bluuebunny/crossref_metadata_2025_split huggingface dataset:
High dose chemotherapy followed by autologous stem cell transplantation for relapsed or refractory Hodgkin’s lymphoma
Authors: Holland D. W. , Engelhardt B. G. , Goodman S. A. , Greer J. P. , Morgan D. S. , Schuening F. G. , Wolff S. , Bitting R. , Sulur P. , Stein R. S. 
Published: March 2020

7552 Background: High dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) can produce long-term durable remissions in patients (PTS) with relapsed or refractory Hodgkin’s lymphoma (HL). We investigated whether previously reported prognostic factors could predict overall survival (OS) and progression free survival (PFS) in a modern cohort of PTS, and attempted to identify any subgroup with a particularly inferior survival. Methods: A retrospective chart review was performed on all PTS with relapsed or refractory HL who received HDT and ASCT at a single institution. Results: From 1990 to 2001, 115 PTS received HDT followed by ASCT for relapsed or refractory HL. 76/109 PTS (70%) had achieved a complete response to initial therapy. Median time from initial therapy to relapse (TTR) was 18 months (range, 0–220 months). 105 PTS (91%) received HDT with cyclophosphamide, BCNU, and VP-16. The source of stem cells was bone marrow in 68 PTS (59%) and peripheral blood in 47 PTS (41%). Five year PFS and OS were 46% and 58%, respectively, with a median follow-up of 58 months (range, 1–175 months). The five year PFS and OS of the 13 PTS (11%) with primary refractory disease was 39% and 54%, respectively, not significantly different. 59 PTS (51%) died after HDT and ASCT. The most common cause of death was relapsed HL. Regimen related mortality accounted for 8 deaths (7%). Male gender and TTR <12 months were associated with decreased OS by univariate analysis (P = 0.04 and P = 0.03, respectively). Similar, but non-significant trends were noted in PFS. In multivariate analysis, only TTR <12 months was associated with a statistically significant decrease in OS (P = 0.04). Five year OS for patients with TTR <12 and ≥12 months was 44% and 63%, respectively. Second malignancies occurred in 9 PTS (8%). The most common diagnosis was myelodysplastic syndrome/acute myelogenous leukemia [n = 6 (67%)]. Conclusions: We have confirmed that HDT and ASCT produces long-term PFS and OS in a proportion of PTS with relapsed or refractory HL. TTR <12 months was associated with a statistically significant decrease in OS by multivariate analysis; however, no group of PTS, including those with primary refractory disease, could be identified who did not benefit from HDT and ASCT. No significant financial relationships to disclose.
Impact of rituximab on outcome of autologous transplantation for mantle cell lymphoma
Authors: Naing A. , Palmer J. , Tsai N. , Kogut N. , Popplewell L. , Rodriguez R. , Krishnan A. , Nakamura R. , Forman S. J. , Nademanee A. 
Published: March 2020

7555 Background: Currently, Mantle Cell Lymphoma (MCL) is an incurable disease. Patients treated with chemotherapy alone experience only transient responses, with no long-term improvement in disease-free/overall survival. While autologous hematopoietic stem cell transplantation (ASCT) in MCL patients has demonstrated prolonged survival, relapse remains the major issue. We evaluate the impact of rituximab (Rituxan, Rtx) on relapse and survival following ASCT. Method: A case-series of 83 MCL patients treated with ASCT at City of Hope (from 02/1991 to 04/2005) were examined; a total of 52 patients received Rtx (with-Rtx) as part of their induction/salvage treatment (pre-ASCT) and/or maintenance therapy (post-ASCT), 31 patients did not receive Rtx (no-Rtx) at any point pre-/post-ASCT. An assessment of baseline patient and disease characteristics (gender, age, KPS, % of pts with bone marrow involvement at diagnosis, disease stage/status at ASCT, % of pts with bulky disease B-symptoms at ASCT, and # of regimens administered prior to ASCT) showed no significant differences among the two groups. Result: To date, 23 patients have relapsed/progressed post-ASCT; 61% of the patients in the no-Rtx group remain disease free at last contact, while 79% in the with-Rtx group remain disease free. The median survival in the no-Rtx group is 77.63 months; the median survival time point for the with-Rtx group has not been reached due to shorter follow-up period. The 2-yr relapse rate for the with-Rtx/no-Rtx groups among 1st CR/PR patients were 19% (95% CI: 10–33%) and 26% (95% CI: 14–43%) (p > 0.05) respectively and the 2-yr relapse rate for the with-Rtx/no-Rtx groups among the beyond 1st CR pts were 33% and 40% respectively (p > 0.05). The survival endpoint showed similar results. The 2-yr survival probability for the with-Rtx/no-Rtx groups among the 1st CR/PR patients were 91% (95% CI: 76–97%) and 82% (95% CI: 64–91%) (p > 0.05) respectively and the 2-yr survival probability for the with-Rtx/no-Rtx groups among the patients beyond 1st CR/PR were 59% and 63% respectively (p > 0.05). Conclusion: Using Rtx as induction/salvage and/or maintenance before and after ASCT therapy may not be associated with decreased relapse and improved survival. Nevertheless, our data indicate that outcome is better when ASCT is carried out at 1st CR/PR. No significant financial relationships to disclose.
Sildenafil citrate suppresses disease progression in patients with Waldenstrom’s macroglobulinemia
Authors: Patterson C. J. , Soumerai J. , Hunter Z. , Leleu X. , Ghobrial I. , Treon S. P. 
Published: March 2020

7556 Background: Responses to sildenafil citrate (Viagra), a phosphodiesterase-5 inhibitor used to treat erectile dysfunction, have been observed in patients with Waldenstrom’s Macroglobulinemia (WM). Moreover, sildenafil citrate induces apoptosis of WM lymphoplasmacytic cells (Clin Lymphoma 5:205, 2004). We therefore conducted a prospective phase II study of sildenafil citrate in patients with slowly progressing WM who did not meet consensus eligibility for active therapy (Semin Oncol 2003; 30:116). Intended therapy was as follows: Week 1 25 mg po qD Week 2 50 mg po qD Week 3 75 mg po qD Week 4, then Months 2–24 100mg po qD or Maximum Tolerated Dose Methods: Thirty patients were enrolled, 18 of whom were previously untreated. All patients demonstrated progressing disease prior to enrollment. Median age was 66 (range 43–85 yrs), baseline BM involvement was 30% (range 5–90%), serum IgM was 3,640 (range 790–6,720 mg/dL), hematocrit was 37.1% (range 32.7–58.5%), and B2M was 2.3 (range 1.5–8.9 mg/dL). Patients were evaluable for response after 3 months of therapy. Results: At a median of 3 months, serum IgM levels declined in 19/30 (63%) patients from a median of 3,640 (range 790–6,720 mg/dL) to 2,965 (range 1,170–6,110 mg/dL). 5/30 patients (17%) demonstrated at least a minor response (≥25% IgM decrease). Two patients were taken off study for non-response to therapy. Toxicities were mild and included headaches, sinus congestion, facial flushing, dyspepsia, and generally resolved on their own with prolonged sildenafil citrate usage. Only two patients required dose modification to 25 mg and 75 mg po qD, respectively. Corollary studies to determine putative mechanisms of action for sildenafil citrate in WM were also performed and will be updated at the meeting. Conclusions: This prospective clinical trial provides preliminary evidence for activity of sildenafil citrate in patients with advancing WM. With minimal toxicity, sildenafil citrate appears to have suppressed disease progression in more than half of patients and has resulted in objective responses, thus warranting further investigation in WM and possibly other B-cell disorders. No significant financial relationships to disclose.
Long-term results of high-dose chemotherapy (HDCT) supported by hematopoietic circulating (ASCT) or bone marrow (BMT) stem cell autografting as first salvage treatment for refractory or relapsed Hodgkin’s lymphoma
Authors: Viviani S. , Bonfante V. , Di Nicola M. , Cortelazzo S. , Carlostella C. , Valagussa P. , Bonadonna G. , Barbui T. , Gianni A. M. 
Published: March 2020

7567 Background: The aim of this retrospective study was to evaluate with a long follow-up the efficacy of HDCT + ASCT or ABMT for refractory or relapsed HL. Methods: Data were collected from 99 pts who failed or relapsed after first-line CT± radiotherapy and were treated with HDCT+ASCT or ABMT between Oct 1984 and Dec 2003. Thirty-two pts had late relapse (CR≥12 months), 31 had early relapse (CR<12 months), while 36 had primary refractory (IF) HL.The main pts characteristics at relapse/progression were as follows: M/F: 50/49; median age 28 years; stage III-IV:54%; B symptoms: 33%; bulky disease 22%; extranodal ± nodal disease 54%; IPI≥3 39%. HDCT program consisted in a debulking phase with sequential high-dose chemotherapy (Cyclophosphamide 7gr/mq followed by ASC or BM harvest, Methotrexate 8 gr/mq+ Vincristine 1.4 mg/mq, VP16 2 gr/mq) in 71 cases; 3–4 courses of Ifosfamide (3gr/mq × 4 days)+ Vinorelbine (25mg/mq day 1+5) in 28 cases. Final myeloablative course was BEAM (63%), or high-dose Melphalan combined with high-dose Mitoxantrone (11%) or with high-dose Carmustine (9%) or TBI (17%) followed by ABMT or ASCT. Results: Ninety-two pts (93%) completed the HDCT program, while seven pts (7%) progressed during debulking CT. Early and late toxicity were mild. After a median follow-up of 66 months both 10-year freedom from second progression (FF2P) and overall survival (OS) were 61% for all pts. FF2P and OS were respectively 70% and 66% for pts with late relapse; 64% and 60% for pts with early relapse; 52% and 56% for primary refractory pts. Multivariate analysis showed that prognostic factors for FF2P were stage III-IV vs I-II (HR 2.09; p=0.04), response to first-line CT: CR≥12 vs CR<12 vs IF (HR 2.19; p=0.058) and bulky vs non bulky (HR 1.96; p=0.07). Prognostic factors for OS were response to first-line CT (HR 2.59; p=0.05), stage III-IV vs I-II (HR 1.37; p=0.39) and bulky vs non bulky (HR 2.06; p=0.06).Conclusion: These long-term results confirm that HDCT + ASCT or ABMT was feasible, safe and very effective for the treatment of relapsed/refractory HL.Our data support the use of this strategy for the salvage therapy even in the unfavourable group of primary refractory pts. No significant financial relationships to disclose.
Association between Chlamydia psittaci infection and extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT)-lymphomas
Authors: Aigelsreiter A. , Stelzl E. , Deutsch A. , Beham-Schmid C. , Beham A. , Lanzer G. , Linkesch W. , Kessler H. , Neumeister P. 
Published: March 2020

7568 Background: MALT-lymphomas are often associated with infectious organisms. Microbial species associated with MALT lymphomas are: Helicobacter pylori (H.pylori), Campylobacter jejuni, Borrelia burgdorferi, and Hepatitis C Virus. Recent studies showed evidence of Chlamydia psittaci (C. psittaci) infection in 80% of ocular adnexal lymphoma and tumor regression following eradication therapy. We studied the presence of C. trachomatis, C. pneumoniae, and C. psittaci DNAs in MALT lymphomas of various sites and in non-malignant controls. Methods: MALT lymphomas from the following sites were selected for analysis: salivary gland (n=13), thyroid gland (n=4), skin (n=2), ocular adnexa (n=2), stomach (n=6), intestinum (n=4). Samples of Sjoegren syndrome (n=10) and samples of H. pylori positive gastritis (n=7) were included as non-malignant controls. Macrodissected tissue containing >80% lymphoma cells from paraffin embedded tissue was processed for DNA isolation. For the presence of C. psittaci and C. pneumoniae DNA real time PCR assays were used. For C. trachomatis a commercially available PCR assay (Roche Molecular Diagnostics) was employed. All samples were tested twice. A sample was regarded as positive if at least one positive result was obtained. Results: C. psittaci was found at variable frequencies in MALT lymphomas of different sites: 4/13 (31%) salivary gland, 2/4 (50%) thyroid gland, 2/2 (100%) skin, 2/2 (100%) ocular adnexa, 1/6 (17%) gastric, and 0/4 intestinal MALT lymphomas. Among the non-malignant specimens, C. psittaci DNA was detected in 4/10 (40%) samples of Sjoegren syndrome and in 0/7 samples of H. pylori positive gastritis. All nongastric MALT lymphomas tested were negative for C. trachomatis and C. pneumoniae. Conclusion: Our data reveal a clear association of C. psittaci infection with extragastric MALT lymphoma. However, no evidence could be established for C. trachomatis and C. pneumoniae infection. Moreover, the high prevalence of Sjoegren syndromes - the most frequent precursor lesion for MALT lymphomas of salivary gland and ocular adnexa - may suggest an involvement of C. psittaci induced antigenic driven lymphomagenesis in a significant proportion of extragastric MALT lymphomas. No significant financial relationships to disclose.
Imaging results after CHOP-rituximab followed by 90Y ibritumomab tiuxetan and rituximab (R) in patients with previously-untreated follicular lymphoma (FL)
Authors: Demonaco N. A. , Wu M. , Osborn J. , Evans T. , Foon K. A. , Swerdlow S. , Kant J. , Joyce J. , Land S. , Jacobs S. A. 
Published: March 2020

7589 Background: There has been some question regarding the predictive value of 111In scans in FL. We report imaging results with fusion PET-CT scans and 111In scans in a single-institution, non-randomized, phase II trial in patients with FL treated with CHOP-R followed by 90Y ibritumomab tiuxetan (Zevalin (Z)) and R. Methods: Eligible patients have CD20 positive FL, Grade 1–3 or transformed, Stage II-IV, no prior treatment with monoclonal antibody or chemotherapy, and symptomatic disease (if grade 1–2). CHOP-R is given every 21 days for 3 cycles. Four weeks after the last dose of CHOP-R, patients receive the Zevalin regimen, which includes 111In imaging and 90Y therapy. One week after Z, patients receive R 375 mg/m2 IV weekly for 4 doses. Bone marrow examination and fusion PET-CT scans are performed at baseline, after CHOP-R, and 12 weeks after Z. The primary endpoint is CR, and responses are reported using the International Working Group (IWG) criteria with the additional requirement of a negative PET scan for CR/CRu. Results: Thirty-six FL patients have been accrued, and 16 patients have completed therapy and follow-up studies. One patient did not have a positive PET scan at baseline. Following therapy, the proportion with a negative PET scan improved from 8 of 15 (53.3%) after CHOP-R to 15 of 15 (100%) after Z. Using IWG criteria in combination with PET scan results, the CR rate increased from 4 of 15 (26.7%) after CHOP-R to 12 of 15 (80%) after Z. Five of 6 patients (83%) with tumor uptake by 111In scan and 7 of 9 (78%) with a 111In scan negative for tumor achieved a CR. Conclusions: There was no significant difference in CR between those patients with 111In tumor uptake versus patients with a negative 111In scan. Functional imaging with PET-CT may be a more sensitive method than CT alone in determining residual disease in FL. This trial continues to accrue patients, and more time is needed to determine the duration of response and time to next therapy. No significant financial relationships to disclose.
Flavopiridol, fludarabine and rituximab (FFR) is an active regimen in indolent B-cell lymphoproliferative disorders and mantle cell lymphoma (MCL)
Authors: Lin T. S. , Fischer B. , Moran M. E. , Shank R. S. , Kraut E. , Porcu P. , Farag S. S. , Blum K. A. , Colevas A. D. , Grever M. R. , Byrd J. C. 
Published: March 2020

7599 Background: The cyclin-dependent kinase inhibitor flavopiridol is active in MCL and chronic lymphocytic leukemia (CLL) when given by 1-hr IV bolus dosing. Flavopiridol induces apoptosis independent of p53 and may eliminate tumor cells resistant to fludarabine and rituximab. Methods: We performed a phase I dose escalation study of flavopiridol, fludarabine and rituximab (FFR) in patients (pts) with MCL, CLL and indolent B-cell non-Hodgkin’s lymphoma (NHL). Pts received fludarabine 25 mg/m2 IV day 1–5 and rituximab 375 mg/m2 day 1 every 28 days for up to 6 cycles. Flavopiridol was given 50 mg/m2 by 1-hr IV bolus day 1 (cohort 1), day 1–2 (cohort 2), or day 1–3 (cohort 3) of each cycle. Growth factor support was prohibited. Results: Twenty-one pts were enrolled and are evaluable for toxicity and response. Median age was 62 years (range, 43–81); 8 pts had CLL, 5 MCL, 4 follicular NHL (FL), and 4 other low-grade NHL. Nine pts had received 1–2 prior therapies; 12 pts were previously untreated. CLL pts were Rai stage III/IV (5) or required treatment for stage I/II disease (3). NHL pts had stage III/IV (10) or progressive stage II disease (3). Dose limiting toxicity (DLT) was not observed in 3 pts in cohort 1. Two of 6 pts in cohort 2 developed DLT (grade 3 seizures; grade 3 renal failure due to nausea and diarrhea). Twelve additional pts were enrolled at the cohort 1 dose level, to define toxicity and efficacy. Pts received a median of 4 cycles (range 1–6), and 9 of 21 pts completed 6 cycles. Therapy was stopped early due to cytopenias (7), infection (2), DLT (2) or progressive disease (1). Response was graded by NCI 96 (CLL) or IWG (NHL) criteria. Overall response rate was 90%, and 14 pts achieved CR (67%). Six pts relapsed a median of 7.5 months (range 4–18) after finishing therapy; 13 pts remain in remission a median of 13.5 months (range 4–25) after therapy. All 9 MCL/FL pts responded (8 CR, 1 PR), and 8 pts remain in remission a median of 17 months (range 6–25) after therapy. Conclusions: FFR showed significant clinical activity in a small group of pts, but cytopenias limited therapy. We are currently studying a modified FFR regimen using a more active flavopiridol schedule (30-min IV bolus followed by 4-hr IV infusion) and allowing the use of prophylactic filgrastim. [Table: see text]
Lenalidomide and bortezomib induce osteoclast cytotoxicity and decrease BAFF secretion in osteoclasts in human multiple myeloma: Clinical implications
Authors: Breitkreutz I. , Tai Y. , Li X. , Coffey R. , Raab M. S. , Song W. , Hideshima T. , Chauhan D. , Munshi N. , Anderson K. C. 
Published: March 2020

7606 Background: Myeloma bone disease is caused by an enhanced osteoclast (OCL) activation, leading to osteolytic bone lesions. OCL have recently been reported to produce abundant B-cell activating factor (BAFF) in the bone marrow microenvironment that is important for myeloma cell growth and survival (Blood 106, 1021–30, 2005; ASH2005, #627). The proteasome inhibitor bortezomib (PS341, Velcade) has potent anti-myeloma activity with impressive clinical responses. A recent study indicated that bortezomib has inhibitory effects on OCL (ASH 2005, #2488). Lenalidomide (CC-5013, Revlimid) is an immunomodulatory derivative of thalidomide that has shown promising anti-myeloma effects in patients with relapsed or refractory multiple myeloma (MM) (ASH 2005, #6 & #1565). However, the effect of lenalidomide on human OCL lineage is unknown. Therefore, the aim of this study is to investigate the effect of lenalidomide and bortezomib on human OCL. Methods: OCL formation from healthy donors and MM patients were stimulated with RANKL (50ng/ml) and GM-CSF (10ng/ml) in 20% FBS/RPMI. Cells were incubated with lenalidomide 2μM or bortezomib 2nM, alone and in combination, for two weeks followed by [3H]thymidine uptake assay to measure growth inhibition of OCL. Similar experiments were also performed in cocultures of CD138-purified cells from MM patients with OCL, in the presence or absence of lenalidomide and bortezomib. In addition, ELISA was performed to measure cytokine release of BAFF produced by OCL in these cultures. Results: OCL growth was decreased by lenalidomide (n=6) (median 49.2%, range 20–62.5%; coculture: 53% and 35%) as well as bortezomib (96 and 49%; coculture 63 and 59%) and by the combination of both drugs (95 and 55%; coculture 42 and 44%). BAFF secretion was dramatically decreased in cultures treated with lenalidomide 2μM (n=3) (median 72%, range 61–75.9%). Conclusions: These results indicate that lenalidomide and bortezomib inhibit OCL growth and survival. Importantly, lenalidomide and bortezomib also block growth and survival of MM cells cocultured with OCL, suggesting that lenalidomide may inhibit OCL growth and survival through inhibition of BAFF and may prevent development of osteolytic lesions in MM. No significant financial relationships to disclose.
Phase I study of bortezomib and 153Sm-lexidronam combination for refractory and relapsed multiple myeloma
Authors: Yeh H. S. , Swift R. A. , Ferretti D. , Mapes R. A. , Goeckeler W. F. , Berenson J. R. 
Published: March 2020

7614 Background: Multiple myeloma (MM) is a highly radiosensitive B-cell malignancy and radiation therapy has been an effective treatment for these patients. Recent preclinical studies have demonstrated that the bone-seeking radionuclide, Samarium Sm153 lexidronam (Sam) in combination with the proteasome inhibitor, bortezomib (Vel), can synergistically inhibit proliferation of myeloma cell lines in vitro and reduce MM growth in mice bearing human MM without significant myelotoxicity. These results provide the basis for a new therapeutic approach of combining Vel and Sam to overcome resistance and to minimize nontumor tissue toxicity among refractory and relapsed MM patients. Methods: The primary objective of this Phase I study is to determine the response rate and tolerability of Vel + Sam combination in patients with relapsed or refractory MM. Patients will be enrolled on this Phase I dose-escalation trial which involves six cohorts. Previous treatment with Vel is permissible. Dose escalation in parallel arms is as follows: A complete treatment cycle is 8 weeks. Vel is given on days 1, 4, 8 and 11 followed by a 45-day rest period. Sam is administered on day 4. The cycle is repeated on Day 57 if disease is stable or improved and platelets and neutrophils recover to at least grade 1 toxicity. DLT is defined as cycle 1 grade 4 hematologic or grade ≥3 non-hematologic toxicity. Results: Cohorts 1 and 4 have been enrolled (3 patients per cohort). One cycle of treatment has been completed thus far. No significant toxicity has been observed except a transient fever in one patient. There have been no dose limiting toxicities to date. The first six patients will be evaluated for response within the next two weeks. Conclusions: The trial will continue to enroll patients in cohorts 2 and 5. Updated results from the trial will be presented at the meeting. [Table: see text] [Table: see text]