bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autologous (Auto) and Allogeneic (Allo) Stem Cell Transplantation (SCT) for Pateints (pts) with Advanced Chronic Lymphoctic Leukemia (CLL): A Comparative Study.
Authors: Jimenez Antonio , Farhat Mohamed I. , Gregory Stephanie A. , Kassar Mohamad , Gimelfarb Alla , Batus Marta , Nangia Julie , Shah Neel , Venugopal Parameswaran , Larson Melissa L. , Christopherson Kent W. , Fung Henry C. 
Published: October 2019

Abstract
Background: AlloSCT is a potential curative treatment for pts with advanced CLL but alloSCT is limited by significant acute and chronic treatment related toxicities and the availability of HLA matched donors. AutoSCT is widely used for treatment of acute leukemia and aggressive lymphoma but rarely used for pts with CLL. This retrospective analysis describes the outcomes of 27 patients from our institution who have undergone either autologous or allogenic SCT for treatment of their advanced CLL. We also compare their transplant outcomes.
Patients and methods: Between 08/98 and 07/07, 27 pts (M;22; median age 54.1, range 37–61) with variable RAI-Sawistsky stage CLL at the time of histological diagnosis (RAI I for 14 patients) underwent SCT (10 autoSCT, 17 matched related donors, 3 matched unrelated donors) Fourteen patients (52%) had a normal karyotype, 13q deletion and trisomy 12 occurring in six and four patients respectively. Median disease duration prior to transplant was 41.7 months (range 5–121). The indication for transplant was refractory disease for most patients. Preparative regimens consisted of Cyclophosphamide (Cy) + TBI (6), Fludarabine (Flu)+Cy (6), Rituximab (R) +Cy+TBI (4) R +melphalan + flu (4) and others (7). NCI complete remission (CR) criteria, flow cytometry, cytogenetics and chimerism data, as available, were used to assess response to therapy.
Results: All 27 patients engrafted, with a mean neutrophil engraftment time of 13.5 days (range 9–24). From the group of patients that received allogeneic transplant, eight (47%) developed acute GVHD, with a median time of 18 days after transplant. Seventeen patients (62%) achieved CR on day +100 by marrow morphology, 15 out of 19 by flow cytometry and 13 out of 15 patients had normal chimerism studies. Non relapse mortality (NRM) on day +100 was 14.8% (17.6% for allo, 0% for auto). Estimated actuarial survival at 3 years for all patients was 68% (65% for alloSCT and 72% for the autoSCT group).Disease free survival at 3 years was defined as the percentage of patients who remained in CR 3 years following transplant. DFS was 62% for the whole group (77% for autoSCT and 51% for the patients who received an alloSCT).
Conclusion: In this study, we have demonstrated high remission rate after both autologous and allogeneic SCT, however, the transplant outcomes (day 100 NRM, DFS and OS) favors autologous over allogeneic with toxicity related death accounted for most of the treatment failures after an alloSCT. Our results suggested that AutoSCT warranted further studies, in particular for older patients and those without a suitable donor.
Effects of Graft Compositions on Hematopoietic Reconstitution and Graft-Versus-Host Disease in Related Donor Peripheral Blood Stem Cell Transplantation.
Authors: Feng Ru , Zhan Yu , Yi Zhengshan , Zhang Yongmin , Huang Feng , Fan Zhiping 
Published: October 2019

Abstract
Objective To explore the effects of graft compositions on hematopoietic reconstitution and graft-versus-host disease(GVHD) in human leukocyte antigen(HLA)-identical related donor peripheral blood stem cell transplantation(PBSCT) for malignant hematological diseases.
Methods A retrospective analysis was made on 107 patients with malignant hematological diseases undergoing HLA-identical related donor PBSCT in our department. The main cell doses in grafts were respectively measured by flow cytometry and evaluated their association with hematopoietic reconstitution and GVHD by statistical analysis. Results The measured cell doses were all not in linear correlation with the time of neutrophil reconstitution.There was a significant negative correlation between mononuclear cell(MNC) or CD34+ cell dose and the time of platelet reconstitution (P<0.05)which indicated the more MNC,CD34+ cells may contribute to accelerate platelet reconstitution. However the absolute values of the correlation coefficients were both below 0.4.There was a significant negative correlation between CD34+ or CD34+CD38− cell dose and the development of acute graft-versus-host disease (aGVHD) (P<0.05)which indicated CD34+, CD34+CD38− cells may play negative regulatory roles in the development of aGVHD. Nevertheless the little absolute values of the correlation coefficients also had little usefulness. Each lymphoid subset measured did not correlate with aGVHD.A significant positive correlation was found between CD25+CD4+,CD3+or CD4+CD3+ cell dose or the CD4+ to CD8+ ratio and the development of chronic graft-versus-host disease (cGVHD) (P<0.05) which indicated these lymphoid subsets may play important roles in the development of cGVHD. Furthermore, the correlation coefficient of the CD25+CD4+ cell reached up to 0.76.CD34+, CD34+CD38-cell doses did not correlate with cGVHD.
Conclusion It was concluded that efforts to further accelerate reconstitution in HLA-identical related donor PBSCT by increasing MNC,CD34+, CD34+CD38- cell doses may be counterproductive when the cell doses had attained a threshold. Besides cGVHD may be enhanced by simultaneously increased lymphoid subsets in grafts.
G-CSF Primed Bone Marrow Is Not Superior to Unprimed Bone Marrow as a Source of Stem Cells in HLA Matched Related Allogeneic SCT for β Thalassaemia Major.
Authors: Rajasekar Reena , Mathews Vikram , Lakshmi Kavitha M. , Viswabandya Auro , George Biju , Chandy Mammen , Srivastava Alok 
Published: October 2019

Abstract
G-CSF stimulated BM (G-BM) offers a source of stem cells that has been reported to be associated with faster engraftment and decreased risk of GVHD. It is possible that these differences are related to the immunological composition of these grafts. We compared G-BM and unprimed bone marrow as a source of stem cells in 33 consecutive thalassaemia major patients who underwent a matched related allogeneic SCT treated with a similar conditioning and GVHD prophylaxis regimen. Twenty patients received G-BM from HLA matched donors primed with G-CSF 10ug/Kg/day for 2 days prior to BM harvest and the rest received unprimed BM. Lymphocyte subsets and progenitor cells contained in the grafts was assessed using FACSCalibur and monoclonal antibodies directed against B, NK and T cell subsets. The median age of the cohort was 7 years (range: 2–14) and there were 22 (67%) males. All patients received Bu/Cy/ATG as conditioning regimen. Cyclosporine and short course Methotrexate were used as GVHD prophylaxis. 88% of patients achieved sustained engraftment. The mean follow up was 37 months. Patient and graft characteristics were similar in both HSC sources (Table 1). The target cell dose of 3x108 TNC/Kg could be achieved with smaller volume of the graft in the G-BM group. Time to neutrophil engraftment (median: 16 days, p= 0.260) and platelet engraftment (median: 30 Vs 26 days, p= 0.163) was identical in both the groups. The incidence of acute GVHD (grade II–IV, 10% vs. 15%) and chronic GVHD (12% vs. 9%) were similar in both the groups. 9 patients rejected their graft, six (30%) in G-BM and three (23%) in BM. There were 4 transplant-related deaths within the first 100 days (two in each group). Survival curve analysis showed no difference in overall and event free survival between the two groups. In this cohort of patients, G-BM resulted in rates of engraftment, GVHD, rejection and TRM that were similar to those produced by unprimed BM. G-BM as a HSC source may not add selective advantage to patients with thalassaemia major undergoing a matched related allogeneic SCT.
Comparison of Graft Source Characteristics BM (n=13) G-BM (n=20) P Age (median years: range) 6 (2–14) 8 (2–13) 0.22 Male (%) 9 (69) 13 (65) 1.00 Lucarelli Class III (%) 5 (39) 9 (45) 0.71 Harvest TNC/mm3 23430±9007 39045±13457 0.000 Harvest Volume 417±173 290±98 0.012 TNC / 10e8/kg 4 (2.9–7.6) 4.8 (2.4–8.8) 0.083 CD34 x 10e6/kg 6.89 (3.3–12.9) 8.3 (1.2–16.4) 0.439 Total CD3 cells x 10e6/kg 45.6 (12.7–120.1) 40.4 (26.2 – 139.8) 0.912 NK cells x 10e6/kg 4.71 (0.9–49.8) 6.7 (0.1–15.2) 0.580 Total B cells x 10e6/kg 19 (0.3 – 47.2) 24.3 (0.8 – 62.2) 0.32 Helper T cells x 10e6/kg 20.8 (7.2 – 48.7) 13.7 (15.4 – 77.8) 0.556 Cytotoxic T cells x 10e6/kg 24.8 (7 – 91) 10.6 (8.8 – 51.2) 0.39
Comparative Study of French Unrelated Registered Stem Cell Donors and Cryopreserved Cord Blood Units.
Authors: Balere Marie-Lorraine M.L. , Lapierre Valerie V. , Garnier Federico F. , Marry Evelyne E. 
Published: October 2019

Abstract
The question of the HLA complementarity between unrelated Donors Registries and Cord Blood banks is often raised. On december 31th 2006, three methods were used to qualify and quantify the genetic diversity and complementarity between French marrow unrelated donors (FMUD) and French cryopreserved cord blood units (FCBU). The first one is based on HLA haplotype frequencies performed according to the EM algorithm method, the second on the contribution in new phenotypes (CinNP), the third on the presence of no, one or two frequent haplotypes within MUD/CBU phenotypes. Preliminary operations on HLA typings were necessary to homogenize data: split level, exclusion of only typed at class I level donors. HLA haplotype frequencies comparison does not lead to a global significant difference between FMUD and FCBU. The 5 most frequent haplotypes are identical in both populations: 01-08-17, 29-44-07, 03-07-15, 02-44-04, 02-07-15. Then some haplotypes, characteristic of either Nord or South of Europe, were more frequent among the FMUD than among the FCBU: 02-44-07, 02-51-13, 11-35-01, 02-60-13. On the contrary, some haplotypes of Middle East and Eastern Europe were more frequent among the FCBU than among the FMUD: 30-18-17, 24-35-11, 02-13-07, 33-65-01. In 2006 CinNP does not differ significantly between FMUD and FCBU. 49% of new MUD/CBU bring new HLA-ABDR low resolution split level phenotypes to the FMUD and FCBU populations present the year before, with differences between regions: Martinique and Reunion islands have the largest CinNP, Britanny the smallest. Effectiveness in term of CinNP have been studied for France during the past 6 years, by 2 year sections: 2001–2002, 2003–2004, 2005–2006. As expected, in order to reach an equivalent rate of CinNP, a growing number of donors must be registered every year. The 25 most frequent haplotypes among the FMUD and FCBU were calculated, and called “frequent haplotypes” (FH) among the French population. We could then categorize individuals according to the number of FH they had: none, one or two. 85% of harvested FMUD for a national patient between 2000 and 2006 had one or two FH versus 54% of infused FCBU. 50% of harvested FMUD/ infused FCBU for an international patient had no FH, versus 26% for a national patient. FMUD registry and FCBU banks are complementary: they answer to various HLA haplotypes needs for national and international patients. Incontestably, international patients benefit from French MUD/CBU, which present HLA characteristics not or under-represented in their Registry of origin.
Regulation of Progenitor Cell Proliferation and Granulocyte Function by microRNA-223.
Authors: Camargo Fernando D. , Johnnidis Jonathan J. , Harris Marian H. , Stehling-Sun Sandra , Wheeler Robert T. , Lam Michael , Kirak Oktay , Fleming Mark D. 
Published: October 2019

Abstract
MicroRNAs are abundant in animal genomes and have been predicted to have important roles in a broad range of gene expression programs. Despite this prominence, there is a dearth of functional knowledge regarding individual mammalian microRNAs. Using a loss-of-function allele in mice, we report here that the myeloid-specific microRNA-223 (miR-223) negatively regulates progenitor proliferation and granulocyte differentiation and activation. miR-223 mutant mice have an expanded granulocytic compartment resulting from a specific and cell-autonomous increase in the number of granulocyte-monocyte progenitors (GMPs). We show that Mef2c, a transcription factor that promotes GMP renewal, is a target of miR-223 and that genetic ablation of Mef2c suppresses progenitor expansion and corrects the neutrophilic phenotype in miR-223 null mice. In addition, granulocytes lacking miR-223 are hypermature, hypersensitive to activating stimuli and display increased fungicidal activity. Consequent to this neutrophil hyperactivity, miR-223 mutant mice spontaneously develop inflammatory lung pathology and exhibit exaggerated tissue destruction following endotoxin challenge. Our results present a new paradigm in miRNA-mediated gene regulation, in which a microRNA can negatively modulate the proliferation and differentiation program of the lineage to which it is most strongly associated.
Effects of Recipients’ Body Weight on Engraftment after Unrelated Bone Marrow Transplantation: Analysis of Clinical Data of 4065 Patients from the Database of the Japan Marrow Donor Program.
Authors: Yamashita Takuya , Ohashi Kazuteru , Akiyama Hideki , Sakamaki Hisashi 
Published: October 2019

Abstract
In allogeneic bone marrow transplantation from unrelated donor of Japan Marrow Donor Program (JMDP), the standard nucleated cell dose for transplantation is regulated as 3.0x10E8 bone marrow nucleated cells/recipient’s body weight. But if a recipient is heavyweight, it it often diffecult to get enough bone marrow from the donor for transplantation. Infused cell number and recipients’ body weight may infuence the engraftment and outcome of transplantation. We retrospectively analysed the clinical data of 4065 adult transplant recipients (median age 35, range 16–70) from extracted the database of JMDP. Based on the previous studies, the possible factors which could influence on engraftment were collected. The correlations of these factors with engraftment and neutrophil recovery after transplantation were analysed by using multiple logistic regression. Variables correlated with an increased possibility of engraftment were: incrased recipient’s body weight (p<0.001), increased transplanted cells/recipient’s body weight (p=0.0016), younger recipient’s age (p=0.0019) and using TBI for conditioning (p=0.0358). Variables correlated with early attaining of neutrophil>500 were: use of G-CSF after transplantation (p<0.0001), increased transplanted cells/recipient’s body weight (p<0.0001), and no use of MTX for GVHD prophylaxis (p<0.0001). But in the subset analysis of G-CSF use group, first 25 percentile group reached neutrophil>500 significantly earlier than other group (p<0.0001). These results suggested that recipients’ heavy body weight positively influenced on engraftment, but obesity of recipients might delay neutrophil recovery. This study may contribute to consider the adequate cell dose for unrelated bone marrow transplantation and assess the value of recipients’ body weight as a risk factor of hematopoietic cell transplantation.
Long-Term Survival after Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation in AML-Patients Is Consistently Sustained and Influenced by Donor Type Selection.
Authors: Sayer Herbert G. , Muegge Lars-Olof , Scholl Sebastian , Schilling Kristina , Klink Anne , Schmidt Volker , Hoeffken Klaus 
Published: October 2019

Abstract
A total of 46 patients (24 female, 22 male) with acute myeloid leukemia (AML) received RIC allogeneic blood stem cell transplants from either fully HLA-compatible family donors (n=14) or unrelated HLA-compatible donors (n=32) between 3/1999 and 3/2007. The unselected consecutive single centre study patients (median age: 52 years, range: 22–64) were at high risk for treatment-related complications (older age, previous infectious complications, impaired organ function). 67% (n=31) of the cohort were not in first remisson but in an advanced status of AML. All patients received 30 mg·m−2 Fludarabine i.v. day −10 to −5, Busulfan 4mg·kg−1 orally day −5 to −4, and 10 mg·kg−1 i.v. Antithymocyteglobulin (ATG-Fresenius®) day −4 to −1 as RIC prior to allogeneic stem cell transplantation. A median of unselected 6.8 x 106 CD-34 positive stem cells (range: 1.9–14.3) were given. GvHD-prophylaxis consisted of Cyclosporin 3mg·kg−1 continuous infusion in case of 10/10 HLA compatibility donor situation (n=34), with the addition of mycophenolate mofetil 2gr. i.v. primarily starting from day +10 in one antigen mismatched HLA-unrelated donor situation (n=12). Nine patients (19.6%) died of therapy related mortality, due to GvHD (n=3), infections (n=4), or both (n=2). Relapses occurred in 18 patients (39%), in five patients even more than one year after transplantation. The median observation time of the study group was 19 months (range: 3–101), the product-limit estimates (Kaplan-Meier) of overall survival (OS) at 36 months were 0.48 (±0.08), of event-free survival (EFS) 0.44 (±0.08), respectively.
Figure Figure
Disease-status (remisson vs. advanced) failed to have a significant impact in OS or EFS, whereas donor status (related vs. unrelated) resulted in OS at 24 months 0.76 (±0.12) for related donors and 0.4 (±0.09) for unrelated donors (p=0.017, log-rank test). RIC with Fludarabine/Busulfan/ATG prior to allogeneic stem cell transplantation results in a consistently sustained long-term outcome for this otherwise adverse patient subgroup, favouring family-matched donor selection.
The Analysis of Chronic GVHD after Cord Blood Transplantation in Comparison with Bone Marrow Transplantation.
Authors: Seo Sachiko , Uchida Naoyuki , Ishiwata Kazuya , Tsuji Masanori , Yamamoto Hisashi , Takagi Shinsuke , Kato Daisuke , Matsuno Naofumi , Masuoka Kazuhiro , Atsushi Wake , Taniguchi Shuichi 
Published: October 2019

Abstract
Backgrounds: Umbilical cord blood can be an alternative stem cell source for the patients with hematological malignancies requiring allogeneic stem cell transplantation. However, little is known about graft versus leukemia/lymphoma (GVL) effect in cord blood transplantation (CBT). Here, we analyzed chronic GVHD (cGVHD) in CBT compared with that in BMT and evaluated the relevance between cGVHD and GVL.
Patients/methods: We retrospectively studied 162 patients who had been free from disease progression for more than 100 days after either unrelated BMT (n=75) or CBT (n=87) at Toranomon Hospital from January 2002 to October 2006. Median age of the patients was 52 years old (BMT vs CBT: 49 vs 53). Underlying diseases were acute leukemia (n=88), myelodysplastic syndrome (n=17), lymphoma (n=39) and others (n=18). Conditioning regimens were mainly composed of Fludarabine 125–180 mg/m2 with several combinations of Melphalan 80–140 mg/m2, Busulfan 8–16mg/kg and/or total body irradiation (4–8 Gy).
Results: The Median observation period after the transplantation was 612 days (range, 109–1944). The cumulative incidence of cGVHD was 84% in BMT and 62% in CBT (p=0.09). The severity of cGVHD was analyzed based on its type; limited or extensive. In CBT, the percentage of the former type was 34% (vs 25% in BMT) and the latter was 23% (vs 48% in BMT). High-risk disease (p=0.03) and preceding acute GVHD(p=0.03) are related to the occurrence of cGVHD. RICBT tended to increase cGVHD compared to CBT using BU/CY or CY/TBI regimen, Multivariative analysis showed that cGVHD increased overall survival (p<0.01) and suppressed recurrence of the disease (p<0.01). During observation period, no patients were died of cGVHD.
Discussion: We demonstrated that cGVHD in CBT is tolerable compared with that in BMT and that the occurrence of cGVHD could result in good prognosis. Our analysis also suggested that CBT could have GVL effect as well as BMT.
Tolerability of PTK787/ZK 222584 in a Phase II Study of Post-Transplant Maintenance Therapy in Patients with Multiple Myeloma Following High-Dose Chemotherapy and Autologous Stem Cell Transplant.
Authors: Mosley James C. , Peles Shachar , Ruddell Alisa , Gao Feng , Abboud Camille , Cashen Amanda , Uy Geoffrey , Westervelt Peter , DiPersio John F. , Vij Ravi 
Published: October 2019

Abstract
Background: Currently, High-Dose Chemotherapy (HDCT) followed by autologous stem-cell transplantation (ASCT) is the standard of care in Multiple Myeloma (MM). This therapy improves overall and event-free survival, but is not curative, necessitating further therapies that will enhance and prolong remission duration. PTK787/ZK 222584 is a potent, orally available, angiogenesis inhibitor that blocks all known VEGF receptors in a dose-dependent fashion. Preclinical studies have demonstrated that PTK/ZK is able to inhibit tyrosine phosphorylation of VEGFR-1 in MM cells, as well as inhibit MM cell migration and proliferation. Based on this, a phase II study was designed to assess efficacy and tolerability of PTK/ZK as maintenance therapy for individuals treated HDCT and ASCT for MM.
Study Design: Patients with MM treated with HDCT and ASCT with persistent measurable paraproteinemia or persistent abnormal serum κ/λ ratio were selected for treatment with PTK/ZK. Primary endpoint is overall response rate and secondary endpoints are time to progression, disease free survival, and safety. Patients were initiated on 750mg daily of PTK/ZK, with doses escalated to 1250 mg daily.
Results: Nine patients have received PTK/ZK and their baseline characteristics are as follows: median number of days on PTK/ZK is 129 (range 3–252); median number of cycles administered is 5 (range 1–14); median age is 57 (range 38–71); stage IIIA (7), stage IIA (1), stage IA (1); IgG isotype (7), IgA isotype (2); median β2-microglobulin level was 1.7 (range 1.2–4.2). Of the nine patients who initially received PTK/ZK, four remain on the medication, three patients have stopped due to progressive disease, and two have stopped due to toxicities. One patient has demonstrated a PR (11%), three patients have SD, and three patients had PD. There have been no deaths. Toxicities are as follows: one patient developed grade 3 elevated ALT as well as motor and sensory neuropathy, one patient developed grade 3 neutropenia, and one patient developed grade 3 prolongation of the QTc interval. Two patients were withdrawn from the study due to toxicities, one with grade 3 prolongation of the QTc interval as well as grade 4 Hypertension, and one patient with grade 4 Hypertension alone. The remaining five patients have had no significant adverse drug events.
Conclusion: Continued patient accrual is underway for analysis of time to progression and disease free survival as well as overall response rate. Bone marrow samples are also being evaluated for change in microvessel density by immunohistochemistry with treatment.