bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venous Thromboembolic Events in Patients with Diffuse Large B cell Non- Hodgkin’s Lymphoma.
Authors: Komrokji Rami S. , Uppal Nikhil P. , Khorana Alok A. , Lyman Gary H. , Kaplan Karen L. , Fisher Richard I. , Francis Charles W. 
Published: April 2020

Abstract
Background:
Venous thromboembolism (VTE) including deep venous thrombosis (DVT) and pulmonary embolism (PE) is a well-known complication of cancer. VTE frequency varies according to the underlying malignancy. Diffuse large B cell Lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma (NHL). VTE during initial treatment of DLBCL is a complication recognized by treating physicians. Little information is available regarding the frequency of VTE and its association with outcomes in DLBCL. We conducted a retrospective cohort study to determine the frequency and timing of VTE during initial treatment of DLBCL, as well as identifying risk factors associated with VTE, and the clinical impact of VTE on survival.
Methods:
We reviewed records of consecutive patients diagnosed with de novo DLBCL seen at University of Rochester from January 1990 to December 2001. Patients with transformed DLBCL, CNS lymphoma, HIV-related NHL, and patients whose complete records were unavailable were excluded. We considered only episodes of VTE that occurred during the initial treatment of DLBCL. For analysis of risk factors for VTE, Chi-square test or Fisher’s exact test was used to compare the categorical variables and t-test was used to compare continuous variables. Kaplan-Meier estimate was used to compare overall survival between patients with or without VTE. Log-rank test was used to compare statistical differences between survival curves.
Results:
A total of 211 patients with DLBCL were included. VTE occurred in 27 patients (12.8%). DVT occurred in 22, PE occurred in 3, and both DVT and PE in 2. Of all VTE, 37% occurred at diagnosis of DLBCL, and 82% in the first three cycles of treatment. VTE involved the lower limb in 44%. Baseline characteristics were similar between patients with or without VTE regarding age, sex, race, ECOG performance status, histology, B symptoms, LDH, and bone marrow involvement. Fewer patients with VTE, however, were stage I compared to the no VTE group (3.7% vs 27.3 %, P = 0.017). Furthermore, patients with VTE were more likely to be in the high-risk international prognostic index (IPI) category (29.6% vs 10.3%, P = 0.048). Median survival time for patients with VTE was 1.04 years (95% CI 0.75–1.33) compared to 5.2 years for patients with no VTE (95% CI 1.8–8.6) (Log rank test, P = 0.038).
Figure Figure
Conclusion:
VTE is a frequent complication of initial treatment of DLBCL. The majority of cases occur at diagnosis or during the first three cycles of treatment. High-risk IPI is associated with increased incidence of VTE during initial treatment of DLBCL. VTE is a poor prognostic factor and is associated with inferior survival. Clinical trials of thromboprophylaxis are warranted.
Extranodal Non-Hodgkin’s Lymphoma. A Study of 182 Patients with Analysis of Prognostic Factors.
Authors: Pogliani Enrico Maria , Rossini Fausto , Coccini Veronica , Larocca Alessandra , Verga Luisa , Marinoni Sara , Brizio Anna , Elli Elena 
Published: April 2020

Abstract
Starting from 1980, 182 cases of primary extranodal non-Hodgkin’s lymphoma were diagnosed in our Division.
Gastrointestinal NHL were the most frequent: 66 patients (36%), followed by head and neck (42 = 23%), skin(23 =13%), urogenital tract (16 = 9%), CNS (10 =5%), chest (9 = 5%), spleen (7 = 4%), bone (5 = 3%) soft tissues (4 = 2%).
Median age was 55,4 (range 20–91); median age was lower in chest, bone and intestinal NHL.
77 patients had stage I disease (48,8%), 74 stage II (46,5%) and 8 patients stage III (5%).
In the whole group, 134/182 (73.6%) patients achieved complete remission (CR); CRs were 81.8% in gastroenteric NHL, 75% in urogenital, 69.5% in skin, 66.6% in head and neck.
Overall survival in the two most important groups are as follows: head and neck: 61% at 50 months and 55% at 100 months; gastrointestinal tract: at 50 months was 80%, at 100 months 75%.
When prognostic factors were considered for the whole group, stage and modified I.P.I. (MIPI) were significantly associated with rate of complete remission and overall survival.
Stage I pts had a significantly better rate of complete remission 83.1%, vs. 68.9% for stage II and 37.5% for stage III. Overall survival of stage I pts was significantly better than for patients with stage II or stage III disease (80% vs. 72.5% at 50 months; 80.1% vs. 62.7% at 100 months).
Modified International Prognostic Index, MIPI is a score ranging from 0 to 5 according to age (&gt;60), LDH (over normal values), ECOG P.S. (&gt;1), Ann Arbor stage (II or III), extranodal sites (&gt;1). Thirty six patients had a MIPI score of 0, 80 pts MIPI 1, 50 pts MIPI 2 and 16 had a MIPI score of 3 or more. A significant correlation between MIPI and achievement of CR was shown with 88.8% of pts with MIPI 0 achieving CR, 78.5% in MIPI 1, 28% in MIPI 2 and 25% in MIPI 3 or more. Overall survival for the four groups was as follows: 96%, 75%, 62%, 61% at 50 months; 96%, 70%, 54%, 24% at 100 months.
Primary Anaplastic Large Cell Lymphoma of the Breast Occurring in Patients with Silicone Breast Implants.
Authors: Popplewell Leslie , Chang Karen , Olevsky Olga , Nademanee A. , Forman Stephen 
Published: April 2020

Abstract
Primary breast lymphoma (PBL) accounts for up to 1% of all primary breast tumors, and 2.2% of all extranodal lymphomas. The vast majority of PBL are of B-cell origin, most commonly of the diffuse large cell histology. Fewer than 20 cases of T-cell PBL have been reported. We report 6 cases of T-lineage PBL occuring in patients who had previously received silicone breast implants for purposes of breast augmentation. None of the patients had a previous diagnosis of malignancy or unrelated prior breast surgery. In each case, the implants had been placed between 5 and 20 years previously. In each case, lymphoma was confined to breast by staging, and met previously defined criteria for PBL. In 5 cases, the lymphoma was identified as a solid mass involving the breast tissue. In one case, lymphoma cells were identified by flow cytometry in a fluid collection surrounding the implant. The implant was replaced, and the patient has subsequently treated with systemic chemotherapy despite negative PET scan. Thus far, reaccumulation of fluid has not occurred several months following replacement of the implant. In patients for whom follow-up information is available, two recurred following initial therapy and received autologous stem cell transplantation in second complete remission, and remain disease free at 2 years post-transplantation. Since 1995, six cases of PBL associated with breast implants have been reported in the literature, all of which are of T-cell lineage. The majority are of anaplastic large cell type. None of these cases have been previously reported, and this is the largest collection of such reported from a single institution. While previous reports have discounted any link between breast implants and lymphoma, this appears to be a specific association of an unusual lymphoma subtype occuring after a significant time period. Given the increasing number of silicone implant procedures recorded each year in the U.S., this represents an environmental association ripe for further investigation. Establishment of a national database would be appropriate to monitor any potential trends in this entity.
PBL Anaplastic Lymphoma, Immunohistochemistry
Age at Diagnosis ALK-1 CD2 CD3 CD20 CD30 CD43 CD45 32 − + − + + 41 + + + + 40 − + − − + − 54 − − − − + + − 49 + − + + + 62 − − − + − + 31 + − − − + − +
Impact of FDG-PET Imaging Versus Conventional Staging Modalities on Staging and Treatment Decisions in Large B-Cell, Follicular, and Hodgkin’s Lymphomas.
Authors: Maillard Ivan , Elstrom Rebecca L. , Kumar Rakesh , Bozkurt Murat F. , Sankaran Srikant , Guan Liang , Zhuang Hongming , Herman David , Downs Lisa , Alavi Abass , Schuster Stephen J. 
Published: April 2020

Abstract
Clinical staging of lymphomas has a critical role in determining appropriate therapy and in therapeutic response assessment. While anatomic imaging by CT or MRI, together with physical examination and bone marrow biopsy (conventional staging modalities or CSM), have historically provided the basis for staging and response assessment, positron emission tomography using 18-fluoro-2-deoxyglucose (FDG-PET) has increasingly been employed in the management of patients (pts) with lymphomas. Studies comparing FDG-PET with anatomic imaging have generally found that FDG-PET identifies more sites of disease; however, the impact of FDG-PET imaging on assignment of clinical stage and treatment decisions is unclear. We retrospectively examined the impact of FDG-PET imaging on assignment of disease stage and treatment decisions compared with CSM alone in 91 pts with large B-cell lymphoma (LBCL; n=30), follicular lymphoma (FL; n=29) and Hodgkin’s lymphoma (HL; n=32). 25/30 LBCL (83%), 26/32 HD (81%) and 17/29 FL pts (59%) were evaluated at initial diagnosis by FDG-PET imaging and CSM, while others were evaluated during subsequent relapse. FDG-PET and CSM defined the same stage in 69/91 pts (76%). Stage assignment was most concordant in LBCL with only 5/30 (17%) of cases having different stages, while stage assignments were discrepant in 7/32 (22%) of cases of HL and in 10/29 (34%) of cases of FL. Of the 22 pts with discrepant results, FDG-PET resulted in upstaging of disease in 11 pts and downstaging in 11 pts. Independent confirmatory tests resolving the discrepancy were obtained in 3 of 11 pts upstaged (27%) and 7 of 11 pts downstaged by FDG-PET (64%). Abnormal FDG uptake in lymph nodes accounted for all cases upstaged by FDG-PET in which no confirmatory test was available (8/8 pts). Among 10 cases resolved by biopsy, discrepant sites included bone marrow (n = 4), bone (n = 1), pelvic or abdominal structures (n = 3), and lymph nodes (n = 2). FDG-PET results were true positive in 2/10, true negative in 1/10, false positive in 1/10, and false negative in 6/10 cases (including 4 cases with BM involvement). Incorporation of FDG-PET led to treatment changes in a minority of patients (2%). We conclude that FDG-PET is an efficient single imaging modality in pts with LBCL, FL and HL, providing information complementary to CSM. However, changes in treatment based on FDG-PET results are rare. Discrepancies between FDG-PET and CSM should be resolved by biopsy when feasible, particularly in cases in which treatment would be altered.
How Much Rituximab Do We Need: A Multicenter, Randomized Trial Comparing 1, 3 or 6 Infusions of Rituximab Added to 6 Cycles of CHOP Chemotherapy in Untreated Patients with Advanced Follicular Non-Hodgkins Lymphoma (HD2000-Trial).
Authors: Hensel Manfred , Scheuer Lars , Salwender Hans , Finke Juergen , Buerkle Dieter , Duerk Heinz Albert , Kaebisch Andreas , Naumann Ralf , Staiger Hans-Juergen , Schmidt-Wolf Ingo , Kornacker Martin , Leo Eugen , Fischer Joseph , Ho Anthony D. 
Published: April 2020

Abstract
Purpose: The combination of chemotherapy with the chimeric anti-CD20 antibody Rituximab has been reported to be highly active in the treatment of follicular lymphoma. The frequency and dosage of rituximab required to induce the maximum effect in follicular NHL is not defined. To evaluate how often rituximab should be added to standard chemotherapy to achieve maximum remission rates, we have initiated a prospective randomized multicenter phase II study.
Methods: Patients (pts) with stage III/IV CD20 positive follicular NHL who were chemotherapy naïve were randomly assigned to receive 6 courses of a standard CHOP-21 chemotherapy, accompanied by rituximab 375 mg/m2 at day 0 only with the first CHOP course (arm A), with the first 3 CHOP courses (arm B) or with all 6 CHOP courses (Arm C). The major endpoint was the rate of molecular remission in bone marrow and peripheral blood in initially t(14;18)-positive pts, assessed by PCR. Other endpoints of the study were overall and complete response rates, toxicity rate and time to progression.
Results: Since September 2000, 104 pts with a median age of 57 years (range 30–80) were recruited. 33 pts were randomized to arm A, 35 to arm B and 36 to arm C. So far 69 pts have been documented completely after all 6 cycles and are evaluable for side effects. All three treatment arms were well tolerated. The incidence of adverse events and Grade 4 toxicity was similar in all groups. One treatment related death was observed 2 months after completion of therapy due to hepatitis B. The overall response rate (ORR) of the whole group, which was evaluable in 69 pts so far, was 90 % (62 of 69 pts), with 20 complete and 42 partial remissions.
Conclusion: This multicenter, randomized, phase II trial addresses for the first time the optimal frequency and dosage of rituximab infusions in the combined immuno-chemotherapy. In the first interim analysis of the ongoing trial, similar hematologic, gastrointestinal and infectious toxicity was observed in all treatment arms.
Relapse Following Chemotherapy in Aggressive Non-Hodgkin’s Lymphoma Occurs Frequently in Original Sites of Disease.
Authors: Wolf Max , Morgan Susan J. , Wirth Andrew , Reynolds John , Stone Janey , Prince Miles 
Published: April 2020

Abstract
Consolidative radiotherapy (RT) for aggressive NHL assumes that relapse is most likely in sites of initial disease involvement, however there is limited data examining this assumption. We examined patterns of failure in patients (pts) following systemic chemotherapy (CT), to determine factors predicting for site of recurrence.
Methods: In 2 ALLG intermediate-grade NHL studies, 234/519 pts (45%) achieved complete remission (CR) with anthracycline-based CT of whom 169 had full data available. Median age was 55 yr (range: 19–76); ECOG PS ≤2, 94%; bulky disease (≥10 cm), 42 (25%); elevated LDH, 79 (47%); stage I, 14 (8%); stage II, 49 (29%); stage III, 37 (22%); stage IV, 69 (41%). Regimens given were CHOP (45), MACOP-B (48), standard CEOP (epirubicin 75 mg/m2 substituted for doxorubicin) (38) and high dose (cyclophosphamide 1500 mg/m2, epirubicin 150 mg/m2) CEOP (38). Ten pts received RT to involved sites.
Results: Median follow-up time was 7.5 yr (range: 2.3–11.6). At close out, 69 pts (41%) had relapsed and 9 (5.3%) had died. Relapse sites: 24 pts local (14.2%), 21 remote (12.4%), 24 both (14.2%). Log-rank tests revealed earlier stage to be associated with increased time-to-first-failure (p=0.039) but not age, CT, histology (B or T cell), response (CR vs. CRu), bulk, RT or IPI. At 4 yr the estimated percentages of failure-free patients were 71%, 78%, 45% and 67% in stages I to IV, respectively. Early stage predicted local vs distant relapse (p=0.027) (Fisher’s exact test), with failures solely at original sites being 0, 2, 13.5 and 14.5% in stages I to IV respectively.
Conclusion: In this study, 70% of relapses included original sites, 35% solely so. Advanced stage was the strongest predictor of early and local relapse. No other criteria were associated with probability of relapse at original sites. RT potentially could prevent 1/3 of relapses and contribute to prevention of another 1/3, as systemic therapy becomes more effective.
Critical Amplification by Gas6 of the Epo-Dependent Erythropoietic Response to Anemia: Novel Opportunities for Anemia Treatment.
Authors: Angelillo-Scherrer Anne , Burnier Laurent , Fish Richard , Plaisance Stéphane , Martinez-Soria Eduardo , Maxwell Patrick , Collen Désiré , Izui Shozo , Conway Edward M. , Carmeliet Peter 
Published: April 2020

Abstract
Many patients with anemia fail, for unknown reasons, to respond to erythropoietin (Epo) - the key mediator of the erythropoietic response. Here, we report that loss of the growth arrest-specific gene 6 (Gas6), a polypeptide binding the receptor tyrosine kinases Tyro 3, Axl and Mer, caused a significant depletion of the reserve of erythroid progenitors in mice. As a result, the compensatory erythropoietic response to anemia induced by hemolysis or blood loss was defective in mice lacking Gas6 (Gas6−/ −). The impaired erythropoietic response was attributable to the hyporesponsiveness of Gas6−/ − erythroblasts to the survival activity of Epo. Only when recombinant Gas6 (rGas6) was administered together with Epo, did these factors synergistically rescue the mutant mice from anemia. Administration of rGas6 alone to Gas6−/ − mice also provided protection from phenylhydrazine (PHZ)-induced anemia, presumably due to the ability of Gas6 to enhance the pro-survival effects of Epo on erythroblasts. This was supported by in vivo and in vitro findings: (i) In the absence of Gas6, more erythroblasts died in the spleen of PHZ-treated mice, despite markedly elevated levels of Epo. (ii) Compared to WT, Gas6−/ − erythroblasts responded less to the pro-survival effects of Epo in vitro, suggesting that Gas6 signaling influences Epo receptor (EpoR) signaling. Absence of Gas6 did not alter tyrosine phosphorylation of the EpoR, but reduced Akt phosphorylation in erythroblasts when treated with Epo. Akt phosphorylation in Gas6−/ − erythroblasts was, however, restored to WT levels, when co-treated with Epo and rGas6. These findings indicate that Epo/EpoR-mediated erythroblast survival and proliferation is stimulated by Gas6 via the PI3K/Akt pathway. (iii) WT erythroblasts secrete Gas6 when treated with Epo. Together, erythroblasts, via a “Gas6 feedback system”, regulate, in an autocrine manner, their own responsiveness to Epo by reinforcing signaling downstream of EpoR. This mechanism is delicately balanced, since treatment of WT anemic mice with rGas6 alone reversed the acute anemia induced by hemolysis without causing polycythemia. A similar beneficial response in hematocrit restoration was observed when a transgenic mouse model with chronic anemia was treated with rGas6. In these mice, co-administration of rGas6 and Epo resulted in sustained rise in the hematocrit, to higher levels than achieved with Epo or rGas6 alone. Gas6 is therefore effective in chronic anemia, augments the effects of Epo, and may have Epo dose-sparing effects, and thus may provides novel and safe therapeutic approach to treat patients with Epo-resistant anemia.
Sphingosomal Vincristine in CHOP +/− Rituximab Is a Promising New Treatment for Patients with High Risk Untreated Aggressive Non-Hodgkin’s Lymphoma (NHL): Follow-Up Results of a Phase II Study Sphingosomal Vincristine in CHOP +/− Rituximab Is a Promising New Treatment for Patients with High Risk Untreated Aggressive Non-Hodgkin’s Lymphoma (NHL): Follow-Up Results of a Phase II Study.
Authors: Rodriguez Maria Alma , Sarris Andreas , Dang Nam H. , Fayad Luis , Goy Andre , Hagemeister Fredrick , McLaughlin Peter , Pro Barbara , Romaguera Jorge , Samaniego Felipe , Younes Anas , Cabanillas Fernando 
Published: April 2020

Abstract
Sphingosomal vincristine (SV) is a novel formulation of vincristine encapsulated in sphingomyelin liposomes or ‘sphingosomes’. SV was well tolerated with 45% ORR in multiply relapsed aggressive NHL (ASH Abst.412, 1999). The addition of rituximab to CHOP improves response in aggressive B-cell lymphomas in the elderly (Coiffier et al., NEJM2002:346; 235–42). Based on these data, a phase II study of RCHOP, substituting SV for free vincristine, was undertaken in patients with previously untreated aggressive NHL (excluding rituximab if T-cell lymphoma).
Methods: Patients were treated with standard dose CHOP that included SV 2.0 mg/m2 without dose capping ± rituximab 375 mg/m2, given every 21 days for 6 to 8 courses (ASH Abst.338, 2002).
Results: Of 73 patients enrolled in the study, 68 were evaluable for response. Median age was 63 (range 22–80). IPI score was 0–2 in 44 pts and ≥ 3 in 24 pts. Patients received a median of 6 study treatments (range 1–8). ORR was 93% (63/68 pts) with 62 pts achieving CR and Cru (91%), and 1 PR (2%). 3 pts had PD (4%) and 2 were not assessed for response (3%). The median PFS and OS have not been reached at a median follow up of 29.5 months. Responses according to IPI score were as follows:
Results IPI 0–2 (n=44) IPI ≥3 (n=24) Total (n=68) ORR 93% (41) 92% (22) 93% (63) −CR 77% (34) 88% (21) 81% (55) −Cru 14% (6) 4% (1) 10 (7) −PR 2% (1) 0% (0) 2% (1) PD 5% (2) 4% (1) 4% (3) Not Assessed 2% (1) 4% (1) 3% (2)
The probability of being progression free at 25 months was 86% (5 relapses and 1 death, reason unknown) for pts with IPI 0–2 and 77% (6 relapses) for pts with IPI ≥3. Overall survival probability was 94% at 28 months (1 death in the group with IPI 0–2 and 2 deaths in the group with IPI ≥3). Neuropathy was generally mild (Gr.1–2). Hematological toxicities were as follows: 64% Gr.3–4 neutropenia, 6% Gr.3 anemia, and 14% Gr.3–4 thrombocytopenia.
Conclusions: CHOP plus rituximab regimen with sphingosomal vincristine substituted for free vincristine demonstrated promising activity with durable responses similar in both groups of patients with IPI score 0–2 and IPI ≥ 3. The treatment was well tolerated with only mild neurotoxicity.
Phase I/II Study of the Rituximab-EPOCT Regimen in Combination with G-CSF in Patients with Relapsed or Refractory Follicular Lymphoma Including Evaluation of Its Cardiotoxicity Using B-Type Natriuretic Peptide and Troponin T Levels.
Authors: Niitsu Nozomi , Khori Mika , Hayama Miyuki , Higashihara Masaaki , Tamaru Jun-ichi 
Published: April 2020

Abstract
Standard treatment for relapsed or refractory follicular lymphoma has not been established. Doxorubicin (DXR) is often administered during the initial treatment. The dosage or drugs chosen for salvage therapy are limited by DXR-induced cardiomyopathy. Pirarubicine (THP) was developed in Japan as a less cardiotoxic and highly effective anti-neoplastic drug. We previously reported that the THP-COPBLM regimen, in which THP was used instead of DXR, showed the same degree of efficacy as the COP-BLAM regimen and that cardiac sympathetic dysfunction and cardiac mitochondrial damage were less common with THP than with DXR (Leukemia12:1457, 1998). The R-EPOCT (rituximab with etoposide, vincristine, THP, cyclophosphamide, and prednisone) regimen, in which less cardiotoxic THP is used instead of DXR, with G-CSF was administered to 20 patients with relapsed or refractory follicular lymphoma. The safety (especially cardiotoxicity) and efficacy of this regimen were studied. As markers of cardiotoxicity, serum troponin T and plasma B-type natriuretic peptide (BNP) levels were measured. Adverse reactions occurred in 14 of the 20 patients, and mainly consisted of grade 3/4 hematological toxicity. In the evaluation of cardiotoxicity, the BNP level was slightly elevated in 2 patients before the treatment (22.4 pg/ml and 25.6 pg/ml; normal, less than 20 pg/ml). After 4 cycles of treatment, the BNP level in these two patients increased to 26.8 pg/ml and 28.8 pg/ml, respectively, but it returned to approximately the previous level one month after completion of treatment. The troponin T level was undetectable before and after the treatment in all patients. The response rate was 100%, with complete remission in 16 patients (80%). G-CSF administration increased both FcγRI expression on neutrophils and ADCC activity. Upon G-CSF administration during the second cycle of treatment, the level of FcγR1 (CD64) expression on neutrophils increased from 60.1 ± 3.6 (MFI) before G-CSF administration to 324.7 ± 33.2 (p = 0.0005) after 9 days of administration of 2 μg/kg G-CSF. After 11 days of G-CSF administration, the level of FcγR1 expression was 346.2 ± 24.2. The expression of FcαRI (CD89) on neutrophils was examined in a similar fashion. There was no remarkable change in the level of FcαRI expression before and after G-CSF administration. We conclude that the combination of R-EPOCT and G-CSF is well-tolerated. This regimen was not cardiotoxic. We are planning a randomized trial to compare the efficacy between R-EPOCT and a combination of R-EPOCT with G-CSF.