bluuebunny/crossref_metadata_2025_split huggingface dataset:
Donor Leukocyte Infusion after Stem Cell Transplantation in Patients with Juvenile Myelomonocytic Leukemia.
Authors: Yoshimi Ayami , Bader Peter , Matthes-Martin Susanne , Starý Jan , Klingebiel Thomas , Duffner Ulrich , Locatelli Franco , Révész7 Tom , Niemeyer Charlotte M. 
Published: April 2020

Abstract
Juvenile myelomonocytic leukemia (JMML) is a rare clonal disorder of early childhood. Currently, only allogeneic stem cell transplantation (SCT) offers long-term cure. Relapse remains the major cause of treatment failure. Although graft-versus-leukemia (GVL) effect most likely plays an important role in controlling JMML, the benefit of donor leukocyte infusion (DLI) following SCT in JMML is currently unknown.
Patients and methods: Twenty-one patients with JMML who received DLI after SCT, including 4 patients after given a second SCT, were studied (BMT 14, PBSCT 6, CB 1). The median age at SCT was 15 (8–99) months. A normal karyotype, monosomy 7 or other aberrations were observed in 15, 2, and 4 patients, respectively. Six patients were transplanted from a matched sibling and 15 from an alternative donor. Chimerism analyses were performed by microsatellite PCR system or FISH for sex mismatch in all the patients. Response was defined as the achievement of complete chimerism (CC) and no evidence of hematological relapse. DLI was given either for the development of mixed chimerism (MC) in 7 patients (MC group) or for cytogenetic/hematological relapse in 14 patients (relapse group). Prior to DLI, cyclosporin A had been stopped in all patients, and no child had received chemotherapy.
Results of DLI: Five of the 21 patients received a single DLI, 16 patients 2–6 infusions (median 3). The total T cell dose given ranged from 9x104 to 2.4 x108/kg. Six of 21 patients responded: 3 of 7 patients in the MC group and 3 of 14 patients in the relapse group. The infusion of at least 1x107/kg T cells was needed for durable response. Response was observed in all karyotype subgroups. None of the 6 patients receiving DLI from a matched sibling responded. Five patients developed acute GVHD following DLI and 4 of them responded to DLI. On the contrary, only 2 of the 16 children who did not show acute GVHD after DLI responded. Chronic GVHD developed in 2 responders. The outcome of even the responders was unfavorable. Only one of the responders is alive in remission, with severe chronic GVHD, 72 months after DLI. Two patients relapsed 26 days and 54 months after DLI (one as gastric chloroma), and 3 died of complications of DLI (acute GVHD, bone marrow aplasia, and hyper-eosinophilic syndrome). Four non-responders and one responder with subsequent relapse were rescued by a second SCT.
Conclusion: This study shows that DLI can induce a GVL effect in some of the JMML patients. However, the benefit of DLI in our series of patients was limited because of severe complications in responders and lack of a durable effect. Some modification of DLI, with previous cytoreduction by chemotherapy or a novel drug such as E21R and concomitant administration of cytokines such as interferon alpha, can possibly improve the result of DLI.
Safety and Efficacy of Large Volume Leukapheresis for Allogeneic Hematopoietic Progenitor Cell Transplantation- the University of Miami Experience.
Authors: Shariatmadar Sherry , Nassiri Mehdi , Goodman Mark , Pereira Denise L. , Fernandez Hugo F. 
Published: April 2020

Abstract
Purpose: To report our experience with large volume leukapheresis (LVL) for allogeneic hematopoietic progenitor cell (HPC) transplantation, evaluating its safety and efficacy in 69 consecutive healthy donors.
Methods: Donor medical records from 1995–2004 were reviewed. These consisted of 38 males, 31 females, age range 16–65 (median: 37). All were mobilized with G-CSF, based on a dose of 7.5 mcg/kg/day (median: 600 mcg, range 300–960 mcg) for four days prior to outpatient LVL (Cobe spectra). Vascular access was femoral vein in 59 and antecubital veins in 10 donors. Pre- and post-LVL determinations included: WBC count, hemoglobin, hematocrit, platelet count, serum potassium, and calcium (Ca++). Oral KCL and oral/intravenous Ca++ were given as indicated by laboratory values and symptoms. Catheter-related complications and blood product requirements associated with collection were assessed. Final CD34/kg recipient body weight (rec. BW) and recipient engraftment data was evaluated.
Results: LVL was well tolerated by all donors undergoing a total of 74 procedures.
Data/LVL Procedure Mean Range Procedures per patient 1 1–2 Blood volume processed (L) 24.2 15.0–34.4 Time (minutes) 273 180–386 Flow rate (ml/min) 92 65–100 ACD–A used (ml) 1008 636–1449 Heparin used (units) 3000 Not applicable CD34/kg rec. BW 8.2 1.36–33.9
Adverse reactions were minor and occurred in 40% of the donors. Local parasthesias accounted for majority (86%) of the adverse events. Bone pain secondary to G-CSF accounted for the remainder of the cases and was well controlled with analgesics. Oral electrolyte supplements were administered in 61% of the donors. Eleven (15.9%) required intravenous Ca++ during collection. There were no catheter-related complications and no requirement for blood products during or after collection. Target values of 2 x 106 CD34/kg rec. BW was obtained in 68 cases (98.6%). Engraftment was achieved in 92% of the cases (6 died prior to engraftment). There were no early or late graft failures. Median time to ANC recovery was 10 days (range 8–25 days). Self-sustained platelet count was achieved in a median of 13 days.
Conclusion: LVL was a safe and efficacious method of allogeneic HPC collection. The use of a lower G-CSF dose for mobilization is more economical and well tolerated. This dose allows for adequate collection of CD34 positive cells. These cells support the sustained recovery from high-dose chemotherapy for allogeneic transplantation.
Characterization of Stat3 Binding in the γ-Globin Promoter: The Role of DNA-Protein Interactions in Gene Silencing.
Authors: Yao Xiao , Cubillos Federico , Sangerman Jose , Pace Betty S. 
Published: April 2020

Abstract
We previously demonstrated that signal transducer and activator of transcription 3β (Stat3β) acts as a negative regulator of γ-globin gene expression. We speculate that Stat3β participates in the γ to β-globin switch recapitulated during erythroid maturation. Regulatory elements located between nucleotide −52 and +36 relative to the γ-globin cap site may define a silencing domain where Stat3β exerts its negative effect. We analyzed DNA-protein interactions in a putative Stat3 binding site at +9γ and an overlapping Stat3/GATA-1 consensus sequence at +26γ. The +9γ motif was required for Stat3β mediated γ-gene silencing in K562 cells and normal erythroid progenitors. Mutating the +26γ site disrupted both Stat3 and GATA-1 binding which was confirmed by electrophoretic mobility shift assay. We demonstrated for the first time direct interaction between Stat3 and GATA-1 using immunoprecipitation techniques and protein extracts isolated from K562 and mouse erythroleukemia cells. We speculate that developmental stage specific DNA-protein interactions in the −52 to +36 region are required for γ-gene silencing. To investigate this hypothesis, we tested the ability of Stat3β to bind in vivo using chromatin immunoprecipitation (ChIP) assay. K562 cells were treated with Interleukin-6 (100ng/ml) to activate Stat3β and then used for ChIP analysis with phosphorylated-Stat3β antibody. Specific PCR primers were designed to amplify the region between nucleotide −52 and +36 relative to the γ-globin cap site. We observed increased Stat3β binding to the γ-globin silencing domain in vivo after Interleukin-6 treatment. To compliment this approach, we modified our ChIP assay as follows. A trypsin digest step was added after cross-linking proteins to the γ-globin silencing domain in vitro. The samples will be analyzed by nanospray LC/MS/MS mass spectrometry to characterize the transcription factors that bind the silencing domain and interact with Stat3β in this region. Understanding the DNA-protein interactions required for γ-globin regulation will provide insights into mechanisms for globin gene silencing.
Prospective Study of Post-Transplant Microangiopathy in Allogeneic and Autologous Stem Cell Transplantation.
Authors: Zeigler Zella Rose , Shadduck R. , Lister John 
Published: April 2020

Abstract
Thrombotic thrombocytopenic purpura-hemolytic uremic syndromes (TTP-HUS) have been described as specific sequelae following stem cell transplantation (SCT).Twenty-two patients undergoing autologous SCT and thirty-three patients undergoing allogeneic stem cell transplantation were prospectively evaluated on days 0, 7, 14, 30, 60, 90, 120 following SCT for the development of Post-Transplant Microangiopathy (PTM) based upon a rising lactic dehydrogenase level and percent fragmented cells (FC). The protocols were approved by the Institutional Review Board of the Western Pennsylvania Hospital where the studies were performed. The grades of PTM were based upon the criteria described by Zeigler et al, Bone Marrow Transplant, 1995) as follows: Grade 0: Normal LDH level and normal percentage fragmented cells (0–1.2%), Grade 1: Increased Fragmented Cells (FC) with normal LDH level, Grade 2: Increased LDH level that is rising with 1.2–4.8% FC, Grade 3: Increased LDH level with 4.9–9.6% FC and Grade 4: Increased LDH level with &gt;9.6% FC. The data is shown below in tabular form. These results indicate that almost all patients have increased fragmented cells following both autologous and allogeneic SCT. The median percent fragmented cells in both allogeneic and autologous SCT patients without evidence for PTM was 1.4% with a range of 0–5.2% Moreoeve the LDH level x ULN was 0.7 with a range of 0.5–1.8 x ULN in patients without evidence for PTM. The table below shows the data for the development of PTM in both allogeneic and autologous SCT patients with regard peak grade. Only two autologous patients had no increase in FC. The Grade of PTM was significantly lower in the autologous SCT patients compared to the allogeneic SCT patients. The table below lists the grades of PTM and the day of the peak Grade of PTM in both types of SCT patients. The Grades of PTM, peak LDH level and highest percent FC were higher in the allogeneic SCT patients. Eleven of twenty-two (50%) of the autologous SCT patients compared to thirty/thirty-three (91%) of the allogeneic SCT patients (p &lt;0.001) had evidence for PTM (grades 2 to 4).
PTM Grade Autologous Allogeneic p Grade 0–1 (no PTM) 11/22 (50%) 3/33 (9%) &lt;0.001 Grade 2 10/22 (45%) 10/33 (30%) NS Grade 3 1/22 (5%) 13 (39%) &lt;0.01 Grade 4 0/22 (0%) 7/33 (21%) NS Day to Peak TM 31 (3–96) 26 (7–120) NS Peak LDH x ULN 1.1 (0.7–31.9) 2.5 (0.9–14.8) &lt;0.001 Peak % FC 2.3 (0.5–4.9) 5.2 (1.9–19.2) &lt;.001
Hepatic Veno-Occlusive Disease (VOD) after Hematopoietic Stem Cell Transplantation in Children: Retrospective Analysis in a Single Institution.
Authors: Kook Hoon , Kim Seok Joo , Sohn Kyoung Ran , Baik Hee Jo , Noh Ha Young , Cho Young Kook , Sung Jun Seung , Nam Ho Song , Hwang Tai Ju 
Published: April 2020

Abstract
Introduction: Hepatic VOD, a potential life-threatening complication, occurs early after stem cell transplantation (SCT). Reliable predictive factors, effective prophylaxis and treatments need to be established in case of severe VOD. To better understand clinical findings in children, we evaluated clinical and laboratory characteristics of hepatic VOD undergoing SCT in children. Methods: We retrospectively reviewed the medical records of all patients (n=116) receiving SCTs in Pediatric BMT unit between May, 1991 to June, 2004. The definition of VOD required two of the following three clinical findings before D+21 following SCT: hyperbilirubinemia (&gt;2 mg/dL), ascites or sudden weight gain, and painful organomegaly. Ursodeoxycholic acid was started before conditioning. No routine heparin prophylaxis was used. Lipo-prostaglandin E1 (0.5 ng/kg/min) was used in most of unrelated transplants (20/23). Results: VOD developed in 11 patients (12.8%). The median age was 9.8 years (range, 2 to 13.9 years). Underlying diagnoses were ALL (n=3), AML (n=2), acute biphenotypic leukemia, severe aplastic anemia, neuroblastoma, and myelodysplastic syndrome (n=1, each). The median day of onset of VOD was D+9 (range, D-3 to D+19). VOD was classified as moderate in 5 (45%) and severe in 6 (55%) cases. At the median of D+12 (range, D-5 to D+56), total serum bilirubin elevated over 2 mg/dL, with the peak bilirubin level at D+18 (range, D-5 to D+59). Maximum level of serum bilirubin was 2.9 mg/dL (range, 2.1 to 9.2) in moderate VOD and 7.3 mg/dL (range, 2.0 to 24.2 mg/dL) in severe cases. Various treatment modalities have been applied. Successful control of VOD was possible with tissue plasminogen activator and heparin (2/5, 40%), ursodeoxycholic acid (2/5, 40%), N-acetylcysteine (3/5, 60%), and defibrotide (1/2, 50%). All of 5 patients with moderate VOD survived (range, 6+ to 67+ months). Five of 6 (83%) patients with severe VOD died of VOD before D+100 (range, D+7 to D+64). Conclusion: This retrospective study showed that the incidence of VOD in children was 12.8%, and the mortality of severe VOD is still unacceptably high, necessitating further development of effective treatment.
Comparison of G-CSF Administration Starting Day +5 Versus Based on White Blood Count Following Autologous Peripheral Blood Stem Cell Transplantation.
Authors: Craig Michael , Yao Yuan , Ericson Solveig 
Published: April 2020

Abstract
Granulocyte colony stimulating factor (G-CSF) is commonly used following autologous peripheral blood stem cell transplantation (PBSCT) to promote bone marrow recovery. However, the optimal timing of G-CSF in this setting is unknown. We randomized 23 patients undergoing autologous PBSCT for a variety of malignant disorders to G-CSF administration 5 μg/kg/day starting day +5 (Arm A) versus when white blood count (WBC) recovered to 0.2 x 109/L or 0.1 x 109/L for 2 consecutive days (Arm B). Results: All patients engrafted. The median time to absolute neutrophil count (ANC) &gt; 1.0 x 109/L in Arms A and B was 12.1 vs. 12.8 days (p=0.77). There was no significant difference in number of days of temperature &gt;38.3°C (4.3 vs. 4.4 days, p=0.71) or hospital stay (23.8 vs. 22.1 days, p=0.93) between Arms A and B respectively. The mean amount of G-CSF administered was 3210 μg/patient in Arm A vs. 2384 μg/patient in Arm B, a significant reduction (p=0.035). Conclusion: Waiting for early signs of engraftment after autologous PBSCT before starting G-CSF administration is associated with a decrease in amount of G-CSF administration by 25%, with no increase in days with fever, time to neutrophil recovery, or length of hospital stay.
Emergence of Mucormycosis in Onco-Hematology after Prolonged Use of Voriconazole: Attention Required.
Authors: Vigouroux Stephane , Morin Odile , Moreau Philippe , Mechinaud Francoise , Harousseau Jean-Luc , Milpied Noel 
Published: April 2020

Abstract
Voriconazole is a broad spectrum antifungal agent however ineffective against Mucor sp. It has proven to have a higher efficacy in the control of invasive aspergillosis when compared to amphotericin B. However, the prophylactic use of voriconazole has not yet been defined. Nevertheless, it has become an attractive option because of the broad spectrum, limited toxicity and possible oral administration of voriconazole. We report here four cases of mucormycosis (3 in 2003, 1 in 2004) that occured after prolonged use of voriconazole in hematologic patients. Patients 1 and 2 (23 and 34 years old, respectively) had relapsed acute myeloid leukemia, patient 3 (3 years old) had chronic myelomonocytic leukemia, and patient 4 (52 years old) had high-grade B cell lymphoma. All patients were severely immunosuppressed. Patient 1 had received a T cell depleted, haploidentical stem cell transplantation (SCT). Patients 2 and 3 had each received a matched unrelated allogeneic SCT complicated by subsequent acute and chronic graft versus host diseases. Patient 4 had been treated for 5 years with mycophenolate mofetil and steroids after a renal transplantation. All four patients received continuous treatment with the oral form of voriconazole for 7 to 30 weeks prior to the diagnosis of mucormycosis: three as primary prophylaxis and one for a bronchial aspergillosis. Mucormycosis was diagnosed 9 weeks after the lymphoma or between 27 and 33 weeks after SCT for the transplanted patients. Patients were subsequently treated with liposomal amphotericin B. Fever was the most common symptom, indicating an invasive infection in the 3 patients who died rapidly at 12, 13 and 45 days after the diagnosis. The surviving patient, an allogeneic SCT recipient, had a localized bronchial mucormycosis. No evidence of mucormycosis had been observed prior to the introduction of treatment with voriconazole beginning in October 2002. In addition, to date, mucormycosis has only been observed in patients that have had pre-exposure to voriconazole. Physicians should be mindful of the potential risk of invasive mucormycosis after prolonged use of voriconazole in immunocompromised hematologic patients. Moreover, the question of prophylactic use of voriconazole needs to be adressed further in randomized trials.
Outpatient High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation for Multiple Myeloma Is Associated with a Low Infection Safety Profile.
Authors: Agha Mounzer E. , Yeager Andrew M. , Evans Carol , Borkowski Nikol , Scekeres Anne Marie , Miller Sarah , Tompkins Cheryl , Schwartz Rowena , Donnenberg Albert D. , Shogan Jeffrey 
Published: April 2020

Abstract
High-dose melphalan (MEL) and autologous hematopoietic cell transplantation (HCT) is now a standard therapy in patients (pts) with multiple myeloma (MM). This HCT procedure is sufficiently tolerable to be performed on either an outpatient (OP) or inpatient (IP) basis. We compared the infection profiles in 16 consecutive pts who underwent OP HCT and 31 consecutive pts who underwent IP HCT for MM over a 24-month period. The median age of each group was comparable (OP 58 yr, range 33–72 yr; IP 59 yr, range 32–74 yr). All pts received MEL 200 mg/m2 before HCT and anti-infective prophylaxis with oral acyclovir, fluconazole and levofloxacin. Empiric treatment of first neutropenic fever in the OP group was imipenem and vancomycin (VAN) and in the IP group was cefepime with addition of VAN for persistent fever and/or positive cultures with VAN-sensitive bacteria. Median time to neutrophils &gt;0.5 x 109/L after HCT was 10 days in both groups (range 8–12 days for OP and 9–12 days for IP). Fever during neutropenia occurred in 7/16 (43.8%) of OP and 16/31 (51.6%) of IP HCT pts. Positive blood cultures (BCs) were identified in 3/7 (42.9%) of the febrile OP and 5/16 (31.3%) of the febrile IP HCT pts. Positive BCs in febrile OP HCT pts were coagulase-negative Staphylococcus (CNS) (2 pts) and Pseudomonas (1 pt). Positive BCs in febrile IP HSCT pts were CNS (2 pts), Streptococcus viridans (1 pt), Enterococcus (1 pt) and Bacillus (1 pt). One febrile OP HCT pt had cytomegalovirus pneumonia, and one afebrile IP HCT pt had a positive BC for CNS. Four febrile IP HCT pts with negative BCs had other infections, including cellulitis (2), facial abscess (1), and Clostridium difficile-associated colitis (CDAC) (1). Two other IP HCT pts (1 with fever and positive BC for CNS, 1 without fever) also had CDAC, for an overall incidence of CDAC of 3/31 (9.7%) after IP HCT. In contrast, no OP HCT pts had CDAC. Overall, the incidence of infections was 4/16 (25%) after OP HCT and 11/31 (35.5%) after IP HCT. We conclude that the infection profile of OP HCT compares favorably with that of IP HCT in pts with MM and is associated with a lower incidence of CDAC.
Clinical Significance of Positive Clostridium Difficile (CD) Toxin in the Stool of Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT).
Authors: Terada Yoshiki , Onishi Yasushi , Kim Sung-Won , Kami Masahiro , Mori Shin-ichiro , Heike Yuji , Takaue Yoichi , Tanosaki Ryuji 
Published: April 2020

Abstract
CD infection is a common complication in immunocompromised patients, including those undergoing HSCT, with reported incidences ranging from 4% to 13%. However, there has been no previous detailed report on the clinical impact of positive CD toxin in patients after allogeneic HSCT with current supportive therapies. Therefore, we retrospectively reviewed the medical records of 422 patients who underwent allogeneic HSCT with a variety of preparative regimens at National Cancer Center Hospital from January 2000 to April 2004. CD toxin in stool samples was measured by the Latex particle agglutination method, and selected patients were examined further by endoscopy. Positive results with CD toxin were observed at least once in 51 patients, at a median time of 40 days (range, −1 to 212 days) following allogeneic HSCT. Most patients had severe watery diarrhea, along with other symptoms including fever, nausea, anorexia and abdominal cramping, which mimics pseudomembrane colitis. Twenty-seven of the 51 patients (53%) underwent endoscopic examination, and macroscopic findings were as follows; normal in 4 (15%), extensive edema in 11 (41%), and mucosal sloughing in 12 (44%), while none had pseudomembrane formation. Histological diagnosis revealed that 26 cases (96%) were compatible with GVHD, including 2 complicated with Cytomegalovirus colitis. Thirty-three patients (65%) were treated with oral vancomycin for a median of 14 days (2 to 46 days), while the remaining 18 were followed conservatively without any specific medication. Forty-four patients were evaluable for follow-up, and, regardless of management, all subsequently became negative for CD toxin. These findings suggest that positive CD toxin in the stool detected during the course of allogeneic HSCT may only reflect nonsignificant colonization or proliferation of CD in the gut, and hence may not necessarily imply clinically relevant pseudomembranous colitis which would require intense medical treatment. Additionally, in patients undergoing allogeneic HSCT, signs and symptoms of intestinal involvement may simply reflect concomitant GVHD per se or a pathology closely related to GVHD.