bluuebunny/crossref_metadata_2025_split huggingface dataset:
Majority of Transformed Lymphomas Have High SUVs on PET Scanning Similar To Diffuse Large B Cell Lymphoma (DLBCL).
Authors: Weissler Matthew , Noy Ariela , Schöder Heiko , Gönen Mithat , Yeung Henry 
Published: October 2019

Abstract
Background: In our previous work, we correlated non-Hodgkin’s (NHL) histology with intensity of FDG uptake (SUVmax) on positron emission tomography in untreated patients: an SUVmax greater than 10 predicted an aggressive lymphoma with >80% certainty and an SUVmax greater than 13 predicted an aggressive lymphoma with >90% certainty. We sought to evaluate SUVmax in a series of patients with transformed lymphoma.
Methods: All PET scans for lymphoma indications at our institution 1999–2005 were evaluated. Patients were included if they had biopsy proven transformation. FDG-PET scans were included if they were no more than sixty days prior to or 90 days after biopsy proven transformation. Patients had no therapy for sixty days prior to PET scan unless there was documented progression of disease after the last treatment.
Results: Among the indolent diagnoses (n= 28), the following specific histologies were identified: 7 follicular lymphoma grade I (FL I), 5 follicular lymphoma grade II (FL II), 5 small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), 6 marginal zone lymphoma (MZL) including one of mucosa associated lymphoid tumor (MALT) type, one mycoses fungoides, and one indolent lymphoma otherwise not specified. Three follicular lymphomas grade III (FL III), including one specified as grade IIIa (FL IIIa) were considered indolent if they preceded a diagnosis of DLBCL. Among the aggressive diagnoses (n= 28), the following specific histologies were identified: 22 DLBCL, one follicular lymphoma grade IIIa included as it was preceded by FLI, one large peripheral T-cell lymphoma, and 4 “Large cell lymphoma” (LCL), not otherwise characterized on account of biopsy size. Standard uptake values (SUV) were measured at the biopsy site when possible (n=25). In 3 patients the biopsy site was completely excised before the PET scan. The SUV of biopsy site ranged from 2.9–26.7, with a median of 9 and mean of 11. Excluding the three patients who had an excisional biopsy, 10/25 (40%) biopsies had an SUV above 10; and 8/25 (32%), above 13. The SUVmax for a transformed aggressive lymphoma ranged from 3.2–30.2, with a median of 10.8 and mean of 14. 16/28 (57%) patients had an SUVmax above 10; and 12/28 (43%), above 13.
Conclusions: Similar to patients with de-novo aggressive lymphoma, the majority of patients with transformed lymphomas have high SUVmax for a given pre-treatment staging study. Therefore, transformation to aggressive lymphoma should be suspected in patients with indolent lymphoma found to have high SUVs on FDG PET, and biopsies should be directed to the site of greatest PET avidity whenever feasible.
Achievement of FDG-PET Negativity Does Not Predict Durable Responses in T-Cell Lymphoma.
Authors: Pro Barbara , Nunez Rodolfo F. , Romaguera Jorge , Rodriguez Maria A. , Hagemeister Fredrick , Fayad Luis 
Published: October 2019

Abstract
Background: T-cell non-Hodgkin’s lymphomas represent approximately 12% of all lymphomas and in general are associated with a worse prognosis compared to their B-cell counterparts. In patients with Hodgkin’s disease and aggressive B-cell lymphoma (18F)fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) represents an important early prognostic tool for predicting outcome. Very little information is available regarding the role of FDG-PET in T-cell lymphoma.
Patients and Methods: A total of 20 patients with newly diagnosed and histologically proven T/NK cell lymphomas where staged with both conventional methods and whole-body PET scanning. Patients underwent FDG-PET, concurrently with CT of neck, chest, abdomen, and pelvis within 3 weeks prior to induction treatment, after 2–4 cycles, and after the end of induction. All patients but three received HCVIDDoxil, using pegylated liposomal doxorubicin as a substitute for doxorubicin in the HyerCVAD regimen, alternating with methotrexate and cytarabine. Three patients received the standard CHOP (cyclophosphamide,hydroxydaunomycin, vincristine, prednisone) regimen. According to the International Prognostic Index (IPI), 35% of patients were stratified as low risk, 25% as low/intermediate, 35% as high/intermediate, and 5% as high risk. Baseline scans were strongly positive in all patients.
Results: During induction therapy (at 2–4 cycles) FDG-PET became negative in 16 (80%) patients and remained positive in 4 (20%) patients. Twelve out of 16 (75%) patients who were PET negative during induction therapy relapsed, and four out of four (100%) in the PET positive group. Two of the “ early” PET negative patients became positive after 4 cycles. Median progression-free survival was 240 days in the PET negative group and 85 days in the PET positive group (Log-rank p=0.07).
Conclusions: In this limited number of patients homogeneously treated with newly diagnosed T cell lymphomas the assessment of metabolic activity by FDG-PET during induction therapy did not predict long-term prognosis.
Human Mesenchymal Stem Cells Isolated from Bone Marrow and Lymphoid Organs Support Tumor B-Cell Growth: Implications in Follicular Lymphoma Pathogenesis.
Authors: Tarte Karin , Ame-Thomas Patricia , Hajjami Hélène Maby-El , Monvoisin Céline , Jean Rachel , Lamy Thierry , Fest Thierry 
Published: October 2019

Abstract
There is accumulating evidence that cellular microenvironment plays a key role in follicular lymphoma (FL) pathogenesis, both within tumor lymph nodes (LN) and in infiltrated bone marrow (BM) where ectopic LN-like reticular cells are integrated within malignant B-cell nodular aggregates. In normal secondary lymphoid organs, specific stromal cell subsets provide a highly specialized microenvironment that supports immune response. In particular, fibroblastic reticular cells (FRC) mediate immune cell migration, adhesion, and reciprocal interactions. The role of FRC and their postulated progenitors, i.e. bone marrow mesenchymal stem cells (MSC), in FL remains unexplored. In this study, we have investigated the relationships between FRC and MSC and their capacity to sustain malignant B-cell growth. Our findings strongly suggest that secondary lymphoid organs contain bona-fide MSC able to give rise at single-cell level to adipocytes, chondrocytes, and osteoblasts. These LN-derived MSC could also differentiate, in response to a combination of tumor necrosis factor-α (TNF) and lymphotoxin-α1β2 (LT), into fully functional FRC, able to construct a dense extracellular reticular meshwork positive for transglutaminase and fibronectin staining, to produce inflammatory (CXCL9, CXCL10, CCL5, CCL2) and LN-specific (CCL19) chemokines, and to favour lymphoma B-cell growth. Bone marrow-derived MSC (BM-MSC) acquire in vitro a complete FRC phenotype in the same culture conditions. As an exemple, BM-MSC had a strong, although not complete, protective effect on serum deprivation-induced apoptosis of BL2 cell line (mean percentage of CD20posCaspase-3pos cells: 24.8 +/− 17.5% in coculture with BM-MSC versus 80.7 +/- 10.4% in medium alone; P < .05; n =5) and pretreatment with TNF/LT fully restored BL2 viability (mean percentage of CD20posCaspase-3pos cells: 7.4 +/− 4.7%; P < .05; n = 5). Moreover, stimulation of stromal cells by TNF/LT before coculture enhanced the number of viable CD19pos primary FL B cells by 2.4-fold for BM-MSC and 2.3 fold for LN-MSC compared with the culture without stromal cells (P < .05; n = 6). Interestingly, cell contact with lymphoma B-cell lines or purified FL B cells trigger the differentiation of BM-MSC into FRC that, in turn, support malignant B-cell migration, adhesion and survival. Altogether, these new insights into the interactions between lymphoma cells and their microenvironment could offer original therapeutic strategies.
CNOP (Mitoxantrone) Chemotherapy Is Inferior to CHOP (Doxorubicin) in the Treatment of Patients with Aggressive Non-Hodgkin Lymphoma (Review).
Authors: Bjorkholm Magnus , Osby Eva , Andersson Tomas , Ahlbom Anders 
Published: October 2019

Abstract
Introduction: Mitoxantrone (M), an anthracenedion, was introduced in the early/mid 1980s as a more tolerable alternative to anthracyclines. This agent has a broad anti-tumour activity including lymphoma with potentially less cardiotoxicity than doxorubicin (D), which may be of particular importance in the elderly patient population. However, an important issue is whether M is as efficacious as D in the treatment of NHL patients.
Methods: Through search of several relevant databases and direct contacts with lymphoma investigators worldwide, we identified seven randomized studies of previously untreated patients comparing CHOP and CNOP chemotherapy in aggressive NHL. In this analysis we included five trials where (D;50mg/m2) was compared with (M;10–12mg/m2; table) and the interval between chemotherapy courses was 3–4 weeks. Patients reported in the Pavlovsky article were included in the Bezwoda report, why analyses were performed separately with either but not both of these reports. Odds ratios of complete remission (CR) and overall survival (OS) were pooled using a fixed effects model.
Results: CHOP was significantly superior to CNOP with regard to both CR rate and OS (figure a–b). No formal testing of side effects could be made. However, myelosuppression was similar with both regimens as was the incidence of infections and neutropenic fever episodes. In addition, clinical evidence of symptomatic congestive heart failure was not more frequent among patients treated with CHOP. In contrast, the incidence of gastrointestinal toxicity and alopecia was significantly higher in this patient group.
Conclusion: CHOP chemotherapy is more efficacious than CNOP at equitoxic (myelosuppression) doses leading to higher CR rates and improved survival. This regimen is, however, also associated with more alopecia and gastrointestinal toxicity.
Table Randomized trials comparing doxorubicin (CHOP) with mitoxantrone (CNOP) in untreated patients with aggressive NHL
Figure Figure
Efficacy and Safety of DepoCyte® (Liposomal Cytarabine) in Patients with CNS Involvement from Non-Hodgkin’s Lymphoma (NHL): A Report on 32 Patients Treated in Spain.
Authors: García-Marco José A. , Navarro B. , Ruiz Sanz E. , Palomera L. , Capote F.J. , de Sevilla A. Fernández , Sánchez E.G. , Cantalapiedra A. , Pérez R. , Casal J.R. , Mediavilla J.D. , García F.R. , Martín Y. , Panizo C. , Alvarez A.L. , García T. , Pérez G. 
Published: October 2019

Abstract
Lymphomatous meningitis (LM) occurs in approximately 7–15% of patients with lymphoma and carries an extremely poor prognosis (Chamberlain et al. CNS Drugs1998;10:25; Chowdary & Chamberlain J Natl Compr Canc Netw2005;3:693). Intrathecal (IT) chemotherapy with standard agents (cytarabine, methotrexate and thiotepa) is limited by the need for multiple injections per week via lumbar puncture or an Ommaya reservoir. Liposomal cytarabine (DepoCyte®) has an extended half-life in cerebrospinal fluid that permits fortnightly administration, improving convenience and reducing the potential for injection-related trauma and infections. Thirty-two Spanish patients (median age 43.5 years [range 19–78]; 22 male) with NHL received IT liposomal cytarabine for the treatment of LM between 2004 and 2006 at 21 treatment centers. Half of the patients had diffuse large B-cell lymphoma (DLBCL; n = 16); the remainder had Burkitt’s lymphoma (n = 4), T-cell NHL (n = 3), mucosa-associated lymphoid tissue lymphoma (n = 3), lymphoblastic lymphoma (n = 2), follicular lymphoma (n = 2) or primary CNS lymphoma (n = 1). A full histological diagnosis was not available for 1 patient. The dosage of liposomal cytarabine was 50 mg per cycle, with a median of 4 cycles (range 1–10). All patients received oral dexamethasone (4 mg 2–4 × daily for 4–7 days per cycle) as prophylaxis for chemical arachnoiditis. Neurological and cytological responses were obtained in 20 (62%; 16 complete responses, 4 partial responses; Figure 1) and 25 (78%) patients, respectively. Neurological progression was subsequently reported in 23 (72%) patients, with a median time to progression of 45 days (range 7–570). Twelve patients were still alive at the time of reporting, including 5 of 16 patients with DLBCL and 2 of 3 patients with T-cell NHL. Eighteen patients reported no adverse effects from treatment. The most commonly reported adverse effects were headache (n = 11), nausea (n = 4) and vomiting (n = 4). Data from this case series show that IT liposomal cytarabine is effective and well tolerated in the treatment of LM; the less intensive administration schedule of the agent may offer additional benefits to patients and their carers during the final months of life.
Figure Figure
Necessity of Intraventricular Chemotherapy with the Modified Bonn Protocol in Primary CNS Lymphoma (PCNSL) Patients.
Authors: Schmidt-Wolf Ingo G.H. , Pels Hendrik , Juergens Annika , Glasmacher Axel , Schulz Holger , Kroschinsky Frank , Egerer Gertlinde , Lamprecht Monika , Wismeth Caecilia , Schlegel Uwe 
Published: October 2019

Abstract
Background: Treatment of primary CNS lymphoma (PCNSL) with a combined systemic and intraventricular chemotherapy (Bonn protocol) has achieved an overall response rate (ORR) of 84% and long term complete remissions in a substantial fraction of patients younger than 60 years.
Purpose: Due to a high infection rate of the Ommaya reservoir the question was addressed if intraventricular treatment is dispensable in this polychemotherapy protocol.
Patients and Methods: Fifty patients with histologically confirmed PCNSL were enrolled onto a phase II-study evaluating chemotherapy without radiotherapy and without intraventricular treatment. A high-dose methotrexate (MTX) (cycles 1,2,4,5) and cytarabine (ara-C) (cycles 3,6) based systemic therapy (including dexamethasone, vinca-alkaloids, ifosfamide and cyclophosphamide) was administered.
Results: In an ongoing trial thirty-five of 50 patients (18 pat. < 60 years, 17 pat. over 60 years) are yet assessable for response after a median follow up of nine months (range: 1 to 26 months). In 18 patients < 60 years, the ORR was 78%. However, median time to treatment failure (TTF) was eight months, and median progression free survival (PFS) only 7 months according to frequent early relapses.
Conclusions: Early relapses are frequent in younger patients treated with the modified Bonn protocol without intraventricular treatment despite a high ORR. These preliminary results support the assumption that intraventricular treatment is essential to achieve sustained remissions after successful treatment of PCNSL.
Phase II Study of Proteasome Inhibitor Bortezomib (Velcade®) in Patients with Relapsed/Refractory T-Cell Lymphoma: Preliminary Results.
Authors: Zinzani Pier Luigi , Tani Monica , Musuraca Gerardo , Stefoni Vittorio , Marchi Enrica , Fina Mariapaola , Baccarani Michele 
Published: October 2019

Abstract
The mechanisms by which Bortezomib elicits its antitumor activity may vary among tumor types, and the extent to which each affected pathway is critical to the inhibition of tumor growth could also differ. The aim of this study was to determine the efficacy and toxicity of Bortezomib in previously pretreated patients with peripheral T-cell lymphoma unspecified (PTCLU) with only skin involvement and cutaneous T-cell lymphomas (CTCL). Eligibility criteria included PTCLU or CTCL (according to REAL/WHO classification) with measurable disease; any stage, any IPI, any bone marrow status; second or more relapse or refractory disease; age ≥18; ECOG performance status ≤ 2; Hb ≥10 g/dL, ANC ≥ 1.5x109/L and platelets ≥ 100 × 109/L; normal hepatic, renal and cardiac functions; and voluntary written informed consent. Bortezomib was given at 1.3 mg/m2 IV push on days 1, 4, 8 and 11 every 21 days. Restaging was done every 2 cycles. Patients were treated for up to a total of 6 cycles unless removed from study for failure to respond or toxicity. The response criteria were those recommended by NCI sponsored Working Group. At data reporting for this abstract, 15 patients were enrolled and 12 were evaluable for response. Of these 12 patients, 10 had CTCL and 2 PTCL; 11 were male and 1 female; 6 were aged >60 years (range 48–80). Overall response rate was 67% (2 CR + 6 PR) and the remaining 4 patients had PD. Histologically the responder patients were 7 CTCL and 1 PTCL. Time to event analyses, including TTP and duration of response are pending further follow-up. Treatment was well tolerated; grade ≥ 3 AEs were seen in 5 patients. The most common grade ≥ 3 AEs were neutropenia, thrombocytopenia and peripheral neuropathy. These preliminary data indicate that Bortezomib is active as a single agent for patients with relapsed/refractory CTCL and PTCL with skin involvement. Final efficacy and safety data will be presented.
New and Comprehensive Cytogenetic Prognostication and Categorization in MDS.
Authors: Haase Detlef , Germing Ulrich , Schanz Julie , Pfeilstoecker Michael , Noesslinger Thomas , Hildebrandt Barbara , Kuendgen Andrea , Luebbert Michael , Giagounidis Aristoteles , Aul Carlo , Truemper Lorenz , Mueller Thomas , Valent Peter , Fonatsch Christa , Steidl Christian 
Published: October 2019

Abstract
The International Prognostic Scorig System (IPSS) was established on the basis of a multicentric analysis of 816 pts. with MDS with 327 individuals (40%) showing clonal cytogenetic abnormalities. Analyses of survival and clinical courses were performed for 11 cytogenetic subgroups. Although the IPSS represents a main and meritorious progress in prognostication in MDS it has shortcomings resulting from the limitated number of pts. Thus, little is known about the prognostic impact of rare and combined anomalies and a lot of abnormalities are assigned to the intermediate prognostic group without knowing their actual prognosis. It was our aim to refine the cytogenetic prognostic categorization in MDS. For this purpose we created a multicentric German-Austrian database of 2072 pts. with MDS and successful cytogenetics of whom 1080 individuals (52%) had clonal abnormalities. Of this group 1202 individuals were treated with supportive care only, and had a well-documented follow-up and blast count. For this group we defined 23 cytogenetic prognostic subgroups (at least 5 pts. with the same abnormality) also considering the number of accompanying abnormalities. Every subgroup was categorized in relation to the IPSS-categorization according to blast counts and a comparison of survival times. The following subgroups (all either isolated or with only one additional abnormality except the complex cases) were thus established: 9q- (median survival: not reached (nr), categorization: good); 15q- (nr, good); t(15q) (nr, good); 12p- (108, good); +21 (108, good); 5q- (77.2, good); −X (56.4, good); normal (53.4, good); −Y (39.0, good); t(1q) (34.7, good); t(7q) (34.7, good); t(11q) (32.1, good); −21 (32.0, good); 11q- (26.1, intermediate I); +8 (int I); +19 (19.8, int II); 7q- (19.0, int II); any 3 abnorm. (17.1, int II); complex with 3 abnormalties (17.0, int II); −7 (14.0, int II); complex with more than 3 abnormalities (8.7, poor); t(5q) (4.4, poor). Applying our new categorization the following results were obtained: good risk (n=802 pts., ms: 55.4 mo); int I (n=170, 29.4 mo); int II (n=103, 14.6 mo); poor (n=127, 8.1 mo). The differences between the respective Kaplan-Meier curves were highly significant (p=0.0000). Our findings could be the basis for a new comprehensive cytogenetic scoring system covering most pts. with MDS by a now well-known prognosis.
Randomized Comparison of Cladribine Single (C) or in Combination with Cyclophosphamide (CC), and COP in Previously Untreated Low Grade B-Cell Non-Hodgkin Lymphoma Patients.
Authors: Kalinka E. , Wajs J. , Sulek K.S. , Blasinska-Morawiec M. , Centkowski P. , Ceglarek B. , Robak T. , Holowiecki J. , Mazur G. , Federowicz I. , Jedrzejczak W. , Watek M. , Warzocha K. 
Published: October 2019

Abstract
To comparatively assess first-line treatment with cladribine single (C) or in combination with cyclophosphamide (CC), and COP (cyclophosphamide, vincristine, prednisone) in low grade B-cell non-Hodgkin lymphoma (NHL), previously untreated patients (pts) with Ann Arbor stage II-IV were randomly allocated to receive 6 monthly courses of either C, CC, or COP. End points were treatment response, freedom from progression (FFP) and overall survival (OS), and tolerance. From June 1, 2000 to June 30, 2005, 196 pts were randomized in 17 centers. Of 153 pts for whom data is available, 55 (36%) were diagnosed as small lymphocytic, 11 lymphoplasmocytoid (7%), 37 marginal-zone (24%), 42 follicular (27.5%), and 8 not otherwise specified low grade B-cell NHL (5.5%). Randomization constituted comparable groups, including International Prognostic Index variables. Compared to C and CC, COP induced lower overall response rates (75%, 90%, 50%, χ2 =7.9 p<.005), including lower complete remission rates (38%, 62%, 9.5%, χ2=19.2 p<.0001). With a median follow-up of 15 months, FFP was superior in patients receiving cladribine-containing regimens (χ2 = 21.8, log-rank p<.0001). No difference in median OS was observed. Incidences of infections (9% versus 3.5% versus 7%) and non-hematological side effects (7.5% versus 3.5% versus 7%) were similar in the randomized groups, whereas CC but not C induced more frequent peripheral cytopenias compared to COP (30% versus 11%, p=.034). This resulted in higher frequency of prolongation of intervals between CC versus COP treated pts (respectively 45% and 21%, χ2=6.04 p=.014) and C versus CC treated pts (respectively 26% and 45%, χ2=4.24, p=.039). Dose reductions because of hematological or other toxicity were comparable in C (9.5%), CC (20%), and COP (21%) groups. Although final results warrant completed data for all randomised pts with longer follow-up, similar tolerance and higher efficacy of cladribine-based regimens over COP provide rationale to combine C or CC with rituximab in future clinical trials.