bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequency and prognosis of Clonal Chromosomal Abnormalities Following Stem Cell Transplantation (SCT) in Acute Myeloid Leukemia (AML)
Authors: Grau Javi er , Cisneros Adela , Zamora Lurdes , Sancho Juan Manuel , Granada Isabel , Ruiz-Xivillé Neus , Xandri Marisol , Guardia Ramon , Fernandez Cristalina , Santafé Encarnación , Villena Carmen , Cabezón Marta , Sancho Esther , Xicoy Blanca , López Laia , Rodriguez Inés , Moreno Miriam , Orna Elisa , Ferra Christelle , Batlle Montserrat , Roncalés Francisco Javier , Flores Alonso , Juncà Jordi , Navarro José Tomás , Ribera Josep Maria , Feliu Evarist , Millá Fuensanta 
Published: April 2020

Abstract
Objective. To study the incidence, type and prognostic significance of clonal chromosomal abnormalities following SCT in patients with AML.
Patients and methods. From February 2000 to March 2008, 74 patients were studied. Karyotypes were analysed by G-banded chromosomes obtained from 24 hours bone marrow cultures, and were described according to ISCN 2005.
Results. Clonal abnormalities were observed in 17/74 patients (23%). Median follow-up was 11 months (range 5–47). Initial diagnosis: AML2 (6 cases), AML5a (3), AML6 (3), AML with inv(16)(p13;q22) (1), AML with multilineage dysplasia (1), AML5b (1), AML1 (1) and AML0 (1). Treatment before SCT: idarubicin, cytarabine and etoposide (16), FLAG-ida (1). All patients presented a normal karyotype at the time of SCT. SCT type: autologous (12 patients), allogeneic (3), allogeneic of reduced intensity (2). Conditioning regimen: TBI and cyclophosphamide (14 cases), busulfan and cyclophosphamide (1), fludarabine and busulfan (2). The median time between SCT and the appearance of clonal abnormalities was 8 months (range 3–36). At the time of clonal abnormality detection, 16 patients were in cytological and/or clinical relapse and 1 in complete remission. In 4 cases the initial clone reappeared, 1 showed the initial abnormalities with an acquired abnormality and 12 presented de novo clonal abnormalities. The median survival from the appearance of clonal abnormalities was 2 months (range 1–40). At the time of the analysis all patients had died.
Conclusions.
The appearance of clonal abnormalities following SCT in patients with AML is frequent. Time between SCT and the appearance of clonal abnormalities is short. The majority of patients presented de novo clonal abnormalities with cytological and/or clinical relapse and poor prognosis.
Haematopoietic Stem Cell Transplantation in Thalassaemic Patient with Renal Failure on Hemodialysis
Authors: Argiolu Francesca , Sanna Maria Adele , Bartoli Antonella , Ferrara Rocco , Piroddi Antonio , Addari Carmen , Orofino Maria Grazia , Rizzo Fabiana , Cossu Fausto , Scalas Maria Rosa , Broglia Monica , Giagu Nicolina , Galanello Renzo 
Published: April 2020

Abstract
Until now few patients with renal failure on hemodialysis have undergone haematopoietic stem-cell transplantation (HSCT), and none with thalassaemia. Case report. Patient of 45 years, UPN 168, with β Thalassaemia major, genetic compound β0 39 C--&gt;T/β0 6-A, non transfusible due to red blood cell immunization (positive DAT, Hb 5–7 g/dl), under hemodialytic treatment for three years for bilateral focal nephrosclerosis. He suffered from cardiopathy (atrial thrombosis, pulmonary hypertension, atrial and ventricular dilatation), hypothyroidism, hepatopathy (HCV positive with grade II haemosiderosis). Quality of life was much harmed by the severe chronic anaemia and nephropathy. In December 2007 we performed HSCT from his HLA identical brother. Conditioning regimen included: Busulfan (Bu) IV (Busilvex Pierre Fabre Médicament) in single daily dose (3.5 mg/kg/day) for 4 days, Cyclophosphamide 40 mg/kg/day for 3 days. GvHD prophylaxis consisted of Cyclosporin 3 mg/kg/day IV (days -2 to +1), 2 mg/kg/day IV (days +2 to +42), changed to oral administration of 4 mg/kg/day from day +43. Hemodialysis was performed every other day in sterile room. Nucleated marrow cells infused: 4.4 × 108/kg. A mixed chimerism (VNTR more than 90% donor) was documented at day +19. ANC &gt;0.5 × 109/L at day +21. PLT &gt;20 × 109/L at day +15. Eight months after transplantation, patient is in good general condition, with stable mixed chimerism (more than 95% donor), haemoglobin above 11 g/dl, leucocytes and platelets in normal range. Substantial improvement of chronic anaemia ameliorated patient’s quality of life and now patient can be considered a kidney transplant candidate. This single case report does not allow definitive conclusions to be drawn regarding HSCT suitability of patients with chronic renal failure on hemodialysis. We can observe that once-daily intravenous busulfan administration (after the hemodialysis session) has made it possible to keep therapeutic range, as has been ascertained by pharmacokinetic study of busulfan.
Febrile Neutropenia Following Autologous Stem Cell Transplantation in Patients with Lymphoma
Authors: Vrhovac Radovan , Peric Zinaida , Kalac Matko , Ostojic Alen , Kovacevic Visnja , Bukovski-Simonoski Suzana , Tambic-Andrasevic Arjana , Minigo Hrvoje , Jaksic Branimir 
Published: April 2020

Abstract
Background: Infections remain a major cause of morbidity and mortality in patients with lymphoma treated with autologous hematopoietic stem cell transplantation. Knowledge of local microbiological epidemiology and patients’ risk factors are essential for optimal management of these infections.
Aims: to determine incidence of febrile neutropenia (FN) in patients with lymphoma treated with autologous peripheral blood stem cell transplantation (PBSCT) and to investigate correlations of a number of variables available on the day of FN onset with the severity of infection.
Patients and Methods: 102 consecutive patients (median age 44, range 19–68 yrs, 58M/44F) with relapsed or refractory Non-Hodgkin’s Lymphoma (NHL, n=78) and Hodgkin’s Disease (HD, n=24) treated with PBSCT in a single center have been evaluated for infectious complications following transplantation.
Results: Febrile neutropenia occurred in 67 (65.7%) patients at a mean of 6 days after transplantation (range 1–9, SD 1.71). Microbiological work-up was done and empirical antibiotic therapy with piperacillin-tazobactam was initiated in all but 15 patients who received a carbapenem. Empirical therapy was modified in 31 (46.3%) patients. Vancomycin was added in 22 patients (32.8%), a sistemic antifungal in 4 (6.0%) and both in 6 (9.0%) patients. Three patiens died as a consequence of sepsis (TRM=2.9%). Twenty two patients (32.8%) had proven bacteremias while 27 (40.3%) had other microbiologically documented infections (MDIs). Gram+ microorganisms were responsible for the majority of all documented infections (63.6% of bacteremias and 54.5% of other MDIs). Correlations of a number of variables available at time of FN onset with the duration of febrile episode have been investigated. Patients with higher CRP levels at FN onset and those with earlier onset of fever following PBSCT had significantly longer (p=0.047 and p=0.0066, respectively) duration of fever. Other variables, including age, No. of previous lines of therapy, No. of stem cells reinfused, ANC and monocyte counts as well as peak temperature values at day of fever onset did not show statistically significant correlations with duration of fever. All patients with diabetes developed FN and, although not reaching statistical significance (p=0.09), its duration was longer in comparison to other patients.
Conclusions: Infections are serious but manageable complications of PBSCT. Gram+ microorganisms remain the major cause of documented infections. Early empirical antimicrobial therapy, tailored according to local microbiological epidemiology is essential for their optimal treatment.
Reduced-Intensity Conditioning Regimen in Allogeneic Haematopoietic Stem Cell Transplantation for Follicular Lymphoma and Chronic Lymphocytic Leukemia
Authors: Vaz Carlos Pinho , Ferreira Rosa Branca , Silva Joao , Barbosa Isabel , Roncon Susana , Carvalhais Alzira , Martinho A. , Campilho Fernando , Campos Antonio 
Published: April 2020

Abstract
Reduced-intensity conditioning (RIC) regimens is being increasingly used for allogeneic haematopoietic stem cell transplantation (HSCT) in recent years for follicular lymphoma (FL) and chronic lymphocytic leukaemia (CLL). The lower risk of transplant related toxicity associated with RIC regimens makes allogeneic transplantation applicable to patients (pt) with haematological malignancies resistant to conventional therapy and/or in poor medical condition, while preserving the putative graft-versus-tumour effect (GVT). From May 99 to January 07, 31 recipients were studied. Twenty two pt (71%) with FL: 14pt CR2; 4pt PR; 2pt resistant relapse; 1pt graft failure; 1pt advanced disease and 9pt with CLL in PR, underwent to allogeneic HSCT from HLA-matched (31) sibling donors, after treatment with fludarabine 30 mg/m2/d iv × 5 + busulfan 4 mg/Kg/d × 2 ± anti-T lymphocyte globuline (10 mgKg/d) × 4 or fludarabine 30 mg/m2/d iv × 5 + cyclophosphamide (1g/m2/d) × 3 + alentuzumab 20mg/d × 5 (pt with graft failure). Stem cell source was unmanipulated peripheral blood progenitor cells. Median number of CD34+ cells infused: 6,0 × 106/Kg (3,3–12,0). CsA 3 mg/kg/d was given from day-1 until day +90 then tapered progressively, associated with Micophenolate mofetil d0 until d+84.
Results: In 31 evaluable pt hematological recovery have a median time to neutrophils ≥0.5×109/L of 13d. (3–37+) and platelets ≥20 × 109/L of 11 d. (9–105+). Transfusion requirements: median: 4 RBC units and 2 platelet transfusions per pt. Median day of discharge: d.15. Hepatic veno-occlusive disease and severe mucositis did not occur. Chimerism analysis (day +28) showed donor engraftment in all pts–mixed in 5 and full in 26 (full in graft failure pt after second transplant). 36±9,2% pts developed clinical grade 2–4 aGvHD and 68,9±10,8% developed cGvHD. Four pt had relapsed/progressive disease. Non relapse mortality occurred in 3 pts with low performance status and chemotherapy resistant disease. At 3,6 years median overall survival (OS) is 85.2±6.9%. Twenty eight pts are alive with a median follow-up of 3.6 years. Progression free survival (PFS) at 3 years is 84,1±7,1 %. Aimed to induce GvT effect, one pt with progressive disease, without GvHD was assigned to receive donor lymphocyte infusions (DLI) at regular intervals achieved stable disease. These results show that RIC regimen are well tolerated, have a low risk of transplant related mortality and are able to ensure a sustained engraftment. RIC is becoming the standard approach in allogeneic HSCT for FL/CLL and the increased risk of late disease progression might be manipulated with GvT effect associated with posterior DLI.
Should All Patients with Acute Myelogenous Leukemia (AML) Other Than Good Risk Cytogenetics Receive Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in First Remission?
Authors: Alpdogan Onder , Lenox Raymond , Barile Amy , Foss Francine , Shlomchik Warren , Reuben Christy , Cooper Dennis , Seropian Stuart 
Published: April 2020

Abstract
There has been little improvement in the standard therapy of AML in the last two decades. Allogeneic HSCT remains the most effective curative therapy for patients with AML; however, risks associated with this therapy have limited its use for patients of advanced age or requiring alternate donors. Improvements in supportive care, donor selection and conditioning protocols have decreased the risk of transplant related mortality and allogeneic HSCT now appears as a feasible option for elderly patients. We reviewed the outcome of 99 patients with AML and MDS who received allogeneic HSCT in our center from 6/98 to 12/07. 85 patients were diagnosed with AML and 14 patients had MDS. 25 patients with AML (29%) had secondary AML including chemotherapy-related (6 patients) and progression from MDS or myeloproliferative disease (19 patients). Median age was 51 (20–72). Patients received allografts from related donors (n=56) and unrelated donors (URD) (n=43). All patients who received URD in first remission had poor prognostic features. 56 patients received myeloablative conditioning protocols (MA) whereas 43 patients were transplanted with reduced intensity protocols (RI) primarily due to age &gt;55. Overall probabilities of 4-year and 8-year survival are 51% and 41% respectively. The median follow-up is 30 months for surviving patients. RI-group (Median age: 62 (37–72) had a similar 4-year survival with MA-group (50% and 54% respectively). 4-Year probability of survival in elderly patients (age&gt;60) after RI-HSCT (n=27) is 48%. Patients who received an URD allograft and RI conditioning (n=21) had a similar survival to those receiving MA conditioning and URD graft (n=22) (4-year survival 52% and 54% respectively). As expected, AML patients in first complete remission (CR1) had better survival than patients who were in second or higher complete remission (CR2) (4-year survival; 53% vs 29%). We conclude that HSCT for AML and MDS from related or unrelated donors, with age and comorbidity-appropriate conditioning, results in a favorable outcome compared to historical experiences with standard therapy. Allogeneic HSCT should be tested in first remission for all patients with AML excluding younger patients with good risk features.
Long Term Survival in Refractory Leukemia Patient Treated with Related HLA Haploidentical Stem Cell Transplantation
Authors: Wu Bingyi , Kunyuan Guo , Wu Jing 
Published: April 2020

Abstract
Objective: To assess the long term survival of patients with refractory leukemia treated by HLA haploidentical stem cell transplantation.
Methods To analysis the outcomes of 48 cases patients with refractory leukemia underwent HLA haploidentical stem cell transplantations from August, 1998 to May, 2008. The median age was 16 years old (7–52 years old). Patients received stem cells from their parants, daughter, son, and sibling donors. Twelve patients received three HLA locus mismatched stem cells and twenty patients received two HLA locus mismatched donors stem cells. Sixteen patients were grafted one HLA mismatched donors stem cells. The conditioning regime consisted of fludara (25mg/m2 × 5d), busulfan (4mg/kg × 4d) and cyclophosphamide (60mg/kg × 2d). Median dose of rabbit anti-human lymphocyte globulin (5mg/kg × 5d) was added. CSA combined with short course of MTX were used for prophylaxis GVHD. A median dose of 6.0 × 108/kg(3–9 ×108/kg) mono-nucleated cells was grafted. The mean CD34+ cells number was 5.5 × 106/kg (3–6.5 × 106/kg)
Results Forty-seven patients were successfully to be engraftment and one failed to be engraftment. The median time of white cells and platelet reconstitution was 14 days (11–20 days) and 18 days (14–20) respectively. Severe acute graft versus host disease occurred in seven patients, and six died. Seven patients suffered from intensive chronic graft versus host disease and four died with fungus infection. Seven patients relapsed and died. The median relapse time was 6 months (3 months to 24 months). Three patients died from severe diarrhea with CMV infection. Four patients died from intensive chronic graft versus host disease. Twenty patients are still survival and disease free with high karnofsky performance scores. The disease free survival is 45 percent as follow up 3 years (1 to 7 years).
Conclusion: HLA haploidentical peripheral blood stem cell transplantation may be an effect therapy to refractory leukemia. And some refractory leukemia patients could benefit from HLA haploidentical peripheral blood stem cell transplantation.
Autologous Stem Cell Transplantation (ASCT) with Busulfan Plus Cyclophosfamide as Conditioning Regimen for Acute Myeloid Leucemia: Retrospective Experience (1991–2007) of Two Bone Marrow Transplant Unit
Authors: Irrera Giuseppe , Messina Giuseppe , Martino Massimo , Console Giuseppe , Milone Giuseppe , Iacopino Pasquale 
Published: April 2020

Abstract
We report our results of ASCT in patients with Acute Myeloid Leukemia (AML) during the last 16 years. Between December 1991 and december 2007, 90 patients with AML received an ASCT. The main characteristics were reported on table 1. The median patient age was 46 years (range17 – 67 years). The conditioning regimen employed for all patients was Busulphan + Cyclophosfamide. The Overall Survival (OS) (Figure1) was 53,5% with a median follow up of 91,6 months. The majority of patients (81) was transplanted in first complete remission (1st CR), 8 in 2nd CR and 1 &gt;2nd CR. The OS considering the disease phase at transplant was different: 55,7% vs 16,7%, p &lt; 0,01 (one pts with &gt; second CR was excluded from analysis). If we considering also the age stratified in two groups: 17–45 vs 46–67 years, all patients in second CR, included into II group died. We have calculated OS stratified for age in these groups that was 46,2% versus 59,6%, respectively, without statistical differences. We also analyzed the OS distributed for sex and cell source without statistical difference. We have documented a statistically significant correlation between FAB group and survival (Figure 2). In fact, the patients with FAB M2 and M4 (excluded M3) had a superior OS than those with other FAB (60,7% vs 40%, p &lt; 0.019)). In 32/40 (80%) patients, the relapse has been documented within 24 months from transplant. The analysis for cytogenetic risk has been performed, but considering only 46 patients assessable. The OS cytogenetic risk-related was 87% for 8 patients with Low Risk, 47% for 36 patients with Intermediate Risk, 2 patients with High Risk died within 11 months from transplant (data not shown). We conclude that autologous bone marrow transplantation is an effective treatment in AML with the possibility of long survivorship, particularly in patients with FAB M2 and M4. In our experience, first complete remission of disease at transplant play an important role and correlates with the longest survival. The analysis of cytogenetic risk reflects the impact of karyotype on OS. Transplant Related Mortality (TRM) has been documented in 6/90 patients, all died before the years 2000.
Figure 1 Figure 1.
Table 1
Number of patientss 90 Sex (M/F) 42/48 Age (range y) (mean ±SD y) 17–67 46,3±11,4 FAB classification: M0 2 (2,2%) M1 16 (17,8%) M2 28 (31,1%) M3 4 (4,4%) M4 28 (31,1%) M5 11(12,3%) M6 Phase of disease: 1 (1,1%) 1st Complete Remission 81 (90%) 2nd Complete remission 8 (8,9%) &gt; 2nd Complete Remission 1 (1,1%) Citogenetic risk (pts evaluable: 46) Low 8 (17,3%) Intermediate 36 (78,2%) High 2 (4,5%) Transplant Related Mortality 6/90 (6,7%)
MicroRNA Expression in Childhood Acute Lymphoblastic Leukemia (ALL)
Authors: Yang Yung-Li , Yu Sung-Liang , Chen Hsuan-Yu , Yang Pan-Chyr , Chen Jiann-Shiuh , Lin Dong-Tsamn , Lin Shu-Rung , Jou Shiann-Tarng , Yen Ching-Tzu , Lin Kai-Hsin , Hu Chung-Yi , Chang Sheng-Kai , Chiou Rong-Jing , Lu Meng-Yao , Chang Hsiu-Hao , Lin Shu-Wha 
Published: April 2020

Abstract
MicroRNAs (miRNAs) are small RNAs of 19 to 25 nucleotides that are regulators of gene expression. A role for microRNAs in leukemia, such as chronic lymphoblastic leukemia, acute myelogeneous leukemia has recently been recognized. However, little is known about the role of microRNAs in childhood acute lymphoblastic leukemia (ALL). To determine whether miRNAs are associated with the clinical features of childhood ALL and its association with cytogenetic abnormalities, we analyzed 60 untreated childhood ALL cases for their miRNA expression using a microarray platform. Leukemic samples were collected from the ALL children between 1–18 years of age. Of the 365 miRNA analyzed with a training group of 40 patients, a miRNA signature was derived that was associated with event-free survival. The signature was tested in a validation group of 20 patients. For the latter, a miRNA compound covariate predictor (i.e., a miRNA risk score) was computed on the basis of weighted levels of the miRNAs forming the outcome signature. The signature identified from the training group contained 5 miRNA highly associated with event-free survival (P&lt;0.05). The summary value of the signature miRNA was also highly associated with event-free survival (P &lt;0.05) in the validation group. After adjustment for the gender, age, initial white counts, immunophenotypes, and cytogenetics, the miRNA risk score remained associated with event-free survival (P &lt;0.05) in multivariable analysis. In conclusion, we have identified a miRNA signature of 5 miRNAs which is highly associated with the clinical outcome, cytogenetic and immunophenotypic subtypes of childhood ALL.
Mir-15a and Mir-16-1 Induce Apoptosis of Raji Cell Line
Authors: Qin Chen , Dongmei He 
Published: April 2020

Abstract
MicroRNAs are endogenous small noncoding RNAs that regulate gene expression negatively at posttranscriptional level. Mir-15a and mir-16-1 are deleted or downregulated in the majority of chronic lymphomatic leukemia(CLL), which is the most common human leukemia and overexpresses the antiapoptotic B cell lymphoma2 (Bcl-2) protein. Here we investigated the effect of mir-15a and mir-16-1 on human lymhpomatic cell line Raji in induction of apoptosis. We transfected chemically synthesized mir-15a and mir-16-1 oligonucleotide into Raji cells using Lipofectamine 2000 reagent. At 24,48,72 hours after transfection, the growth inhibitory effect of Raji cells was measured by trypan blue dye exclusion method and CCK8 assay. Apoptosis was determined by morphological observation and flow cytomertry analysis after AnnexinV/PI double labeling. The expression levels of Bcl-2 protein were detected by immunofluorescence assay. Trypan blue dye exclusion method and CCK8 assay showed that transfection of mir-15a or mir-16-1 decreasesd the cell growth at 24, 48 and 72 h, which were significantly lower than those cells transfected with control oligonucleotide and untransfected cells, respectively (P&lt;0.05). Using Hoechst staining, cells treated with mir-15a or mir-16-1 oligonucleotide displayed changes of apoptosis at 48,72h after transfection. AnnexinV/PI double dyeing assays showed early and late apoptotic cells at 48 and 72 h post-transfection. At 48,72h after transfection with mir-15a or mir-16-1 oligonucleotide, early and late apoptotic cell rate were obviously higher than untransfected cells and control miRNA group. Indirect immunofluorescence assay demonstrated that the expression of Bcl-2 was degraded at post-transfection, suggesting that Bcl-2 is a direct target of mir-15a and mir-16-1. These results show that mir-15a and mir-16-1 can induce apoptosis of human lymhpomatic cell line Raji. Our results suggest that mir-15a and mir-16-1 could be used for therapy of Bcl-2 overexpression tumors.