bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rituximab Combined with M/VACOP-B and Radiotherapy in Primary Mediastinal Large B-Cell Lymphoma (PMLBCL): A Prospective Italian Phase II IIL Study.
Authors: Martelli Maurizio , Stefoni Vittorio , Cabras Giuseppina , Cortellazzo Sergio , Brusamolino Ercole , Levis Alessandro , Botto Barbara , De Vivo Antonio , Natalino Fiammetta , Erica Finolezzi , Foa Robert , Zinzani Pier Luigi 
Published: April 2020

Abstract
Background: Third generation regimens such as MACOP-B or VACOP-B (M/VACOP-B) in combination with involved-field radiotherapy (IFRT) seem to improve lymphoma-free survival of PMLBCL. The superiority of R-CHOP over CHOP-like regimens has been recently demonstrated in younger low risk DLBCL. Recently, the addition of Rituximab to CHOP has also improved survival in PMBLCL.
Aims: To evaluate the effectiveness and safety of Rituximab added to the standard M/VACOP-B regimens (R-M/VACOP-B) +/− IFRT in PMLBCL.
Patients and Methods: A total of 40 patients with PMLBCL has so far been treated in the six participating centers between February 2002 and July 2005. The median age was 38 years (range 17–54); 21/19 (53%) were females; 30 patients had stage II and 10 stage IV; 38 (95%) presented a bulky disease; LDH was increased in 26 (65%) and 21(53%) had a superior vena cava syndrome. According to the age-adjusted IPI score, 24 patients had an IPI = 0–1 and 16 an IPI = 2–3. All patients were treated with standard MACOP-B (30 patients) or VACOP-B (10 patients) regimens plus six cycles of Rituximab (375mg/m2) given at weeks 3, 5, 7, 9, 11 and 13. Twenty-six patients (65%) received mediastinal IFRT at a median dose of 36 Gy. The response was evaluated in all patients after six cycles of chemo-immunotherapy, at the end of the planned chemotherapy and after IFRT.
Results: The response rate after six cycles of the scheduled R-M/VACOP-B regimen was CR/CRu = 20 (50%), PR = 19 (47%) and NR = 1 (3%). Eight of the 40 patients received a second line therapy followed by HDT-ASCT (6/8 patients) because considered as low responders (PR = 7 and NR = 1). At the end of the chemo-immunotherapy program, 28 patients witnessed a CR/CRu (70%) and 12 a PR (30%). Seven of the 12 PR patients obtained a CR/CRu following IFRT for an overall CR/CRu rate of 87% (35/40). After a median follow-up of 13 months, the 2-year OS and PFS are 75% and 78%, respectively. No additional toxicities other than those related to chemotherapy were observed during and after Rituximab infusion.
Conclusions: R-M/VACOP-B are active therapeutic regimens devoid of severe toxicity for the management of patients with PMLBCL. The addition of Rituximab to M/VACOP-B regimens does not seem to improve the lymphoma-free survival of this group of patients. An update of these results on a broader number of patients will be presented at the meeting.
Single Institution Experience with Y-90 Ibritumomab Tiuxetan in the Treatment of Non-Hodgkin Lymphoma.
Authors: Martin Peter , Michel Rene , Galal Ahmed 
Published: April 2020

Abstract
Background: Radioimmunotherapy (RIT) is an effective treatment of Non-Hodgkin Lymphoma (NHL). Nonetheless, the use of RIT outside of clinical trials has been limited. We report here the experience in 25 patients treated with Y-90 ibritumomab tiuxetan off-protocol at a single institution.
Patients and Methods: The charts of all patients treated with RIT between October, 2004 and May, 2006 were retrospectively reviewed in accordance with Good Clinical Practice guidelines. 19 patients were treated with RIT alone while 6 were treated with RIT in combination with high-dose chemotherapy and autologous hematopoietic stem cell transplant (HSCT). Dosimetry was not performed.
Results: The median age of patients was 56 years (range 43–71 years). 13 of 25 had high-grade lymphoma (either transformed lymphoma or diffuse large B-cell lymphoma). The median IPI was 3. The median number of prior regimens was 3 (range 1–6). 6 patients had received fludarabine. 3 patients had undergone prior autologous HSCT and one had undergone allogeneic HSCT. The median time to platelet recovery &gt;20 × 109/L was 35 days. One patient continues to have platelets &lt;20 × 109/L 380 days post-RIT. The median time to recover platelets to &gt;20 × 109/L was 72 among patients who had previously received fludarabine. Prior HSCT also appeared to be associated with prolonged thrombocytopenia. 7 patients remained neutropenic (ANC&lt;0.5 × 109/L) for &gt;30 days. One patient who had been treated with 4 lines of prior chemotherapy, including prolonged chlorambucil, developed acute myeloid leukemia at 6 months post-RIT. There have been 3 deaths to date, all due to disease progression at 1, 1, and 3 months post-RIT. The overall response rate in 21 of 25 patients was 84% with 9 patients achieving CR. With a median follow-up of 7 months, 5 patients have progressed.
Conclusion: The use of off-protocol RIT in our institution was associated with similar response rates to those reported in patients treated on-protocol. Off concern, however, is the significant hematologic toxicity. There was an association between prior fludarabine and prolonged thrombocytopenia that has not been reported previously.
Late Onset Neutropenia like a Complication of Treatment with Anti-CD20.
Authors: Rubio-Martinez Araceli , Recasens Valle , Godoy Ana , Padron Noelia , Giraldo Pilar 
Published: April 2020

Abstract
Introduction: The occurrence of unexplained peripheral blood cytopenia, particularly neutropenia, has been recently reported after rituximab ®. Its prevalence may be underestimated since it may occur late after treatment (Cattaneo C et al Leuk Lymphoma. 2006 Jun;47(6):965–6, Chaiwatanatorn K et al Br J Haematol 2003). Apparently the risk is higher when R is associated with Fludarabine in combination therapy, producing a decrease in bone marrow precursors. Patients and methods: observational and retrospective study in order to determine the incidence of WHO grade III – IV neutropenia (neutrophils: ≤ 0.6×109/L) and the development of infection complications in patients treated with R-CMF or R-CF in our hospital from 6/8/2003 to 20/3/2006. We have compared these data with the incidence of delayed neutropenia during 621 courses of R or R-CHOP administered as outpatient schedule in the same period.
Data source: clinical reports. Variables: demographic data (age, gender), date of diagnosis, histological type, schedule therapy, number of cycles, clinical response (complete remission (CR), partial remission (PR), and non response (NR), prophylaxis with G-CSF, blood counts (leucocytes, neutrophils, hemoglobin and platelets) during all treatment and follow-up, infections and number of admissions in the hospital. Kaplan-Meier survival and Cox regression were calculated.
Results: From 78 courses of Immuno-chemotherapy in 16 consecutive patients diagnosed of follicular NHL: 10, B-CLL: 5, mantle NHL: 1. R-CMF (14 patients), R-CF (2 patients). (9 males/7 females), mean age 58.75 (20–78). In first line 8, second line 6 and third line 2. Number of courses received: mean 4,8 (1–6). Response: CR:13, NR: 1, Non valuable: 2. G-CSF prophylaxis during therapy in 50%. 9 patients (56.2%) developed neutropenia during the treatment or in the following year, one of them had also anemia and thrombocytopenia. In 4 patients the combination therapy was administered in first line, 3 as second line and 2 as third line therapy. Patients received 5 (6 courses), 1 (5 courses), 1 (3 courses), 1 (2 courses) and 1 (1 course), 8 developed infections that required admission into hospital (1 died after third course by sepsis). Another two patients developed severe infections without neutropenia. A late and persistent neutropenia after to finish therapy (1–6 months later), was observed in 4 patients (duration:3, 12, 11 and 4 months); 2 patients got over at 11 and 12 months after and in two of them is present now. They were treated with G-CSF, prednisone and cyclosporine in 2 cases without response and reached normal values when we associated IV immunoglobulins extract. OS: mean 26.4 months (6–49), RFS: 10.6 months (1–30).
Conclusions: Delayed-onset cytopenia, particularly neutropenia, is a clinically significant complication of rituximab treatment when it is administered in combination with Fludarabine increasing the risk of severe infections.
Comprehensive Analysis of Homeobox Genes in Hodgkin Lymphoma Cell Lines Identified Dysregulated Expression of HOXB9 Mediated by Constitutive Active ERK5 Signalling Pathway and BMI1.
Authors: Nagel Stefan , Burek Cristof , Venturini Letizia , Scherr Michaela , Quentmeier Hilmar , Meier Corinna , Rosenwald Andreas , Drexler Hans G. , MacLeod Roderick A.F. 
Published: April 2020

Abstract
Within the human genome nearly 200 homeobox genes have been identified. These are functionally involved in distinct developmental processes during embryogenesis and in the adult. Many have been implicated in cancer mostly following ectopic expression. In this study, we analyzed homeobox gene expression in Hodgkin lymphoma (HL) cell lines using degenerate primers for RT-PCR and Affymetrix U133A expression arrays followed by extended RT-PCR analysis of candidate homeobox genes in additional hematopoietic cell lines. We identified upregulated HOXB9 expression in HL, as well as in anaplastic large cell lymphoma and mediastinal B-cell lymphoma cell lines. Analysis of HOXB9 regulation in HL cells revealed activation by E2F3A, and repression by BMI1, respectively. Constitutive ERK5 pathway activation was identified in all HL cell lines analyzed together with primary HL lymph nodes biopsies. Our data show that ERK5 regulates HOXB9 expression, probably mediated via BMI1 repression. Expression analysis of microRNA gene mir-196a1 which is located upstream of HOXB9 indicated coregulation together with HOXB9. Functional analysis of HOXB9 by knockdown or overexpression assays revealed its influence in both proliferation and apoptosis in HL cells. In summary we identified upregulated expression of HOXB9 in HL, and its regulation mediated by constitutively active ERK5 signalling, thus representing novel therapeutic targets in both HL and NHL subtypes.
Response to Re-Treatment with Rituximab Plus Salvage-Chemotherapy in Refractory or Relapsed Aggressive Non-Hodgkin’s Lymphoma.
Authors: Borgerding Andrea , Hasenkamp Justin , Chapuy Bjoern , Truemper Lorenz , Wulf Gerald , Glass Bertram 
Published: April 2020

Abstract
The efficacy of re-therapy with rituximab immuno-chemotherapy was analysed in 20 consecutive patients with relapsed or progressive aggressive Non Hodgkin’s lymphoma after initial treatment with rituximab plus chemotherapy. Ten patients had a diffuse large B-cell lymphoma, seven had a mantle cell lymphoma and three a grade III follicular lymphoma. At primary diagnosis, the IPI was high-intermediate or high in 75% of the patients and the median age was 55 years (range 36–72 years). The overall response rate of primary immuno-chemotherapy was 75% (15/20 patients) with a complete remission in 8/20 patients (40%). After relapse, 53 % of these patients (8/15) responded again to immunochemotherapy: two patients had a second complete and six a second partial remission. None of the five patients with primary progressive disease responded to a conventional immuno-chemo salvage therapy. After re-therapy with rituximab plus salvage chemotherapy, ten patients received at least one cycle of high dose chemotherapy followed by SCT. One patient did receive HD-chemotherapy and an autologous graft solely, two patients did receive HD-radio-immunotherapy followed by an autologous graft and seven patients finally received HDT and an allogeneic transplant. Allogeneic SCT resulted in a CR in 6 out of 7 patients. One of these ten patients relapsed after HDT consolidation. Six out of ten patients without HDT consolidation after immuno-chemotherapy progressed after secondary treatment, 4 patients are alive without progression (SD, PR) but follow up is short (7, 10, 13 and 16 months). Conclusion: A substantial proportion (53%) of patients with relapse after rituximab immuno-chemotherapy did response to rituximab containing salvage therapy. Patients with progressive disease under immuno-chemotherapy did not respond to such salvage therapy. Without additional consolidation by HDT the risk of progression after successful salvage with rituximab and salvage-chemotherapy is high.
Pentostatin Combined with Cyclophosphamide, and Rituximab Induces High Response Rates in Patients with Untreated Indolent B-Cell Lymphoma.
Authors: Samaniego Felipe , Fayad Luis E. , Pro Barbara , McLaughlin Peter , Rodriguez Maria Alma , Hagemeister F.B. , Fanale Michelle , Neelapu Sattva , Younes Anas , Kwak Larry W. 
Published: April 2020

Abstract
The addition of rituximab to combination chemotherapy has improved treatment outcomes of indolent lymphomas. Combination therapy with purine analogs, akylating agents, and monoclonal antibodies is a promising approach for treating indolent B-cell lymphoma. Nucleoside analog-based regimens selectively target lymphoid cells, making them attractive drugs for lymphoid cancers. Pentostatin is a nucleoside analog that compared with other nucleoside analogs appears to have less bone marrow cell toxicity. The combination of pentostatin, cyclophosphamide, and rituximab (PCR) is an effective regimen for relapsed chronic lymphocytic leukemia and relapsed indolent B-cell lymphoma. In this study, we examined the efficacy of pentostatin, cyclophosphamide, and rituximab for the treatment of B-cell lymphoma. Pentostatin (4 mg/m2), cyclophosphamide (600 mg/m2), and rituximab (375 mg/m2) were given on day 1 of a 21-day cycle with restaging after every 3 cycles. Patients received prophylaxis with acyclovir 400 mg/po bid and trimethoprim-sulfamethoxazole 3 times per week. Small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), was stained for ZAP70 staining and immunoglobulin heavy chain gene mutations. At the time of abstract submission, 29 patients are eligible for response and toxicity. There were 12 patients with follicular lymphoma, 13 with SLL/CLL, and 4 with mucosa-associated lymphoid tissue (MALT), and the median age was 63 years. This regimen was used as first-line therapy for 26 patients and second-line therapy in 3 patients. We observed an overall response of 27 out of 29 (93%), CR/CRu in 19 out of 29 (65%), PR in 8 out of 29 (27%), and mixed response in 2 out of 29 (7%). The main toxicities were nausea and vomiting. No prolonged pancytopenia or myelodysplasia were observed. The correlation of ZAP70 and immunoglobulin heavy chain gene mutations with response is ongoing. Our preliminary data demonstrate that PCR therapy is an effective regimen in previously untreated indolent lymphoma.
Phase II Study of Denileukin Diftitox (ONTAK®) in Patients with Relapsed/Refractory B-Cell Non-Hodgkin’s Lymphoma (B-NHL) and Poor Bone Marrow Reserve.
Authors: Czuczman Myron S. , Pinter-Brown Lauren , Lechowicz Mary Jo , Bartlett Nancy , Lazarus Hillard , Lister John , Goy Andre , Kahanic Stephen , Rosen Peter , Acosta Mark 
Published: April 2020

Abstract
Therapeutic options for patients (pts) with relapsed/refractory B-NHL and poor bone marrow reserve are limited. Denileukin diftitox (DD), a recombinant fusion protein, which when given at the standard dose, is not myelosuppressive and achieved a response rate of 25% in pts with relapsed/refractory B-NHL (Dang JCO22:4095–4102, 2004). We conducted a phase II, open label, multi-site study to evaluate efficacy and tolerability of DD given weekly in pts with relapsed/refractory B-NHL who had diminished bone marrow reserve. This is the first study of DD in NHL to use a dosing regimen other than the standard 18 mcg/kg/day for 5 days repeated every 21 days. Pts were required to have failed to respond or have progressive disease (PD) after ≥2 prior treatment regimens, bi-dimensional disease of at least 4cm2, and mild to moderate cytopenia defined as one or more of the following: ANC ≥1000 but &lt;1500, platelets ≥40,000 but &lt;150,000, and WBC ≥2000 but &lt;4000, or have relapsed after prior stem cell transplantation (SCT). Denileukin diftitox was administered at 18 mcg/kg/day ×3 days followed by 21 mcg/kg weekly. Evaluation of response was performed after 8 wks of treatment, and pts with stable disease or objective response were to receive another 8 weekly infusions. Twenty-two pts enrolled; the median age was 67 yrs (range 45–78), median number of previous treatments was 4 (range 2–9), 12 had prior SCT. There were 14 pts with diffuse large cell lymphoma (DLCL), 5 follicular lymphoma (FL), and 3 small lymphocytic lymphoma (SLL). The median lesion size at entry was 21cm2 (range 10–598cm2). Twenty of 22 pts discontinued therapy prematurely, 14 due to PD, 1 with SD, and 5 due to toxicity. The median number of weekly doses given was 4 (range 1–16). No objective responses have been observed to date and enrollment has been suspended. Fourteen pts are alive (10 DLCL, 3 FL, 1 SLL) ranging from 2–14 months from entry. Adverse events observed with weekly dosing were similar to those seen with the standard regimen; however, incidence of most common grade 3–4 toxicities was less, with fatigue 24%, transaminase elevation 18%, and hypoalbuminemia 12%. Although all pts had mild to moderate cytopenia at enrollment, only 2 pts (9%) experienced grade 3–4 neutropenia, none with neutropenic infection, and 1 pt had worsening of thrombocytopenia from grade 3 at study entry to grade 4. In conclusion, weekly dosing of DD is well tolerated, even in pts with diminished marrow reserve, but has not demonstrated significant anti-tumor activity in this heavily pretreated B-NHL population with bulky disease. Follow-up will continue for survival analysis.
CHOP-Rituximab-Interferon Therapy in Follicular Lmphoma (FL): High Remissions with Reasonable Toxicity.
Authors: Bseiso Ali W. , Hocking William G. , Mercier Richard J. , Krawisz Bruce , Birhiray Ruemu 
Published: April 2020

Abstract
Background: Rituximab (R) plus chemotherapy (CTP) results in highly durable remissions in FL. IFN-α-2b has activity against FL and may demonstrate synergism when given concurrently with CTP. Some studies showed clinical benefit to adding IFN to CTP concurrently or as maintenance. We hypothesized that adding IFN to RCHOP may enhance the anti-lymphoma effect via enhancing the ADCC effect of R by generating effector NK and T-cells.
Methods: pts ages ≤75, stages II-IV, classified as B, C and D on IWF were enrolled.
Treatment: 6 cycles of CHOP with R added prior to cycles 1, 3 and 5. Growth factor support was allowed. IFN at 3× 106 U TIW SQ was concurrently given. Subsequently, 4 weekly R doses were given followed by 1 year of maintenance IFN at 5× 106 U TIW SQ for a total of 80 wks of therapy.
Results: 15 pts were enrolled. 1 pt with MZL was taken off study. Among 14 pts with FL, there were 8 males and 6 females. 10 pts were stage IV, 4 stage III, 3 had PS of 0, 9 PS of 1, and 1 PS of 2. Age was 29 to 72 (median 62). 11/14 achieved CR, 2 had PR. At median f/u of 62 mo (36–67), 10/14 pts remain alive and progression-free, including 1 pt with PR who later developed ovarian ca. 2 died of PD, 1 at 13 months after stopping therapy, and the other of CNS transformation during CTP. 1 patient had molecular progression while in clinical CR, responding to additional R and 1 was lost to follow-up. At diagnosis, 8 showed bcl-2 translocation by PCR in BM. AT week 29, 6 of the 8 showed disappearance of the bcl-2 translocation while 1 (who had PR) had persistence of the translocation. 7 completed maintenance; 5 withdrew during maintenance due to IFN toxicity. Grade 3–4 toxicities, included fatigue in 3 pts, neutropenic fever in 2 patients, sensory neuropathy in 1 patient, rash in 1 pt and depression in 1 pt.
Conclusions: treatment of FL with RCHOP plus IFN was reasonably tolerated with high durable responses. Five of 12 pts had to discontinue IFN in the maintenance phase due to toxicity.
Intestinal Marginal Zone B-Cell Lymphoma of MALT Type: Clinical Manifestation and Outcome of a Rare Disease.
Authors: Oh Sung Yong , Kim Won Seog , Ryoo Baek-Yeol , Kang Hye Jin , Park Yeon Hee , Kim Kihyun , Ko Young Hye , Kwon Hyuk-Chan , Nam Eunmi , Lee Jae-Hoon , Kim Jung Han , Kim Hyo-Jin 
Published: April 2020

Abstract
Purpose: Intestinal marginal zone B-cell lymphoma of MALT type (I-MZL) is a relatively uncommon type of lymphoma. Because of the rarity, the natural history and optimal treatment modality has not been well defined. Therefore, we performed a retrospective analysis of the clinical features and treatment outcomes of I-MZL.
Methods: From 1990 to 2005, a total of 27 patients with histologically confirmed I-MZL were analyzed.
Results: The median age was 51 (range: 19–83) years. The study involved 16 males (59%) and 11 females (41%). Patients initially presented with abdominal pain (62.9%), diarrhea (22.2%) and various symptoms. The most common involving site was ileo-cecal area (40.7%) followed by small intestine (25.9%), colorectal (18.5%), multiple intestine involvements (14.8%) in the decreasing order of frequency. Musshoff stage IE, IIE1, IIE2, IIIE, and IV were present in 44%, 15%, 11%, 7.4%, and 22%, respectively. B symptom was observed in 11%. Twenty one (78%) and five (19%) patients were in low or low-intermediate risk group according to international prognostic index (IPI). Sixty-three percents (17/27) were in low risk group in follicular lymphoma international prognostic index (FLIPI). Treatment was mainly combined with surgical modality. Complete and partial remissions were achieved in 22 (82%) and 1(4%). After the median follow-up duration of 56.1 months, Median progression free survival (PFS) were 8.8 (95% CI: 3.8–13.8) years. The estimated 5-year overall survival (OS) and PFS were 86% and 54%, respectively. Stage ≥ IIE2 was poor prognostic factor of PFS and OS.
Conclusion: I-MZL trends to be an indolent disease - prolonged survival with frequent relapse like other site MZL of MALT type. They present commonly early stage, low risk state and respond well local and systemic treatment. I-MZL has favorable prognosis.