bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Spectrum Of Pathological Findings Of Kidney Injury In The Cases Of Multiple Myeloma: A Clinico-Pathological Study Of 93 Consecutive Autopsy Cases
Authors: Mine Sohtaro , Hagiwara Shotaro , Hirai Risen , Tanimura Akira , Nakamura Miki , Takeshita Masataka , Miwa Akiyoshi , Igari Toru 
Published: October 2019

Abstract

Background
Kidney injury and/or renal failure are common complication in multiple myeloma. Well known mechanism is deposition of free immunoglobulin light chains in renal tubules leading to cast nephropathy and renal failure. In addition, not only cast nephropathy, but also invasion of myeloma cells is frequently found in autopsied cases of multiple myeloma.
Recent development of treatment improved the remission rate and survival of multiple myeloma. Few data exist about pathological findings of kidney injury and it is not well known about kidney findings in autopsy cases at era of novel agent. We investigated the pathological findings and the factors associated with kidney injury in the consecutively autopsy cases.

Methods
We reviewed the autopsy reports and medical records of 93 consecutively autopsied multiple myeloma cases between 1979 and 2012 at the National Medical Center for Global Health and Medicine in Tokyo, Japan. Patient profile, the clinical records including treatment and the duration of illness, the type of monoclonal gammopathy, clinical stage and history of treatment were studied. Durie & Salmon's criteria was used for diagnosis and staging. The pathological findings like cast nephropathy, invasion of myeloma cell at kidney and the other findings of whole samples were studied gross and microscopically. Immunohistochemistry and Congo-red stain were performed.
The pathological findings and the factors were statistically analyzed using Student's t-test and the chi-square test.

Results
In 93 autopsy cases, 58% was male. Mean age and the duration of illness were 64.3(38-85) years old and 41 months (24.4-37.5). Thirteen patients and 14 were treated with SCT and hemodialysis (Table. 1). Cast nephropathy and direct invasion about kidney were observed in 51.2% and 29.3%, respectively. Other frequent finding associated with myeloma was renal amyloidosis (29%). Frequent non-specific findings were arteriosclerosis (76 %), glomerulosclerosis (61%). Combination of findings were found in 66% cases (Fig.1).
The tumor volume in bone marrow (percentage of myeloma cells in cellular component) had correlation to incidence of direct invasion (Pearson's correlation factor is 0.55, p<0.005).

Conclusion
Autopsy findings of the kidney are various, complicated pathological findings of two or more was not uncommon. Frequency of cast nephropathy was high, but the direct invasion of the tumor cells was observed in about one-third of the cases. Correlation was observed between the kidney and invasive tumor burden in the bone marrow. Therefore, in the advanced stage myeloma, when tumor cell occupy more than about 60% of the bone marrow should be considered renal failure mechanism by myeloma cell infiltration.

Disclosures:
No relevant conflicts of interest to declare.
Observations On Eosinophil Ifiltrates in The Bone Marrow Of Patients With Multiple Myeloma. Clinicopathological Correlates
Authors: Brito-Babapulle Finella MC , Cranfield Tanya , Corser Robert B , Dignum Helen , James Christopher , Ganczakowski Mary 
Published: October 2019

Abstract
Mouse eosinophils have been shown in 2011 to be required for the maintenance of long lasting plasma cells in the bone marrow and in maintaining the bone marrow plasma cell microenvironment. Human eosinophils have been shown by Wong et al to support multiple myeloma cell proliferation via a mechanism independent of IL6.
We looked at bone marrow biopsies taken from patients who had a paraprotein and in whom a diagnosis of multiple myeloma was suspected. These samples were taken solely for the purposes of diagnosisng multiple myeloma and were retrospectively reviewed from the point of view of degree of eosinophil infiltration and its correlation with tumour load, bone lytic lesions, plasma cell morphology, whether blastic, crystalline inclusions, Mott cells, flame cells and or lymphoplasmacytoid. There were no cases of IGD or E myeloma or osteosclerotic myeloma.Nonsecretory myeloma and cases of light chain myeloma with or without amyloid were included in the series. Biopsies were not performed from osteolytic lesion unless biopsy was necessary to make a diagnosis of myeloma. Myeloma was diagnosed when plasma cell infiltrate was greater than 10% on bone marrow aspirate with a paraprotein and or lytic lesions. Eosinophil infiltration did not correlate with any of the tumour clinicopathological markers but showed an inverse correlation with degree of plasmacytosis. Eosinophils were hardly ever found in marrow aspirates that had over 70% plasma cells. They were usually found in trephine sections of bone marrow in areas where there was Grade I/II fibrosis and were often found in close proximity to focal areas of plasma cell infiltration. Whether eosinophils play a role in preventing or maintaining malignant plasma cell recurrence is currently being studied.

Disclosures:
No relevant conflicts of interest to declare.
Conservative Management Vs. Allogeneic Hematopoietic Cell Transplantation For Polycythemia Vera: A Systematic Review and Decision-Analysis
Authors: Lacevic Jasmin , Reljic Tea , El Jurdi Najla , Kharfan-Dabaja Mohamed A , Nishihori Taiga , Komrokji Rami S. , Kumar Ambuj , Djulbegovic Benjamin 
Published: October 2019

Abstract

Background
Conservative treatment which typically includes phlebotomy or hydroxyurea or other cytoreductive therapy (plus aspirin) (ConsRxAsa) is effective treatment with acceptable complications for management of polycythemia Vera (PV) but is not considered curative [thus resulting in a shorter life expectancy (LE) in comparison to LE in the general population]. On the other hand, an allogeneic hematopoietic cell transplantation (allo-HCT) from a HLA compatible donor is considered a curative treatment option, but is potentially associated with high-risk of life-threatening complications. We sought to answer the question of which of these two treatment options results in better survival.

Methods
Because there are no direct randomized controlled trials (RCT) addressing the question if ConsRxAsa is superior to allo-HCT, we resorted to a decision-analysis to answer this question. We constructed a Markov model to represent and analyze the decision of ConsRxAsa vs. Allo-HCT. The results of the model were expressed in terms of life expectancy (LE) and survival probabilities. We performed a systematic review (and when possible a meta-analysis) to inform parameters in the model. ConsRxAsa arm was modeled by simulating the natural history of PV. For Allo-HCT arm, we adopted our previously published model (Biol Blood Marrow Transplant 2009;15:1415-21) but modified it to evaluate the effect of both conventional and reduced-intensity allo-HCT performed in chronic phase of PV.

Results
We identified 165 relevant articles of which only 7 described testing various treatments for PV in RCTs. However, most data used to populate the decision model came from one RCT and one cohort study. Using base case of age of 45 years, we estimated a probability of survival at 10 and 20 years of 86% and 67% for ConsRxAsa versus 55% and 32% for allo-HCT (Fig). This translates into an average LE of 17.1 years for ConsRxAsa vs. 11.6 years for allo-HCT, respectively. Sensitivity analysis according to age, early transplant-related mortality, risk of bleeding or thrombosis did not affect the results. Adopting median age of 65 years and comparing reduced-intensity allo-HCT vs. ConsRxAsa, we found that the average LE was 8.6 years for allo-HCT vs. 12.5 in the conservative treatment arm. Again, conservative treatment remained superior under a wide range of assumptions.

Conclusions
integration of current best existing evidence into the decision model shows that conservative management of PV appears to provide a better survival compared to offering an allo-HCT in chronic phase of P. Vera.

Disclosures:
No relevant conflicts of interest to declare.
Low Expression Of Abelson Interactor-1 Is Linked With Systemic Persistence and Acquired Drug Resistance In Bcr-Abl-Induced Leukemias
Authors: Dubielecka Patrycja Marta 
Published: October 2019

The basis for persistence of leukemic stem cells in the bone marrow microenvironment (BMME) remains poorly understood. We present evidence that signaling crosstalk between α4 integrin and Abelson interactor-1 (Abi1) is involved in acquisition of an anchorage-dependent phenotype and drug resistance in Bcr-Abl positive leukemia cells. Comparison of Abi1 (ABI1) and α4 integrin (ITGA4) gene expression in relapsing Bcr-Abl positive CD34+ progenitor cells demonstrated a reduction in Abi1 and an increase in α4 integrin mRNA in the absence of Bcr-Abl mutations. This inverse correlation between Abi1 and α4 integrin expression, as well as linkage to elevated phospho-Akt and phospho-Erk signaling, was confirmed in imatinib mesylate (IM) resistant leukemic cells. These results indicate that the α4-Abi1 signaling pathway may mediate acquisition of the drug resistant phenotype of leukemic cells.

Disclosures:
No relevant conflicts of interest to declare.
Severe Adverse Skin Reaction Used For Sclerodermatous Chronic Graft Versus Host Disease Of The Skin
Authors: Hamm Caroline , Kanjeekal Sindu M. , Shum David , Elfiki Tarek , Mathews John 
Published: October 2019

Abstract
Treatment of sclerodermatous chronic graft versus host disease remains a daunting challenge. Supportive care measures remain the primary mode of therapy with little evidence of treatments that reverse the process. Photopheresis has been used with varying success in this disorder. Recently, case reports and case series have reported on the successful use of imatinib in this disorder(1, 2) Drug intolerance was reported in four of the patients treated.
We report a case of a 40 year old man with extensive scelerodermatous chronic graft versus host disease (GVHD) of the skin ( Skin : score of 3 using the NIH Criteria).
Four years earlier, he underwent a matched unrelated stem cell transplant for chronic myelogenous leukemia. His transplant course was complicated with TTP associated with all standard immune suppressive agents (cyclosporine, tacrolimus, sirolimus). This gentleman developed progressive sclerodermatous skin GVHD. Photopheresis was carried out for two years with stabilization, but no improvement in his symptoms. Imatinib was started due to persistent symptoms (joint restriction Score of 2 in NIH criteria, > 50% of skin involvement, joint Ð score of 3 NIH). 3
Imatinib was started for progressive symptoms and within five days, he was hospitalized with a generalized erythroderma with associated skin sloughing. The Imatinib was stopped and he received high dose steroids with slow improvement of his symptoms. Skin biopsy at that time revealed subcorneal pustular dermatosis; there was no herpes viral effects and special stains were negative for bacterial or fungal organisms. There was a diffuse infiltration of neutrophils. Histological differential diagnosis included pustular psoariasis and Sneedon-Wilkinson syndrome. In view of the history, the concluding diagnosis was exanthematous pustulosis secondary to imatinib.
We recommend that close attention be paid to patients with chronic GVHD treated with imatinib and early intervention with stopping the Imatinib. Steroid worked in this case and should be considered.Blood 2009 Mar. Magro et alArch Dermatol 2008 Sept; 144(9): 1106-9
National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. Diagnosis and Staging Working Group Repor Alexandra H. Filipovich,1 Daniel Weisdorf,2 Steven Pavletic, et al Biology of Blood and Marrow Transplantation 11:945-955 (2005).

Disclosures:
No relevant conflicts of interest to declare.
CMV Reactivation Is Associated With a Lower Incidence Of Relapse After Allo-SCT For ALL
Authors: Tian Hong , Xu Yang , Yang Zhen , Chen Guanghua , Qiao Man , Liu Huiwen , Depei Wu 
Published: October 2019

Abstract

Background
CMV reactivation is an important cause of morbidity and mortality of allogeneic stem cell transplantation (allo-SCT). Recent studies demonstrated reduction of relapse risk after early replicative CMV infection in acute myelocytic leukemia (AML) and chronic myeloid leukemia (CML) patients. Here, we studied the relationship between CMV reactivation and leukemic relapse in acute lymphoblastic leukemia (ALL) patients.

Patients and Methods
115 patients (median age, 28 years; range, 14-56) with de novo ALL underwent allo-SCT from HLA-matched sibling (n=59) donors or unrelated (n=56) donors. CMV pp65 antigenemia was used for monitoring posttransplant CMV reactivation.

Results
CMV reactivation before day 100 was observed in 47 patients (40.9%) (median day, 44 days, range, 10-100 days). The follow-up time varied from 10 to 90 months (median, 43 months), the estimated overall survival at 5 years was 52% in patients without opposed to 68% in patients with early pp65-antigenemia (P =.035). The 5-year disease free survival (DFS) was 39% vs 47% (P =.018). CMV pp65 antigenemia was associated with a decreased risk of relapse by day 100 among patients with ALL (HR 0.41, 95%CI 0.2-0.9) by multivariate analysis. Furthermore, CMV reactivation was associated with increased non-relapse mortality (HR 1.15, 95% CI 0.3-3.6).

Conclusion
Early replicative CMV infection is an independent and substantial factor associated with decreased leukemic relapse risk in ALL transplant recipients.

Disclosures:
No relevant conflicts of interest to declare.
Low Dose Thymoglobulin Results In Improved Outcomes After Allogeneic Unrelated Hematopoietic Stem Cell Transplantation (HCT) For Patients With Acute Myeloid Leukemia/ Myelodysplastic Syndrome Conditioned With Intravenous Busulfan and Fludarabine
Authors: Khaled Yasser , Smith Megan , Smith Tori , Balls Jason , Matar Abraham , Lamontagne Deborah , Ambinder Roy M. , Zakari Ahmed , Solh Melhem M. 
Published: October 2019

Abstract
Low Dose Thymoglobulin Result in Improved Outcomes after Allogeneic Unrelated Hematopoietic Stem Cell Transplantation (HCT) for Patients with Acute Myeloid Leukemia/ Myelodysplastic Syndrome Conditioned with Intravenous Busulfan and Fludarabine.
Intravenous Busulfan/Fludarabine (Bu/Flu) based conditioning regimens have resulted in lower treatment related mortality (TRM) after allogeneic HCT in both reduced and full intensity dosing in AML/MDS. The addition of thymoglobulin to such regimens to minimize the risk of graft versus host disease after unrelated donor (MUD) HCT has been linked to the increased concerns of relapse risk.

Method
In order to study the impact of addition of low dose thymoglobulin to Bu/Flu regimens in MUD recipients, the medical records of 38 consecutive AML/MDS patients who underwent MUD HCT with BU/Flu and low dose thymoglobulin were retrospectively reviewed. All the patients received single daily dose of iv Bu 3.2 mg/kg for 2 days (RIC, Bu2-Flu) or 4 days (FIC, Bu4-Flu) based on age, older or younger than 65 respectively. Fludarabine was given as a single daily dose of 40 mg/Kg for 4 days. Graft versus host disease prophylaxis was Tacrolimus/Methotrexate in FIC recipients and Tacrolimus/Mycophenolate in RIC recipients. Additionally, all the patients received thymoglobulin 1.5 mg/Kg on day -3, -2 and -1. All patients received peripheral stem cells except one patient with mismatch MD who received bone marrow product.

Results
Patient Characteristics are shown in Table 1. All the patient engrafted except one who received marrow product. All the patients but 3 (8%) achieved 90% or more donor chimerism by day 100. With Mean follow up of 500 days (range, 100-1242) the overall survival (OS) was 77% ± 7 (CI 63-91%) at 1 year and 67% ± 9 (CI 49-85%) at 2 years. Similarly, disease free survival was 66% ±8 (CI 50-82%) at 1 and 2 years. Cumulative incidence of acute GVHD grade II-IV was 55% with grade III-IV 12%. Cumulative incidence of chronic GVHD at 1 year was 43% with extensive chronic GVHD in 17%. The regimen was associated with low treatment related mortality (TRM) with cumulative incidence of only 5% at one year, CI 14-21%. The cumulative incidence of relapse at one year was 29%, CI 17-49%. On univariate analysis only high risk CIBMTR status was predictive of poor OS (p=0.05).

Conclusion
The addition of low dose thymoglobulin to RIC and FIC regimens with iv Busulfan/Fludarabine prior to MUD HCT results in low TRM and improved OS for patients with AML/MDS. Relapse rate does not seem to be increased in this cohort by the addition of low dose thymoglobulin in comparison to historical control.

Disclosures:
No relevant conflicts of interest to declare.
The Role Of Vitamin D In Pediatric Hematopoietic Stem Cell Transplantation
Authors: Hansson Magnus EA , Norlin Anna-Carin , Omazic Brigitta , Wikström Ann-Charlotte , Winiarski Jacek , Remberger Mats , Sundin Mikael 
Published: October 2019

Abstract
Gathering evidence suggest that sufficient vitamin D levels are beneficial for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Vitamin D deficiency seems common in the pediatric population, especially in children undergoing treatment for hematologic malignancies. In the present study we followed 123 pediatric patients for up to eight years post-HSCT with the main objective to evaluate the clinical importance of vitamin D status in children following HSCT.
The patients underwent HSCT at our center mostly due to hematologic malignancies, but patients with non-malignant conditions and primary immunodeficiency disorders were also included. Procedures and conditioning regimens followed international guidelines. Data on each patient were obtained from medical records and included basic parameters, transplant characteristics, outcome parameters, data on vitamin D and immunoglobulin substitution and data on nutritional support.
Patients were divided into two cohorts based on calcidiol (25-OH-vitamin D) level pre-SCT; low level (<50 nM) and sufficient level (≥ 50 nM). The distribution of ethnic origin differed between the groups and patients with insufficient levels were older. No differences in other characteristics were seen between the groups.
Acute GvHD (aGvHD) occurred in almost every other patient with higher frequency in the sufficient level group (47 vs. 29 %). Chronic GvHD (cGvHD) occurred in 17 % of patients with higher frequency of moderate to severe cGvHD in the low level group. Neutrophil granulocyte numbers rose faster during the first 3 months in the sufficient group whereas no such difference was observed during the later follow-up. The number of infections did not significantly differ between the groups. Overall survival in patients with malignant diseases was significantly better in the sufficient level group (87 % vs. 50 %). Graft rejection did not occur in patients with sufficient levels of vitamin D. Relapse was more common among patients in the low level group.
We conclude that vitamin D seems to have a role in the outcome for children undergoing HSCT as hypovitaminosis D was associated with increased risk of death, relapse and cGvHD. At the same time effects on immune reconstitution and risk of infections were not obvious and aGvHD occurred more frequently among patients with sufficient vitamin D levels at baseline. It might be postulated that vitamin D has both inhibiting and stimulatory effects on the immune system. This study is an important step towards understanding the role of micronutrients such as vitamin D in pediatric HSCT.

Disclosures:
No relevant conflicts of interest to declare.
Serum Levels Of Vitamin D In Patients Undergoing Hematopoietic Stem Cell Transplantation
Authors: Pereira Andrea Z , Silva Juliana Bernardo , MF Pivocari Silvia , Tanaka Marcia , Lucio Fabiana , N Barrere Ana Paula , Castro Claudio Galvão , Feitosa Ribeiro Andreza Alice , Hamerschlak Nelson 
Published: October 2019

Abstract

Introduction
There are few studies on the behavior of vitamin D in patients undergoing Hematopoietic Stem Cell Transplantation (HSCT), although vitamin D serum levels are associated with use of corticosteroids and immunosuppressive drugs. In some studies, vitamin D deficiency in patients after HSCT is associated with reduced bone density, increased of parathyroid hormone and GVHD.

Objectives
To study vitamin D deficiency in patients undergoing to HSCT.

Methods
51 patients who underwent HSCT at Albert Einstein Hospital, São Paulo, Brazil, were studied (28 male, 23 female) with a mean age of 50 ± 16 years, in the period from 2012 to 2013.

Results
54 % had serum levels of vitamin D ≤ 50 nmol/l. And, 12% had serum levels of vitamin D ≤ 25 nmol/l. A multivariate analysis showed that more age and higher Body Mass Index (BMI) were significantly associated to lower serum levels of vitamin D. A negative correlation was found between BMI and serum level of vitamin D (rp=0,37).

Conclusion
The use of corticosteroids, immunosuppressive drugs and less lack of sun exposure during the HSCT and during the first year post-HSCT are associated with a greater tendency to deficiency of vitamin D. This deficiency can cause muscle and bone diseases, which can be prevented with diagnosis and early treatment. The deficiency of vitamin D should be carefully investigated in the elderly and obese patients.

Disclosures:
No relevant conflicts of interest to declare.
Impact Of ABO Incompatibility On Overall Survival After Unrelated Cord Blood Transplantation a Single Institute Experience In China
Authors: Zimin Sun , Mengmeng Ji , Wen Yao , Changcheng Zheng , Juan Tong , Huilan Liu , Liangquan Geng , Tang Baolin , Xiaoyu Zhu , Kaidi Song , Ding Kaiyang 
Published: October 2019

Abstract
Umbilical cord blood transplantation (UCBT) has now become a more common treatment for patients with hematologic malignancies who lack matched related or unrelated donors. However, few reports have addressed the impact of ABO incompatibility on the clinical outcomes, such as engraftment, transfusion requirements and survival after UCBT. Therefore, we retrospectively analyzed the impact of ABO mismatching on the clinical outcomes of 121 patients, including 51 ABO-identical, 23 minor, 39 major, and 8 bidirectional ABO-incompatible recipients after UCBT. With a median follow-up of 11 months (range, 5-151 months), the disease-free survival (DFS) rates among the ABO-identical, minor, major, and bidirectional ABO-incompatible groups were 71.7%, 60.0%, 37.1%, and 71.4%, respectively (P=0.014), whereas the OS did not differ significantly among the four groups (76.1%, 65.0%, 48.6%, and 71.4%, respectively; P=0.078). The DFS (68.2%, 42.9%; P=0.009) and OS estimates (72.7%, 52.4%; P=0.031) of the ABO identical/minor incompatible group also differed significantly from the ABO major/bidirectional incompatible group. These results were confirmed in the multivariate analysis. No signiﬁcant differences in the engraftment times, transfusion requirements, graft-versus-host disease (GVHD), relapse, and non-relapse mortality (NRM) were noted among the groups. Severe immune hemolysis or pure red cell aplasia did not occur among these patients. These results indicate that ABO incompatibility somewhat affects the DFS and OS in UCBT, but further studies are still required.

Disclosures:
No relevant conflicts of interest to declare.