bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chlamydia psittaci (Cp)-eradicating therapy with doxycycline is an active treatment against ocular adnexa MALT lymphoma (OAML): Final results of a multicentre prospective trial
Authors: Ferreri A. J. , Ponzoni M. , Guidoboni M. , Cortelazzo S. , Demeter J. , Zallio F. , Palmas A. , Politi L. , Doglioni C. , Dolcetti R. 
Published: March 2020

7559 Background: An association between OAML and Cp infection has been reported. Preliminary data suggest that patients (pts) with Cp-related OAML could achieve lymphoma regression after eradicating therapy with doxycycline, while data on the activity of this strategy in Cp-negative OAML are not available. Methods: In this multicentre prospective trial, 27 consecutive pts with OAML and measurable disease, at diagnosis (n = 15) or relapse, were treated with doxycycline 100 mg, bid orally, for 3 weeks. Objective response was the primary endpoint. The presence of Cp DNA in lymphoma samples was evaluated by TETR-PCR. Results: Tolerability was excellent in all pts but one. At a median follow-up of 13 mo. (range 3–45), response was complete (CR) in 6 pts and partial in 7 (ORR = 48%; 95% CI:30%-66%); three pts had a response <50%, 9 had stable disease (3–13 mo.), two had progressive disease. Response was slow; 5 pts achieved the best response only after one year of follow-up (median time to the best response: 6 mo.). TETR-PCR resulted positive in 11 (41%) pts and negative in 16. Lymphoma regression was observed in both PCR-positive and -negative pts (64% vs. 38%; p = 0.25), with a CR rate of 36% and 13% (p = 0.18), respectively. Response rate was similar between pts with conjunctival and intra-orbital lymphomas (43% vs. 54%, p = 0.71). The three pts with regional lymphadenopathies and three of the 5 pts with bilateral OAL achieved objective response (4 CRs), which lasted 3+, 13+, 16+, 22+, 26+, and 37 mo. In relapsed pts, objective response was observed in 3 of 5 previously irradiated pts and in 5 of 7 non-irradiated pts (p = 0.99). Twenty pts are failure-free, with a 2-yr FFS of 66±12%. Conclusions: Doxycycline is a fast, cheap and safe therapy, able to induce durable regression in 64% of Cp-related OAML. This antibiotic is a valid alternative against OAML, even in pts with multiple failures, involving previously irradiated areas or regional lymph nodes. We report for the first time responses also in PCR-negative OAML; this finding stimulates the development of more sensitive and specific methods for Cp detection and the study of potential associations with other infectious agents responsive to doxycycline. No significant financial relationships to disclose.
Sequential radioimmunotherapy with tositumomab/Iodine I131 tositumomab followed by CHOP for mantle cell lymphoma demonstrates RIT can induce molecular remissions
Authors: Zelenetz A. D. , Noy A. , Pandit-Taskar N. , Scordo M. , Rijo I. , Zhou Y. , O’Donoghue J. A. , Divgi C. 
Published: March 2020

7560 Background: Mantle cell lymphoma remains a clinical challenge particularly for pts not candidates for consolidation with ASCT or treatment with leukemia induction regimens. Methods: We investigated sequential radioimmunotherapy (RIT) cytoreduction with tositumomab/Iodine I131 tositumomab followed by CHOP chemotherapy as initial therapy for patients either ineligible for or unwilling to undergo high dose therapy and stem cell transplantation. In addition, pts had to have less than 25% of the intratrabecular bone marrow space involved with lymphoma. Results: Twenty-five patients (pts) were enrolled but only 24 were treated with the therapeutic dose of RIT because a manufacturing problem prevented the treatment of one patient. The median age was 66 (45–80), there were 23 men and 2 women. All patients had advanced stage (III/IV) disease and bone marrow was involved in 48% and the GI tract was involved in 48% of the patients. The overall response rate (ORR) to RIT was 83% (CR/CRu 46%; PR 38%). Two pts withdrew consent following the RIT (and are censored from that point); 1 pt with disease progression requiring alternative therapy is included in EFS and OS analyses. Twenty-one pts proceeded to the CHOP consolidation and 19 completed planned therapy (1 pt died of a CVA; 1 pt chose not to complete chemotherapy after two cycles of CHOP). At the completion of delivered therapy the ORR was 86% (CR/CRu 67%, PR 19%). The median follow up is 2.1 years (0.7 to 4.2). The median EFS was 1.4 years though there have been no events beyond 1.7 years with 7 pts at risk; median OS has not been reached (92% at 2.1 years). Minimal residual disease (MRD) was evaluated with a clonotypic PCR (cPCR) capable of detecting about 1:105 tumor cells; this assay was informative in 17 pts. Following induction with RIT 6 pts (46%) were molecularly negative in blood and bone marrow. Despite the increase in clinical CR following CHOP consolidation, no additional pts became molecularly negative. Conclusions: RIT with tositumomab/iodine I131 tositumomab is a very active agent in the treatment of MCL; unfortunately, MRD is not effectively eliminated by subsequent CHOP chemotherapy. We are planning to explore chemotherapy induction followed by RIT. [Table: see text]
Phase II study of R-CHOP with GM-CSF cytokine support for elderly patients with untreated diffuse large B-cell lymphoma (DLBCL): A Wisconsin Oncology Network study
Authors: Kahl B. S. , Go R. S. , Rodrigues G. , Sanchez F. A. , Saphner T. J. , Werndli J. E. , Kirkpatrick H. M. , Longo W. L. 
Published: March 2020

7566 Background: According to mature data from the GELA study, approximately 55% of elderly patients with DLBCL will be cured with R-CHOP. We hypothesized that sargramostim (GM-CSF), added to R-CHOP may potentiate the efficacy of rituximab by upregulating tumor cell CD20 expression and by augmenting antibody dependent cellular cytotoxicity (ADCC). Methods: Patients > 60 years old with untreated stage I-IV DLBCL were eligible if they had PS ≤ 2, measurable disease, adequate organ function, and provided informed consent. R-CHOP for 6–8 cycles was given every 21 days with GM-CSF given subcutaneously at a dose of 250 mg/m2 days 3–10 of each cycle. The primary endpoint was to estimate the CR/CRu rate. Secondary endpoints included estimates of the ORR, EFS, and OS. Results: Thirty-eight/forty patients have been enrolled to date and data are available for 36. One patient is too early and another was deemed ineligible after centralized pathology review. Baseline characteristics include median age 72 (range 61–86), 25% PS 0, 44% PS 1, 31% PS 2, 80% stage III/IV, 56% elevated LDH, 8% IPI 0–1, 25% IPI 2, 36% IPI 3, 31% IPI 4–5. Thirteen/thirty-six (36%) patients did not complete 6 cycles of protocol therapy, 8 due to intolerance of R-CHOP and 5 due to intolerance of GM-CSF. By intent-to-treat analysis, 17/36 patients achieved CR/CRu (47%) and 9/36 achieved PR (25%) for an ORR of 72%. No patients progressed while on study and all non-responders were deemed so secondary to inability to complete protocol therapy. The median follow-up time for surviving patients is 19 months. Considering inability to complete protocol therapy as an event, the 2-year EFS is 38%, the 2-year PFS is 56%, and the 2-year OS is 74%. Conclusions: Any benefit that may be conferred by GM-CSF is likely to be offset by toxicity and intolerance, with 14% of patients in this series unable to complete GM-CSF therapy. Additionally, R-CHOP is more toxic in elderly patients than is commonly appreciated with, 22% of patients unable to complete 6 cycles. Despite recent advances, DLBCL in the elderly remains a difficult problem and new approaches to therapy must be developed. [Table: see text]
Idiotype vaccine therapy of follicular lymphoma in first remission: Association of t(14;18) and disease free survival in a phase II cohort
Authors: Gause B. L. , Neelapu S. S. , Cohen C. M. , Katz L. M. , Watson T. , Stergiou A. M. , Kwak L. W. 
Published: March 2020

7582 Background: A single-arm Phase 2 study (Nature Med 5:1171–7,1999), evaluated the ability of tumor-specific idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) administered with granulocyte-monocyte colony-stimulating factor - GM-CSF (BiovaxID vaccine) to induce complete remission (CR) and molecular remission (MR) in follicular NHL patients in first CR after chemotherapy. We reported (ASH 2005, Abstr 2441) that at 9.2 years follow-up, disease free survival (DFS) and overall survival (OS) were 45% and 95%, respectively; median DFS was 8.0 years. Previous studies indicated that the t(14;18) chromosomal translocation is associated with follicular NHL. We tested the hypothesis that absence of t(14;18) in peripheral blood (PB) of patients after Id vaccination is predictive of DFS. Methods: A 20-patient cohort in first CR treated with the vaccine was evaluated. t(14;18)- (MR) is defined as <1 t(14;18)+ cell in 105 cells using PCR of the MBR breakpoint cluster on DNA from tumor biopsies or PB. Of the 20 patients, 11 had t(14;18)+ tumors and PB before chemotherapy. Following chemotherapy all 11 patients continued to have t(14;18)+ PB despite being in CR. However, at 1 month following final vaccine treatment, 8 of these patients had converted to t(14;18)- . In this ad hoc analysis, the proportion of patients remaining in DFS was stratified by t(14;18) status; Kaplan-Meier analysis compared median DFS of patients across t(14;18) status following vaccination. Results: At median follow-up of 9.2 years, 55% of patients had clinically relapsed. Although not statistically significant, of the 17 patients t(14;18)- post-vaccine, only 47.1% had clinically relapsed while 100% of the 3 t(14;18)+ patients had relapsed [Chi-square test; P=0.089]. Median DFS in t(14;18)+ patients was 60 months (5.0 years) and had not yet been reached in t(14;18)- patients at 91 months (7.6 years) [Log-rank test; P=0.069]. Conclusions: These data show a possible association between t(14;18) negativity following vaccine and prolonged DFS. Additional follow-up on these patients is needed, as well as similar analyses in other cohorts, to further explore this association. [Table: see text]
R-CHOP-14 in patients with diffuse large-B-cell lymphoma (DLBCL) younger than 70 years: A multicentric and prospective study
Authors: Rueda A. , Sabin P. , Rifá J. , Llanos M. , Gómez-Codina J. , Lobo F. , García-Arroyo R. , Herrero J. , Provencio M. , Jara C. 
Published: March 2020

7592 Background: Several studies have shown that the addition of rituximab (R) to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisona), or shortening the interval between cycles of chemotherapy to two weeks, improves survival of patients with DLBCL. These studies prompted our group (GOTEL) to evaluate in a prospective study, the feasibility and efficacy of R-CHOP-14 in patients (pts) with DLBCL. Methods: Patients (younger than 70 years) with stage II bulky, III or IV DLBCL, and no significant co-morbidities were included in the study. R was administered on day 1 before chemotherapy. R-CHOP was recycled every 14 days. No antimicrobial prophylaxis was administered. All pts received filgrastim (5 μg/kg) from day +3 to +10. Pts received 6 cycles if CR was achieved after 3 cycles; those in PR, and those pts with bone marrow disease at diagnosis, received 8 cycles. Involved field radiation therapy was permitted for pts with stage II bulky disease. Results: From May 2002 to august 2004, 77 pts were included. Median age was 54 years (range, 15–70); 55 patients were younger than 60 years. According to the age adjusted International Prognostic Index (aaIPI), 13 pts (17%) had low risk disease, 27 pts (35%) low-intermediate risk, 29 pts (38%) high-intermediate risk, and 8 pts (10%) high risk disease. Grade 3–4 toxicity occurred as follow: neutropenia in 15 pts (19%), anaemia in 7 pts (9%), thrombocytopenia in 4 pts (5%), mucositis in 4 pts (5%) and peripheral neurotoxicity in 4 pts (5%). Ten pts were hospitalized (febrile neutropenia: 8 cases, one case of gastric perforation and one pulmonary embolism). After therapy, 61 pts (79%) achieved a CR/CRu (C.I. 95%: 57%-90%) and 14 pts (18%) a PR. 2 pts (3%) had refractory disease. With a median follow-up of 20 months, progression-free and overall survival at 24 months were 68% and 87%, respectively. Conclusions: Administration of R-CHOP-14 (with filgrastim support) is feasible and effective in patients younger than 70 years. [Table: see text]
Primary ocular adnexal MALT lymphoma (POAML): A long-term follow up study of 114 patients (pts)
Authors: Tanimoto K. , Kaneko A. , Suzuki S. , Sekiguchi N. , Watanabe T. , Kobayashi Y. , Kagami Y. , Maeshima A. M. , Matsuno Y. , Tobinai K. 
Published: March 2020

7593 Background: Although POAML is a recently recognized distinct entity, its natural history, prognostic factors, behavior of progression and death, and standard initial management have not been fully elucidated. Methods: 114 pts with a histologically verified POAML treated at our institution between 1970 and 2003 were retrospectively analyzed. Results: With a median follow-up duration of 5.7 years (0.6–34.0), estimated overall survival (OS) rate and progression-free survival (PFS) rate at 10 years was 89% and 57%, respectively. Older pts (>60) showed significantly worse OS (p=0.002). However, other clinical factors did not affect significantly OS or PFS. 13 (11%) pts died, but only 3 (3%) due to progressive lymphoma. 31 (27%) pts progressed, 7(6%) at systemic diseases, 8 (7%) at contra lateral sites, and 16 (14%) at the same sites, and only 2 (2%) transformed high-grade lymphoma. All 8 pts who progressed at contra lateral sites were limited to those who had involved initially in the orbit (p=0.036) and their time to progression was significantly longer (p=0.039). Pts who received initially radiation-containing therapy were superior in PFS but not OS than those initially treated with other modalities (p=0.016 and 0.091, respectively). Moreover, when we compared the outcomes of no initial therapy cohort and immediate therapy cohort, there was no significant difference in OS and PFS (p=0.499 and 0.073, respectively). Conclusions: The majority of pts with POAML showed the behaviors of very indolent diseases, and only age was significant prognostic factor. Our preliminary observation suggesting that no initial therapy is an acceptable approach for selected pts (Ann Oncol 2006;17:135–40) was further confirmed in this study for all cohorts. Considering the possible heterogeneity of POAML among initial sites suggested by the present study and the genetic heterogeneity revealed by our previous study (Blood 2005;106:289a), further investigations on POAML are warranted. No significant financial relationships to disclose.
Treatment of primary CNS lymphoma with induction high-dose methotrexate, temozolomide, rituximab followed by consolidation cytarabine/etoposide: A pilot study with biomarker analysis
Authors: Issa S. , Hwang J. , Karch J. , Fridlyand J. , Prados M. , Batchelor T. , Aldape K. , Haqq C. , Damon L. , Rubenstein J. 
Published: March 2020

7595 Background: There is currently no consensus on the optimal treatment for patients diagnosed with primary CNS lymphoma (PCNSL). Between 2001–2004, UCSF PCNSL patients were treated with combination high-dose methotrexate, temozolomide, rituximab (MTR) as induction therapy. Patients in CR with this regimen were treated with high-dose cytarabine plus etoposide as consolidation. The purposes of this study were: (1) Pilot analysis to determine the safety and efficacy of intensive methotrexate-based induction therapy followed by high-dose consolidation with elimination of whole brain irradiation; (2) Analysis of molecular markers in PCNSL which predict sensitivity to chemotherapy and outcome. Methods: 21 untreated, CD20 +, immunocompetent PCNSL patients were treated with combination methotrexate (8 gm/m²), temozolomide (150 mg/m²/day)and rituximab (375 mg/m²). Patients in CR received consolidation cytarabine (2 g/ m² x 8 doses) plus etoposide (40 mg/kg over 96 hours). IHC analysis of potential biomarkers predictive of outcome was performed on paraffin sections from these patients. Candidate markers for validation were selected by gene expression analysis of an independent, multicenter dataset of 20 cases. Results: Mean age was 58.6 y (range 40–81). Median KPS was 60. MTR and cytarabine/etoposide consolidation was well-tolerated with no treatment-related mortality or evidence for neurotoxicity. One case of post-remission cytopenia occurred after consolidation and resolved spontaneously. Eleven patients (52.4%) attained CR with induction; eight received consolidation; three patients in CR deferred consolidation. Median PFS was 11.5 months. Median OS for all 21 patients has not yet been reached with median follow-up of 27.5 months. Expression of the apoptotic regulator DAP-1 by lymphoma cells as determined by IHC was associated with improved PFS (p<0.028) and OS (p<0.021). Conclusions: Combination MTR followed by intensive consolidation appears to be well tolerated in PCNSL. PFS appears at least similar to regimens that contain whole brain irradiation. A larger phase II study has been initiated to evaluate this regimen in a multicenter setting. [Table: see text]
Prediction of survival using absolute lymphocyte count for newly diagnosed patients with multiple myeloma
Authors: Ege H. , Gertz M. , Markovic S. N. , Lacy M. Q. , Dispenzieri A. , Hayman S. R. , Kumar S. K. , Litzow M. R. , Gastineau D. A. , Porrata L. F. 
Published: March 2020

7605 Background: In the setting of autologous stem cell transplantation (ASCT) in multiple myeloma (MM), it has been shown that peripheral blood absolute lymphocyte count (ALC) on day 15 is an independent prognostic factor for clinical outcomes. Recently the International Staging System (ISS) for MM has been developed as a simple staging system to assess survival in newly diagnosed MM patients. The role of ALC on survival in newly diagnosed MM patients is unknown. Methods: Between 1994 and 2002, 1,835 consecutive MM patients were evaluated at the Mayo Clinic, Rochester. Of these patients, we retrospectively analyzed 584 MM patients that were originally diagnosed and followed at the Mayo Clinic. The primary end point was to assess the role of ALC at the time of MM diagnosis on overall survival (OS). OS was measured from the date of diagnosis to time of death or last follow-up. ALC was analyzed as a continuous variable and dichotomized based on finding the optimal cut point based on the log-rank statistic. ALC was then compared to the ISS. Results: The median age of the cohort was 67 years (range: 29–94 years), including 234 females and 350 males. The median follow-up was 32 months (range: 1–136 months). The median ALC at diagnosis was 1.2 x 109/L (range: 0.12–5.44 x 109/L). ALC, as a continuos variables was identified as a prognostic factor for OS (HR= 0.466, 95%CI= 0.396–0.547, p < 0.0001). MM patients with an ALC ≥ 1.3 x 109/L experienced a superior OS compared with MM patients with an ALC < 1.3 x 109/L (55.5 months versus 22.6 months, p< 0.0001). In the multivariate analysis, ALC was independent prognostic factor when compared to the ISS (HR = 0.580, 95%CI=0.518–0.647, p< 0.0001). Conclusions: Our study shows that ALC at diagnosis for MM is an independent prognostic factor for OS, suggesting how the host immune status plays a critical role in the survival of patients with MM. No significant financial relationships to disclose.
Update of melphalan 280 mg/m2 plus amifostine cytoprotection before autologous stem cell transplantation as part of initial therapy in multiple myeloma patients
Authors: Reece D. E. , Flomenberg N. , Badros A. , Phillips G. L. , Filicko J. , Howard D. S. , Meisenberg B. , Rapoport A. , Vesole D. H. 
Published: March 2020

7608 Background: Autologous stem cell transplantation (ASCT) using melphalan 200 mg/m2 is a standard part of inital therapy in younger multiple myeloma (MM) patients (pts). We have previously reported an augmented regimen of melphalan 280 mg/m2 with the cytoprotectant agent amifostine (AF) to try to improve the anti-tumor response without increased mucosal toxicity (The Hematol J 2003; 4[suppl]: S207). We now update our experience with this regimen. Methods: Pts without disease progression and adequate organ function (creatinine clearance at least 60 cc/min) were eligible. Pts were treated as part of phase I-II trials approved by each center’s institutional review board. AF 740 mg/m2 was given IV over 5–15 min 24 hr and 15 min prior to melphalan 280 mg/m2 (infused over 15 min). Blood stem cells were reinfused 24 hrs later. The primary endpoint was response rate at day 100. Regimen-related toxicity using the Seattle criteria, progression-free (PFS) and overall survival (OS) were also assessed. Results: 24 pts were transplanted between 5/99–7/02. Median age was 50 (32–65) yrs; 1 pt had primary amyloidosis; median beta2-microglobulin level at diagnosis was 1.98 (0.88–11.80) mg/L. Prior therapy included VAD in 14, dexamethasone alone in 7 plus other regimens in 7. Day 100 responses compared with with pre-ASCT values included CR in 11, near CR (immunofixation positivity only) in 1, VGPR (greater than 90% reduction in serum M protein) in 3, PR in 5 and stable disease in 3. Maximum grade of mucositis was 2 (5 pts); no grade 3 or 4 toxicity was seen. The median day of ANC recovery to 0.5 x 109/L and median day of last platelet transfusion were 11 (6–16) and 10 (7–32), respectively. 4 received thalidomide (1 briefly), while 1 was treated with maintenance alpha interferon after day 100. Median follow-up is 52 (9–72) mos. 7 pts are alive without progression, including 5 in CR and 2 in PR. 16 have progressed at a median of 15 (7–36) mos post-ASCT. 8 have died from MM (7) or lung cancer (1). The 4 yr actuarial PFS is 28% (95% C.I. 34–76%) and OS 58% (95% C.I.11–47%). Conclusions: 1) Melphalan 280 mg/m2 with AF is well-tolerated; 2) the CR + nCR + VGPR rate of 62% warrants further evaluation, perhaps as part of tandem transplants or in conjuction with novel agents. [Table: see text]