bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactive Oxygen Species Are Differentially Regulated in Chronic Myeloid Leukemia Versus Philadelphia Negative Myeloproliferative Neoplasms
Authors: Guerin Estelle , Belloc Francis , Etienne Gabriel , Duffau Pierre , Mahon Francois-Xavier , Lippert Eric 
Published: April 2020

Abstract
Deregulation of tyrosine-kinases is a characteristic of most Myeloproliferative Neoplasms (MPN); evolution from chronic phase to acute leukemia depends on the acquisition of additional mutations. Reactive Oxygen Species (ROS), the production of which is increased by tyrosine-kinase activation, can be responsible for additional mutations. The role of ROS in generating genetic aberrations has been mainly studied in BCR-ABL-positive cell lines. Little is known of ROS metabolism in primary cells from CML or Philadelphia-negative MPN (Ph-MPN). After informed consent, cells from blood or bone marrow were obtained from patients diagnosed with CML (12 bone marrow (BM), 8 peripheral blood (PB)), or Ph-MPN (4 Polycythemia Vera, 6 Essential Thrombocythemia, 3 Primary Myelofibroses, 2 atypical CML) and from healthy donors (bone marrow donors) or patients devoid of hematological disease undergoing thoracotomy. Cells were incubated with DCFDA, a fluorogenic marker of ROS production, labelled with an anti-CD45 antibody, stimulated with either the oxidant hydrogen peroxide (H2O2) or the PKC activator Phorbol Myristate Acetate (PMA), and analysed for ROS production by flow cytometry. CD45/SSC gating allowed separate analysis of granulocytes, monocytes or lymphocytes. The basal level of ROS was not higher in CML cells as compared to normal BM or PB leukocytes. It was even significantly lower in CML lymphocytes, either from the BM (2.35 Arbitrary Units vs 8.3 AU, p=5.5 10−5) or PB (2.47 AU vs 7.4 AU, p=3.10−5) and in CML granulocytes from peripheral blood (14 AU vs 45 AU, p =10 −5), but not bone marrow. The ROS levels of Ph-MPN cells were similar or slightly higher than control cells. Upon H2O2 stimulation however, ROS production increased significantly more in CML cells as compared to normal cells (6 fold increase), whatever the cell type (granulocytes, monocytes and lymphocytes) or their origin (PB or BM). In contrast, for Ph-MPN cells, H2O2-stimulated ROS production was close to that of normal cells, with only BM lymphocytes showing ROS generation four fold higher than control BM lymphocytes. After PMA stimulation, which yielded a more modest ROS production than H2O2, CML cells behaved similarly to normal cells, whereas ROS production was four fold higher in Ph-MPN cells, whatever their type and origin. In conclusion, ROS levels at the basal stage are not higher in MPN cells, whether they are Philadelphia positive or negative, as compared to normal cells. Various kinds of stimulation induce different patterns of response, CML cells being more sensitive to oxidants whereas Ph-MPN cells respond more to the cytokine-mimicking agent PMA. These results suggest that the mechanisms of ROS generation and thus of genetic instability are different in CML and Ph-MPN.
Chronic Myeloid Leukemia Patients Present Elevation of the Circulating Endothelial Cells
Authors: Godoy Carla Rosa Teixeira , Meireles Ana Luiza Langanke Pedroso , Brocardo Graciela Aparecida , Chamone Dalton , Pereira Juliana 
Published: April 2020

Abstract
The increase of the angiogenesis is a prognostic factor in solid tumors. In oncho-hemathology, it is associated to the Myelodysplastic syndromes, Acute Leukaemia and Multiple myeloma. The impact of the raise in the expression of the growing endothelial (VEGF) in the course of chronic myeloid leukaemia (CML) is yet unknown. Yet, there are reports that those patients have presented a higher vascular density in bone marrow (BM) than healthy individuals, specially in blastic phase. Some authors suggest that abnormalities in the angiogenesis may be involved in the phatogenesis in the CML, as well as to its transformation in blastic phase. The increase of the circulating endothelial cells (CEC) is associated to the phatogenesis and to the prognostic of breast cancer and Non-Hodgkin lymphoma, but there are no studies in CML. Thus, we have elaborated a study in order to quantify the CEC in patients with CML in accelerated, chronic and blast phases for flow cytometry. Up to the moment, samples of 46 patients with CML (15 in accelerated phase, 24 in chronic phase and 7 in blastic phase) have been evaluated. Thirty six platelet donors for apheresis with negative sorology were used as a control group. The samples were processed at the same day of the collection, using monoclonal antibodies (MoAb) previously validated in cell of lineage HUV-EC. For the research of the CEC, we used the MoAb CD146 FITC, CD34 PE, CD133 APC e CD62E PE. O AcMo CD45 PC5 was used as a gate strategy for the analysis. The samples were acquired in flow cytometry FACS-Calibur G5 (100.000 events) and analysed in software CellQuest Pro. We noticed an increase statistically significant of CEC in the chronic (p&lt; 0,01), accelerated (p = 0,02) and blastic (p = 0,01) phases of the CML in comparison to the control group, given that these endothelial cells were found in a mature stage. The precursor endothelial cells did not present any statistically significant difference. Patients with LMC present an increment in the amount of CEC in all the phases. The quantification of these cells can be used in the evaluation of therapeutic response, of prognostics and as potential therapeutic target in LMC. The mechanisms involved in the increase of the CEC must be evaluated in future studies. Financial Support: FAPESP
Atypical Chronic Myeloid Leukemia: An Analysis of 9 Cases
Authors: Ma Yan , Xu Xiaoping , Wang Xiaoqin , Chen Bobin , Lin Guowei 
Published: April 2020

Abstract
Objective FTo investigate the clinical characteristics of atypical chronic myeloid leukemia (aCML) and characterize the aCML.
Methods FFrom 2003 to 2007, the consecutive samples of 54 MDS/MPD patients in Sino-US Shanghai Leukemia Cooperative Group were collected by prospective methods and diagnosed with WHO classification. We identified 9 aCML cases and analyzed the clinical and laboratory data of these cases.
Results FThe median age of 9 cases was 66 years old(range 38~78y). The ratio of male and female is 1:1.25. Median hemoglobin concentration was 76.5g/L(range 43.3~116), median white blood cell count 27.5×109/L(range 7.55 ~317.2), median neutrophil percentage 66.4%(range 43.3~83.5), median basophil percentage 2.86%(range 0.24~5.79), median monocyte percentage 7.59%(range 0.92~16.3), median platelet 77.6×109/L(range 20.7 ~504)and median marrow blast percentage 2.5 %(range 0.5~6). Abnormal karyotype occurred in 20% of all patients. Median survival was 11.5 months(2.5 `44months).
Conclusions FaCML occurs rarely and is associated with a poor prognosis. The major distinguishing features of aCML are Ph(−)or BCR/ABL(−)and severe dysgranulopoiesis. In addition, hepatosplenomegaly and leukocytosis are less prominent in aCML than chronic myeloid leukemia(CML) and chronic myelomonocytic leukemia (CMML). Anemia is much severe than CML and CMML.
Reduced-Intensity Allogeneic Peripheral Blood Stem Cell Transplantation for High-Risk Acute Lymphoblastic Leukemia: A Potential Therapeutic Approach for High Risk ALL Patients Not Eligible for Full Intensity Transplantation
Authors: Stein A. , Palmer J , O’Donnell M , Kogut N. , Spielberger R , Slovak ML , Tsai NC , Forman S. J 
Published: April 2020

Abstract
Acute lymphoblastic leukemia has a poor prognosis in adults, with a two-year survival rate of 35–40% despite aggressive therapy (American Cancer Society: Cancer Facts and Figures 2008 Atlanta, GA: American Cancer Society, 2008). Reduced-intensity allogeneic stem cell transplantation (SCT) relies mainly on graft versus leukemia (GVL) for its efficacy; however, the role of GVL in ALL is less well-defined. Between 5/7/02 and 6/15/07, 25 adult ALL patients were uniformly treated with fludarabine 25mg/m2 daily for 5 days and melphalan 140mg/m2 followed by ALLO-SCT using peripheral blood stem cells. The indications for the reduced intensity regimen were:
≥ 50 years (10 pts) (40%), decreased organ function (9 pts) (36%) and previous ALLO-SCT (6 pts) (24%).
Patient demographics include: median age, 47 years (range, 23–68 yrs.), remission status at ALLO-SCT: first complete remission (CR) (12 pts) (48%), first relapse (3 pts) (12%), second CR (5 pts) (20%), &gt;second CR (4 pts) (16%), induction failure (one pt) (4%), t(9;22) or Philadelphia positive (Ph+) ALL(9 pts) (36%). Donor source was matched sibling in 9 pts (36%), and matched unrelated in 16 pts (64%). Graft versus host disease (GVHD) prophylaxis: was cyclosporine (CSA)/+ mycophenylate (MMF) (3 pts) (12%), CSA/MMF/methotrexate (MTX) (8 pts) (32%), CSA/MMF/ATG (one pt) (4%), tacrolimus/sirolimus (7 pts) (28%) and tacrolimus/sirolimus/MTX (6 pts) (24%). With a median follow-up for surviving patients of 28.5 months (range: 12.8–72.5 months), the two year cumulative probability of overall survival and disease-free survival were both 59% (95% CI: 46–69.2%). The relapse rate was 16% (95% CI: 6.4,–37.4%),. Incidence of acute GVHD was 60% for grade II–IV and 20% for grade III–IV. Of the patients at risk for chronic GVHD, 8% developed limited chronic GVHD and 60% developed extensive chronic GVHD. The 100-day, one year and two year non-relapse mortality rates were 12% (CI: 4.6–29.3%), 24.2% (CI: 14–39.9%) and 29.3% (CI: 18.4–44.6%), respectively. There was no difference in survival outcomes based on donor source. The results of this study show that reduced intensity ALLO-SCT using fludarabine/melphalan based conditioning with primed peripheral stem cells from a matched related or unrelated donor provides a curative option for patients with high risk ALL who are not eligible for full intensity transplant.
Figure Figure
Adoptive Immune Cell Therapy for the Control of Fungal Infections in Hematopoietic Stem Cell Transplant Patients
Authors: Chang Lung-Ji , Liang Yin , Lien Lily , Tong Chun- Rong , Dong Lu-Jia , Wu Tong , Fu Yinchieh , Yang Fu-Hung , Tang Jih-Luh , Lu Dao-Pei 
Published: April 2020

Abstract
Similar to virus infections, fungal infections are commonly seen in immunosuppressed transplant patients and can be life-threatening. Invasive Aspergillosis and Candidiasis are principal fungal infections among hematopoietic stem cell transplant (HSCT) patients, but Aspergillosis and other molds are the leading cause of deaths by fungal infections in immunocompromised allogeneic HSCT patients. The most effective treatment for fungal infections is preemptive and empirical anti-fungal therapies using agents such as fluconazole and amphotericin B deoxycholate (AmB-D). However, the success rate of antifungal therapy is generally low (in the 30–40% range) and associated with high toxicity. Both diagnosis and treatment for fungal infections are expensive and often ineffective. While improved formulations of AmB-D, second-generation triazoles, and echinocandins may be tolerable, newer generations of anti-fungal agents are very expensive. In animal studies, it has been shown that Aspergillosis can be successfully treated using Aspergillus-specific cytotoxic T cells (CTLs). Therefore, it is conceivable that CTLs specific to fungal antigens are effective in controlling fungal infections in allogeneic HSCT patients. To explore anti-fungal immune cell therapy, we used two different approaches to generate fungus-specific immune cells:
Trichoderma and Rhizopus fungal lysates as antigen source to pulse dendritic cells (DCs), and pooled antigenic peptides to pulse DCs.
The antigen-primed DCs were then co-cultured with lymphocytes to generate antigen-specific immune effector cells. The ex vivo generated anti-fungal immune cells displayed antigen-specific effector functions as illustrated by intracellular IFN-γ and CD107a staining. Interestingly, the fungus-specific immune effector cells are mostly CD4 T cells for all three species of fungal antigens. In a pilot clinical study, patients were selected when diagnosed with invasive aspergillosis based on galactomannan and beta-glucan assays, radiographs, CT scans, and/or blood cultures, or after an extended unsuccessful anti-fungal treatment with non-tolerable organ toxicity. Early indications suggest that the infusion of anti-fungal immune cells is safe, with therapeutic efficacy based on objective clinical evidence and importantly, is cost-effective. Nevertheless, more effective diagnosis and surveillance tools are needed to document the effectiveness of our anti-fungal immune cell treatment.
Respiratory Tract Lophonomas Blattarum Infection of Allograft Hemopoietic Stem Cell Transplantation: A Case Report and Review of the Literature
Authors: Miao Miao , Depei Wu , Sun Aining , Yan Lingzhi , Wu Xiaojing , Tie Tiemei 
Published: April 2020

Abstract
Objective To explore the features of respiratory tract lophonomas blattarum infection in allograft hemopoietic stem cell transplantation.
Methods A 16 year-old male, was diagnosed of chronic myelolytic leukemia by MICM. On 2007-10-23, he underwent HLA-matched sibling donor allograft hemopoietic stem cell transplantation(Allo-HSCT). The preconditioning of transplantation is BU/CY(CCNU 250mg/m2*1d, HU40mg/Kg*2, Ara-C 2g/m2*1d, Bu 0.8mg/Kg/6h*3d, CTX 1.8g/m2*2d). CSA and MTX were used to prevent GVHD. Chest CT scan showed left inferior pneumonia on 18 days after transplantation. The patient underwent anti-bacteria, fungi and virus treatments, but his symptoms didn’t improve. Fiberoptic bronchoscopy(FOB) and bronchial alveolar lavage(BAL) was performed. It was confirmed that the pathogen was lophonomas blattarum We reported the clinical manifestation and management of respiratory tract lophonomas blattarum infection after Allo-HSCT and reviewed the clinical features of another eleven cases from the literature.
Results Infection with lophonomas blattarum mostly occurs in patients of hypoimmunity, its living conditions many in south hot and damp area. The clinical symptoms are severe and difference. Lophonomas blattarum can be observed under microscope. Metroindazole is always effctive.
Conclusion Lophonomas blattarum is a recessive infection in patients with Allo-HSCT, and co-infection of different pathogen may be involved. In Allo-HSCT patients with unexplained respiratory tract infection which do not respond to ordinary therapy, rare pathogens such as lophonomas blattarum need to be considered. Bronchoalar lavage and fiberoptic bronchoscopy examination are safe and fiberoptic bronchoscopy examination are safe and effective method in the early pathogenic diagnosis of respiratory tract infection after Allo-HSCT.
Long-Term Outcomes of Myeloablative Conditioning and Matched-Related Donor Hematopoietic Cell Transplantation for Patients with High-Risk and Advanced-Stage Hematolymphoid Malignancies
Authors: Benjamin Jonathan E. , Laport Ginna G. , Johnston Laura J. , Arai Sally , Weng Wen-Kai , Shizuru Judith A. , Miklos David B. , Wong Ruby M. , Elder Linda V. , Blume Karl G. , Negrin Robert S. , Lowsky Robert 
Published: April 2020

Abstract
Patients with high-risk hematolymphoid malignancies who relapse or who do not achieve a complete remission to induction chemotherapy generally do not achieve long-term survival when treated with the best available non-transplant therapies. The benefit of allogeneic hematopoietic cell transplantation has been well described for patients in first complete remission, but less so for patients with advanced disease. We report the long-term follow-up of 131 patients with leukemia or lymphoma who received an HLA-matched related donor transplant following myeloablative conditioning with fractionated total body irradiation (1320cGy), etoposide (60mg/kg), and cyclophosphamide (60mg/kg). Eligibility for transplantation under this protocol included induction failure or high-risk disease that was beyond first remission. All patients were treated at a single institution. Diagnosis at the time of transplantation included ALL (n=57), AML (n=38), NHL (n=20), CML (n=10), MDS (4), JMML (n=2). Of the 95 patients with acute leukemia, 62 (65%) were not in remission at the commencement of the conditioning regimen. The median age at transplantation was 29 years (range 2–55). Seventy-four (56%) patients received unmanipulated bone marrow and the remainder received filgrastim-mobilized peripheral blood. Median follow-up of surviving patients was 8 years (range 0.3–17). The estimated five-year overall survival and event-free survival were 34% (95% confidence interval: 22–42%) and 32% (95% confidence interval: 24–39%), respectively. Leading causes of death included relapse (n=43), infection (n=11), acute graft-versus-host disease (n=8), respiratory failure (n=5) and hepatic veno-occlusive disease (n=4). Grade II–IV acute graft-versus-host disease occurred in 26% of patients. The cumulative incidence of extensive chronic graft-versus-host disease among those patients who survived beyond day 100 was 32%. These results indicate that patients with high-risk or advanced disease can experience long-term disease-free survival following an aggressive conditioning regimen that combines radiotherapy, etoposide, and cyclophosphamide. Relapse remains the most significant cause of mortality, and future efforts should focus on augmenting the graft-versus-malignancy effect.
Factors Affecting the Results of Allogeneic Hematopoietic Stem Cell Transplantation in Hematologic Malignancies
Authors: Mehta J. , Frankfurt O. , Altman J. , Evens Andrew M , Gordon L. , Tallman M. , Williams S. , Winter J. , Krishnamurthy J. , Grinblatt D. , Kaminer L. , Singhal S. 
Published: April 2020

Abstract
130 patients who were unsuitable for conventional-intensity conditioning underwent RI-HSCT after 100 mg/m2 melphalan (+ 50 mg/kg cyclophosphamide if no prior autograft). GVHD prophylaxis comprised cyclosporine (HLA-matched siblings) or tacrolimus (all others) and MMF.
Table 1: Patient characteristics
Age (y) 19–71 (median 55) Male 55% Refractory disease 57% ECOG performance status 0 34% 1 48% 2 14% 3 4% Diagnosis Lymphoma 42% Leukemia 36% Myeloma 22% Donor Matched sibling 49% Mismatched sibling 2% Matched unrelated 33% Mismatched unrelated 15% Donor age (y) 21–71 (median 44; 45% &gt;45) Male donor 65% Prior autograft 45%
Refractory disease, HLA mismatch, donor age &gt;45, elevated creatinine, low DLCO, thrombocytopenia, male donor, poor performance status, and low albumin affected OS adversely in univariate analysis. The following factors affected outcome independently:
Table 2: Cox analysis
Adverse variable Relative risk P TRM HLA mismatch 4.78 0.0003 Performance status 2–3 3.07 0.044 Relapse Donor age &gt;45 y 2.0 0.012 Male donor 1.98 0.026 Refractory disease 1.84 0.05 EFS Performance status 2–3 0.48 0.022 HLA mismatch 0.53 0.023 Refractory disease 0.55 0.016 Male donor 0.61 0.039 Donor age &gt;45 y 0.63 0.034 OS Performance status 2–3 0.44 0.025 HLA mismatch 0.31 0.0001 Refractory disease 0.49 0.007 Donor age &gt;45 y 0.55 0.012 High LDH 0.53 0.007 Platelets &lt;100 0.58 0.021
These prognostic factors were similar to those found on studying the first 63 patients in this series (Mehta et al. Bone Marrow Transplant 2006) –with the additional emergence of HLA mismatch and thrombocytopenia which were significant in univariate but not multivariate analysis then.
These data suggest that RI-HSCT is useful for some patients with hematologic malignancies who are ineligible for conventional-intensity HSCT. However, alternative HSCT techniques or non-HSCT options are needed for high-risk patients.
Figure 1 shows the effect of the number of adverse prognostic factors on the cumulative incidence of relapse and transplant-related mortality. Figure 1. shows the effect of the number of adverse prognostic factors on the cumulative incidence of relapse and transplant-related mortality. Figure 2 shows the effect of the number of adverse prognostic factors on survival. Figure 2. shows the effect of the number of adverse prognostic factors on survival.
Study of the Relationship of Product Infused with Survival in Patients with Hodgkin’s Disease and No Hodgkin’s Lymphoma Undergoing Autologus Stem Cell Transplantation
Authors: Salido Eduardo , Majado Maria Juliana , Minguela Alfredo , Moraleda Jose Maria , Gonzalez Consuelo , Parrado Antonio , Funes Consuelo , Martinez-Sanchez Maria Victoria , Morales Alfonso 
Published: April 2020

Abstract
Absolute lymphocyte count (ALC) at diagnosis (ALC-D), as well as ALC recovery, have been described as prognostic factors in overall survival (OS) and progression free survival (PFS) in patients with non-Hodgkin’s and Hodgkin’s lymphoma(NHL and HL) who underwent autologous stem cell transplantation (ASCT). The aim of this study is to verify those findings, as well as the influence of infused lymphocyte, MNC, CD19 and CD3 in OS and PFS in our patients, in order to give some support to the importance of the immune system for disease control.
A total of 55 patients were reviewed, 35 males and 20 females, 44 had NHL and 12 HL. Variables analyzed with regard to PFS and OS were: ALC-D, ALC at day 15 post-transplant (ALC15), infused lymphocyte ×106/Kg, MNC X108 / Kg, CD19 X106/ Kg and CD3×106/ Kg. Variables were dichotomized at the median, and PFS and OS estimates were calculated with the Kaplan-Meier method and compared using log-rank test; regression Cox test was used for multivariate study.
Results: The median follow-up was 71 months (14–180). Relapse or progression occurred in 20 patients (36%) between 1 and 148 months (median 32). Eighteen patients (33%) died at a median of 28 months (14–110). Median ALC-D was 1.5×109/L (0.2–5.2 ×109/L). ALC15 count was 0.6 ×109/L (0.1–1.9). Infused MNC were 5.0×108/Kg (0.04– 22.2). Infused lymphocytes were 241.6 ×106/Kg (0.1–1222). Median CD19 cells infused were 1.12 ×106/Kg (0.0–79.7). Infused CD3 cells were 106.8 ×106/Kg (0.02–678.2). No difference was found in OS or PFS in patients in groups above and below median in ALC-D, ALC15 counts, neither in MNC, lymphocytes, CD19 nor CD3 cells infused in Kaplan-Meier study. MNC infused have statistical significance in OS (p=0.042) and PFS (p=0.023) in Cox regression analysis. In our series we do not find a clear predictor in relation to the immune reconstitution in NHL and HL patients receiving an ASCT; althoug it is possible that among MNC should be immune progenitors able to offer a better outcome to these patients, that could be studied in future.