bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stem Cell Transplantation (SCT) for Acute Myeloid Leukemia (AML): A Single Center in over 25 Years Experience.
Authors: Santarone Stella , Di Bartolomeo Erminia , Di Bartolomeo Paolo 
Published: October 2019

Abstract
In this study we report the results of SCT in 116 patients (M51, F65) with AML transplanted from HLA identical (n=111) or 1 antigen mismatched (n=5) related donors between 1981 and 2006. The median age was 33 years (1–63). At time of SCT, 76 patients were in CR1, 23 in CR2 and 17 in CR>2 or in relapse. The stem cell source was bone marrow for 94 patients, PBSC for 21 and cord blood for 1. The conditioning regimen was myeloablative for 110 patients (BU CY for 87 and TBI CY for 23) and not-myeloablative for 6 (Thiotepa CY). For GvHD prophylaxis, 30 patients received cyclosporine (CSA) alone and 86 were given CSA and short course methotrexate. All patients engrafted with a median time to achieve 0.5 ×109/L neutrophils and 50×109/L platelets of 20 (10–37) and 22 (11–103) days respectively. One patients lost the graft six months after SCT and was successfully retransplanted. Acute GvHD grade II–IV occurred in 24%. Chronic GvHD occurred in 21% (9% limited, 12% extensive). The overall transplant related mortality (TRM) was 15.5% at 12 months (14,4% in CR1, 8,7% in CR2 and 29% in CR>2 or in relapse). Causes of death were: GvHD in 6 patients, infection in 6, multiorgan failure in 3, renal insufficiency in 1, encephalopathy in 1, pancreatitis in 1. The overall incidence of relapse was 29% (25% in CR1, 26% in CR2, 53% in CR>2). Twelve patients (1 in CR1, 5 in CR2 and 6 in >CR2 or relapse) underwent a second SCT from the same donor after a median interval from the first and second SCT of 456 (203–1946) days. The TRM post-second SCT was 16%. Nine of 12 patients are now living and cured after a median follow-up of 5,4 years (1–16,8). Overall, after a median follow-up of 8.08 (0.3–22) years, 71 out of 116 patients (61%) are living and cured. The 20 years probability of disease free survival is 68% for patients in CR1, 74% for patients in CR2 and 18% for patients in CR>2 or relapse (Fig. 1). In univariate analysis the patient age < 30 years, the BUCY regimen as compared to the TBI regimen and a dose of marrow cells > 3.0 × 108/Kg are associated with a better survival. We conclude that SCT is a curative treatment for patients with AML. In our experience second SCT gives results comparable to those of first transplant.
Fig 1. Probability of DFS according to phase of disease at SCT Fig 1. Probability of DFS according to phase of disease at SCT
Successful Bone Marrow Transplantation with an Intensively Immunosuppressive Conditioning with Low Toxicity for High-Risk Chronic Granulomatous Disease Patients.
Authors: Miki Mizuka , Kajiume Teruyuki , Nakamura Kazuhiro , Kawaguchi Hiroshi , Sato Takashi , Kurita Emi , Onodera Rie , Hiraoka Asako , Mizukami Tomoyuki , Nunoi Hiroyuki , Kobayashi Masao 
Published: October 2019

Abstract
Chronic granulomatous disease (CGD) is an inherited disorder characterized by recurrent bacterial and fungal infections, often resulting in impaired quality of life and death. Allogeneic hematopoietic stem cell transplantation (HSCT) is the curative therapy for patients with CGD. HSCT in certain CGD patients is associated with a significant risk of therapy-related morbidity due to toxicity, rejection, GVHD, and/or infectious complications. Recently successful HSCT with nonmyeloablative conditioning for CGD patients has been developed. However, the results of HSCT in adult CGD patients have been insufficient in adult patients with CGD. In this study 5 patients with adult CGD underwent bone marrow transplantation after undergoing an intensive immunosuppressive regimen with reducing toxicity and optional donor lymphocyte infusion (DLI). All patients were diagnosed by the absence of oxidase activity and confirmed by the lack of the expression of 91phox using monoclonal antibody by flow cytometry. All patients were more than twenty years of age and suffered from critical and life-threatening infections, such as brain abscess, osteomyelitis, and granulomatous colitis at transplantation. Patients underwent a conditioning regimen consisting of cyclophosphamide (30 mg/Kg × 4), fludarabine (30 mg/m2 × 5), anti-lymphocyte globulin (15 mg/Kg × 4), and low-dose (3 Gy) of total body irradiation. Four of five patients were transplanted from HLA-identical siblings and one patient from HLA-haploidentical brother presenting microchimerism between donor and recipients. After transplantation prompt engraftment with mixed chimerism was observed without severe conditioning-related complications in all patients. Their infections were immediately improved within one month after transplantation during the period of mixed chimerism. The degree of chimerism was serially assessed by microsatellite DNA sequences and by the presence of 91phox-positive neutrophils using flow cytometry. Based on the chimerism assay, DLI was performed in two patients without developing GVHD. All patients have achieved complete chimerism without therapy-related complications. These results using an intensively immunosuppressive conditioning with low toxicity is a promising treatment modality for high-risk patients with CGD.
Peripheral Blood Stem Cell Transplantation in Children with Thalassemia.
Authors: Tezcan Gulsun , Uygun Vedat , Kupesiz Alphan , Hazar Volkan , Yesilipek Akif 
Published: October 2019

Abstract
Although improvements in conventional treatment have enhanced the prognosis of thalassaemia, stem cell transplantation remains the only cure. Studies have shown that peripheral blood stem cell transplantation (PBSCT) results in rapid hematological and immunological recovery but increased risk for graft versus host disease (GVHD). We report the PBSCT experience of Akdeniz University School of Medicine Pediatric Hematology&Oncology department concerning 54 patients with beta-thalessemia. Median age was 6 years (1–18 years), 26 were girls, 28 were boys. Thirteen were Class I, twenty-two were Class II, nineteen were Class III according to Pesaro criteria. 12 patients were given BU+CY and 39 BU+CY plus ATG as conditioning regimen. Three Class III patients were conditioned with Pesaro protocol 26. BU dosage was 16 mg/kg for Class I and Class II patients followed by CY 200 mg/kg totally. Class III patients received 14 mg/kg BU and 160 mg/kg CY. All patients received MTX (+1, +3, +6) and CsA for GVHD prophylaxis. All of the donors were HLA identical (51 sibling, 3 parents). Median age of the donors was 7 years (range: 2–40 years). G-CSF was given for 5 days with the dosage of 5 μgr/kg/day to child and 10 μgr/kg/day to adult donors for peripheral blood stem cell mobilization. Stem cell apheresis was performed on fifth day, but continued to day 7 if adequate cell count was not achieved. In older children and parents if appropriate, antecubital veins were used for harvesting but for younger donors, femoral dual lumen catheters were emplaced. Fresenius AS. TEC204 or Haemonetics MCS+ cell separators were used for apheresis. The median apheresis count was 1 (range 1–3). Median transfused MNC and CD34 cell counts were 10.1×108/kg (range:5.3–27.7×108/kg) and 4,65×106/kg (range:1.1–29.4×106 /kg) respectively. Median neutrophil and platelet engraftment times were day 14 and day 15, respectively. Grade II–IV acute GVHD were observed in five patients, chronic GVHD were in four of two were extensive. One patient died on posttransplant day 32 because of acute GVHD. Death because of chronic GVHD was not observed. At a median follow-up of 26 months (1–92 months), overall survival for the whole group is 92.6 % and evet-free survival is %80.4. Autologous reconstitution developed in six patients and graft failure in two.
Protein 4.1R Exon 16 Splicing Mediated by Regulated Expression of RBM9 and PTB during Erythroid Differentiation.
Authors: Yang Guang , Huang Shu-Ching , Benz Edward J. 
Published: October 2019

Abstract
Protein 4.1R (4.1R), a vital component of the red cell membrane cytoskeleton, stabilizes the spectrin-actin lattice and attaches it to the embedded membrane proteins. The inclusion of exon 16, which encodes peptides critical for spectrin/actin binding, occurs via an intricate interplay between the auxiliary cis-elements and transacting factors. An intronic splicing enhancer, UGCAUG, is present in triplicate and is situated between two polypyrimidinetract-binding (PTB) sites, TCTT, in the intron downstream of exon 16. In addition, PTB binding sites are also present in triplicate in the upstream intron of exon 16. In this study, we characterized the splicing factors that orchestrate the erythroid differentiation stage-specific switch in exon 16 splicing through these cis-elements using two cell systems: mouse erythroleukemia cells (MELC) that can be induced to erythroid differentiation and G1E-ER cells that undergo synchronous erythroid maturation after induced GATA-1 expression. We identified two RBM9 isoforms (RBM9-1A and RBM9-1F) with distinct amino-termini that interact with the intronic splicing enhancer UGCAUG. The expression of RBM9-1A is erythroid-specific while RBM9-1F can be detected in a wide variety of cell types. Real-time PCR and Western blot analyses showed that RBM9-1A expression is significantly increased while RBM9-1F is reduced during induced erythroid differentiation in both MELC and G1E-ER4 cells. The up-regulation of RBM9-1A correlated with exon 16 inclusion in differentiated cells. Furthermore, the inhibition of RBM9 expression by isoform specific-shRNA reversed 1A enhancing activity, but not that of 1F on exon 16 inclusion in differentiated cells. Thus, exon 16 splicing is mediated by a cell type-specific RBM9 isoform and its up-regulation in late erythroid differentiation is vital for exon 16 splicing. However, over-expression of PTB completely diminished the enhancing effect of RBM9-1A on exon 16 splicing in both differentiated MELC and G1E-ER4 cells, suggesting that PTB plays a role in exon 16 splicing. We analyzed PTB expression and its effect on the exon 16 splicing switch during erythroid differentiation. PTB, a repressive regulator of alternative splicing, binds to the exon 16 upstream and downstream intronic silencers. Its over-expression reduced exon 16 inclusion in both endogenous 4.1R and transfected exon 16 minigenes. Moreover, PTB expression was down-regulated and coincided with increased exon 16 splicing during erythroid differentiation suggesting that regulated expression of repressor PTB mediates exon 16 splicing. Our results further suggest that the differentiation-specific exon 16 splicing switch is achieved by varying the amount of either ubiquitously expressed or cell-type specific activators and inhibitors, and hence the relative efficiency of spliceosome recruitment in the exon inclusion pathway.
High Incidence of Posttransplant Lymphoproliferative Disorder after Unrelated Cord Blood Transplantation.
Authors: Yoo Keon Hee , Lee Soo Hyun , Sung Ki Woong , Jung Hye Lim , Ki Chang Seok , Ko Young Hyeh , Koo Hong-Hoe 
Published: October 2019

Abstract
Though posttransplant lymphoproliferative disorder (PTLD) is a well-documented complication arising in recipients of solid organ or hematopoietic stem cell transplantation, data about PTLD following cord blood transplantation (CBT) are limited. Currently less than 20 cases of PTLD have been described after CBT in the literature world-wide. However, we hypothesized that several factors such as relatively lower number and naïve nature of cord blood T-lymphocytes, frequent donor-recipient HLA disparity and in vivo T-cell depletion by ATG might lead unrelated cord blood recipients more susceptible to PTLD. We retrospectively reviewed the medical records of 45 pediatric recipients who received unrelated CBT at our institution from Jan 2002 to Jan 2006. At least 4/6 matched cord blood units were selected for transplant and some patients (n=10) received double cord blood units. ATG was included in the preparative regimen in all but one case. Cyclosporine with either methyl-prednisolone or mycophenolate mofetil were used for GvHD prophylaxis. We assessed the cumulative incidence, clinical features, pathologic findings, and treatment results of PTLD after unrelated CBT. Only pathologically proven cases were included for analysis. Five patients developed PTLD at 3 to 8 mo posttransplant (median, 4 mo). The cumulative incidence of PTLD was 14.1% at 2 year estimated by Kaplan-Meier method. Four of the 5 patients were positive for EBV serology before transplant. The involved sites were variable such as lymph nodes, brain, lung, liver, kidney, parotid gland, and colon. Three patients had multiple sites of PTLD involvement. Biopsied samples of 5 patients revealed diffuse CD20 positivity (n=4), positive for EBV in situ hybridization and/or EBNA/LMP (n=4), monomorphic (n=2), and polymorphic (n=3) histology. One patient had lesions showing diffuse CD3 positivity instead of CD20 suggesting T-PTLD. Two patients with monomorphic disease were cured with rituximab therapy and 2 of 3 with polymorphic PTLD became free of disease after immune withdrawal. The other one with polymorphic B-PTLD underwent progressive course despite immune withdrawal and rituximab therapy. In conclusion, the incidence of PTLD after unrelated CBT in this study was much higher than previously reported. Clinical suspicion and thorough diagnostic work-up followed by early therapeutic intervention should be given not to miss the potentially curable disease.
Therapeutic Angiogenesis in Arterial Limb Ischaemia by Autologous Bone Marrow Transplantation.
Authors: Novoa J.E. , Medina M.A. , Portillo F. , Salgado M. , Sequeira T. , Nuñez N. , Olivet C. 
Published: October 2019

Abstract
Background: therapeutic angiogenesis has recently been developed as a new method of treatment for several ischaemic diseases; both experimentally and clinically there is preliminary data suggesting that implantation of bone marrow-mononuclear cells into ischaemic limbs increases collateral vessels formation.
Aims: to evaluate viability of the therapeutic angiogenesis using hematopoyetic bone marrow progenitors mobilized by G-CSF (granulocyte colony stimulating factor) and saffety of the procedure.
Methods: 28 patients developing critical arterial limb ischaemia (candidates to amputation) were included in this study (International Working Party). 15 men and 13 women. Median age 65 years old (58 – 74). Mobilized by filgrastim (Neupogen ®) 5 μg/kg weight daily (5 days). Bone marrow harvest at 5th day. Local anaesthesia was employed in all the patients. Unmanipulated cells were injected in the affected limb in 2 ml aliquots into the gastrocnemius muscle. All the patients received injections unless in one limb. 1 patient received treatment in both. Each patient were evaluated regularly for rest pain, amount of required analgesia, healing of the ulcers, peack walking time, Doppler and angiographic findings. The mean number of injected mononuclear cells was 1,5 ×109/kg. All the patients received low molecular weight heparin (nadroparin, Fraxiparine ®) 3800 – 5600 IU anti-Xa subcutaneously, aspirin 81 mg and pentoxifiline 400 mg daily, as medical treatment after the procedure for at least 60 to 90 days. A control population of 27 vascular patients affected by critical arterial limb isquemia was considered. They don’t received angiogenic treatment, only the same medical antithrombotic schedule described.
Results: there were no secondary effects for the mobilization or injection of cells in the 28 treated patients. There were no dead patients secondary to the procedure. Moreover, in 22 patients with a median follow up of 18 months, 20 patients showed an improvement of all parameters, mainly pain at rest, peack walking time and skin trophic lesions. One patient suffered amputation of the affected extremity because obstruction of an old by-pass (3,6%). On the control population, amputation of the affected extremity was necessary in 25 of the 27 patients evaluated with medical treatment only (90,7%). The statistical differences between the two groups were highly significant in favor of the angiogenic group. They were evaluated by the chi square test and log rank test (p<0,05).
Conclusions: our preliminary data suggest that autologous bone marrow transplantation can be performed safely and appears to be a benefical therapy for selected patients with severe peripheral arterial disease.
(drnovoa51@yahoo.es or drnovoa@netgate.com.uy).
Different Outcome for Angioimmunoblastic T-Cell Lymphoma (AIL) and Peripheral T-Cell Lymphoma Unspecified (PTCL-U) Following Upfront Autologous Stem Cell Transplantation.
Authors: Reimer Peter , Ruediger Thomas , Weissinger Florian , Mueller-Hermelink Hans Konrad , Engert Andreas , Einsele Hermann , Wilhelm Martin 
Published: October 2019

Abstract
Introduction: Peripheral T-cell lymphomas (PTCL) are rare diseases and optimal treatment strategies still remain to be defined. With the exception of the ALK-positive anaplastic large cell lymphoma (ALCL) that shows a favourable outcome following conventional chemotherapy, PTCL are known for their poorer prognosis compared to aggressive B-cell lymphomas. However, the impact of the different PTCL-subtypes on treatment outcome has not been clearly demonstrated in prospective studies. PTCL unspecified (PTCL-U) and angioimmunoblastic T-cell lymphoma (AIL) represent the most common subtypes of PTCL in Western countries, accounting for approximately 70% of PTCL. We therefore analysed the data of our study on myeloablative radiochemotherapy followed by autologous stem cell transplantation (ASCT) in primary diagnosed PTCL with regard to the main histologic subtypes.
Material and Methods: From 06/00 to 06/06 92 patients with confirmed diagnosis of PTCL entered the study. Primary cutaneous PTCL and ALK+ ALCL were excluded from the trial. Main subtypes were PTCL-U (n= 37) and AIL (n= 28) accounting for 65 of the 92 patients (71%). 0f these patients 53 (PTCL, n= 31; AIL, n= 22) were evaluable for the analysis (82%).
Results: Median age was 50 years in the PTCL-U and 47.5 years in the AIL group, respectively. The International Prognostic Index (IPI) did not differ in both groups. In the PTCL-U and the AIL group a low/intermediate-low risk was found in 35% and 36%, respectively and a high/intermediate-high risk in 65% and 64%, respectively. There were slightly more patients in stage IV in the AIL group compared to the PTCL-U group (64% versus 53%). In addition, more patients in the AIL group complained of B-symptoms and had bone marrow involvement compared to the PTCL-U group (86% versus 66% and 48% versus 39%, respectively). However, in an intent-to treat analysis only 58% in the PTCL-U group compared to 82% in the AIL group underwent ASCT mainly due to a higher rate of patients with progressive disease in the PTCL-U group. The median overall survival (OS) was 11 months in the PTCL-NOS and 20 months in the AIL group. Regarding only patients undergoing ASCT, the median OS was 13.5 months in the PTCL-U and 25.5 months in the AIL group.
Conclusion: Our analysis suggests that patients with AIL, although showing a slightly more unfavourable risk profile at diagnosis, benefit more from upfront autotransplantation than patients with PTCL-U in our study.
Curable Potential with TBI Containing Regimen (L-PAM/TBI) Followed by In Vivo Purged Auto-PBSCT for Patients with Relapsed or Refractory Follicular Lymphoma.
Authors: Tsujimura Akane , Taji Hirofumi , Kato Harumi , Kagami Yoshitoyo , Yamamoto Kazuhito , Ogura Michinori , Morishima Yasuo 
Published: October 2019

Abstract
Background: High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is one of the treatment options for relapsed or refractory follicular lymphoma (FL). However, whether ASCT is able to bring cure for relapsed FL, or what optimal high-dose regimen is remaining to be established.
Patients and Methods: Chemotherapy to obtain response and in vivo purging effect was CHASER regimen reported previously: rituximab 375 mg/m2 on day 1; cyclophosphamide 1200mg/m2 on day 3; cytarabine 2g/m2 on days 4–5; etoposide 100mg/m2 on days 3–5. Patients who achieved partial or complete response by CHASER were treated with L-PAM/TBI regimen comprised four fractionated TBI (8–12Gy) on days -6 to -5 or -5 to -4 and high-dose L-PAM 60 mg/m2 on days -3 to -1 followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) on day 0.
Results: Seventeen patients (median age 45 yrs; range, 26–59 yrs) were treated by this regimen. A median value of infused CD34 positive cells was 3.1×106/kg (range, 1.7–10.1). All patients experienced grade 4 hematological toxicities and febrile neutropenia (FN) were observed in most of patients. Protracted thrombocytopenia was observed in some patients. No grade 4 non-hematologic toxicity was observed. Major grade 3 non-hematologic toxicities were FN and gastrointestinal. Two patients experienced grade 3 vomiting (11.8%), and nine patients experienced grade 3 diarrhea (52.9%), and two patients experienced grade 3 mucositis (11.8%). Two patients developed interstitial pneumonitis on days 130 and 229. They improved by steroid treatment immediately. The median times to reach a white blood cell count greater than 1.0×109/L and platelet count 50×109/L were 11days and 17days, respectively. Engraftment was obtained in all patients. There was no treatment related mortality within days 28 after auto-PBSCT. At a median follow-up of 2.6 years (range, 0.3–4.5 years), all patients were alive without relapse. No second malignancies was observed until now.
Conclusions: L-PAM/TBI regimen followed by in vivo-purged auto-PBSCT collected by CHASER might bring high %CR and have curable potential for patients with relapsed or refractory advanced FL, although large-scaled study is needed.