bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful Treatment with Imatinib Mesylate Significantly Decreases Plasma Levels of Vascular Endothelial Growth Factor (VEGF) and Soluble Endoglin (sCD105) but Not Basic Fibroblast Growth Factor (bFGF) or Angiopoietin-2 (Ang-2) in Patients with Chronic Myeloid Leukemia (CML) in Chronic Phase
Authors: Smolej Lukas , Andrys Ctirad , Voglova Jaroslava , Belohlavkova Petra , Rabasova Jana , Beranek Martin , Maly Jaroslav 
Published: April 2020

Abstract
Introduction: Angiogenesis is an essential process in the biology of solid tumors as well as hematological malignancies. Several studies have recently reported increased markers of angiogenesis in chronic myeloid leukemia (CML). However, much less is known on the possible impact of tyrosine kinase inhibitor imatinib mesylate (IM), the current cornerstone of CML treatment, on angiogenic signaling.
Aims: To analyze peripheral blood levels of angiogenic cytokines in patients with newly diagnosed CML and during imatinib treatment. Methods: Peripheral blood plasma concentrations of key angiogenic activators, namely vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), soluble endoglin (sCD105), and angiopoietin-2 (Ang-2) were quantified using commercially available sandwich enzyme-linked immunosorbent assay (ELISA) in 27 patients with chronic-phase CML and 80 healthy blood donors; furthemore, repeated samples during the therapy with IM were analyzed.
Results: We detected significantly elevated levels of VEGF (p&lt;0.0001), bFGF (p=0.026), and sCD105 (n=25, p&lt;0.0001) in comparison to the control group. Elevation of Ang-2 was of borderline significance (n=14, p=0.051). Levels of VEGF and sCD105 significantly decreased in patients who achieved complete cytogenetic response (p&lt;0.0001 and p=0.01) whereas bFGF or Ang-2 did not change significantly (p=0.978 and p=0.625, respectively). VEGF and sCD105 remained low in repeated samples taken during IM treatment. Interestingly, there was a trend towards higher VEGF in patients who did not achieve complete cytogenetic response (p=0.058).
Conclusions: Peripheral blood levels of angiogenic activators VEGF, bFGF and sCD105 (and borderline Ang-2) were elevated in CML patients. Successful treatment with IM resulted in significant and durable suppression of circulating VEGF and sCD105 but not bFGF and Ang-2. Our results point to the potential significance of angiogenic signaling (especially VEGF pathway) in CML biology. Further research in this field is therefore highly desirable.
A Retrospective Evaluation of Clonal Cytogenetic Abnormalities in Ph Negative Clones in Patients with CP-CML on Therapy
Authors: Hartley Monique A , Shah Bijal D. , Armada Sady , Tinsley Sara , Pinilla Javier 
Published: April 2020

Abstract
Cytogenetic clonal aberrations in CML are a well recognized indicator of transition to blast phase. However, it is unclear how to interpret such changes when they occur in cells not harboring a Philadelphia Chromosome (Ph-), considering that some of these changes are often seen in patients with MDS/AML. In this retrospective review of 208 cases, we sought to determine the frequency, onset, character, and general course among CML patients harboring clonal chromosomal abnormalities (ChA) in Ph- cells during treatment with tyrosine kinase inhibitors (TKI’s). In this cohort, we were able to identify 13 ChA among 11 patients (5% of initial cohort), with most cases demonstrating trisomy 8 (31%), monosomy 7 (23%), and loss/gain of chromosome Y (38%). The median number of treatments per patient was 2 (1–3), with a median followup of 77.5 months (18–196 mo) among these 11 patients. Of the 13 ChA, 9 occurred during Imatinib therapy, and 5 of these 9 resolved without a change in medication. Of the remaining 4 patients, 2 presented with ChA prior to therapy, and 2 developed ChA while on a second generation TKI (Nilotinib, Dasatinib). The ChA persisted in the patient taking Nilotinib and resolved in the Dasatinib treated patient without change in therapy. Among those with ChA prior to therapy, the ChA resolved in one after the addition of INNO-406 (a lyn-abl inhibitor), and in the other despite going untreated between interval marrow specimens (this patient later went on to receive Imatinib with no ChA over an 18 month followup). CML disease course in patients with ChA in Ph- clones does not appear to be more severe, with only one patient having gone on to receive bone marrow transplantation for accelerated phase disease, and one other not currently in cytogenetic remission. Ten patients have attained complete (6) and major (4) molecular responses. Seven patients demonstrated cytopenias at last followup. Accompanying marrow dysplasia was seen among 4 of these patients. Interestingly, cytopenias are most pronounced in those with persistence of the ChA, including one patient with 5q deletion and another with chromosome 7 deletion. In summary, while clonal cytogenetic changes in Philadelphia Chromosome positive cells are a well recognized marker of disease progression, their presence in cells lacking this translocation does not seem to reflect a similar disposition. However while cytopenias of varying severity are noted in the patients reported, there is no evidence of transformation to MDS/AML nor a more resistant disease course. Long term follow up still is needed to confirm these data.
Survival Outcome of Hematopoietic Stem Cell Transplant Recipients Admitted to the Intensive Care Unit: A Single-Center Report of 53 Patients
Authors: Jaswal Jasbir K , Narayanan Sujaatha , Song Kevin W , Chittock Dean R , Griesdale Donald E.G. 
Published: April 2020

Abstract
BACKGROUND: Intensive care unit (ICU) admission following hematopoietic stem cell transplantation (HSCT) has traditionally been associated with a poor prognosis; particularly for those patients requiring mechanical ventilation.
OBJECTIVE: To determine 28-day and 1-year survival of patients admitted to the ICU following autologous or allogeneic HSCT. Data was collected from a single transplant center.
STUDY DESIGN: Retrospective cohort study of all adult patients who received a HSCT at Vancouver General Hospital from April 1st, 2000 to July 31st, 2006.
RESULTS: During the 6 year period of the study, a total of 862 hematopoietic stem cell transplants were performed (367 allogeneic, 486 autologous). Overall 28-day and 1-year survival for those receiving an allogeneic transplant was 97.6% and 68.4%. Patients receiving an autologous transplant had a 28-day and 1-year survival of 98.4% and 78.0% respectively. Fifty-three (6%) of our cohort were admitted to the ICU (34 allogeneic, 19 autologous), of which 43 (81%) required mechanical ventilation. The 28-day and 1-year survival of those patients admitted to the ICU was 42/53 (79.3%) and 18/53 (34.0%), respectively. Recipients of allogeneic stem cell transplants had a 28-day and 1-year survival of 26/34 (76.5%) and 9/34 (26.5%). This is in comparison to 28-day and 1-year survival of 16/19 (84.2%) and 9/19 (47.4%) for those receiving autologous stem cell transplants.
CONCLUSION: These data indicate that the survival of HSCT patients who require ICU admission is better than what has been previously reported in the literature. Limitations of this study include potential selection bias in those patients admitted to the intensive care unit. Future research will be directed at finding prognostic factors for ICU admission. However, based on these results, patients who receive hematopoietic stem cell transplantation should be offered admission to the ICU.
Administration of Rituximab 375 Mg/m2 on Days +1 and +8 after Allogeneic Hematopoietic Stem Cell Transplantation (allo-HCT) Regimens for Patients with Advanced CD20+ Lymphoid Malignancies
Authors: Kharfan-Dabaja Mohamed A , Tate Cheryl , Perkins Janelle , Field Teresa , Fernandez Hugo F. , Alsina Melissa , Ayala Ernesto , Raychaudhuri Jyotishankar , Perez Lia , Ochoa-Bayona J. Leonel , Brand Linda , Pinilla-Ibarz Javier , Sotomayor Eduardo , Sullivan Dan , Anasetti Claudio 
Published: April 2020

Abstract
We evaluated the safety of adding rituximab 375 mg/m2 only on days +1 and +8 following allo-HCT in 18 patients (M=12, F=6), median age 56 (41–66) years, with advanced CD20+ lymphoid malignancies [CLL=9 (CR2=3, PR2=3; ≥PR3=3); Mantle cell lymphoma (MCL)= 5 (CR1=1, PR2=2, ≥PR3=2); follicular (FL)=3 (CR3=2, ≥PR3=1); DLBC NHL=1 (≥PR3=1). Source of stem cells consisted of matched-related (MRD)=11 (61%), matched-unrelated (MUD)=5 (28%), or mismatched-unrelated (MMUD)=2 (11%) donors. Conditioning regimens consisted of fludarabine plus targeted doses of IV busulfan (FLU-BU) (N=11) or 200 cGy TBI (N=4), or cyclophosphamide (FLU-CY) (N=1). ATG was administered on days −3 and −1 in 2 MMUD cases (FLU-BU-ATG). Fifteen patients received rituximab on day +1 (±3) and all on day +8 (±3). GVHD prophylaxis was tacrolimus plus mycophenolate mofetil (N=11) or methotrexate (N=7). Non-relapse mortality at 100 days was 6%. Median time to neutrophils and platelets engraftment was 15 (6–27) days and 12.5 (9–18) days, respectively. Eight patients never dropped platelets below 20,000/uL. Median CD3 and CD33 chimerisms at day +90 (±10) were 89% (50%–100%) and 100% (15%–100%), respectively. DLI was required in 2 patients (FLU-BU=1, FLU-TBI=1) due to poor CD3 engraftment. Response rates after 90 days post allo-HCT, according to diagnosis, were as follows: CLL (evaluable=8/9; CR=7/8; PR=1/8); MCL (evaluable=4/5; CR=4/4); FL (CR=3/3); DLBC (PD=1/1). Twelve (67%) patients remain alive in remission at a median follow up of 9.4 (2.3–42.3) months. The incidence of grade 0,I, II, and III–IV acute GVHD (aGVHD) was 6%, 33%, 50%, and 11%, respectively. Time to onset of aGVHD was 29 (16–77) days. The incidence of chronic GVHD (cGVHD), per NIH consensus criteria, was as follows in 15 evaluable patients: no cGVHD= 27%, mild= 33%, moderate= 13%, and severe=27%. These findings suggest that administration of rituximab 375 mg/m2 only on days +1 and +8 is safe. Response rates are encouraging; but controlled studies will be needed to conclusively determine the effect of post-transplant rituximab on efficacy.
Alternative Schedule of Filgrastim after Autologous Transplantation: Less Dosing, Same Efficacy
Authors: Sousa Aida B. , Costa Fatima , Ferreira Gilda 
Published: April 2020

Abstract
Administration of colony-stimulating factors (CSF) after autologous peripheral-blood progenitor cell transplantation is the current standard of care, and G-CSF is usually given from day +5 or +7 until engraftment. Recent preliminary data in a non-transplant setting suggest that 2 doses of G-CSF may be equivalent to the standard schedule. In this pilot study, we evaluated the safety and efficacy of giving only 2 doses of filgrastim post-transplant (days +7 and +9) in non-myeloma pts; exclusion criteria were re-transplants and clinical instability at day +7. From July 07 to June 08, 19 consecutive pts were included (16 lymphomas, 3 acute leukaemias) and their outcome was compared to a historical control group of 42 similar pts transplanted from Jan 06 to Jun 07, who received filgrastim from d+7 until 1000 neutrophils/ul (4–18 days, median 9). There were no significant differences in primary endpoints: median time to neutrophil engraftment (500/ul reached on day +12 vs +11) rate of documented infections (with bacteremia in 23% of transplants in the study group vs 36% in the control group) and median length of hospitalisation (both 22 days). Median duration of intravenous antibiotics (11 vs 12 days) median time to platelet engraftment (20,000/ul reached on day +13 vs +14) incidence of grade 3/4 mucositis and transfusion requirements were also similar. There were no deaths at day +30 in the study group. In 2 of the 19 pts a secondary prescription of filgrastim was made (for 2 and 4 days). In this pilot study, reducing filgrastim administration to 2 doses seems possible without undue risks. If confirmed in a randomized trial, these findings could have a significant impact on the cost of transplantation.
Hypocalcemia during Autologous Stem Cell Transplant with Concurrent Biphosphonate Use in Patients with Multiple Myeloma
Authors: Wudhikarn Kitsada , Vercellotti Gregory M. , Arora Mukta 
Published: April 2020

Abstract
Autologous hematopoietic stem cell transplantation (HSCT) is one of the treatment options which has been shown to enhance remission rate and survival in patients with multiple myeloma. Biphosphonates are used in conjunction with standard therapy and can ameliorate and prevent bony complications, i.e. bone pain, hypercalcemia or fracture, via direct inhibition of osteoclasts and possible anti-tumor effects on malignant plasma cells. With more frequent use of biphosphonates, there are increasing reports of noticeable adverse effects such as osteonecrosis of the mandible, renal failure and hypocalcemia. In this study we report three patients with multiple myeloma who received autologous HSCT accompanied with monthly administration of bisphosphonates and developed significant hypocalcemia post HSCT. All three patients had normal serum calcium levels at diagnosis and prior to transplant. The maximum drop in serum calcium was noted four to ten days post HSCT, and corrected by five to 13 days post HSCT. All three patients received biphosphonates eight to 20 days prior to the episode of hypocalcemia. All patients noted resolution of hypocalcemia with oral and intravenous calcium supplementation over three to ten days. Two patients required ongoing oral calcium supplementation for approximately one month after resolution of hypocalcemia. Multiple potential mechanisms can be postulated for the hypocalcemia in these patients undergoing HSCT such as chronic nutritional deficiency, GI losses, renal losses, vitamin D deficiency in addition to bisphosphonate use. Potentially melphalan, IV fluids, and furosemide may also play roles. Osteoclasts, bone marrow stromal cells and myeloma cells all can modulate calcium levels directly or indirectly through cytokine production. Future laboratory and clinical studies will focus on biochemical marker of complication and attention is needed while using bisphosphonates during autologous HSCT in myeloma patients.
Investigation of Polyomavirus BK in the Late-Onset Hemorrhagic Cystitis Following Hematopoietic Stem Cell Transplantation
Authors: Han Yue , Xie Ying , Sun Aining , Cen Jian nong , Zhu Zi ling , Gao Haili , Depei Wu 
Published: April 2020

Abstract
Background Late-onset hemorrhagic cystitis (LOHC) is a frequent and sometimes life-threatening complication after hematopoietic stem cell transplantation (HSCT). Our aim in this study is to analyze the risk fators for LOHC after HSCT, then determine the role of polyomavirus BK in the development of LOHC following HSCT.
Methodology 113 patients undergoing HSCT and 30 normal subjects were enrolled in this study. BK virus DNA were detected with PCR in the plasma and urine samples, while cytomegalovirus (CMV) antigen in peripheral blood was identified by immunofluorescence histochemical examination. All patients with LOHC were classified into three groups as grade 1, grade 2 and grade 3–4 by the severity of HC.
Results 22 patients developed LOHC (19.47%), all of them were allogenetic transplants recipients, with a median time of 44 days after HSCT. BK viruria was detected in 50 of all 113 patients following HSCT (44.2%), and no positive BK virema was found at the same time, while CMV virema was detected in 21 patients (18.5%). Of the 22 LOHC patients, 21 were detected BK viruria (95.5%), which was much more than that of non-HC patients (31.9%, P©‚0.01). The first time of BK viruria detection is earlier than the onset time of HC (25.09±16.63 days vs 47.42±29.02 days, P©‚0.01), accompanied with a longer median persistence time than that of HC (6 weeks vs 11 days), no difference was found in the onset and persistence time of HC among all the HC groups of three grades. Both CMV and BKV detection were negative in the control subjects. The occurrences of severe infection (45.5%), CMV reactivation (40.9%) and grade II-IV aGVHD development are much higher in HC group than that of non-HC group(P©‚0.01). Cox’s proportional hazard regression analysis showed that CMV reactivation and the development of grade II-IV acute graft-versus-host disease (GVHD) were associated with the occurrence of BK viruria, while BKV viruria and aGVHD of grade II-IV were independent risk factors of LOHC.
Conclusion BK polyomavirus may contribute to the pathogenesis of LOHC after HSCT, manifested as BK viruria. CMV infection and GVHD could be involved in the occurrence of BKV-related HC.
The Relative Percentage of Recipient T (CD3+) and Activated Lymphocytes (CD25+) Allows to Predict the Dynamics of Chimerism and the Risk of Complications after Allogeneic Stem Cell Transplantation
Authors: Borde Ismael Buno , Manzano Cintia , Balsalobre Pascual , Serrano David , Macias Gabriela Rodriguez , Gomez-Pineda Alfonso , Diez-Martin Jose L. 
Published: April 2020

Abstract
Introduction : The success of allogeneic stem cell transplantation (SCT) is conditioned by the dynamics and the result of the bidirectional interaction of immune reactions exerted by donor and recipient (alloreactivity/tolerance). Quantitative chimerism monitoring after SCT, mainly if performed on leukocyte lineages such as T lymphocytes (TL, CD3+), allows assessment of the immune interaction between donor and recipient.
Objective : To evaluate the usefulness of chimerism quantification in activated lymphocytes (AL, CD25+) for the early detection of complications (graft failure/rejection, GVHD, relapse, etc.) which, eventually, would improve the efficacy of current therapeutic strategies.
Material and methods: Chimerism quantification was done by microsatellite PCR (short tandem repeat, STR-PCR) on peripheral blood (PB) samples obtained every other week from 20 transplanted patients, as well as on leukocyte lineages, TL and AL, purified by immunomagnetic means (autoMACS, Miltenyi Biotec, purity&gt;95%).
Results : Three different patterns of chimerism dynamics were observed:
10 patients showed complete chimerism (CC) in all samples analyzed post-SCT. 6 patients showed mixed chimerism (MC) with lower percentage of recipient cells in AL than in TL. All this 6 patients spontaneously evolved to CC. 4 patients showed MC with higher percentage of recipient cells in AL than in TL.
All these 4 patients showed decreasing MC (increasing percentage of recipient cells) in PB, TL and AL. Moreover, 3 of them showed complications involving the graft:
graft failure (not recovered after two succesive transplants) and graft rejections (1 incipient), which recovered and achieved CC after donor leukocyte infusions.
Concerning disease relapse, 1 case was observed in each of groups A and B, and three cases were observed in group C.
Conclusions: Our results suggest that higher percentages of recipient cells in AL than in TL are associated with stronger host-versus-graft immune reactions and, therefore, with decreasing mixed chimerism and subsequently with various complications after SCT. On the contrary, lower percentages of recipient cells in AL than in TL predict the achievement of CC. Quantitative follow up of chimerism in AL (CD25+) increases the usefulness of the analysis of PB and TL (CD3+) samples, allowing to predict the dynamics of chimerism after SCT and favouring the early establishment of the appropriate therapeutic option in each transplanted patient.
Phosphoinositide-3-Kinase Plays a Vital Role in Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cells Transplantation
Authors: Xing Haizhou , Du Xin , Weng Jianyu , Lu Zesheng 
Published: April 2020

Abstract
Phosphoinositide-3 kinase (PI3K) plays a vital role in T-cell signaling pathway including cell proliferation, differentiation, migration and so on. Scholars have found that PI3K expression is limited to cells related with transplant rejection activation of the immune cells. PI3K plays a crucial role in GVHD occurrence: 1 crucial, PI3K are located in main areas in T-cell activation signal, resulting in affecting GVHD significantly; 2 selective, PI3K expression is limited to the participation of activated cells with immune rejection. But the expression of PI3K in GVHD patients has been not clear. In order to give the more experimental evidence for prophylaxis and treatment of GVHD, PI3K gene expression in patients with different state of GVHD was detected. This research collected the peripheral blood lymphocytes in 32 patients after allogeneic hematopoietic stem cell transplantation from January 2007 to January 2008. The cases include 15 male and 17 female cases, the median age was 27.9 (14–43) years. In accord with the classification of GVHD, all cases were divided into ALL (12), AML (7), CML (10), CMML (2), MDS (1). After one year after transplantation, the number of patients with no-GVHD is 9, simply aGVHD is 8, single-cGVHD is 8, aGVHD and cGVHD is 7. The total sample number is 122(state of blood reconstruction 32, no GVHD 37, aGVHD 27, cGVHD 26). By real-time PCR, PI3K expression were determined of patients at normal blood reconstruction, and at the 30th day, the 60th day, the 90th day, the 180th day, the 270th day, the 360th day after allogeneic hematopoietic stem cell transplantation. Matching with own blood reconstruction, PI3K expression in acute or chronic GVHD patients is statistical difference significantly. At the state of No-GVHD, aGVHD and cGVHD, it was 2.51 ± 1.16, 7.15 ± 5.92, 4.35 ± 3.14 respectively. Results suggest that, comparing with no-GVHD, PI3K expression with aGVHD increase significantly. And PI3K expression increase significantly when occuring cGVHD, but it is less than with aGVHD. In the experiment we also found, PI3K expressed in lymphocytes correlated with the increasing degree of GVHD. Particularly in the cGVHD, PI3K expression increased significantly when GVHD becoming more serious; with access to stable cGVHD, PI3K expression gradually become flat. We can draw the conclusions from this study: PI3K gene expression increased significantly in patients with GVHD than that of patients with no-GVHD, and related to different stages of GVHD. PI3K expression increased in cGVHD patients than that of patients with normal hematopoietic reconstruction, but the amplitude is not significant than that of aGVHD.