megakaryocytes and localized to the membrane of alpha granules. Activation of platelets results in granule secretion and P-selectin surface exposure allowing for recruitment of leukocytes to sites of vascular injury and the formation of leukocyte-platelet aggregates. Here, we examined the expression and function of P-selectin in platelets during murine embryogenesis. Platelets were isolated from timed pregnant outbred-ICR mice at embryonic day 12.5 (E12.5), E15.5, postnatal day 1 (PN1), PN7, PN21, and were assayed for thrombin induced integrin activation and P-selectin translocation. While no significant differences were seen in the ability of embryonic platelets to be activated by thrombin, P-selectin surface expression after thrombin stimulation was significantly reduced in embryonic compared to adult platelets (E15.5 p=.0006, E12.5 p=.0004, PN1 p=.01, n=3, unpaired t-test). Surprisingly, P-selectin expression began to appear on the surface of activated platelets only after birth, approaching 50% and 75% of maternal expression at PN7 and PN21, respectively. No significant difference was seen in VEGF secretion after thrombin activation of E12.5, E15.5 and adult platelets (n=5), suggesting that the lack of P-selectin surface expression was not due to a loss of alpha granule secretion. To further characterize expression of P-selectin, real-time qPCR was performed on mRNA harvested from platelets at E12.5, E15.5, PN1 and adult stages. P-selectin transcript levels were significantly lower in embryonic and PN1 platelets, suggesting that P-selectin expression is transcriptionally regulated. Consistent with this concept, Imagestream analysis indicates that P-selectin protein is absent in megakaryocytes derived from the fetal liver. P-selectin expression on platelets is an important mediator of platelet-leukocyte interactions; therefore, we assayed the ability of platelets to bind to leukocytes in embryonic whole blood. Preliminary data suggest that embryonic platelets do not form leukocyte-platelet aggregates upon ex vivo stimulation with AYPGKF, a Par4 agonist. Taken together, our data indicate that P-selectin expression is developmentally regulated in primary mouse platelets. The absence of P-selectin expression in embryonic platelets correlates with an impaired ability to interact with leukocytes.

Disclosures
No relevant conflicts of interest to declare.