bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autologous and allogeneic transplantation for aggressive T-cell lymphomas: A single institution experience
Authors: Lansigan F. , Cooper D. , Seropian S. , Foss F. 
Published: August 2020

8558 Aggressive T-cell lymphomas (ATCL) represent 10–15% of non-Hodgkin lymphoma and have a worse prognosis than aggressive B-cell lymphomas. Both autologous (Auto) and allogeneic (Allo) stem cell transplantation have been used as consolidation in first remission and at relapse, but the role of transplantation has not been clearly defined. There were 24 Auto and 18 Allo between 8/1997 and 12/2007. The Allo group consisted of 4 PTCLu, 3 angioimmunoblastic(AITL), 2 panniculitis-like, 2 cutaneous(CTCL) with large cell transformation, 2 NK-cell, 2 anaplastic large cell(ALCL), 1 hepatosplenic, 1 enteropathic, and 1 refractory CTCL. The Auto group consisted of 6 PTCLu, 12 ALCL (5 Alk+, 5 Alk-, 2 Alk unk), 4 AITL, 1 CTCL with transformation, and 1 T-lymphoblastic lymphoma. The median age was 51y(Allo) and 52y(Auto). Median prior therapies were 3(Allo) and 1(Auto). There were 14 matched- and 4 matched-unrelated Allo transplants; 7 were ablative and 11 were reduced-intensity. Median time from diagnosis to Allo or Auto was 18 and 8mo, respectively. Median follow-up was 29mo (Allo) and 24mo (Auto). The day 100 TRM was 11%(Allo) and 4%(Auto) respectively. The relapse mortality was 11%(Allo) and 33%(Auto). The non-relapse mortality was 33%(Allo) and 8%(Auto). The 1- and 2-year overall survival(OS) rates were similar within the Allo and Auto groups (78% vs 74%, and 67% vs 60% respectively). The 1- and 2-year progression-free survival (PFS) for the Allo vs Auto groups were 68% vs 52%, and 53% vs 45%, respectively (p=0.28). Within the Auto group, 14(58%) were transplanted in first complete remission(CR1), and 10(42%) in CR2, beyond CR2, or PR. Patients in CR1 had significantly better PFS (57 vs 17mo, p=0.007) and OS (76 vs 29mo, p=0.004) than those in CR2, beyond CR2, or PR. Allo patients with prior Auto(6) had a poorer OS than patients with no prior Auto(12), 32 vs 60mo, respectively, but the results were not statistically significant, p=0.15. One Allo was transplanted in CR1 and is still alive at 33mo. We conclude that outcomes for Auto are best in CR1. For patients with resistant or relapsed disease, Allo should be strongly considered rather than Auto. These results also suggest that a prospective randomized trial comparing Auto and Allo for ATCL in first remission is warranted. No significant financial relationships to disclose.
A phase II trial of gemcitabine, ifosfamide, dexamethasone, and oxaliplatin (GIDOX) for patients with refractory or relapsed non-Hodgkin's lymphoma
Authors: Park B. , Kim W. , Eom H. , Kim J. , Oh S. , Suh C. 
Published: August 2020

8559 Background: Gemcitabine combined with cisplatin has been known as an effective regimen for lymphoma treatment in salvage setting. However, this regimen has the modest response with severe nephrotoxcity and neurotoxicity, especially to heavily treated patients. We investigated the response rate and toxicity of gemcitabine, ifosfamide, dexamethasone, and oxaliplatin (GIDOx) for recurrent or refractory aggressive B-cell non-Hodgkin lymphoma (NHL), looking for the more effective and less toxic therapy. Methods: Patients with recurrent or refractory diffuse large B-cell NHL or mantle cell lymphoma, measurable disease, and more than one previous chemotherapy regimen were eligible. Treatment consisted of gemcitabine 1000 mg/m2 intravenously (i.v.) on Days 1 and 8, ifosfamide 2000 mg/m2 i.v. on Day 1, dexamethasone 40 mg orally on Days 1–4, and oxaliplatin 130mg/m2 i.v. on Day 2, every 21 days. The primary end point was a response after three cycles. Patients could then proceed to stem cell transplantation (SCT) or receive up to six treatment cycles. Results: Twenty-seven eligible patients were evaluable for toxicity and response. The median age of the patients was 54 years (range, 18–75 years) and most had diffuse large-cell lymphoma. After 3 cycles, there were 4 complete responses (CR; 15%) and 10 partial responses (PR; 37%). There was an overall response rate (RR) of 52%. The RR after completion of all protocol chemotherapy including SCT was 44% (10 CR, 2 PR). In total 88 cycles of GIDOx, grade 3 and 4 neutropenia occurred in 33% and 16% of cycles, respectively. Grade 3 and 4 thrombocytopenia occurred in 14% and 16% of cycles, respectively. Tow patients (2%) experienced febrile neutropenia. Seven patients (26%) proceeded to SCT. Conclusions: GIDOx is an active salvage regimen in aggressive B-cell NHL and can be administered with acceptable toxicity. No significant financial relationships to disclose.
Efficacy of lenalidomide oral monotherapy in relapsed or refractory indolent non-Hodgkin's lymphoma: Final results of NHL-001
Authors: Witzig T. E. , Wiernik P. H. , Moore T. , Reeder C. , Cole C. , Justice G. , Kaplan H. , Voralia M. , Pietronigro D. , Vose J. M. 
Published: August 2020

8560 Background: Lenalidomide has shown activity in a wide range of hematological malignancies. We conducted a phase II trial of single-agent lenalidomide in indolent non-Hodgkin's lymphoma (NHL). Methods: Patients with relapsed or refractory indolent NHL were eligible, with no limit on the number of previous therapies. Oral lenalidomide 25 mg was self-administered once-daily on days 1–21 of every 28-day cycle for up to 52 weeks as tolerated, or until disease progression. The primary endpoint was overall response rate (ORR), with secondary endpoints of response duration, progression-free survival (PFS), and safety. Results: Forty-three patients were enrolled and were evaluable for response and safety. Patients had received a median of 3 prior systemic therapies (1–17) and half of all patients were refractory to their last therapy. The ORR was 23% (10/43), including a complete response (CR) or unconfirmed CR (CRu) rate of 7%. The median time to first response was 3.6 months (1.7–4.2) and the median time to CR or CRu was 4.2 months (1.9–11.1). Twenty-seven percent (6/22) of patients with follicular lymphoma grade 1 or 2, and 22% (4/18) of patients with small lymphocytic lymphoma responded to therapy. The median duration of response has not reached, but is longer than 16.5 months with 7 of 10 responses ongoing at 15–28 months. Median PFS was 4.4 months (2.5–10.4). Adverse events were consistent with the known safety profile of lenalidomide and manageable; the most common grade 3 or 4 adverse events were neutropenia (30% and 16%, respectively) and thrombocytopenia (14% and 5%, respectively). Conclusions: Oral lenalidomide monotherapy produces durable responses with manageable side effects in relapsed or refractory indolent NHL and warrants further investigation in the treatment of indolent NHL. [Table: see text]
Vorinostat in combination with bexarotene in advanced cutaneous T-cell lymphoma: A phase I study
Authors: Dummer R. , Hymes K. , Sterry W. , Steinhoff M. , Assaf C. , Kerl H. , Ahern J. , Rizvi S. , Ricker J. L. , Whittaker S. 
Published: August 2020

8572 Background: Vorinostat, a histone deacetylase inhibitor, is registered for the treatment of advanced cutaneous T-cell lymphoma (CTCL) in the US. Preclinical studies suggest that vorinostat may enhance the activity of chemotherapeutic or biological anticancer agents in a variety of cancers. This Phase I, multicenter, open-label study systematically evaluated vorinostat combined with the retinoid bexarotene in patients (pts) with advanced CTCL. Methods: Eligible pts were aged ≥18 years with stage ≥IB progressive, persistent, or recurrent CTCL refractory to ≥1 systemic therapy. Primary objective was to determine the maximum tolerated dose (MTD). Phase Ia Part I: dose escalation of vorinostat (200–400 mg/day) and bexarotene (150–300 mg/m2/day); Part II: fixed vorinostat dose (400 mg/day) with bexarotene dose escalation (150–450 mg/day). Cycles were repeated every 28 days for ≤6 cycles. Clinical activity and safety of the combination was also assessed. Results: 23 pts received ≥1 dose of study medication. Three pts in dose level (DL) 2 experienced dose-limiting toxicities (DLTs) ( Table ). No DLTs were observed in the first cycle of DL 2a and 2b. The MTD (Part I) was vorinostat 200 mg/day plus bexarotene 300 mg/m2/day. The Part II MTD was not reached as the study was discontinued early due to low enrollment; no DLTs were observed at DL 6 or 7. The most common drug-related adverse events (DRAEs) were hypothyroidism (35%), fatigue (30%), and hypertriglyceridemia (30%). No Grade 4 or 5 DRAEs were reported and 4 pts had serious DRAEs (Grade ≤3). Eighteen pts have discontinued: 5 due to AEs, 5 due to progressive disease, and 8 withdrew consent. Of 22 pts evaluable for efficacy, 4 (18%) had an objective response, and 7 (32%) derived clinical benefit (pruritis relief). Conclusions: These preliminary data suggest that the vorinostat/bexarotene combination is feasible in pts with advanced CTCL; however, the dosage of either drug must be reduced to avoid unacceptable side effects. [Table: see text] [Table: see text]
Analysis of prognostic factors in patients with adult T-cell leukemia/lymphoma
Authors: Beltran B. E. , Morales D. , Quiñones P. , Salas R. , Castillo J. 
Published: August 2020

8575 Background: Adult T-cell leukemia/lymphoma (ATLL) is associated with human T-cell lymphotropic virus type-I (HTLV-1) described in Southern Japan, Europe, Caribbean and South America. Risk-stratification tools for ATLL have not been adequately evaluated. This study attempts to define prognostic factors for patients with ATLL. Methods: A total of 102 cases from our Institution were collected between January 1997 and September 2008. Diagnosis was based on clinical history and histological findings consistent with ATLL and either positive HTLV-1 serology or evidence of HTLV-1 integration. Survival curves were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were evaluated using log-rank and Cox regression tests, respectively. Results: Median age was 61 years with a female:male ratio of 1.15:1. Clinical types were acute (n=45), lymphomatous (n=43), cutaneous (n=10), smoldering (n=3) and chronic (n=1). Median OS for acute, lymphomatous, smoldering and cutaneous subtype were 2, 11, 17 and 39 months, respectively (log-rank 28.5, p<0.00001). In the univariate analysis, presence of B symptoms, ECOG performance status 2, clinical stage II or higher, elevated LDH level and bone marrow (BM) involvement were independent factors for survival with p<0.05. The IPI score was available in 92 patients; 13 (14%), 12 (13%), 29 (32%) and 38 (41%) patients were low, low-intermediate, high-intermediate and high-risk, respectively. Median OS by IPI risk group was 40, 13, 6 and 2 months, respectively (p<0.005). The prognostic index for T-cell lymphoma (PIT) score was determined in 80 patients; 20 (25%), 17 (21%), 33 (41%) and 10 (13%) patients had scores of 0–1, 2, 3 and 4, respectively. Median OS by PIT risk group was 19, 5, 3 and 2 months, respectively (p<0.005). In multivariate analysis, BM involvement and elevated LDH were significant for survival. Conclusions: This retrospective series represents the largest Latin-American experience on ATLL, which is a heterogeneous disease with distinct clinical features and outcomes. The IPI ant PIT scores, used for risk-stratification of aggressive B-cell and peripheral T-cell lymphomas, respectively, appear as good prognostic indicators for ATLL as well. Further research is needed to better risk-stratify this unique lymphoma. No significant financial relationships to disclose.
Bortezomib plus modified R-CHOP as initial therapy for indolent B-cell lymphomas: Phase I results
Authors: Flowers C. , Sinha R. , Kaufman J. , Shenoy P. , Lewis C. , Bumpers K. , Rogatko A. 
Published: August 2020

8577 Background: Adding rituximab (R) to chemotherapy improves survival for patients (pts) with follicular lymphoma (FL) and other indolent non-Hodgkin lymphomas (NHL), but not all pts respond. Bortezomib (B) + RCHOP has a high complete response (CR) rate, but higher doses of B with standard vincristine produced severe neuropathy. We developed a phase I/II trial to test if adding B to RCHOP with modified vincristine dosing can be well-tolerated and yield a high CR rate. Methods: Untreated pts with indolent NHL and indications for treatment based on GELF criteria or FLIPI ≥3 received R 375mg/m2, cyclophosphamide 750mg/m2, doxorubicin 50mg/m2, vincristine 1.4mg/m2 (capped at 1.5mg) on day 1, B 1.0- 1.6mg/m2 days 1 and 8, and prednisone 100mg days 1–5 for 6–8 cycles. The maximum tolerated dose (MTD) was defined as the regimen at which <30% grade ≥3 non-hematological or grade ≥4 hematological toxicity (>14 days) occurs. Dose escalation used the Escalation with Overdose Control Bayesian method with upper bound (θ=0.3). This facilitated MTD finding with fewer pts given prior data on B+RCHOP. Functional Assessment of Cancer Therapy (FACT) Neurotoxicity (11-item; 4 point scale), EMG, nerve conduction velocity and epidermal nerve fiber density measures were taken at baseline and after cycle 4. Results: 11 pts with FL (n=6) or other indolent NHL enrolled in phase I. Median age was 59 years (range 29–69). 6 pts (55%) had stage IV disease; 8 (64%) had FLIPI ≥2. Pts received RCHOP + B at 1.0 mg/m2 (n=1), 1.3 mg/m2 (n= 6) or 1.6 mg/m2 (n= 4) and together completed 67 cycles. Treatment was well tolerated. Neuropathy occurred in 4 pts (36%), with 2 grade 1, 1 grade 2 and 1 grade 3 toxicity ( Table ). Grade 4 neutropenia occurred in 4 pts (36%), but none >14 days. Overall response rate was 100% with 5/8 finished pts (63%) achieving CR. 3 continue on treatment. Mean FACT Neurotoxicity after cycle 4 remained < 1 for all items. Conclusions: Adding bortezomib to RCHOP produces limited toxicity when vincristine is capped at 1.5 mg. Phase II will explore the efficacy of this regimen. [Table: see text] [Table: see text]
Prognostic value of stringent complete response (sCR) post-autologous stem cell transplant (SCT) in multiple myeloma (MM)
Authors: Kapoor P. , Kumar S. , Dispenzieri A. , Lacy M. Q. , Hayman S. R. , Buadi F. K. , Dingli D. , Greipp P. R. , Rajkumar S. V. , Gertz M. A. 
Published: August 2020

8587 Background: The measurement of serum immunoglobulin free light chains (FLC) has diagnostic and prognostic utility in MM. Normalization of the FLC ratio may define a deeper complete response after therapy than by standard criteria of CR. A sCR requires normalization of the FLC ratio and absence of clonal plasma cells in the bone marrow (BM) in addition to the standard criteria for CR. The objective of our study was to evaluate the impact of specific types of CR [sCR, CR or near CR (nCR/ immunofixation positive CR)] post-SCT on time to progression (TTP) and overall survival (OS). Methods: 468 MM patients who had achieved at least a partial response post-SCT were studied. The results of serum and urine protein studies, serum FLC assay, and BM evaluation, including measurement of marrow plasma cell clonality by immunohistochemistry obtained ≥60 days after SCT were used to determine the best response. TTP was defined as the time from SCT to progression, with non-myeloma related deaths censored. Results: 179 patients achieved varying degrees of CR as their best response. 39, 35 and 105 patients achieved nCR, CR and sCR, respectively. The median estimated follow-up for the entire cohort was 52 months from the diagnosis and 41 months from SCT. The median TTP was 15, 29 and 35 months for patients achieving nCR, CR and sCR, respectively (P<0.0001). The median OS for patients achieving nCR was 53 months from the diagnosis, but not reached for those with a CR or sCR (P=0.0009). The 5-year OS was 80% and 79% for patients with CR and sCR, respectively (P=NS). Similarly, OS from SCT was significantly shorter in patients achieving nCR (42 months vs. not reached for patients in CR and sCR; P<0.001). Conclusions: Achievement of a sCR represents a deeper response state compared to conventional CR, translating to a longer response duration post SCT, validating its inclusion in the modified uniform response criteria. While we did not see a significant improvement in OS with sCR compared to CR in this group, this question needs to be addressed in a larger study. The step wise improvement in the response duration across nCR, CR and sCR highlights the contribution of immunofixation studies, marrow assessment of clonality and FLC estimates. [Table: see text]
Gene expression profiling (GEP)-defined risk and molecular subgroups assessed at baseline and at relapse: Collective impact on post-relapse survival of multiple myeloma (MM) treated with total therapies 2 and 3
Authors: Nair B. , Shaughnessy J. , Alsayed Y. , Haessler J. , van Rhee F. , Hollmig K. , Pineda-Roman M. , Crowley J. , Barlogie B. 
Published: August 2020

8589 Background: GEP-defined risk has evolved as the most robust predictor of overall and event-free survival (OS, EFS) in MM with TT2 and TT3 protocols, distinguishing 85% with low-risk (LR) and 15% with high-risk (HR). Upon relapse, the original risk designation may change typically in the direction LR to HR. Here we examine, among patients with available GEP data at baseline (BL) and relapse (REL), the contributions of both observations on post-relapse survival (PRS). Methods: Paired REL-BL GEP data were available in 77 patients, while information on metaphase cytogenetic abnormalities (CA) was obtained in 76 patients at both time-points. Results: PRS was significantly affected by both BL and REL HR status so that, among the 52 patients with LR at BL, HR status at REL conferred significantly poorer outcome compared to those with LR at REL (p=0.0005) with 30-mo estimates of 71% v 13%; likewise, among the 25 patients with HR at baseline, HR present also at relapse further diminished PRS (p=0.09) with 30-mo estimates in both settings of less than 20%. Similar considerations for CA status revealed, among the 29 patients without CA at BL, marked attrition of PRS with CA v no CA at REL with 30-mo estimates of 29% v 81% (p=0.04); for the 47 patients with CA at BL, CA also at REL further diminished the poor PRS from 46% to 22% (p=0.06). When all standard BL and REL prognostic factors were examined in a multivariate model, GEP-derived HR contributed to poor PRS both when present at BL (HR=2.79, p=0.005) and at REL (HR=2.77, p=0.002), in addition to CA at BL (HR=2.44, p=0.018). Conclusions: In estimating PRS in TT protocols, genetic characteristics at BL (HR, CA) have enduring adverse consequences aggravated further by HR status at REL. Therefore, in HR/CA BL settings, aiming at REL prevention appears as the best overall treatment strategy. [Table: see text]
Comparison of lenalidomide plus dexamethasone therapy used at first relapse versus later salvage therapy in relapsed or refractory multiple myeloma patients
Authors: Stadtmauer E. A. , Weber D. M. , Nieszvizky R. , Belch A. , Prince H. M. , San Miguel J. F. , Facon T. , Yu Z. , Knight R. D. , Dimopoulos M. A. 
Published: August 2020

8594 Background: The benefit of initiating lenalidomide plus dexamethasone at first relapsed was evaluated in this subset analysis from phase III studies in patients with relapsed or refractory multiple myeloma (MM). Methods: Patients from the randomized, multicenter clinical trials MM-009 and MM-010 who had received at least 1 prior treatment and were not resistant to dexamethasone were treated with lenalidomide (25 mg daily for 21 days of every 28 day cycle) plus dexamethasone (40 mg on days 1–4, 9–12, and 17–20 every 28 days for 4 months, then 40 mg on days 1–4 every cycle thereafter until disease progression or intolerance), or dexamethasone (same dose and schedule) plus placebo. Baseline characteristics such as age, sex, ECOG score, and baseline β2-microglobulin levels between the 2 patient groups were similar, however, median time from diagnosis and prior therapy were statistically different. Results: Multivariate analysis showed that more prior therapies is associated with shorter time-to-progression (TTP). Patients who received 1 prior therapy demonstrated a significant improvement in outcomes such as TTP, progression-free survival (PFS), overall response rate (ORR), complete response/very good partial response rate (CR/VGPR), median duration of treatment and overall survival (OS) after first relapse compared with those who received ≥ 2 prior therapies ( Table ). Toxicity, rate of dose reduction, or treatment discontinuation in the cohort with 1 prior therapy did not increase, despite longer treatment. Conclusions: When used at first relapse compared with salvage therapy, lenalidomide plus dexamethasone treatment resulted in significantly prolonged TTP, PFS, and OS, and an improved quality of response. Lenalidomide plus dexamethasone should be considered at an early stage of therapy for patients with MM. [Table: see text] [Table: see text]
MDS-associated cytogenetic abnormalities (MDS-CA) after total therapy (TT) regimens for newly diagnosed multiple myeloma (MM): Apparent surge after introduction of post-transplant consolidation chemotherapy (CONS) in TT2 and TT3
Authors: Hollmig K. , Waheed S. , Nair B. , Haessler J. , Petty N. , Pineda-Roman M. , Alsayed Y. , van Rhee F. , Crowley J. , Barlogie B. 
Published: August 2020

8595 Background: We have previously reported on the variables associated with the development of MDS-CA in the context of autologous transplant-supported high-dose therapy regimens for MM (Barlogie et al, Blood 2008). Methods: Due to a perceived increase in MDS-CA frequency, our MM data base was reviewed again to determine the potential effect of CONS introduced in TT2 and retained in TT3 trials. The frequency of MDS-CA post-transplant was determined, using Kaplan-Meier estimate plots, for 183 patients who received TT1, 554 enrolled in TT2 and 305 receiving TT3. Persistence of MDS-CA implied their documentation on 3 successive occasions. Results: 3-year MDS-CA estimates were 2% for both TT1 and TT2 and 4% for TT3 (TT3 v TT2, p=0.04; TT3 v TT1, p=0.11); persistent MDS-CA were also more frequently observed in TT3 in comparison with TT2 and TT1 (2% v 0% v 0%, both p=0.01). Multivariate analysis of features associated with transient and persistent MDS-CA revealed TT3 as an adverse feature (HR=2.84, p=0.043), along with incomplete platelet recovery of <165,000/uL 3mo after 1st transplant. Conclusions: Despite reduced induction chemotherapy prior to and CONS after tandem melphalan (200mg/m2)-based autotransplants from 4 in TT2 to 2 in TT3, overall and persistent MDS-CA increased significantly in TT3. Clinical MDS and AML were rarely observed and a full account of hematopathologic findings will be presented. [Table: see text]