bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors Associated with the Determination of Predominant Unit in Two Units Cord Blood Transplantation for Pediatric Acute Leukemia.
Authors: Kang Hyoung Jin , Koh Sang Hyeok , Jang Mi Kyung , Park Jeong Ah , Shin Hee Young , Ahn Hyo Seop 
Published: October 2019

Abstract
Cord blood transplantation (CBT) is a promising alternative means of allogeneic stem cell transplantation. However, limited cell doses may compromise outcome. To enhance engraftment, CBT has been conducted using two units with promising results. Our preliminary results showed the dominance of one unit which occurred early after CBT (Bone Marrow Transplant. 38:197). However, little is known about the mechanism of engraftment and factors influencing the dominancy. To improve the outcomes, CBT was performed with 2 partially HLA-matched units in pediatric acute leukemia with the analysis of factors that affect the determination of dominancy. The median age and body weight of patients (M:11, F:4) were 13 years (3–17) and 45.0 kg (10.5–62.9), respectively. Patients received various conditioning regimens according to the disease status. The median number of the infused nucleated cells by the sum of 2 units after thawing was 5.28×107/kg (0.72–15.09×107/kg). Engraftment achieved in 14/15 Patients. The median number of days required for ANC of more than 0.5×109 or 1.0×109/l were 18 days (13–31 days) and 21 days (14–34 days), respectively. Spontaneous platelet recovery to more than 20×109/l required a median 50 days (19–93 days). The early engraftment kinetics reveals that dominancy of one of two units determined from the day of engraftment (ANC > 0.5×109/l). The numbers of total nucleated cells, CD34+ cells, CD3+ cells, CFU-GM, order of infusion, and donor-recipient HLA disparities of the UCB units were viewed as factors that potentially influence dominancy. Among them infused CFU-GM per patient body weight was associated with the dominancy (P = 0.017). Interestingly, CFU-GM could not be found from each cord blood units in patient failed engraftment. Multiple factors associated with outcomes of CBT could influence the determination of dominancy, such as those factors that affect the recipient environment (underlying disease, previous treatment, conditioning regimen, use of ATG and the method of GVHD prophylaxis), the characteristics of each UCB unit and HLA disparity. For this reason, the selection of the two units requires consideration of the above factors. However optimal selection guidelines that take into account influencing factors are unavailable. CFU-GM was associated with the dominancy in our preliminary result but this kind of data is hard to get before CBT practically. Introducing the analysis of new parameters such as CFU-GM before freezing could help the selection of optimal cord blood unit and improve the outcomes with the consideration of cost-benefit.
Unrelated Donor Umbilical Cord Blood Transplantation in Children with Acquired Aplastic Anemia. Korean Experience of 12 Cases.
Authors: Kook Hoon , Baek Hee-Jo , Hwang Tai-Ju , Koo Hong-Hoe , Yoo Keon-Hee , Sung Ki-Woong , Lee Young-Ho , Seo Jong-Jin , Im Ho-Jun , Cho Bin , Kim Hack-Ki , Kim Heung-Sik , Park Jun-Eun , Kang Hyoung Jin , Shin Hee-Young , Ahn Hyo-Seop ,   for Aplastic Anemia Working Party of Korean Society of Pediatric Hematology/Oncology Cord Blood Committee of the Korean Society of Hematoipoietic Stem Cell Transplantation
Published: October 2019

Abstract
Matched unrelated donor transplants have been reserved for patients with severe aplastic anemia (SAA) who fail a round of immunosuppressive therapy (IST). Despite the general acceptance of cord blood as an alternative stem cell source, unrelated donor cord blood transplantation (CBT) has not yet been recommended for SAA because of the high risk of graft failure and infectious complications. Only a few cases of successful CBT in SAA have been reported in the literature. From July, 2003 to Dec., 2005, twelve cases of unrelated donor CBTs in Korean children with acquired SAA were performed, and enrolled in this retrospective study. Two of them received double unit CBT. One patient who rejected a CBT received the second transplant with double unit CBT. All patients had no matched family donors. The median age and weight at the time of transplant were 7.0 years (2.8–18.8 years) and 23.3 kg (12.1–49.4 kg), respectively. Seven patients received previous IST including ATG/ALG plus cyclosporine (CyA). The median interval from the diagnosis to transplant was 20.5 months. The HLA discrepancy between the single unit umbilical cord blood and the patient was 0/6 in 1, 1/6 in 8, and 3/6 in 1. The conditioning regimen was heterogeneous, but included radiation in 3, and fludarabine in 3. The median infused nucleated cell dose was 3.3 × 107/kg (0.3–9.4 × 107/kg), and median CD34+ cell dose was 1.7 × 105/kg (0.4–6.6 × 105/kg) of recipient weight. Graft-versus-host disease (GvHD) prophylaxis was CyA plus methylprednisolone in 9 cases. Primary engraft failure was encountered in 3. The absolute neutrophil count ≥500/μL was achieved at 17.0 days (15–34 days), and platelet count ≥20,000/μL at 57.0 days (32–122 days), respectively. Complete donor chimerism was promptly observed in 8, with transient mixed chimerism in another patient. Acute GvHD ≥ II was observed in 5 cases, and extensive chronic GvHD was found in 2 among 8 evaluable cases. The 3-year overall survival was 74.1%, and 3-year estimated failure-free survival was 58.3%. The causes of death were sepsis, cytomegloviral pneumonitis, and chronic GvHD with intracranial hemorrhage in each patient. Cytomegaloviral disease was found in 3 cases. These results are comparable with those from unrelated donor BMT in refractory SAA. Considering the better tolerability of HLA mismatching, CBT should be considered as an alternative source of transplants. A randomized, prospective study comparing the 2nd-line IST, unrelated bone marrow transplants, or CBT is warranted to answer the best option for those who fail to 1st line IST without matched siblings.
Impact of Chimerism Analysis and Kinetics on Haploidentical Stem Cell Transplantation.
Authors: Tang Xiaowen , Wu De Pei , Sun Aining , Yang Mingzhen , Wang Ying 
Published: October 2019

Abstract
Haploidentical transplantation (H-SCT) has been an alternative allogenetic transplant option for the high risk lukemia patients who do not have an HLA-identical related donor. The high dose of stem cell infusion and intensive GVHD prophylaxis treatment were applied in H-SCT to overcome the haploidentical major histo compatibility barrier and to achieve engraftment. We speculated that the dynamics of donor chimerism are different from conventional myeloablative allogeneic bone marrow transplantation(allo-BMT). Methods Quantitative analysis of chimerism were performed by multiplex PCR amplification of STR markers (STR-PCR) in unfractionated nucleated cells from bone marrow or whole blood of 30 high risk leukemia patients who received H-SCT(14 females,16 males; median age 25 years). Eighteen of 30 patients received G-CSF primed bone marrow transplantation and another 12 patients received G-CSF primed bone marrow and peripheral blood stem cell transplantation. The conditioning regimen consisted of modified BU/CY or modified total body irradiation(TBI) plus CY. One patient received cyclosporine (CSA), short-term methotrexate(MTX) and mycophenolate mofetil (MMF) as the regimen of prophylaxis of GVHD. Twenty-four patients received CSA, MTX and MMF plus ATG/ALG for GVHD prophylaxis. The combination of CSA, MTX, MMF, ATG/ALG and CD25 monoclonal antibody for preventing GVHD in 5 patients.
Results: All of the patients except one showed initial donor engraftment and just one patient presented primary graft failure. The early chimerism and its kinetics after transplantation showed that the donor chimerism became dominant (DC 84.1% >60%) by day +3, which preceded the detection of hematologic engraftment by a median of 9 days. On day +7, donor cells of majority patients had achieved stable engraftment. The median chimerism was 92.4%;The probability of achieving full donor chimerism (FDC) in PB was 56.3% on day +14, 61.5% on day +28;Comparing with the group of standard allo-BMT, median quantity of CD34+ cells and CD3+ T lymphocyte cells of H-SCT group were 2 and 3 times higher. Furthermore GVHD prophylaxis was more intensive with ATG/ALG and MMF in H-SCT group. The median percentage of donor chimerism of H-SCT was significantly higher than that of BMT on the day of +7d, +14d and +1month. Meanwhile there were difference in the rates of FDC among H-SCT and BMT(61.5% VS 20%, p<0.01)on day of +28.The median overall follow-up was 24 months(range, 1.5–34.5), and 12 (40%) patients were alive.Two of them maintained stable mix chimerism (DC>90%), and another 10 patients achieved stable FDC(DC ≥95%).
Conclusion: In the early stage after transplantation, the engraftment of donor cells of H-SCT was more rapidly and completely than that of conventional BMT owing to the high quantity of donor CD34+ cells, T lymphocyte cells and the more intensive immunosuppressive therapy.
Individual Treatment with Stem Cell Rescue in Patients with Germ-Cell Tumors. Results of One Centrum.
Authors: Nepomucka Jana , Abrahamova Jitka , Foldyna Martin , Donatova Zuzana , Kordikova Drahomira , Pagacova Ludmila , Kalanin Jan , Greplova Marcela , Bartova Markyta 
Published: October 2019

Abstract
Background: Treatment with high dose chemotherapy and autologous stem cell rescue in pacients with poor risk germ cell tumors is still controversial. Results of multicentric randomized EBMT study IT 94 presented at ASCO 2002 show benefit in 1-year EFS in high dose arm (52% versus 48%), 3-year EFS was the same in both arms (53%) in salvage treatment. Individual treatment with stem cell rescue as upfront treatment offers a survival benefit.
Methods:Autologous stem cell rescue was provided in our center, from September 1997 to May 2006 to 52 patients. High dose chemotherapy was indicated to 32 patients in salvage setting after 2nd line of treatment (VeIP) and to 20 patients as upfront treatment after 1st line treatment (BEP). Median age was 29 years and tumor markers were elevated: HCG in 9 pts, AFP in 13 pts.
Stem cell mobilization was performed after the 3rd cycle of VeIP or BEP in combination with G-CSF. The amount of CD34+ cell/kg b.w. was between 2,0 – 13.4×106. High - dose conditioning regimen CARBOPEC (carboplatin 1600 – 2 200 mg/m2, etoposide 1 800mg/m2, cyclophosphamide 6 400 mg/m2) was used. The treatment was well tolerated without transplant - related mortality.
Results: WHO criteria non - hematological toxicity was predominantly grade 2 to 3. Engraftment was rapid, recovery of hematopoiesis in neutrofils over 1.0×109/l and platelets over 50×109/l was reached an average on days +10 and +13 respectively. Additional post-transplant treatment for persistence, progression or relaps had 20 patients (8pts had 2nd line treatment VEIP, 12pts had 3nd line treatment with paclitaxel+gemcitabine and 5 pts had retroperitoneal lymfadenectomy).
The follow - up period ranges from 3 to 99 months, at present 38 (73 %) patients are alive, 14 (27 %) pts died. Median TTP of all pts is 10 months, median OS of all pts is 39 months. Median DFS of surviving pts is 38 months.
Conclusion: high-dose chemotherapy with autologous stem cell rescue in patients with poor risk germ cell tumors is feasible and beneficial method of the individual treatment. High-dose chemotherapy as upfront treatment for poor prognosis germ cell tumors and as salvage treatment in good risk pts seems to be good possibility of the individual treatment.
Fully Retargeted Oncolytic Measles Virus for Multiple Myeloma Therapy.
Authors: Hummel Horst D. , Kuntz Gaby , Nakamura Takafumi , Greiner Axel , Russell Stephen J. , Einsele Hermann , Topp Max S. 
Published: October 2019

Abstract
Multiple Myeloma (MM) is a disseminated plasma cell malignancy with approximately 14,600 new cases diagnosed in the USA annually. Despite recent progress in current therapeutical options the median survival is 3 to 5 years and cure is extremely rare. Therefore the evaluation of new treatment modalities for MM is highly warranted. An attractive approach to treat Myeloma with a minimum of undesired side effects is the use of a tumour antigen specific for MM cells. Wue-1, a monoclonal antibody binds very selectively normal and malignant plasma cells (50 of 51 MM samples, 14 of 15 immunocytoma and 13 of 13 MALT type lymphomas with plasma cell differentiation were Wue-1 positive, normal tissue including hematopoietic cells were negative) and offers the possibility to define MM cells as targets. The tool for selective killing of MM cells recognized by Wue-1 monoclonal antibody is in this study the measles virus vaccine strain Edmonston B in an ablated variant (MV-Wue) which no longer binds the usual measles receptors CD46 and CD150 (SLAM) expressed on almost every human cell type displaying a single-chain antibody (scFv) derived from the monoclonal Wue-1-antibody which has been tethered to the C-terminus of the H protein to restrict and retarget its interaction to malignant plasma cells especially MM cells. In addition, MV-Wue encodes EGFP facilitating the read out of infected cells. To determine if the fully retargeted MV-Wue would be able to infect MM cell lines and primary MM cells selectively an array of infection assays were performed using the MM cell lines U266 as well as primary CD138 positive MM cells expressing the Wue-1 antigen as expected targets and CD138 negative cells and normal B cells as controls negative for Wue-1. In these experiments selective infections of the MM cell line and primary MM cells were observed whereas the control cells were not infected with MV-Wue. In all cell types GFP expression indicating replicative infection correlated with the expression of the Wue-1 antigen determined by FACS. Infection experiments performed in the presence of monoclonal Wue-1 antibody showed a decreased GFP expression of about 78% in CD138 positive MM cells demonstrating specificity of the infection by MV-Wue. These results indicate that the engineered virus can be a safe and potential curative oncolytic agent to face the main problem in Multiple Myeloma which is responsible for frequent relapses, the minimal residual disease (MRD).
Intravenous Injection of Manganese Superoxide Dismutase Plasmid/Liposome Complexes (MnSOD-PL) Protects the Bone Marrow from Irradiation Damage.
Authors: Epperly Michael W. , Franicola Darcy , Smith Tracey , Greenberger Joel S. 
Published: October 2019

Abstract
Radioprotection of tissues including lung, esophagus, oral cavity and bladder has been demonstrated by local administration of MnSOD-PL. One potential use of the MnSOD-PL is protection of bone marrow as well as other tissues against total body irradiation (TBI) perhaps applicable for first responders who enter areas of high irradiation. To determine if systemically delivered MnSOD-PL protects bone marrow from TBI, groups of C57BL/6NHsd mice were injected intravenously with MnSOD-PL (100 μg of plasmid DNA in 100 ul volume) and irradiated 24 hrs later to 9, 9.5 or 9.75 Gy whole body irradiation. The mice were followed for bone marrow failure. Mice injected with MnSOD-PL showed improved survival at all irradiation doses. After 9 Gy TBI, 93% of the mice injected with MnSOD-PL survived past day 30 compared to 80% of control irradiated mice. At 9.5 Gy, 87% of the MnSOD-PL treated survived past day 30 compared to 53% of control irradiated mice (p = 0.0402). Following 9.75 Gy, the control irradiated mice had a median survival of 16 days with 12.5% survival at 30 days compared to 75% of the MnSOD-PL treated mice (p = 0.0016). To determine the efficiency of marrow transfection mice were injected with a plasmid containing the HA (hemagglutinin) epitoped tagged MnSOD transgene. The marrow was harvested 24 hr later, cytospun, and immunohistochemically stained for HA. The bone marrow demonstrated that 22.1 ± 3.7% of the bone marrow cells expressed HA-MnSOD protein. The results demonstrate that systemically delivered MnSOD-PL protects against TBI induced murine bone marrow damage and improves survival.
VELCADE/Dexamethasone (Vel/Dex) Versus VAD as Induction Treatment Prior to Autologous Stem Cell Transplantation (ASCT) in Newly Diagnosed Multiple Myeloma (MM): An Interim Analysis of the IFM 2005-01 Randomized Multicenter Phase III Trial.
Authors: Harousseau Jean-Luc , Marit Gerald , Caillot Denis , Casassus Philippe , Facon Thierry , Mohty Mohamad , Maloisel Frederic , Maisonneuve Herve , Chaleteix Carine , Benboubker Lofti , Esseltine Dixie-Lee , Attal Michel 
Published: October 2019

Abstract
ASCT is considered the standard of care for patients up to 65 years of age with MM. The optimal induction treatment prior to ASCT is still unknown. VAD is a commonly used regimen but is associated with a number of toxicities, administrative inconvenience, and a complete remission (CR) rate of typically less than 10%. Recently the combination thalidomide/Dex was reported to induce a higher overall response rate than Dex alone in newly diagnosed patients, but with significantly more toxicities, especially deep vein thrombosis, and a 4% CR rate (Rajkumar et al, J Clin Oncol 2006;24:431–6). In a phase II trial we have evaluated the combination of Vel 1.3mg/m2 D1, 4, 8, 11 with Dex 40mg/D D1-4, D9-12, for 4 consecutive 21-D cycles (Dex only on D1-4 during cycles 3–4). This combination was well tolerated and yielded a 21% CR/nCR rate with successful stem cell harvest and engraftment (Harousseau et al, Haematologica 2006). In 2005, the IFM initiated a multicenter randomized phase III trial comparing Vel/Dex with VAD as induction treatment of patients with newly diagnosed MM up to the age of 65. The primary objective of the study is the CR (negative immunofixation) plus nCR (CR but positive immunofixation) rate after 4 cycles. A secondary objective is to evaluate the role of consolidation with 2 courses of DCEP (Dex, cyclophosphamide, etoposide, cisplatin). Patients were randomized at diagnosis among 4 arms (A1: 4 cycles of VAD; A2: 4 cycles of VAD + 2 cycles of DCEP; B1: 4 cycles of Vel/Dex; B2: 4 cycles of Vel/Dex + 2 cycles of DCEP); stratification was by cytogenetics and β2 microglobulin. Stem cell collection was performed between cycle 3 and cycle 4 after priming with G-CSF (10μg/kg/D × 6 D). At the end of induction (± DCEP consolidation) treatment, patients received melphalan 200mg/m2 plus ASCT. Enrollment of 480 patients is planned, to detect a 10% higher CR/nCR rate with Vel/Dex (20% vs 10%) with 80% power (two-sided test, significance level 0.05). An interim analysis is planned when 222 patients have been evaluated for response at the end of induction. As of July 2006, 304 patients have been enrolled. Randomization of the 222 patients to be considered for interim analysis was completed on May 19th. Baseline characteristics include: median age 55y; 140M, 82F; β2 microglobulin >3mg/L in 54%; del13 by FISH in 45%. The occurrence of serious adverse events (SAEs) was similar between the VAD and Vel/Dex arms (31% with VAD, 33% with Vel/Dex). The most frequent SAEs were pneumopathy (5.3% VAD, 4.0% Vel/Dex), thrombosis (2.7% VAD, 3.3% Vel/Dex), and peripheral neuropathy (1.3% VAD, 3.3% Vel/Dex). We intend to present results from the interim analysis.
Hyperchidam Verona897 Regimen Is Effective in Treatment of Advanced Peripheral T Cell Lymphoma (PTCL): The GITIL Experience in 33 Cases.
Authors: Todeschini Giuseppe , Corradini Paolo , Cortelazzo Sergio , Rambaldi Alessandro , Gallamini Andrea , Benedetti Fabio , Ferreri Andres , Olivieri Attilio , Tecchio Cristina , Bonifacio Massimiliano , Frungillo Niccolo , Castellino Claudia , Rossi Andrea , Toldo Chandrakala , Crocchiolo Roberto , Attolico Immacolata , Pizzolo Giovanni 
Published: October 2019

Abstract
Background. Peripheral T cell Lymphoma (PTCL) represent a major therapeutic challenge. In the previous Verona experience (Todeschini G et al. Cancer2005;104:555–560), the novel intensive regimen HyperCHiDAM Verona897 (high-dose IV MTX 2 g/sqm 400 sqm bolus, 1600 sqm CI day 1 with IV leucovorin rescue; hyperfractionated IV CTX 300 mg/sqm Q12h, dd 2–4; high-dose IV AraC 2g/sqm Q12h, dd 2-4; plus G-CSF) achieved salutary results in refractory/relapsed aggressive lymphomas, in particular in PTCL. Supportive measures included hydratation 3000 ml/sqm/day, antimicrobial prophylaxis comprising oral ciprofloxacin, itraconazole, trimethoprim/sulfamethoxazole. CMV antigenemia (pp65) was monitored 2 times a week. Patients. Following these results, 7 centers belonging to the Italian co-operative group GITIL (Gruppo Italiano Terapie Innovative Linfomi) treated with 2 cycles of HyperCHiDAM Verona897, 33 patients affected by PTCL (17 upfront, 16 refractory/relapsed) followed in the majority of cases by stem cell transplant. Patients: M/F 21/12, median age 49 (19–63) years; histology: PTCL-NOS 15, ALCL ALK-negative 9, EALTC 4, AIL 3, T-NK nasal 1, Angiocentric 1; stage IV 19/33 (57.5%), bone-marrow positive 10/33 (30.3%), extranodal involvement 24/33 (72.7%), high LDH 18/33 (54.5%). Seven patients needing urgent treatment were treated before HyperCHiDAM with 1 cycle of Campath-CHOP (4 patients) or CHOP + L-ASE (3 patients).
Results. Upfront patients: after 2 cycles of HyperCHiDAM, CR were 82.3% (14/17), early toxic deaths 0 (1 late toxic death occurred after SCT, due to CMV pneumonia), relapses 3/14. With a median follow-up of 21 months (3–90+), 11/17 (64.7%) patients are disease-free, 10 in first CR, 1 after rescue with stem cell transplant. Three of the CCR patients received HyperCHiDAM alone. Refractory/relapsed patients: CR were 5/16 (31.2%), CCR 4/16 (25%), with a median follow-up of 24 months (5–64+). The progression-free survival was significantly superior in upfront patients (p=0.036). Overall, toxic deaths were 3/33 (9%), 1/17 (5.8%) in upfront and 2/16 (12.5%) in refractory/relapsed patients. One patient had major cerebellar toxicity.
Conclusions. The intensive regimen HyperCHiDAM Verona897 is effective in inducing CR in aggressive PTCL, in particular as upfront therapy. The intensiveness of this treatment requires a careful supportive therapy. Following these results, HyperCHiDAM has been included in a national trial for treatment of PTCL, after 2 cycles of Campath-CHOP and before stem cell transplant (allogeneic or autologous depending on the availability of an HLA-matched sibling). The co-operative study is recruiting.