bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro Monitoring of Defibrotide Prophylaxis for Endothelial Complications Following Allogeneic Stem Cell Transplantation.
Authors: Eissner Gunther , Wiesner Julia , Hahn Nancy , Iacobelli Massimo , Haubitz Marion , Andreesen Reinhard , Holler Ernst 
Published: October 2019

AbstractDefibrotide (DF) is a polydisperse mixture of 90 % single-stranded polydeoxyribonucleotides with anti-thrombotic, pro-fibrinolytic and anti-apoptotic functions. DF is already successfully used in the treatment of hepatic veno-occlusive disease in allogeneic stem cell transplantation (SCT). Our observation that DF can also protect endothelial cells (EC) from conditioning (fludarabine (F-Ara))-mediated apoptosis(1) prompted us to apply it prophylactically to patients (pts) at risk for endothelial complications. Pending on the magnitude of risk, pts received 200–800mg every 6h in 2h-infusions, usually from day (d) −7 until d+21 post SCT.Circulating EC (CEC) as a marker of conditioning-mediated endothelial toxicity(2) were detected by magnetic bead separation of CD146+ cells from EDTA blood of 50 SCT pts (33 DF, 17 NO DF) and co-staining with Ulex Europaeus antigen lectin 1. CEC maxima until d+100 post SCT were compared between the two groups. DF pts showed significantly lower maxima of CEC than untreated pts (1085 [±1012] in the DF treatment group vs. 2595 [±1910] CEC/mL in non-DF pts, respectively, p=0.0007). Similarly, when CEC maxima were compared in the time period of DF prophylaxis, again, DF pts had less cell counts (562 [±794] vs. 1548 [±1575] CEC/mL in control pts, respectively, p=0.005). Interestingly, this observation also held true for the heavily pre-treated diagnostic subgroup of acute myeloid leukemia (AML) pts (683 [±807] DF vs. 3467 [±2664] non-DF, p=0.007). These preliminary analyses suggest the protective efficacy of DF prophylaxis in the course of SCT. The final proof of principle is to be validated in long-term clinical follow-ups.
Clinical Outcome of a Second Autologous Hematopoietic Stem Cell Transplant (HCT) for Non-Hodgkin (NHL) and Hodgkin Lymphoma (HL) Relapsing after a First Autotransplant.
Authors: Smith Sonali M. , van Besien Koen , Carreras Jeanette , Vose Julie M. , Lazarus Hillard M. , Hari Parameswaran 
Published: October 2019

Abstract
Autologous HCT (autoHCT) salvages many patients (pts) with relapsed lymphomas but few relapsing after an autoHCT are cured. We determined feasibility of stem cell collection, engraftment kinetics, treatment-related mortality (TRM), progression free survival (PFS), and overall survival (OS) for a second autoHCT (HCT2) for lymphoma relapsing after prior HCT (HCT1). We studied 35 pts, 20 with HL and 15 with diffuse or follicular large cell and immunoblastic NHL, receiving a HCT2 for relapse between 1986 and 2003 and reported to the CIBMTR. Median (range) age at HCT2 was 36 yrs (16–61); 61% had a performance score less than 90. HCT2 was performed >1 year after HCT1 in 80%. Median (range) time from diagnosis to HCT1 was 20 mo (4–162 mo), from HCT1 to relapse, 17 mo (3–68 mo), and from relapse to HCT2, 5 mo (1–40 mo). 83% underwent a 2nd stem cell / marrow harvest prior to HCT2. Median time to ANC >0.5 x 109/L was 11d. CBV or BEAM were the conditioning regimens for HCT1 in 80% and for HCT2 in 60%. The best response to HCT2 was complete remission in 22 pts and partial remission in 5; 8 pts had either no response or progressive disease. At a median follow up of 92 mo (32–124 mo) after HCT2, 26 pts (74%) have died with 17 (65%) dying of relapsed lymphoma. Two (6%) patients developed therapy-related MDS. The probability of TRM at day 100 was 12% (95% CI, 3–25%). The 1, 3 and 5 yr probability of PFS were 45% (95% CI, 29–62%), 33% (95% CI, 18–50%) and 30% (95% CI, 15–46%), respectively. The 1, 3 and 5 yr probability of OS were 63% (95% CI, 46–78%), 34% (95% CI, 19–50%) and 31% (95% CI, 17–47%), respectively. There were no differences in outcomes between HL or NHL. Pts relapsing >6mo after HCT1 appeared to have better OS (fig 1 and 2). In summary, HCT2 is feasible in pts with lymphoma after relapsing an HCT1. Stem cells harvested prior to HCT2 resulted in rapid engraftment with a day 100 TRM (12%) lower than that reported for alloHCT in this setting. Relapse is the primary reason for failure, but approximately one-third of pts enjoy long-term disease free survival. HCT2 should be considered for young pts with relapsed HL or NHL post-HCT1 without alternative transplant options.
HCT1 (%) HCT2 (%) Sensitive disease status pre-HCT 26 (79) 24 (75) Stem cell source BM 15 (43) 10 (29) PBSC 13 (37) 21 (60) Both 7 (20) 4 (11) Median days to platelet recovery ≥ 20 x 109 /L 17 (7–376) 20 (1–101) Stem cell harvest between HCT1 and HCT2 29 (83) Different conditioning regimen for HCT2 25 (74) Outcomes TRM @ 1 yr 21 (9–37) PFS @ 5yrs 30 (15–46) OS @ 5 yrs 31 (17–47) Figure 1 Figure 1. Figure 2 Figure 2.
Prior Therapy with Rituximab (R) in Patients (pts) with Diffuse Large B-Cell Lymphoma (DLBCL) Does Not Affect Disease-Free (DFS) or Overall Survival (OS) Following High Dose Therapy (HDT) and Autologous Stem Cell Transplantation (ASCT).
Authors: Thakkar Snehal G. , Sweetenham John William , Rybicki Lisa , Sobecks Ronald , Andresen Steven , Dean Robert M. , Pohlman Brad , Kang Tyler Y. , Kalaycio Matt , Brown Stacey , Bolwell Brian J. 
Published: October 2019

Abstract
The addition of R to first line chemotherapy regimens for DLBCL has resulted in improvements in DFS and OS. HDT and ASCT have been shown to improve outcome for pts with relapsed DLBCL compared with conventional dose salvage regimens. The effectiveness of HDT and ASCT in pts with DLBCL who have received prior therapy including R is unknown. We reviewed 257 consecutive pts with DLBCL treated with ASCT from 1/94–12/02. Of these, 161 (63%) had received R as part of their initial therapy and 65 (25%) had not received prior R. A third group (N = 31, 12%) who had been treated with R as part of salvage therapy prior to ASCT were excluded from further analysis.
Patient characteristics are shown in Table 1. All patients received a preparative regimen of Busulfan, Cyclophosphamide, and Etoposide. Greater than 75% of patients in both groups had evidence of disease at time of transplant. Univariable and multivariable analyses demonstrated no difference between the pts previously treated with R and those not treated with R. After median follow up of 76 months (13–142) no statistical difference in DFS or OS was observed between the two groups. Patients were then adjusted for age, gender, stage, prior chemotherapy/radiation, time from diagnosis to CR, IPI, and disease status and compared again. The matched propensity analysis also showed no significant difference in DFS (p=0.87) and OS (p=0.22) (Figures 1 and 2).
Despite concerns that pts with DLBCL previously treated with regimens containing R may have more resistant disease at relapse, our results suggest that HDT and ASCT is equally effective for these pts compared with those who have not received prior R. A prospective analysis is needed to confirm these results.
Table 1. Patient Characteristics Categories No Rituximab (n=65) Rituximab (n=161) Age-median (range) 48 (19–70) 53 (23–72) Gender (M/F) 42/23 93/68 Stage IV (n) 75% (49) 61% (98) Prior Chemo Regimens-median (range) 2 (1–4) 2 (1–6) Prior Radiation (n) 25% (16) 32% (51) IPI (Low/Low-Intermediate vs High-Intermediate/High) 66% vs 34% 55% vs 45% CD34 collection (x 10^6)-median (range) 8.3 (2.9–39.2) 4.4 (0–52.8) Time to Transplant (mos)-median (range) 14.7 (2.8–274.3) 14.5 (5.1–192.6) Diffuse Large B-cell Lymphoma - Matched Groups Diffuse Large B-cell Lymphoma - Matched Groups Diffuse Large B-cell Lymphoma - Matched Groups Diffuse Large B-cell Lymphoma - Matched Groups
The Influence of PET/Gallium (PET/Gal) Status and High-Dose Rituximab (HDR) in Patients with Aggressive, Large, B-Cell Lymphoma (LBCL) Receiving Autologous Stem Cell Transplants (ASCT).
Authors: Alousi Amin M. , Saliba Rima M. , Okoroji Grace-Julia , Hosing Chitra , Samuels Barry I. , Champlin Richard E. , Khouri Issa F. 
Published: October 2019

Abstract
Background: PET/Gal status has been reported to be an important predictor of outcome in patients with LBCL who receive an ASCT. Newer conditioning regimens which include high-dose rituximab (HDR) have been shown to improve results (Khouri, JCO, 2005). The impact of HDR on the outcome of patients based on PET/Gal status has not been determined.
Methods: A retrospective review of patients with chemo-sensitive, LBCL who received an ASCT on a research protocol at MD Anderson between 1995 and 2005 was performed. Factors that were considered for outcome included: Age, IPI, # of prior chemotherapies, B2-microglobulin, disease status at transplant, HDR and PET/Gal status. In patients who received HDR, it was given with stem cell mobilization and then again on days +1 and +8 following transplant.
Results: A total of 188 patients were identified. Median age was 49 years with 108 (57%) male patients. 147 patients (78%) had de novo LBCL and 41 (22%) had a LBCL of follicular origin (LBCL-F). 83 (39%) patients received HDR. At transplantation, 95 patients (50%) were in PR, 71 (38%) in CRU and 22 (12%) in CR. 142 (76%) patients were PET/Gal negative, 37 (20%) PET/Gal positive and 9 (4%) were unknown. Median follow-up was 47 months. On multivariate analysis, for patients with de novo LBCL, PET/Gal status and HDR were the only predictors for progression and progression free survival (PFS). Patients who were PET/Gal negative and those that received HDR had a hazard ratio (HR) of 0.3 (p<0.001) and 0.5 (p=0.02) for progression, respectively (see the table below for the cumulative incidence (CI) for progression and PFS at 54 months according to HDR and PET/Gal status for de novo LBCL undergoing ASCT). PET/Gal Status and HDR were also found to be predictive for patients with LBCL- F on univariate analysis, however due to the small numbers in this subset; multivariate analysis could not be performed. PFS at 54 months for patients with LBCL-F who were PET/Gal negative was 40% versus 17% in the PET/Gal positive group, (p=0.006). PFS for those LBCL-F patients who received HDR was 81% as compared to 23% for those who did not receive HDR, (p=0.007).
Conclusions: The two most important predictors of outcome following ASCT are PET/Gal status and whether HDR was given with the transplant regimen. The addition of HDR to the transplant regimen decreases the risk for progression irrespective of PET/Gal status; however the improvement is more significant in patients with a negative PET/Gal scan.
C.I. for progression and PFS at 54 months for de novo DLBCL PET/Gal Status HDR CI of Progression (%) Progression Free Survival Positive No 83 17 Positive Yes 54 45 Negative No 35 55 Negative Yes 22 75
S0204: Melphalan (MEL)-Based Tandem Autotransplants (TAT) for Multiple Myeloma (MM) with Thalidomide/Dexamethasone (TD) Induction and Thalidomide/Prednisone (TP) Maintenance: A Phase II Trial of the Southwest Oncology Group.
Authors: Hussein Mohamad A. , Jakubowiak Andrzej J. , Bolejack Vanessa , Zonder Jeff , Crowley John , Barlogie Bart 
Published: October 2019

Abstract
Background: TAT has recently been shown to double the 7-yr event-free (EFS) & overall survival (OS) rates achieved with a single AT (20% & 40%; IFM94). Completion of TAT in most randomized & phase II trials seldom exceeds 70%, due to toxicities encountered with prolonged induction chemotherapy & posed by the 1st AT. TD is effective salvage therapy &, when used up-front, effects high response rates including ~10% CR.
Patients and Methods: To reduce induction toxicities & thus deliver TAT in a timely fashion to the majority of pts, SWOG embarked on a trial of TD induction, modest-dose cyclophosphamide (CTX) for PBSC mobilization, melphalan (MEL)-based TAT & subsequent TP maintenance.
Results: Between July 2002 and December 2005, 147 newly diagnosed patients with MM were enrolled from 28 institutions. Among 138 eligible, analyzable patients, the median age was 56.5yr (range, 23.2–66.0), 83% were white, 62% male. Baseline prognostic features included serum levels of albumin <3.5g/dL in 21%, beta-2-microglobulin (B2M) >5.5mg/L in 21%, creatinine >=2mg/dL in 7%; ISS stage distribution I-48%, II-30%, III-22%. With a median follow-up of 14mo, 64 patients have come off protocol: 15 patients were removed from study due to adverse events, 10 refused further participation, 14 suffered progression or relapse, 1 died, 9 came off for other reasons, and 15 are presently under review. Therapy was well tolerated except for an increased incidence of hyper-coagulable events at the start of the protocol 27% (8/30); following an amendment to decrease the start dose of thalidomide to 50mg, the incidence of hyper-coagulable events decreased to 7% (7/101). Through the induction and PBSC mobilization phases, 4.4% achieved CR & 64.3% achieved Response (SWOG: >=75% M-protein reduction) or partial response (PR, >=50% M-protein reduction) pre-transplant for an overall response rate of 68.7%. 102 eligible patients proceeded to 1st transplant (74%) and 66 (47%) to 2nd transplant, with a median time to 2nd AT of 8mo and 96% of patients receiving 2nd AT within 4mo from 1st AT. Confirmed and unconfirmed CR after the transplant phase was 22%. Two-year OS from 1st transplant registration among 98 patients was 84% and 2-yr OS from TP maintenance among 62 patients was 87%.
Conclusion: Our data show that hyper-coagulable events with the TD regimen could be reduced by decreasing the starting dose of thalidomide from 100mg to 50mg/d. In a multi-institution setting, MEL200-based TAT could be performed safely. Timeliness of the 2nd AT was achieved where 96% of the patients were able to received the procedure within 4 months of the 1st AT. Response rates and quality are promising. Longer follow up should clarify the impact of the improved timeliness of 2nd AT, quality and response rate on PFS and OS.
Unrelated Allogeneic Stem Cell Transplantation with Myeloablative Preparative Regimen for Adult Patients with Acute Lymphoblastic Leukemia in CR: A Survey from the European Group for Blood and Marrow Transplantation (EBMT).
Authors: Basara Nadezda , Labopin Myriam , Ruutu Tapani , Zander Axel , Arnold Renate , Rocha Vanderson 
Published: October 2019

Abstract
Data from the EBMT indicate that approximately 46% of Unrelated Allogeneic Stem Cell Transplantation (UD-SCT) in Europe utilize peripheral blood (PB) and 54% bone marrow (BM) as a graft source for adult patients with ALL since January 1998. However, prospective randomized trials comparing the two stem cell sources are lacking. This study describes the results of 782 adult patients with ALL in remission (422 BM and 360 PB) transplanted in different centers affiliated with the EBMT from 1998 to 2004 with an HLA identical unrelated donor (HLA-A and -B low resolution and HLA-DRB1 allelic typing). Median age was 27 years for BM (range 16–63, male 60%) and 30 years for PB (range16–63, male 62%), respectively. Fifty four (54%) and 64% of patients were transplanted in first complete remission (CR1) in the BM and PB groups, respectively. The frequency of female donor to male recipient was 18% in the BM and 15% in the PB group. Total Body Irradiation (TBI)-based preparative regimens were given in 85% and 88% of patients in the BM and PB group respectively. Graft-versus-Host Disease (GvHD) prophylaxis consisted of cyclosporine A (CsA) (6% and 4%), CsA and methotrexate (77% and 58%) or in vitroT-cell depletion (17% and 38% in BM and PB group, respectively). With the median follow-up of 17 (range 1–92) and 11,3 (range 1–71) months, the incidence of GvHD grade II–IV was 37% in the BM group and 39% in the PB group (p=0.39). Probabilities of LFS, TRM and relapse were calculated using the Kaplan-Meier estimate. LFS was 45+/−3% vs 36+/−3% (p=0.04) transplant related mortality (TRM) was 33+/−2% and 39+/−3(p=0.29 while incidence of relapse was 32+/−3% and 41+/−4%(p=0.06), in the BM and PB groups respectively. Two years leukemia-free survival (LFS) for the patients transplanted in CR1 was 48% (BM) and 42% (PB, p=0.48). However, 2-years LFS for patients transplanted in CR2 or CR3 was significantly higher in the BM compared to the PB group (42% and 26%, p<0.004). The probability of relapse was significantly lower in BM compared to PB (32% vs 54%, p<0.001) without there being a detectable difference in TRM at 2 years (38% vs 43%, p= 0.31).
In conclusion, the results of this retrospective comparative study confirm that UD-SCT with BM and PB as a graft source have similar results for patients in CR1. However, patients transplanted in CR2 or CR3 with a bone marrow graft, have decreased relapse incidence and better LFS, probably reflecting disease and transplant related differences compared to PB transplants such as in vitro T cell depletion more used in those transplants.
Engraftment and Survival Following Hematopoietic Stem Cell Transplantation for Osteopetrosis Using a Reduced Intensity Conditioning Regimen.
Authors: Tolar Jakub , Bonfim Carmem , Grewal Satkiran , Orchard Paul 
Published: October 2019

Abstract
Autosomal recessive osteopetrosis (OP) is a disease characterized by osteoclast dysfunction, leading to multisystem morbidity and death of most affected children. Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for OP, but this patient population is particularly prone to post-transplant complications and death after myeloablative conditioning. To determine the potential of achieving improved overall outcomes in these patients by decreasing pre-transplant mortality, we investigated engraftment and survival following a reduced intensity regimen including busulfan, fludarabine and total lymphoid irradiation. We report outcomes in 11 patients:
Age years Graft and HLA match NC dose (x108) CD34 dose (x106) Follow-up (years) Donor chimerism 1 2.1 URD BM 5/6 3 1.4 0.8 (dead) 100% 2 0.6 UCB 4/6 0.9 0.4 2.5 (dead) Transient partial 3 24 REL PBSC 6/6 12.1 9.2 3.25 (alive) 100% 4 1 URD PBSC 6/6 47 29.6 3 (alive) 100% 5 2.5 UCB 6/6 0.7 0.2 0.2 (dead) No donor engraftment 6 0.9 UCB 5/6 0.8 NK 2.25 (dead) No donor engraftment 7 0.6 UCB 5/6 0.9 0.2 4 (alive) No donor engraftment 8 1 URD PBSC 6/6 15  7.5  24.4 6  3  7 1.9 (alive) Transient partial  No donor engr.  78% donor 9 0.5 UCB 5/6, 4/6 3.5 5.3 0.75 (alive) Transient partial 10 4.4 UCB 4/6 1.1 0.7 0.6 (dead) 100% 11 2 URD BM 6/6 5 2.7 5.2 (alive) 100%
Legend: NC, nucleated cell; URD, unrelated donor; REL, related donor; BM, bone marrow; UCB, umbilical cord blood; PBSC, peripheral blood stem cells; engr., engraftment; NK, not known; HLA matching is reported for 6 antigens. All six patients who received a bone marrow or peripheral stem cell graft engrafted with > 75% donor chimerism. In contrast, all five recipients of unrelated cord blood as a stem cell source for a first graft failed to demonstrate donor hematopoietic chimerism. The day 100 and 6 month mortality was low at 9%. At 1-year after HSCT, 6 of 11 patients (55%) were surviving. Our data suggests that this regimen results in low peri-transplant mortality without compromising engraftment when a marrow or peripheral stem cell graft is used. An umbilical cord blood graft, however, should be used with caution for patients with OP when this or similar reduced intensity regimen is used.
Comparison of Results from a Phase 1/2 Study of Lumiliximab (Anti-CD23) in Combination with FCR for Patients with Relapsed CLL with Published FCR Results.
Authors: Byrd John C. , Castro Januario , O’Brien Susan , Flinn Ian W. , Forero-Torres Andres , Kipps Thomas J. , Heerema Nyla A. , Lin Thomas , Kheoh Thian , Wynnem Dee , Molina Arturo 
Published: October 2019

Abstract
Lumiliximab is a PRIMATIZED® anti-CD23 monoclonal antibody with human IgG1 constant regions and macaque variable regions. Preclinical data demonstrated that lumiliximab enhanced both fludarabine- and rituximab- mediated apoptosis in CLL cells. Thus, a Phase 1/2, open-label, dose-escalation, multicenter study (Study 152–30) evaluating lumiliximab + fludarabine, cyclophosphamide, and rituximab (L + FCR) for relapsed CD23+ B-cell CLL was initiated. Treatment has been completed and follow-up is ongoing. Thirty-one patients (pts) received either 375 mg/m2 (n=3) or 500 mg/m2 (n=28) of lumiliximab in combination with a 28-day cycle of FCR for up to 6 cycles. Median age at study entry was 58 yrs. The majority of pts (74%) were Rai Stage I/II. The most common adverse events included nausea (77%), pyrexia (61%), chills (55%), neutropenia (55%), and fatigue (48%). Twenty pts (65%) experienced a Grade 3 or 4 event. An overall response rate of 71% was demonstrated: 48% complete response (CR), 10% partial response (PR), and 13% unconfirmed PR. Currently, baseline cytogenetic data is available for 21 pts who received 500 mg/m2 of lumiliximab. Although preliminary, 1 of the 4 pts with del(17p13.1) responded; of the 6 pts with del(11q22.3), 5 responded with 4 attaining a CR. A comparison with published data from a study of FCR alone in 177 pts with relapsed or refractory CLL conducted at the M.D. Anderson Cancer Center (MDACC) (Wierda W, O’Brien S, Wen S, et al. J Clin Oncol.2005;23:4070–4078) demonstrated that L + FCR has an acceptable safety profile, does not appear to increase the toxicity (including myelosuppression) of the FCR regimen, and compares favorably with the CR rate of the FCR regimen alone, as displayed in Table 1. Most pt characteristics (age, gender, median number of prior therapies, and WHO performance status) were similar between the 2 studies; however, more pts in the MDACC study were Rai Stage III-IV (50% vs 22%) and were rituximab-naïve (88% vs 40%). Furthermore, there were no obvious differences in hematologic toxicity between the 2 studies and the tolerability of L + FCR was similar to that of FCR, with approximately 50% percent of pts completing 6 cycles of treatment in both studies. These data suggest that L + FCR may produce a higher complete response rate than FCR without additional toxicity. Based upon this data, a multicenter, global, randomized study of L + FCR vs. FCR alone is being initiated.
Table 1. Comparison of Responses in Study 152–30 and the MDACC Study Study 152–30, L + FCR (N=31), n (%) MDACC, FCR (N =177), n (%) 1CR and PR response criteria were the same in both studies. 2PRu is included in the OR. Overall Response 22 (71%) 130 (73%) Complete Response1 15 (48%) 45 (25%) Partial Response1 3 (10%) 85 (48%) Unconfirmed Partial Response2 4 (13%)