bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the Novel Chromosomal Translocation t(17;19)(q23;q13) in a Pediatric Patient with Acute Myeloid Leukemia.
Authors: Shardy Deborah L. , Azim Mohammed F. , Naeem Rizwan C. , Plon Sharon E. 
Published: October 2019

Abstract
Chromosomal rearrangements have been associated with many hematologic malignancies. Identification of the genes involved in several of these rearrangements has provided information about the development of malignancy and has led to therapeutic interventions. Historically, a considerable number of pediatric acute myeloid leukemia (AML) cases have been reported as cytogenetically normal. However, with improved cytogenetic techniques and the use of fluorescent in situ hybridization (FISH), new translocations are now being identified. We present the case of a 10-year-old male with AML (FAB subtype M1) and a subtle chromosomal translocation. G-band karyotype analysis revealed a balanced, reciprocal translocation between chromosomes 17 and 19 involving bands 17q23 and 19q13. This translocation was present in 20 out of 20 bone marrow cells examined. Peripheral blood chromosome analysis ruled out a constitutional chromosomal abnormality. Metaphase FISH with telomere-region specific probes for chromosomes 17 and 19 confirmed the reciprocal translocation between 17q and 19q. This patient was treated according to the SJCRH AML 2002 protocol and was randomized to receive high-dose cytarabine. Because he had minimal residual disease following induction therapy, he also received Gemtuzumab Ozogamicin. The patient was in cytogenetic remission for one year after completion of therapy, and then he relapsed with the original leukemic clone and additional cytogenetic abnormalities. The t(17;19)(q23;q13) has not been reported previously in malignancies or other disorders, and therefore identification of the genes at the chromosomal breakpoints may provide new insights into the pathogenesis of AML. As an initial step to map the breakpoint regions, we performed FISH with a commercially available probe encompassing the CRX, GLTSCR2, and GLTSCR1 loci on 19q13 (Vysis, Downers Grove, IL). This revealed that the 19q breakpoint is centromeric to these loci. We are further mapping the translocation breakpoint region on chromosome 19q using FISH-mapped bacterial artificial chromosomes (BACs).
Global Gene Expression Changes during Arsenic Trioxide -Induced Apoptosis in Myeloma Cell Lines Expressing Mutant or w.t p53.
Authors: Gazitt Yair , Akay Cagla , Kircelli Fatih 
Published: October 2019

Abstract
Arsenic trioxide (ATO) is an effective chemotherapeutic agent for the treatment of acute promyelocytic leukemia and is being tested in phase II studies in various types of hematological malignancies and solid tumors. We have previously shown that ATO is a potent inducer of apoptosis in multiple myeloma cells, engaging primarily the intrinsic apoptotic pathway in cells expressing w.t. p53. In contrast, in cells expressing mutant p53, both the intrinsic and extrinsic apoptotic pathways are engaged. These findings were further supported by a recent study using a p53 temperature sensitive (p53Ts) mutant cell line, BRK, expressing w.t. p53 at 32°C and mutant p53 phenotype at 37°C (Akay et al. Akay et al., AACR; Abstract #5344, 2005). Furthermore, myeloma cells expressing w.t. p53 transfected with SiRNA for p53 or p21 behaved like cells with mutant p53 (Kircelli et al. ASH presentation,2005). In order to identify new genes affected by ATO we used the Affymetrix Microarray technology to compare global gene expression in IM9 myeloma cells (w.t. p53) and U266 myeloma cells (mutant p53) following 0, 1,5 and 10 hours of treatment with ATO. We found ≥2 fold increase in gene expression by Affymetrix Microarray Suite Software (MAS) in 94 genes at 5 h and 455 genes at 10 h with an increase in 134, at both 5 and 10 h of treatment. By similar analysis, 263 genes were decreased at 5 h and 679 genes were decreased at 10 h with 204 genes decreased at both time points. Similar analysis with GeneSpring (GS) software revealed an increase in 202 genes and a decrease in 233 genes at both 5 and 10 h. Combination of the 2 analysis methods yielded 90 consistent increasers and 64 consistent decreasers. A great number of these genes in whom we detected changes in this study are genes that were previously identified by us and by others using Western immunoblotting. In addition, we observed differential effect of ATO in IM9 and U266 myeloma cells in apoptosis-related genes (HRK, BID, MCL1); cell cycle-related genes (GADD45, Cyclin D1, cyclin D2 and cyclin D3); signal transduction proteins (ERK, NFkB, ATM, ATR, CHK2, TRAILR2, TNF-R5/6 and VEGF); in chaperon proteins; cyclophyllin B; SAT, ToPoIIA and others. Systematic validation of these changes on the protein levels is ongoing.
Ikaros 6 Immortalizes Murine Hematopoietic Precursors In Vitro.
Authors: Ruiz Anna , Brady Hugh J.M. 
Published: October 2019

Abstract
The Ikaros transcription factor has been shown to play an important role in the differentiation of both the myeloid and lymphoid lineages. The ikaros gene encodes for a zinc finger protein containing seven exons that can be alternatively spliced generating several isoforms with differing functional properties. Isoforms with less than three DNA binding domains act as dominant negative (DN) by forming complexes with longer isoforms and interfering with their DNA binding and transcriptional activation ability. Mice heterozygous for a DN ikaros isoform develop T cell leukemia and lymphoma with 100% penetrance. Overexpression of DN Ikaros isoforms has been found in some forms of leukemias. We have previously reported overexpression of the DN Ikaros6 (Ik6) isoform in a subset of leukemia patients harboring t(4;11) translocations. In addition, we inducibly expressed Ik6 in BaF3 cells and found that Ik6 overexpression delayed cell death after IL-3 withdrawal.
To further investigate the leukemogenic properties of Ik6 overexpression, we have transduced murine hematopoietic precursors with a retroviral Ik6 expression vector and have analysed the effects on proliferation and differentiation of these precursors by in vitro colony formation assays. We have found that Ik6 can immortalize murine hematopopietic precursors in these in vitro assays. We are currently analysing the leukemogenic potential of Ik6 in vivo by transplanting Ik6 expressing cell lines into NOD/SCID mice.
Aldehyde Dehydrogenase (ALDH) Activity in Fresh (Pre-Freezing) and Post-Thawing Leukapheresis and Cord Blood Collections.
Authors: Perotti Cesare , Viarengo Gianluca , Del Fante Claudia , Bellotti Laura , Parisi Cristina , Marchesi Andrea , Salvaneschi Laura 
Published: October 2019

Abstract
Introduction: Primitive hematopoietic progenitor cells may be characterized by the detection of the intracellular enzymatic activity of aldehyde dehydrogenase (ALDH ). The use of a fluorescent substrate for ALDH (Aldefluor) permits the cytofluorimetric study of different stem cell populations in the functional way rather then as markers of cell surface. Aim of this study was to evaluate the ALDH activity of the stem cells in pre-freezing (fresh) leukapheresis (LKF) colllections and in cord blood (CB) units, to verify the feasibility of detecting the ALDH activity in the post-thawing units and finally to compare the results between the fresh and post thawed stem cells to be transplanted.
Materials and methods: Samples containing 2 x106 total nucleated cells obtained from 5 LKF and 5 CB units immediately after collection and from the same units after thawing, were incubated with Aldeflour (StemCo Biomedical, Durham, NC, USA) at 37°C for 45 min. and successively for 15 min. with anti CD34 PE, (Beckman Coulter, Fullerton, CA, USA) and anti CD45 PerCP (BD Biosciences, San Jose, CA, USA). Viability of CD34+ cells was evaluated using 7AAD, (Beckman Coulter, Fullerton, CA, USA). The setting of thawed samples was carried out immediately after thawing, taking care to make the sample dilution very quickly, in order to avoid the detrimental action on the cells exerted by DMSO at 37°C and at room temperature. All samples were analized using a BD Biosciences FACSCalibur flow cytometer device (San Jose, CA, USA).
Results: The results of the ALDH and CD34+ cell analysis and stem cell viability on fresh and thawed samples are detailed in table 1.
Conclusions: Our results demonstrate the feasibility of ALDH determination even in post thawed samples on condition that the test is conducted with accuracy with particular attention at the dilution step that must be completed in a very short time. The ALDH activity tends to decline in thawed stem cells demonstrating the detrimental action on stem cell functionality of the entire cryopreservation and thawing processes. In particular the contact of the stem cell with cryoprotectant mixture (DMSO) at room temperature has a negative, time dependent, impact on stem cell quality, confirming that the reinfusion phase of the graft must be carried out as soon as possible. The introduction of a functional test to evaluate the graft quality may be helpful in transplant clinical practice.
Table 1: Results of ALDH assayes on pre-freezing and post-thawing leukapheresis and cord blood collections. CD34+ (%) ALDH+ (%) CD34+/ALDH+ (%) ALDH+/CD34+ (%) Viability (%) Fresh LKF n=5 0.56 0.12 64.6 97.8 99.2 Fresh CB n=5 0.28 0.23 76.7 99.8 98.1 Thawed LKF n=5 0.48 0.09 65.5 94.4 81.2 Thawed CB n=5 0.24 0.19 71.5 96.8 77.3
Usefulness of Recombinant Human Erythropoietin during Induction-Consolidation Chemotherapy for Chronic Hematological Lymphoid Malignancies: Improving Stem Cell Harvest and Reducing Blood-Product Support for Patients Receiving Autologous Stem-Cell Transplantation.
Authors: Bijou Fontanet D. , Tabrizi Reza , Legay Thibaut , Melot Cyril , Bouabdallah Krimo , Pigneux Arnaud , Boiron Jean-Michel , Marit Gerald 
Published: October 2019

Abstract
Many discrepancies remain on how to use the combination of G-CSF and Epo in patients (pts) with hematological malignancies. Some studies have shown efficacy of this combination in autologous stem cell transplantation (ASCT) when they are used throughout the procedure, while other have demonstrated no benefit when this combination is used after ASCT particularly for Epo. We reviewed retrospectively 30 pts (NHL= 6, HD= 2, MM= 22)who received ASCT for myeloma and lymphoma between September 2003 and May 2005. The main goal of this observation was to evaluate the impact of Epo combination (epoetin beta, alfa or darbepoetin) with G-CSF during chemotherapy administered before ASCT in order to achieve a better hemoglobin (Hb) level before the ASCT procedure. We also evaluated a possible efficacy of this combination upon hematopoietic recovery, transfusion support and stem cell harvest for this population of pts. We used G-CSF (5 μg/kg) alone after stem cell reinfusion in our therapeutic scheme. Patients characteristics were F/M 19/11; 6 pts were in complete response and 24 in partial response of their disease. Conditioning regimen preparations were standard with Melphalan at doses between 140–200 mg/m2 (22 pts), BEAM (7 pts), Cyclophosphamide and Total Body Irradiation (1 pt). After at least 12 weeks of treatment, median Hb level before ASCT was 11.6 g/dl (8.5–14.8) and epoetin beta was used in most patients. Median CD34 cells reinfused were 4.4 (1.2–13.7) with a median number of leukapheresis of 3 (2–9). Hematopoietic reconstitution was fast according to published data and local experience, with a median duration of neutropenia (absolute neutrophils count < 0.5 x 109/l) of 7 days (5–11); the median number of days with platelets counts < 20 x 109 /l and 50 x 109/l was 3 (0–14) and 7 (2–17) respectively. Median transfusion requirement was 1 red cells unit (0–6) and 2 platelets units (0–8) respectively. Median duration of hospitalization was 18 days (15–26).
In conclusion, the use of combined G-CSF and Epo has probably improved clinical course of ASCT by reducing transfusion requirement, duration of hospitalization and neutropenia even when it is used before ASCT. Attempts have to be made to identify the place of Epo administration during ASCT procedure. Randomized prospective study might bring some important information about influence of this combination upon stem cell harvest particularly when it is used before the ASCT during induction and consolidation chemotherapy.
Does Early Lymphocyte Recovery Predict Superior Survival in Children and Young Adults Undergoing Hematopoietic Stem Cell Transplantation?.
Authors: Imran Hamayun , Khan Shakila P. , Arndt Carola A.S. , Rodriguez Vilmarie , Allen Julia A. , Trotz Barbara A. 
Published: October 2019

Abstract
Introduction: Early lymphocyte recovery predicts outcome in adults undergoing high dose chemotherapy followed by autologous stem cell transplantation for a variety of malignancies (Porrata et al; 2001, 2002, 2005). Whether rate of lymphoid recovery is predictive of outcome post-hematopoietic stem cell transplantation (HSCT) in children and young adults has not been studied.
Objective: To explore the association between early ALC recovery and survival in children and young adults undergoing allogeneic and autologous (HSCT) for leukemia or lymphoma.
Methods: Retrospective chart review was performed for all consecutive patients (age 6 months to 21 years) undergoing first HSCT for hematologic malignancies and lymphomas at Mayo Clinic, Division of Pediatric Hematology/Oncology from 1995 to 2004. Day 15 and day 28 ALC were calculated for all patients. The primary end point was 1-year relapse free (RFS) and overall survival (OS). To explore the association between ALC and primary outcome, patients were stratified in 2 groups: ≥ or < than median ALC and Kaplan Meier survival curves were generated for both the groups and compared with the log-rank test. Matched related donor (MRD), matched unrelated donor (MUD) and haploidentical (as one group) and autologous transplantations were analyzed separately.
Results: There were a total of 50 patients. 28 received MRD, 2 MUD, 10 haploidentical and 10 autologous transplant. The underlying malignancies were AML n =25, Biphenotypic Leukemia n=1, ALL n =7, NHL n=3, HD n=7, JMML n=5, CML n=2, CLL n=1). No patient was lost to follow up during that time and data was available for all except (day 28 ALC) for one patient. The 1-year RFS and OS rate was the same; 81% for the MRD, 50% for MUD and haploidentical and 70% for autologous transplant populations, respectively. In patients receiving MRD transplants, higher ALC at either day 15 or day 28 post transplantation was associated with better, albeit statistically non-significant, RFS/OS rates at 1 year (85% for ≥ median (0.23) vs. 78% for < median p=0.69 and 86% for ≥ median (0.47) vs. 77% for < median p= 0.59 respectively). Opposite results were observed for MUD and Haploidentical transplantation group (33% for ALC ≥ median (0.05) at day 15 vs. 67% for < median p=0.2, 33% for ALC ≥ median (0.35) at day 28 vs. 66% for < median p=0.28) and for autologous transplantations (67% for ALC ≥ median (0.23) at day 15 vs. 75% for < median p=0.68, 40% for ALC ≥ median (0.48) at day 28 vs. 100% for < median p=0.07).
Conclusions: Our data generated conflicting findings of the association between ALC and RFS/OS in different patient populations undergoing HSCT. However, our results are limited by the small sample size. Further collaborative studies are needed to explore this association.
Co-Transplantation Haploidentical Mesenchymal Stem Cells and Hematoietic Stem Cells with Nonmyeloablative Condition for Treatment of Relapsed or Refractory Acute Leukaemia.
Authors: Ai Hui-Sheng , Guo Mei , Yu Chang-Lin , Wang Dan-Hong , Qiao Jian-Hui , Sun Qi-Yun , Liu Li-Hui , Shi Zhang , Zhao Robert Chunhua , Sun Zhao 
Published: October 2019

Abstract
Background The major problems of haploidentical stem cell transplantation is severe graft versus host disease (GVHD) and graft rejection because of MHC barrier. Recently, some studies shown that mesenchymal stem cells (MSCs) which can be differentiat into various cells of MSCs origin has some good ability of immunosuppressive activity which may be used for enhance hematopoietic engraftment and lessen GVHD after transplant. So we desinged the protocole of co-transplantation haploiddentical MSCs and perpheral blood stem cell with nonmyeloablative conditions based on our past clinical trails of NST with HLA-march donor and haploid transplant experiment of Rhesus and want to improve the effective of haploidentical transplant in relapsed or refractory acute leukaemia
Methods Eleven parients(year range 8–33) with HLA-mismarch donor(3/6=6, 4/6=3,5/6=1) in relapsed or refractory acute leukaemia were received reduced toxicity condition(cyclophosphamide, fludarabine, anti-thymocyte gloubin, and low dose totol body irradiation(2.0GY) following a MSCs injection of bone marrow and perpheral blood stem cells with apheresis CS-3000 machine later 30 minutes. GVHD prophylaxis consisted of cyclosporine A, Mycophenolate mofetil(MMF) and CD25 antibodies.
Results All eleven patients passed smoothly the hematopoietic suppression stage and white blood cells and plate count was recovery normal in 11–15 days and 15–21 days after transplant. Eight patients get full donor chimerism(FDC) and three patients get mixed chimerism (MC) in which two patients converted to FDC in 28 days and 1 patient still remained of the MC after three months. In two patients the bone marrow derived MSCs cotained 5% donor MSCs in MSCs cultrued by STR-PCR on day +30, +60 and +90d after MSC infusion. Among the all of eleven patients, the incidence of aGVHD(grade I-II=4, and grade III=1) was 45.5%(n=5), the incidence of cGVHD was 27.3%(n=3) and leukaemia relapsed rate is 9.1%(n=1). Follow-up 3 to 18 months, survive rate of patients is 72.7%(n=8) and the following is continous.
Conclusions We conclude that co-transplantation haploiddentical MSCs and PBSCT with reduced toxicity condition is safe and effective. MSCs may play an very important rules in improving the donor engraftment and reduce the GVHD in haploidentical transplant.
Unique Reversible but Serious Adverse Events in Very Young Infants Undergoing Unrelated Donor Umbilical Cord Blood Transplantation for Non-Malignant Conditions: Increased Autoimmune Cytopenias and Hypertrophic Cardiomyopathy.
Authors: Lakshminarayanan Sonali , Szabolcs Paul , Parikh Suhag , Wood Susan J. , Allison June , Kurtzberg Joanne 
Published: October 2019

Abstract
Between September 1998 and June 2004, 15 young infants, <3 months of age, 60% males, 14 Caucasian, 1 African American, underwent unrelated donor umbilical cord blood transplantation for treatment of non-malignant conditions [early infantile Krabbe disease (n = 9), MLD (n = 1), MPS I (n = 1), MPS II (n = 2), Tay Sachs Disease (N = 1) or Beta Thalassemia major (n = 1)]. All infants were prepared for transplant with oral busulfan 20mg/m2/dose (targeting a steady state of 600–900ng/ml), cyclophosphamide 50mg/kg/dose daily x 4, and equine ATG 30mg/kg/dose daily x 3. Cyclosporine and solumedrol were used for prophylaxis against GvHD. All infants engrafted with donor cells, although 1 patient with MPS II never achieved >50% donor chimerism. Two patients died 3 and 5 years post transplant from respiratory failure (1 patient with MPS II and incomplete chimerism) and progressive Tay Sachs Disease, respectively. Grafts were mismatched at 1 (n = 8) or 2 (n = 7) HLA loci and 8/15 donor/recipient pairs were ABO mismatched. Nine patients developed mild to moderate acute GvHD. Within 6–10 months of transplant, six of the 15 patients developed autoimmune cytopenias (autoimmune hemolytic anemia +/− ITP), diagnosed clinically by Coombs positivity and antiplatelet antibodies respectively. They required therapy with steroids, imuran, dacluzimab, rituximab, and in one patient, splenectomy. There was no correlation with ABO or HLA matching or GvHD and the incidence of autoimmune disease. All patients recovered within 3–24 months. Eight of the 15 newborns developed concentric cardiomyopathy while on solumedrol and either cyclosporine or FK506 for GvHD treatment and/or prophylaxis. One patient required intubation and prolonged mechanical ventilation. The others remained relatively asymptomatic. Over time and with weaning of steroid therapy, their left ventricular hypertrophy resolved and heart function returned to normal. Both autoimmune cytopenias and hypertrophic cardiomyopathy occur in higher frequency in very young infants undergoing unrelated donor umbilical cord blood transplantation. The etiology of the autoimmune disease is not currently known while the cardiac disease is a result of therapies used to treat and prophylax against GvHD.
Long Term Survival Analysis after High-Dose Melphalan Chemotherapy Followed by Autologous Stem Cell Transplantation for Treatment of AL Amyloidosis: A Single Centre Experience.
Authors: Perz Jolanta B. , Rahemtulla Amin , Giles Chrissy M. , Szydlo Richard , Apperley Jane F. 
Published: October 2019

Abstract
Introduction: AL amyloidosis (AL) is a clonal plasma cell disease with a median survival of 10–14 months without therapy. Phase II studies report remission rates in up to 50% of patients (pts) after high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT). We retrospectively analysed AL pts who underwent HDM and ASCT at the Hammersmith Hospital in London since 1996.
Patients and methods: 19 pts (12 m, 7 f), median age 51 y (40 – 63 y) with lambda (14) or kappa (5) AL (2 pts with multiple myeloma stage IA) had the following leading organ involvements: 10 kidney, 3 cardiac, 3 liver or gut, 3 other. 12 pts had more than 2 involved organs. According to risk criteria for HDM (Comenzo and Gertz, 2002) 12 pts were high, 2 pts intermediate and 5 pts low risk. Stem cells were mobilised with Cyclophosphamide (4 g/m2) in 3 pts, Etoposide (1.6 g/m2) in 1 patient, G-CSF alone in 14 pts, 1 bone marrow harvest was performed. Melphalan dose was: 8 pts 200 mg/m2, 5 pts 140 mg/m2, 6 pts 100 mg/m2. The median number of infused stem cells was 3.45 x 106 CD 34+ /kg bw (1.96 – 11.3 x 106 CD 34+ /kg bw).
Results: Treatment related mortality (TRM) was 26%. In 14 patients who survived longer than 100 days from ASCT 6 pts achieved a haematological remission (5 a complete remission, 1 a partial remission) but in 8 patients no remission was achieved: 2 pts received a second ASCT, 2 pts further chemotherapy, 2 pts required haemodialysis. The mean survival from HDM and ASCT is 58.1 months (SD 9.64 months, 95% CI 39.21 – 76.99). The 1 - year and 2 - years overall survival from HDM and ASCT was 73% and 62%, respectively. The overall survival dropped to 42% after 6 years and the main cause of death was progressive or relapsed AL.
Conclusions: HDM and ASCT is feasible for patients with AL, however, TRM was high at 26% in a group of maily high risk patients. 62% of patients survived longer than 2 years, but disease relapse and deaths from relapsed or progressive disease occurred after longer than 2 years from HDM. Thus, new treatment strategies have to be investigated to treat disease progress and relapse in order to improve the long-term survival after HDM and ASCT in patients with AL.