bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are There Two Distinct Mechanistic Pathways That Explain the Varying Clinical Presentations, Laboratory Findings, and Outcomes of Thienopyridine-Associated Thrombotic Thrombocytopenic Purpura (TTP)?.
Authors: Kim Benjamin , Carson Kenneth R. , McCaffrey Kathryn , Finley Denise , Zakarija Anaadriana , Bandarenko Nicholas , Pandey Dilip K. , Raisch Dennis W. , Kwaan Hau C. , Yarnold Paul R. , Bennett Charles L. 
Published: October 2019

Abstract
Introduction: The antiplatelet agents ticlopidine and clopidogrel are thienopyridine derivatives that are commonly used for secondary prevention of cerebrovascular events, prevention of coronary artery stent thrombosis, and for treatment of acute coronary syndrome. While these chemically related agents are the first and third most common causes of drug-associated TTP respectively, clinical presentations, laboratory findings, and outcomes suggest that there may be two distinct mechanistic pathways.
Methods: Clinical and laboratory data for 60 cases of ticlopidine-associated TTP and 35 cases of clopidogrel associated TTP were reviewed.
Results: Type 1 thienopyridine-associated TTP, characterized by onset of disease > 5 days after drug initiation, occurred in 98% of the ticlopidine patients versus 63% of the clopidogrel patients. Laboratory studies identified severe deficiency of ADAMTS13 activity and the presence of IgG inhibitors in 7 ticlopidine (Tsai, et al.; Annals of Internal Medicine, 2000) and 2 clopidogrel (Bennett, et al.; NEJM, 2000) patients. Survival was 68% in the ticlopidine patients versus 91% in the clopidogrel patients. Type 2 thienopyridine-associated TTP, consisting of TTP onset within 5 days of drug initiation, occurred in 2% of the ticlopidine patients versus 37% of the clopidogrel patients. Laboratory studies failed to identify deficient ADAMTS13 activity or the presence of IgG inhibitors in 1 clopidogrel patient (Zheng, et al.; Blood, 2004). Survival was 0% in the ticlopidine patients versus 38% in the clopidogrel patients.
Conclusion: The proposed type 1 and type 2 thienopyridine-associated TTP may be distinguished on the basis of clinical presentation, ADAMTS13 levels, and outcome. Type 1 thienopyridine-associated TTP—characterized as occurring after > 5 days of thienopyridine treatment, severely deficient ADAMTS13 activity and presence of IgG inhibitors, and high survival rates with plasmapheresis—is more likely to occur in patients receiving ticlopidine. Type 2 thienopyridine-associated TTP—characterized as occurring within 5 days of thienopyridine therapy initiation, normal ADAMTS13 activity and undetectable IgG inhibitors, and poor survival rates despite plasmapheresis—is more likely to occur in patients receiving clopidogrel. Additional confirmatory studies on larger numbers of patients are needed.
Autologous Transplant Event-Free Survival (EFS) Following Failure of CHOP-Rituximab (CHOP-R) for Diffuse Large B-Cell Lymphoma (DLBCL) Is the Same as the EFS Following Failure of CHOP Alone.
Authors: Vose Julie M. , Bierman Philip J. , Lynch James C. , Bociek Gregory , Armitage James O. 
Published: October 2019

Abstract
Several studies have now identified that the addition of rituximab (R) to CHOP chemotherapy has increased the complete response, EFS, and overall survival (OS) for patients with previously untreated DLBCL. However, concerns of increased resistance of DLBCL following failure of CHOP-R and the inability to salvage those patients with high-dose chemotherapy and autologous stem cell transplantation have been raised. In an attempt to address this issue, we evaluated 103 patients with high risk, relapsed, or refractory DLBCL receiving high-dose chemotherapy and autologous stem cell transplantation at our center between 1999 and 2003. Fifty-six (54%) of the patients received CHOP as their initial induction therapy and 47 (46%) received CHOP-R. The patients ranged in age from 20–73 years (median 50). Sixty patients were male and 43 female. Sixty two of the patients were transplanted < 12 months from diagnosis and 41 were transplanted ≥ 12 months from diagnosis. The patients had received a median of 2 prior therapies (range 1–4). The majority (81%) were chemotherapy sensitive at the time of transplantation. The median follow-up of surviving patients is 27 months ( range 3–74). All patients received a BEAM (C) - based regimen [carmustine, etoposide, cytarabine, melphalan or cycylophosphamide] +/− anti-CD20 monoclonal antibodies. There was no difference in the 2-year EFS for patients failing CHOP vs. CHOP-R (60% vs. 68%, p=0.49). In addition, there was no difference in the 2-year overall survival (OS) of patients failing CHOP vs. CHOP-R (72% vs. 68%, p=0.63). In a multivariate analysis, the only factor predicting for an event (relapse or death) post-transplant was having received ≥ 2 prior chemotherapies (Relative Risk (RR) 7.5, p=0.048) and predicting for death from any cause was chemotherapy resistance (RR 2.5, p=0.037) and an increased lactic dehydrogenase at transplant (RR 4.1, p=0.002). The additional use of a monoclonal antibody with the transplant regimen did not significantly impact outcome in this analysis. This study demonstrates that patients with DLBCL failing CHOP-R are able to be salvaged with high-dose chemotherapy and autologous stem cell transplantation and have a similar 2-year EFS and OS as patients being transplanted following CHOP failure.
Hematopoietic Stem Cell Transplant (HSCT) as Primary Treatment for T-Cell Lymphobastic Lymphoma (T-LBL) : An Intention to Treat Analysis.
Authors: Song Kevin W. , Nevill Thomas J. , Gascoyne Randy D. , Toze Cynthia L. , Barnett Michael B. , Forrest Donna L. , Hogge Donna E. , Lavoie Julye C. , Nantel Stephen H. , Shepherd John D. , Smith Clayton A. , Sutherland Heather J. , Voss Nicholas J. , Connors Joseph M. 
Published: October 2019

The role of HSCT for T-LBL is not well defined. Most series are subject to referral bias and do not address the true impact of HSCT, especially as primary treatment. Since 1987 all patients in British Columbia with T-LBL have been considered eligible for HSCT as part of primary treatment. Between 6/87–12/03, 27 patients were diagnosed with T-LBL. Patients with > 25% involvement of the bone marrow were excluded.
Characteristics: Age range 18–56 y (median 26); M:F 19:8; Ann Arbor stage I-II 6; III-IV 21; bone marrow involved 7/27; peripheral blood involved 2/27; CNS involved 1/27; LDH elevated 15/25; mediastinal mass 23/27.
Initial treatment: All received an anthracycline-containing regimen similar to CHOP. All achieved at least a partial remission.
HSCT: 23/27 (85%) proceeded to HSCT in first response.
Source of stem cells: 4, related donor (2 marrow, 2 peripheral blood); 19, autologous (15, mafosphamide purged marrow; 1, 4-hydroperoxy-cyclophosphamide purged marrow; 1, unpurged marrow; 1, unpurged peripheral blood; 1, combined unpurged marrow and peripheral blood). Conditioning was cyclophosphamide (150 mg/kg) and TBI (750–1200 cGy) +/− etoposide 1.8 g/m2 in 22 of 23 patients. CNS prophylaxis with intrathecal methotrexate and cytarabine was planned for all patients. All 23 had maintained chemosensitivity at time of HSCT. Time from diagnosis to HSCT was 1.3–6.4 months (median 2.2). Reasons for not proceeding to HSCT 2 refused; 1 decided to wait until relapse; 1 did not have adequate organ function. Median follow-up of living patients was 33 months (range 4–142 months).
Results: Overall survival (OS) and event free survival (EFS) at 3 years for all patients were 79% (95% CI 61–97%) and 75% (95% CI 57–93%); patients who underwent HSCT 85% (95% CI 70–100%) and 81% (95% CI 64–98%). 4 patients relapsed post HSCT at 2.2, 10.8, 11.7 and 40.4 months post HSCT.
Sites of relapse: 2, mediastinum; 1, bone marrow; 1, mediastinum and bone marrow. One patient who received HSCT died of a treatment related complication (interstitial pneumonitis). Significant factors for improved survival post HSCT (univariate): Absence of bone marrow involvement [EFS at 3 years 92% vs 57% (p=0.026)].
Non-significant factors: normal LDH, stage I/II at diagnosis, age < 30 yrs.
Conclusions: Patients with T-cell lymphoblastic lymphoma treated with a CHOP-like regimen achieve adequate control of disease to proceed to HSCT. HSCT as primary treatment results in excellent long-term disease free survival with acceptably low treatment related mortality. Bone marrow involvement at diagnosis, even though < 25%, predicts for a worse outcome.
Front-Line High-Dose Chemotherapy (HDT) Combined with Rituximab for Adults with Aggressive Large B-Cell Lymphoma (DLBCL) : Goelams 074 Trial.
Authors: Milpied Noel-Jean , Lamy Thierry , Casassus Philippe , Deconninck Eric , Gressin Remy , Maisonneuve Herve , Le Maignan Christine , Ramee Jean-Francois , Tournilhac Olivier , Dugay Jacqueline , Legouffe Eric , Delwail Vincent , Colombat Philippe 
Published: October 2019

Abstract
Background: The beneficial effect of adding rituximab to CHOP has been shown for elderly patients with DLBCL (Coiffier et al, N.E.J.M 2002). We have shown that HDT with autologous stem cell transplantation is superior to CHOP in young adults with DLCL ( Milpied et al GOELAMS 072 trial, N.E.J.M 2004). The feasibility of adding rituximab to front-line HDT remains to be established.
Methods: A prospective pilot trial was proposed to patients with DLBCL, with intermediate-high or high adjusted IPI, up to the age of 60 y.o. This program consisted of 2 courses of high-dose CHOP-like regimen, 15 days apart, with rituximab (375/mg/m2) on day 1 of each course, followed by rituximab on d 22, harvest of G-CSF mobilised peripheral blood stem cells on d 28,29, then rituximab on d 36 followed by a course of high-dose methotrexate with cytarabin. For patients who achieved at least a PR after these 3 courses, a BEAM regimen started on d 66 to 80 followed by the infusion of stem cells.
Results: Between 04/2002 and 05/2003, 42 pts gave their informed consent and were included in that trial. Median age was 50 y.o (18–60 y.o), 23 had WHO PS ≥ 2, the LDH level was >N in 41 pts and 38 had stage III or IV disease. The age-adjusted IPI was intermediate-high in 23 and high in 19 pts. The program was completed in 30 pts (71%), 3 pts died of toxicity before the BEAM regimen, 8 pts failed to achieve at least a PR after the first 3 courses and 1 refused the autologous transplant. On an intent-to-treat basis, the response rate at the end of the treatment was CR/Cru=64%, PR=7%, less than PR or progression= 22% and toxic death=7%. No toxic death was directly attributable to the addition of rituximab. With a median FU of 19 m, the KM 2y probability of OS and EFS are 79% and 59% respectively, these figures compare to those achieved without rituximab in the previous trial as shown on the table:
Conclusion : The addition of 4 doses of rituximab to this HDT program is feasible with no unexpected toxicity, allows the harvesting of sufficient numbers of stem cells to support an autologous transplant with a BEAM regimen in responding patients. This treatment is now being randomly prospectively compared with CHOP-14-rituximab in youg adults with DLBCL (Goelams 075 trial).Supported in part by Roche which kindly provided rituximab for that trial and by DRC Nantes programme N°:02/2N 2002.
GOELAMS 072 (IPI 2 only) GOELAMS 074 (IPI 2–3) 2y OS 80% 79% 2y EFS 60% 59%
Autologous Stem Cell Transplantation as First Line Therapy in Peripheral T Cell Lymphomas. Update of a Prospective Multicenter Study.
Authors: Reimer Peter , Ruediger Thomas , Schertlin Tobias , Geissinger Eva , Weissinger Florian , Mueller-Hermelink Hans Konrad , Wilhelm Martin 
Published: October 2019

Abstract
Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of non-Hodgkin’s lymphomas, which in general show a poor outcome following conventional chemotherapy. Long-term remissions are achieved in only 15 to 35 %. However, the impact of more aggressive therapeutic approaches such as myeloablative therapy with autologous stem cell transplantation (ASCT) as first line therapy is poorly defined mainly due to the lack of prospective PTCL-restricted studies. In 6/00 we initiated the first prospective PTCL-restricted multicenter study of myeloablative radiochemotherapy in primary diagnosed PTCL. The results of the first 30 patients (pts) are in press. We update our data on all pts entering the study.
Study design: Pts < 65 years with PTCL of all subtypes without primary cutaneous lymphoma and ALK1 expressing anaplastic large cell lymphoma were included. Treatment consisted of 4–6 courses of CHOP protocol followed by DexaBEAM or ESHAP regimen and collection of stem cells. Subsequently pts underwent total body irradiation (TBI) and high dose cyclophosphamide chemotherapy (60 mg/kg body weight) with ASCT.
Patient characteristics: From 6/00 to 8/04 65 pts (42 male) with a median age of 50 years were enrolled. Main subtypes were Peripheral T-cell lymphoma not otherwise specified (NOS, n= 26) and Angioimmunioblastic T-cell lymphoma (AILT, n= 19). According to the Ann Arbor classification, 81% of the pts had stage III/IV disease. The International Prognostic Index (IPI) was low/low intermediate in 54% and intermediate high/high in 46% of the pts, respectively.
Results: So far 54 of 65 pts are eligible for evaluation, while the remaining 11 pts are still under therapy. Thirty-three pts could be transplanted (61%). After a median follow up of 10 months after transplantation 22 pts (67%) are in sustained remission and 8 pts (27%) had relapsed. Post transplantation two pts died treatment-related (one secondary AML, one multiorgan failure). Twenty-one pts (39%) did not proceed to ASCT mainly due to progressive disease (n= 16). Treatment-related toxicity was comparable to other high-dose studies in malignant lymphomas.
Conclusion: Our data show feasibility and efficacy of first-line ASCT following myeloablative radiochemotherapy in PTCL. Sustaining remission seems achievable for a majority of pts. However, additional treatment strategies are required to prevent early progression prior myeloablative therapy. Longer follow-up is necessary to confirm long-term remission rate.
Time-Dependent Effect of Non-Hodgkin’s Lymphoma Grade on Disease Free Survival (DSF) of Relapsed/Refractory Patients Treated with High-Dose Chemotherapy (HDC) Plus Autologous Hematopoietic Stem Cell Transplant (AHSCT).
Authors: Fu Pingfu , Van Heeckeren Willem J. , Wadhwa Punit D. , Bajor David J. , Creger Richard J. , Cooper Brenda W. , Laughlin Mary J. , Lazarus Hillard M. , Gerson Stanton L. , Koc Omer N. 
Published: October 2019

Abstract
HDC and AHSCT is an effective treatment option for patients with relapsed or refractory NHL. The outcome of this treatment depends on the histological grade (indolent versus aggressive) with a well documented time dependent difference in temporal relapse pattern. We developed statistical models to describe the time dependent outcome after AHSCT based on histologic grade and other variables. During January 1993 to December 2003, 114 relapsed or refractory NHL patients were treated at single institution using high-dose BCNU 600 mg/m2, etoposide 2400 mg/m2, and cisplatin 200 mg/m2 IV over 5 days and AHSCT. Median age was 53.5 (range: 25–70) years, 78 patients had aggressive NHL and 36 indolent NHL. Immediately before transplant, 75 patients received involved-field radiotherapy (IFR) to sites of prior bulky (> 5 cm) disease. Twenty-seven patients had mobilized stem cell transplant (13 with in vivo purging and 14 with ex-vivo purging). At a median follow up of 33 (range: 3 to 118) months, the estimated 5 year Kaplan-Meier probabilities of overall survival (OS) and DSF were 61% and 51%, respectively. DFS was similar up to about 1.2 years between indolent and aggressive NHL (Figure 1). DFS of the group who had purged stem cells was improved marginally over non-purged group. Cox proportional hazards model was used to adjust for differences in baseline characteristics between grades that might affect DFS. The proportionality assumption of Cox model was tested by adding a time-dependent covariate for each variable. This showed that the proportionality did not hold for lymphoma grade, indicating the relationship between the grade and DFS differed over time. The results of piece-wise Cox model after controlling age, IFR, purging status indicate there was no difference of DFS between the grade groups up to 1.2 years (optimal cut-off point) post-transplantation (p = 0.748). However, the relative risk for experiencing relapse after 1.2 year in patients with indolent compared with patients with aggressive NHL was 4.22 (p = 0.006) with 95% confidence interval (1.5, 11.9). Our results statistically prove the previously described biological differences in outcomes of patients with indolent and aggressive NHL following HDC. The time-dependent effect of lymphoma grade on DFS indicates the need for early (within first year) incorporation of novel therapeutic approaches, such as post-transplant immunotherapy, tandem high-dose therapy and, allogeneic transplant to generate graft-versus-lymphoma effect, in management of patients with indolent NHL undergoing autologous transplantation.
Figure 1: DFS by tumor grade. Figure 1: DFS by tumor grade.
Lack of Prognostic Implications of Induction Response to Total Therapy 2 (TT-2) in Newly Diagnosed Patients with Multiple Myeloma (MM) for Post-Transplant Even-Free Survival (EFS) and Overall Survival (OS).
Authors: Tricot Guido , Crowley John , Stover Julie , Milner Teresa , Fassas Athanasios , Zangari Maurizio , Thertulien Raymond , Anaissie Elias , van Rhee Frits , Talamo Giampalamo , Hollmig Klaus , Barlogie Bart 
Published: October 2019

Abstract
Between October 1998 and February 2004, a total of 668 recently diagnosed myeloma patients were enrolled in TT-2, of whom 566 completed the first and 417 the second autotransplant. Twenty percent of patients were ≥ 65 years of age and 34% had abnormal metaphase cytogenetics; 24% had received a single cycle of chemotherapy prior to enrollment and 32% had a B2 microglobulin level of ≥ 4mg/L. All patients who completed at least the first transplant could be assessed for response to induction therapy consisting of VAD, DCEP, CAD and DCEP given with hematologic growth factor support at 4 to 5 week intervals. We examined whether the quality of induction response had an impact on event-free (EFS) and overall survival (OS). Responses were defined as complete remission (CR) if serum and urine immunofixation were negative with normal bone marrow plasmacytosis in aspirate and biopsy; partial remission (PR) if serum M protein was reduced by ≥ 75% and urine M-protein ≥ 90% with a normal bone marrow plasmacytosis and < PR for all other responses. Superior EFS (p=.04) and OS (p=.06) from first transplant were observed among the 86 CR patients (15%) with a 4-year estimate of EFS of 69% and OS of 83%, compared with 59% and 72%, respectively, for PR patients (N=214) and 52% and 68%, respectively, for < PR patients (N=266) (Figure 1 and 2). With a median follow-up of 3 years from the first transplant, we conclude that, although a stringently-defined CR after induction therapy resulted in a better EFS and OS, there was no difference in outcome between PR and < PR patients, who had virtually super imposable survival curves. These data, as well as a review of the literature (Vesole et al. Blood1994; 84: 950, Alexanian et al. Blood1994, 84: 4278 and Singhal et al. Bone Marrow Transplant2002, 30: 673) provide a strong argument for change in current Medicare policy, which denies autotransplants to myeloma patients who have failed primary induction therapy. Even with intensive induction therapy as applied in TT-2, more than two-thirds of patients achieving < PR prior to the first transplant are projected to be alive at 4 years after their autotransplant.
Figure Figure Figure Figure
Angiotensin-I Converting Enzyme Inhibitors and the Survival of Patients with Multiple Myeloma Treated by Autologous Stem Cell Transplantation.
Authors: Buchler Tomas , Krejci Marta , Svobodnik Adam , Adam Zdenek , Minarik Jiri , Bacovsky Jaroslav , Scudla Vlastimil , Mayer Jiri , Vorlicek Jiri , Hajek Roman 
Published: October 2019

Abstract
Introduction:
The aim of our study was to analyze the impact of angiotensin-I converting enzyme inhibitors (ACEI) on the outcome of patients with multiple myeloma (MM) treated by autologous peripheral blood stem cell transplantation (APBSCT), as it has been reported that low angiotensin-converting enzyme (ACE) activities are associated with poor prognosis in multiple myeloma (MM).
Patients and Methods:
Patients with MM who underwent APBSCT (n=168) were studied retrospectively. Patients taking ACEI alone or in combination with other antihypertensive agents during the APBSCT were allocated to the ACEI group (n=25; 15%). The ACEI group was compared both to all other patients (n=143; 85%) and to patients with hypertension who were taking other or no antihypertensive medication (n=44). The induction chemotherapy consisted of 4 cycles of VAD. For stimulation, cyclophosphamide was given, followed by G-CSF. High-dose melphalan was used as conditioning.
Results:
The ACEI and non-ACEI groups were similar in terms of age, initial levels of albumin, beta2-microglobulin, CRP, LDH, performance status, stage according to IPI and Durie-Salmon criteria, myeloma type, and maintenance treatment. Patients with hypertension (n=69) and patients without hypertension (n=99) had similar overall survival (OS) after APBSCT (65.5 months versus 60.9, respectively; p=0.561), and progression-free survival (PFS) after APBSCT (32.6 months versus 29.6 months; p=0.635). Patients taking ACEI had significantly worse OS after APBSCT (32.7 months) compared to patients not taking ACEI (65.2 months; p=0.033). Among patients with hypertension, OS was significantly shorter in the ACEI group than in the non-ACEI patients (p=0.024). Statistically significant differences were also observed in PFS between hypertensive patients treated by ACEI and other hypertensive patients (19.3 months versus 48.6 months, respectively; p=0.041). Most deaths in both groups were myeloma-related. Renal failure was a main or contributing cause of death in 3 patients from the ACEI group and in 8 patients from the non-ACEI group (p=0.233). Also, there was a trend favoring non-ACEI hypertensive patients in comparison to ACEI hypertensive patients in the number of complete responses after PBSCT (40% versus 17%; p=0.058).
Conclusion:
In this retrospective study we have found that patients with MM and hypertension treated with ACEI at APBSCT have worse survival in comparison to patients with MM receiving other or no antihypertensive drugs. Further research in this area could lead to important insights into the pathophysiology of MM and to the reevaluation of ACE activity as a prognostic factor in MM.