bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Outcomes of Patients with T Cell NHL Undergoing Allogeneic Stem Cell Transplant.
Authors: Zain Jasmine , Palmer J. , Tsai N. , Popplewell L. , Nadamanee A. , Krishnan A. , Nakamura R. , Rodriguez R. , Forman S. J. , Kirschbaum M. 
Published: October 2019

Abstract
Background: T cell NHL represent approximately 10–15% of all lymphomas. Pts with T cell NHL are often treated similarly to patient with B cell NHL, although the clinical outcomes of most patients with T- NHL tend to be worse with the exception of ALK positive anaplastic large cell lymphomas (ALCL). Updated classifications in recent years have recognized specific clinical and pathologic T cell entities with distinct clinical courses and this poses a challenge to the systemic study of these diseases. The exact role of allogenic transplant in T- cell NHL is unknown.
Methods: We looked at 45 pts who underwent an allogeneic HSCT for T cell lymphomas between Jan 2000 to Dec 2005. There were 18 males, 27 females. Median age at transplant was 32 (7–74). Histology was Mycosis fungoides /Sezary syndrome (SS/MF) n=10, T cell lymphobalstic leukemia (PTLL) n=16, PTCL including AILD and ALCL n=14, NKT cell n=5. Syngeneic donor 1, Sibs 31, MUD 13. Median time from diagnosis to transplant was 12.5 (3.6–88.3) mo. Source of stem cells BM 9, PBSCT 35, cord blood 1. Conditioning, fully ablative 29, reduced intensity 16. Median number of prior regimens MF/SS 5, PTLL 2, PTCL 3, NKTL 2 with only 2 pts with prior auto transplants. 18 pts were in remission at the time of transplant and 12 pts had induction failure.
Results: Median follow up from transplant was 45.3 mo(0.7–64.7) with a 55.6%OS. Incidence of GVHD was Acute n= 27 extensive chronic n=20. Cause of death was transplant related in 16 pts with only 3 pts dying of disease progression. The overall survival is 61.2 % at 1 year,55.4% at 2 years and 48.5% at 5 years with a 5 year progression free survival at 48.5%. Based on different histologies, the results are 50.0% overall survival at 1 year and 40.0% at 2 and 5 years for SS/MF, 55.6% at 1 and 2 years for PTLL, 70.1% at 1 and 2 years and 52.6% at 5 years for PTCL and 80% at 1 year for NKT shown in fig 1 and 2.
Conclusion: Allogenic transplant can result in long term survival for some patients with T cell NHL suggesting a graft vs lymphoma effect. Timing of transplant needs to be better defined. Most patients are heavily pretreated which may have resulted in more transplant related mortality with 11/20 pts dying of infection. Most patients did not have a prior auto transplant indicating early progression of disease after standard therapies defined for B cell malignancies.
Overall Survival by Histology  T-Cell Lymphoma with Allogenic Transplant  Sample Size: 45 patients Overall Survival by Histology  T-Cell Lymphoma with Allogenic Transplant  Sample Size: 45 patients Progression-Free Survival by Histology  T-Cell Lymphoma with Allogenic Transplant  Sample Size: 45 patients Progression-Free Survival by Histology  T-Cell Lymphoma with Allogenic Transplant  Sample Size: 45 patients
Persistent Centre Effect but Improvement of Leukemia-Free Survival of HLA Identical Hematopoietic Stem Cell Transplantation for Adults with AML in First CR in Europe over the Period 1987–2005 an Analysis on Behalf of the ALWP of EBMT.
Authors: Katsahian Sandrine , Labopin Myriam , Frassoni Francesco , Rocha Vanderson , Chevret Sylvie 
Published: October 2019

Abstract
Background. Among major European centres which had undertaken more than 30 bone-marrow transplantations(BMT) between Jan 1, 1987, and Dec 31, 1995, the outcome of allogenic BMT for acute myeloid leukemia (AML) in first complete remission has been shown to be influenced by the centre in which the procedure is done. To determine whether similar variation exists 10 years later, we analysed leukaemia free survival (LFS), relapse incidence (RI) and treatment related mortality (TRM) across the same 13 transplant centres.
Methods. Thirteen centres were included in the analysis which enrolled 515 patients (aged 16–55 years), between 1987 and 1995, for acute myeloid leukaemia in first complete remission and 455 patients were enrolled between 1996 and 2005. Patients were followed from the date of transplantation to the time of event (Relapse and/or deaths). Regression models taking into account centre effect was adapted to the outcome and adjusted for relevant covariates
Findings The overall results at 5 years were 57% (95% CI 54–61) for leukaemia-free survival (LFS), 22% (19–25) for relapse incidence (RI), and 21% (18–24) for treatment related mortality (TRM) with a range for centres of 41–67%, 13–41%, and 13–41%, respectively. LFS at 5 years before 1995 was significantly lower 54% than after 1995 62% (p=0.02). Relapse Incidence at 5 years before 1995 was not significantly lower 23% than after 1995 21% (p=0.34). Treatment-related mortality incidence at 5 years before 1995 was not significantly lower 25% than after 1995 21% (p=0.13). Analysis showed the centre effect to be highly significant for LFS and TRM, but not for RI.
Interpretation These findings show that the results of BMT have improved over time in Europe. At the same time this study confirms a significant centre-specific variation in the success of bone transplantation in Europe. This effect has persisted despite advances in transplantation, which have lead to improvements in patient outcomes (leukaemia free survival and Treatment Related Mortality). Further studies are needed to elucidate the causes of this variation, with the goal of developing strategies to minimize the centre effect and ensure the best possible outcomes for all transplant recipients.
The Use of Intravenous Compared with Oral Busulfan in High-Dose Chemotherapy and Autologous Stem Cell Transplantation (ASCT) for Lymphoma Is Associated with Improved Relapse-Free Survival.
Authors: Dean Robert , Pohlman Brad , Sweetenham John William , Sobecks Ronald , Kalaycio Matt , Andresen Steven , Rybicki Lisa , Lowe Christopher , Brown Stacey , Curtis Julie , Bolwell Brian 
Published: October 2019

Abstract
The efficacy of high-dose chemotherapy and ASCT for lymphomas is generally believed to be independent of the preparative regimen used, although toxicities may vary. Delayed toxicities after ASCT led us to investigate IV busulfan in older patients as a substitute for oral busulfan in a preparative regimen of busulfan/cyclophosphamide/etoposide (BuCyVP), based on data suggesting lower treatment-related mortality after ASCT with the IV formulation. We then queried whether other outcomes of ASCT for lymphomas were improved by substituting IV busulfan for oral busulfan. We retrospectively analyzed the outcomes of 308 patients over age 50 years who underwent ASCT for NHL (93%) or HL (7%) at the Cleveland Clinic from 1996 through 2/2006. Oral BuCyVP (“PO Bu”) was used in 261 patients and IV BuCyVP (“IV Bu”, 0.8 mg/kg IV x 14 doses given without monitoring or adjustment for serum Bu levels) in 47 patients. Differences in baseline characteristics were that the IV Bu group was more heterogeneous in the number of prior chemotherapy regimens (P=0.013), more often received chemotherapy for stem cell mobilization (P=0.026), had fewer NHL patients with a high-intermediate or high IPI score (P<0.001), and had fewer patients with stage III or IV disease (P=0.046). Follow up from ASCT was significantly longer in the PO Bu group (median 45.7 vs. 8.8 months). CD34+ cell doses and hematopoietic recovery were similar between groups.
Median overall survival was 43.6 months after ASCT with PO Bu but was not reached for the IV Bu group. Kaplan-Meier analysis demonstrated the unanticipated finding that IV Bu was associated with a lower rate of relapse (P=0.013), superior relapse-free survival (P=0.008), and a marginal improvement in overall survival (P=0.06).
Figure Figure
Univariate Cox models identified the route of busulfan administration and disease status at ASCT as significant predictors of relapse. Age at transplant, the number of prior regimens, and LDH at transplant were significant predictors of mortality. Only the route of busulfan administration significantly predicted RFS in univariate analysis. In a multivariable model, the route of busulfan administration was the strongest predictor of RFS (P=0.043). Age was also predictive of RFS (P=0.047). These preliminary results suggest that replacing PO Bu with IV Bu is associated with a reduced relapse rate and improved RFS following ASCT for lymphoma. In contrast to other reports, we observed these improvements without targeting Bu dosage according to serum levels. Further study is necessary to confirm these findings and to ascertain whether IV Bu will favorably influence overall survival in this setting.
Prospective, Randomized Comparison between Double Transplantation (T) with Melphalan (200 mg/m2) and Triple T with Intermediate Dose Melphalan (100 mg/m2) in Patients with Multiple Myeloma (An Interim Analysis).
Authors: Ludwig Heinz , Linkesch Werner , Kasparu Hedwig , Krieger Otto , Spicka Ivan , Gastl Gunther , Greil Richard , Drach Johannes , Thaler Josef , Kuhn Ingrid , Zojer Niklas , Hinke Axel 
Published: October 2019

Abstract
In this study we compare the efficacy and toxicity of double T with M 200 with triple T using M 100 in newly diagnosed pts with MM. 175 pts have as yet been enrolled and 135 have been randomized after VAD induction treatment and stem cell collection to either tandem or triple transplantation. Reasons for non-randomization were too early for T (n=22), PD after induction (n=5), early death (n=3), toxicity (n=3), pt. refusal (n=3), and others (n=4). Median age of the 135 pts randomized was 59 years (range: 27–70 years). Stage I: 8%, stage II: 17%, stage III: 75%, Paraprotein Isotypes: IgG: 55%, IgA: 25%, IgD: 2%, IgM: 1%, Light chain: 17%. Induction treatment: 3 cycles of VAD; stem cell priming: IEV (ifosfamide (2g/m2)-etoposide (150mg/m2), d1–3; epirubicin (50mg/m2), d1) and G-CSF (5mg/kg) from d4. Conditioning regimen: M 200 mg/m2 or M 100 mg/m2 plus G-CSF; day 5 until WBC >2000/ml. Pts with ≥ SD after T were subsequently randomized to interferon 3MU, TIW (Schering Plough) plus prednisone (25mg, po., TIW), or interferon alone. QoL was assessed with the EORTC QLQ C30 instrument. Chi2 test for trend was used for comparison of response and survival endpoints were estimated by the Kaplan-Meier product limit method. Response rates after VAD were CR: 11%, PR: 65%, SD: 22% and PD: 2%. Median time from start of VAD to start of T was 137 in the double and 139 days in the triple T arm. Response rates did not differ between pts treated with double or triple T (CR: 47% vs. 43%, PR: 47% vs. 47%, SD 2% vs. 6%, PD: 4% vs. 4%, p=0.60, respectively). Median PFS for both groups combined was 36 mos, but showed a tendency for shorter PFS in pts on triple T (23 mos. vs. 37.5 mos; HR 1.26, 95% CI: 0.72–2.23, p=0.21). Median of OS has not been reached yet, but did not differ between both groups. Hematological toxicity was similar in both groups. There was a tendency for more grade 2–4 mucositis and for grade 3–4 vomiting, nausea, and fatigue in the double T group. Global QoL (questions 29 and 30) was comparable between both groups, before (5 (2.5–6.5) vs. 5 (4.5–6)) and after double (5.8 (3–8.5) or triple T (6 (2.5–7)). In conclusion, triple T with intermediate dose M resulted in similar response rates, slightly shorter PFS but similar OS and was associated with less mucositis and slightly less vomiting, nausea and fatigue.
Progression-free survival by randomization group Progression-free survival by randomization group
Second Stem Cell Harvest from Unrelated Donors for Patients with Relapse or Graft Failure after First Transplantation: Patient Age >50 Years and Relapse of Malignant Disease Are Associated with Poor Outcome.
Authors: Platzbecker Uwe , Zapf Susanne , Theuser Cathrin , Schmidt Alexander , Rutt Claudia , Ehninger Gerhard , Bornhauser Martin 
Published: October 2019

Abstract
Introduction: Hematopoietic progenitor cells from unrelated donors are increasingly used for allogeneic stem cell transplantation (SCT). A second donation of peripheral blood stem cells (PBSC) or bone marrow is widely accepted in case of graft failure of relapse.
Patients and methods: We retrospectively investigated the outcome of seventy (n=70) patients with hematological malignancies (AML/MDS n=29, CML n=19, ALL n=17, other n=5) receiving a second SCT using PBSC (n=67) or bone marrow (n=3) from the same unrelated donors. Patients had a median age of 30 years (range 1–59) and the reason for a second donation of stem cells consisted of either relapse (n=37) or graft failure (n=33). Whereas in 21 patients no conditioning was used in the remaining patients it was busulfan or TBI-based in the majority of cases.
Results: After a median follow-up of 33 months (range 7.9–76.2) after 2nd SCT a total of 55 patients died due to treatment-related mortality (63%) or relapse (16%) resulting in a median overall survival (OS) for all patients of 3 months. The OS was significantly better in patients < 50 years (38 vs. 8 %, p=0.01) and in case of graft failure (37% vs. 7%, p=0.02). Time interval between SCT, HLA-disparity, disease type (AML/MDS vs. CML vs. ALL), infused CD34+ cells/kg or graft source at first transplant had no impact.
Conclusion: These data show the lack of efficacy of a second infusion of HSC from the same donor especially in older patients and in cases in which relapse of malignancy is the reason for second transplant. Given the currently unknown long-term effects of a repeated exposure to G-CSF, the factors mentioned above should be kept in mind whenever a request for a second HSC donation is considered.
Reduced-Intensity Allogeneic Transplantation after Failure of Autologous Transplantation: A Prospective Multi-Center CALGB Study.
Authors: Bashey Asad , Owzar Kouros , Johnson Jeffrey L. , Devine Steven M. , Shadduck Richard K. , Shea Thomas C. , Linker Charles 
Published: October 2019

Abstract
Relapse of malignancy (RM) remains the most important cause of treatment failure following high-dose chemotherapy and autologous hematopoietic transplantation (AHCT). Allogeneic transplantation (allo-HCT) can salvage some patients who relapse or develop MDS following AHCT. However, myeloablative allo-HCT has been associated with a prohibitive transplant-related mortality (TRM) in such patients. CALGB study 100002 prospectively assessed the safety of reduced-intensity allo-HCT (RICT) in patients who failed prior AHCT. Eligibility required the development of RM or MDS > 6 months following AHCT for a hematologic malignancy and an available HLA-identical sibling (MSD) or 9/10 locus matched related donor, or a 10/10 matched unrelated donor. Between Dec 02 and Mar 06, 82 patients were registered from 11 CALGB centers. Patient characteristics: median age = 51 (17–70); male-63%; diagnoses - NHL 30%, HD 26%, MM 18%, MDS 16%, AML 8%, CLL 2%; donor - MSD 43%, MUD 55%, 9/10 MRD 2%. Median time between AHCT and RICT was 2.6 yrs (0.6–5.7 yrs). Preparative regimen for patients with MSD was fludarabine 30 mg/m2/d x 5 d, busulfan (i.v.) 3.2 mg/kg/d x 2 d. For patients without MSD rabbit ATG (Thymoglobulin ®) 2.5mg/kg/d x 4 d was added. PBSC 2–8 x 106 CD34+ cells/kg was used as the graft. GVHD prophylaxis consisted of tacrolimus tapering at d +90 and methotrexate 5 mg/m2 x 3 doses for MSD patients. For non-MSD patients, tacrolimus was tapered starting d +180, a fourth dose of methotrexate and MMF (d 0 to d +60) were added. Primary endpoint was TRM at 6 months. For 56 patients with > 6 months post-RICT follow-up (median follow-up 1.3 yrs), 6 month TRM was 8.7% (MSD patients 4.2%, non-MSD patients 9.3%). Total cumulative TRM was 14.3% (MSD 16.7%, non-MSD 12.5%). Reported cumulative rates of II–IV and III–IV acute GVHD are 28.2% and 11.8% respectively. Chimerism studies were performed centrally on peripheral blood (PB) specimens. The percentage of patients from MSD patients who achieved full (> 90%) donor T-cell (CD3) chimerism in PB on day 30, 60, 90 and 180 post transplant are 15, 40, 47, 57 and 60% respectively. In contrast, for non-MSD patients the corresponding rates are 78, 68, 86 and 91 % respectively. Both MSD and non-MSD patients achieved full (>90%) donor chimerism in myeloid cells by d 30 in > 80% of patients. This study observed a <10% 6-month TRM for RICT following AHCT failure in the multi-center, co-operative group setting. Also, the use of a more potent GVHD prophylaxis regimen seems to enable TRM rates for non-MSD patients to approximate those seen for MSD patients. MSD patients achieve slower onset of full-donor chimerism in T-cells with this regimen. A successor study will assess means of increasing early T-cell chimerism in the MSD patients.
Beyond HLA: Impact of Immunoreactive Mismatches of Minor Histocompatibility Antigens on Probability of Relapse and Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplantation from HLA-Matched Unrelated Donors.
Authors: Markiewicz Miroslaw , Siekiera Urszula , Wojnar Jerzy , Wieczorkiewicz Agata , Wylezol Iwona , Giebel Sebastian , Karolczyk Agnieszka , Holowiecki Jerzy 
Published: October 2019

Abstract
Factors contributing to relapses and GVHD following allogeneic Hematopoietic Stem Cell Transplantations (HSCT) from HLA-matched unrelated donors are not well established. We analyzed 35 patients (pts) transplanted from HLA 10/10 alleles (A, B, C, DRB1, DQB1) matched unrelated donors (URD) in the Dept. of Hematology and BMT, Katowice, Poland, with use of the same standard operating procedure from January 2004 until March 2006. Indication for HSCT was AML (13 pts), ALL (8), CML (7), MDS (2), PNH (3), CLL (1), myeloid sarcoma (1). Preparative regimen was Treosulfan+Fludarabine (23 pts), TBI+Cy (9) and Bu+Cy (3). Alleles encoding 11 minor Histocompatibility Antigens (mHA: HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1, ACC-2, HwA-9, HwA-10, UGT2B17, HY) were analyzed for each donor-recipient pair with use of Dynal AllSet mHA typing kit and PCR-SSP method. Only immunogenic mHA mismatches were analyzed. Information on whether mHA mismatches might result in Host-versus-Graft or Graft-versus-Host responses was established with use of the minor Histocompatibility Knowledge Database of Leiden University Medical Center’s minor Histocompatibility Workshop.
Patients transplanted from donors with mHA mismatched in HVG direction had significantly higher probability of relapse (64+/− 8% versus 10+/− 9%, p=0.003) when compared to pairs without mHA HVG immonogenicity. Patients transplanted from donors with mHA mismatched in GVH direction had higher probability of aGVHD (88+/− 8% versus 53+/− 11%, p=0.14) and cGVHD (41+/− 16% versus 37+/− 17%, p=0.65) when compared to pairs without GVH immunogenicity. GVHD was also observed more often on day +100 (33% versus 6%, p=0.06) when mHA mismatch in GVH direction was present. Observed influence of HVG and GVH immonogenicity on probability of relapse and GVHD did not lead to significantly different survival in observed groups of pts. These results indicate that mHA immunogenic mismatches in HVG and GVH direction may be responsible for relapse and GVHD, respectively, in HSCT recipients from HLA-matched unrelated donors. The study is being continued to confirm these primary observations and to establish the associations of specific mHA mismatches with HSCT outcomes.
Impact of mHA mismatch on probability of relapse and GVHD Immunogenicity of mHA mismatches HVG no HVG p # of patients 18 17 Relapse at 1 year 64%+/−8 10%+/−9 0.003 Immunogenicity of mHA mismatches GVH no GVH p # of patients 16 19 aGVHD 88%+/− 8 53%+/−11 0.14 cGVHD at 1 year 41%+/−16 37%+/−17 0.65 Impact of mHA mismatch on probability of survival Immunogenicity of mHA mismatches HVG GVH only HVG only GVH no HVG no GVH p # of patients 9 9 7 10 Survival at 9 months 63%+/−17 57%+/−25 83%+/−15 69%+/−15 0.86
Allogeneic Cytokine-Induced Killer Cells Traffick to GVHD Target Tissue but Cause Less GVHD, While Retaining Tumor Cytotoxicity and Facilitating Bone Marrow Engraftment.
Authors: Nishimura Ryosei , Baker Jeanette , Beilhack Andreas , Negrin Robert 
Published: October 2019

Abstract
Cytokine-induced-killer cells (CIK), generated from splenocytes in mice and PBMC in human by the timed addition of IFN-γ, anti-CD3 MAbs and IL-2, express both T cell and NK cell markers and have cytotoxic activity against autologous and allogeneic tumors. We previously showed that adoptive transfer of allogeneic CIK in a murine model did not cause severe acute GVHD, leading to full survival. However the precise mechanism of reduced GVHD and retained GVT activity is not fully understood. To this end, we first evaluated the trafficking patterns of luciferase-transgenic CIK in a major MHC mismatched BMT model. In vivo bioluminescence imaging (BLI) showed that both CIK and fresh splenocytes homed to and proliferated initially in secondary lymphoid organs including the spleen, followed by infiltration of the gut and skin by day 7. All mice receiving fresh splenocytes died by day 10. Signal from gut mucosa in animals receiving allogeneic CIK cells was transient, however signals from other sites such as mesenteric lymph nodes were high and persistent. By day 21 allogeneic CIK reinfiltrated intestinal tissue without causing severe GVHD. To further investigate potential changes in the expression of surface molecules in vivo, we transplanted GFP positive fresh splenocytes and GFP positive CIK cells into major mismatched irradiated hosts, and then on day 7 analyzed activation markers, homing molecules, apoptosis related genes, and peripheral tolerance induction molecules such as CTLA-4 and PD-1 by FACS. No significant differences were noted between CIK and splenocytes. However we found that the cell division rate of CIK cells in vivo was much slower than those of splenocytes utilizing a CFSE based cell proliferation assay. This might lead to less GVHD in mice receiving CIK cells. Next we evaluated whether CIK retained tumor killing activity in vivo using A20 luciferase lymphoma cells into lethally irradiated MHC major mismatched receipients subcutaneously. We visualized the reduction of tumor by BLI. GFP positive CIK, which were extracted on day 7 following their transplantation into MHC-mismatched allogeneic recipients, retained tumor cytotoxicity in vitro. Finally, to study whether CIK facilitate BM engraftment, we quantified the absolute number of cells from the peripheral blood in MHC major-mismatched nonmyeloablative BMT. On day 30 mice receiving CIK showed rapid BM engraftment, especially in CD4 (p=0.0007) and CD8 (p<0.0001) subpopulations. In conclusion, allogeneic CIK homed to and expanded in GVHD target organs without causing acute GVHD, retained tumor killing activity and promoted BM engraftment.