bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimal Disseminated Disease (MDD) in BM of Childhood T-Cell Lymphoblastic Lymphoma (Stage III), Detected by Flow Cytometry (FC) and Real Time Quantitative Polymerase Chain Reaction (RQ-PCR).
Authors: Stark Batia , Luria Drorit , Manor Sigal , Ronen Taly , Kodman Yona , Avrahami Gali , Yaniv Isaac , Avigad Smadar 
Published: October 2019

Abstract
Despite overlapping features between T cell Lymphoma and T cell ALL and generally good response to T-ALL type of treatment there are some clinical and biological differences between the two entities. The aim of this study was to evaluate in children with stage III T cell Lymphoma the prevalence of minimal BM dissemination at diagnosis, its prognostic significance and early response kinetics. Bone Marrow (BM) at diagnosis from 14 children with T- cell lymphoblastic lymphoma (T-LBL) was assessed for minimal disseminated disease (MDD) by flow cytometry (FC) with four colour antibody combinations and real time quantitative PCR (RQ-PCR) with specific junctional regions for T-cell receptor and immunoglobulin heavy chain gene rearrangements. 13 pts. had stage III mediastinal lymphoma, and one stage II cervical disease. Morphological BM involvement of almost 5% blasts was suspected in only one patient. All, but one, were treated according to the NHL-BFM 90/95 protocols medium risk group (without irradiation). In addition, 7 pts were assessed for early response on week 5 and 12 of treatment with PCR only (2 pts) FC only (2 pts) and both methods (3 pts). Lymphoma associated immunophenotype with a sensitivity of at least 0.01% was detected in all patients (100%) (2 combinations), and PCR targets with a sensitivity of 0.01% and 0.1% in 10 and 2 examined patients respectively (92%). A sample with a level of above 5X10−4 was considered as positive MDD or minimal residual disease (MRD) by both methods. By FC, 10 patients exhibited positive and 4 negative BM MDD levels at diagnosis. By RQ -PCR, 7 patients presented positive and 4 negative BM MDD levels. Both methods gave consistent results with only one case of discordance: negative in PCR and positive in FC (>5x10−4). In 7 other pts there was a difference of between 0.5 and 1 log level that did not change the classification of involvement (in 5 pts PCR higher, in 2 pts FC higher). At a median follow up of 5 years, 3 patients relapsed (2 in the mediastinum and one in BM) their MDD level at diagnosis was 2x10−3 (2 pts), 6x10−2. MRD level in 4 patients out of 5 patients with a high MDD level (1–6x10−2) at diagnosis, decreased by 2 logs (<5x10−4) on week 5, and on week 12 all were below <2x10−4. The one patient with a higher level (1.5x10−2) at day 33 suffered a relapse.
In conclusion: in the majority of patients with mediastinal stage III T-cell lymphoma molecular BM dissemination (>5x10−4) was present. It’s prognostic significance in the context of ALL-BFM therapy could not be demonstrated. However, early BM molecular treatment response in T-cell Lymphoma may correlate with outcome, similarly to T-cell leukemia.
Hepatitis C Virus Infection and B-Cell Non-Hodgkin’s Lymphoma.
Authors: Grudeva Janet G. 
Published: October 2019

Backgroud: An increasing number of bacterial and viral infections have been linked with specific subtypes of lymphoma. Preliminary evidence suggests that hepatitis C virus (HCV) might play a pathogenetic role in autoimmune-related, non-malignant B-cell lymphoproliferation, as well as a subset of B-cell non-Hodgkin, s lymphomas (B-NHL), often with extranodal localization.
Design and methods: The study was conducted in the Department of Hematology and consisted 149 (86 male, 63 female) untreated patients with a new diagnosis of B-NHL for 5-years period (2000–2004). HCV infection was investigated by testing for HCV antibodies in serum samples. The controls were 587 patients (without intravenous drug users) in other departments of the same hospital.
Results: HCV infection was documented in 13 cases (8,4%) with NHL. The infected patients were not clinically relevant cryoglobulinemic activity, increased rate of autoimmune disorders and extranodal localizations prevalence. There was statistically significant difference between the NHL and control group (p<0,01) and no statistically significant difference between man/women carriers (p>0,05) into the NHL group. Overall, the clinical outcome of HCV-positive NHL does not seem to be different from that of NHL patients without HCV infection. However, the evidence of a significant liver injury may predict a worse prognosis in these cases.
Conclusions: Our date suggest that HCV infection may be associated with B-NHL. With regard to the mechanism(s) by which HCV might favor B-cell expansion and malignant transformation, most date support an indirect pathogenetic role of the virus as an exogenous trigger. A direct oncogenetic role of HCV by direct cell infection and deregulation has only been hypothesized on the basis of the lymphotropism of the virus.
Caspase 3 Expression in Mantle Cell Lymphoma: An Immunohistochemical Study of 84 Patients.
Authors: Schrader Carsten , Klapper Wolfram , Riis Paul , Meusers Peter , Brittinger Guenter , Siebmann Jens U. , Kneba Michael , Parwaresch Reza 
Published: October 2019

Abstract
Mantle cell lymphoma (MCL) is a malignant lymphoma associated with a relatively aggressive clinical course and a median overall survival time of 3–4 years. We investigated immunohistochemically the expression of the apoptotic marker caspase 3 in relation to the clinical course. Biopsy specimen from 84 untreated patients enrolled in two multicenter prospective trials were investigated immunohistochemically with monoclonal antibodies against CD20, CD5, CD3, CD23, cyclin D1, Caspase3. The Caspase3 expression was analyzed in three groups: less than 1 positive cell per high power field (HPF), more than 1 positive cell per HPF and more than 2 positive cells per HPF. The expression was compared with the overall survival data analysed according to Kaplan and Meier. In 75 cases the caspase 3 staining could be analyzed. The caspase 3 expression had a range of 0.1–4.7 positive cells per HPF (median value:1.1, mean:1.3). Patients with mantle cell lymphoma that had less than 1 caspase 3 positive cell per HPF (33 cases) had a median overall survival time of 48 months compared to 27 months for patients with more than 1 positive cell per HPF (24 cases) and 15 months for more than 2 positive cells per HPF (18). The Kaplan-Meier analysis showed a significant difference in the overall survival time between these groups (p<0.0001). The immunohistochemical detection of caspase 3 in mantle cell lymphoma is a predictor for survival in MCL.
Methylenetetrahydrofolate Reductase and Methionine Synthase Polymorphism and Risk of Non-Hodgkin’s Lymphoma.
Authors: Nam Hee , Kim Yeo-Kyeoung , Lee Il-Kwon , Yang Deok-Hwan , Park Kyeong-Soo , Lee Je-Jung , Kim Hyeoung-Joon 
Published: October 2019

Abstract
Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are key enzymes in folate metabolism, which is essential for DNA methylation and synthesis. It is known that polymorphisms in its genes have been associated with some forms of cancer including lymphoma. Previous studies have shown MTHFR 677TT was associated with decreased risk of non-Hodgkin’s lymphoma(NHL). However, recent two reports have shown MTHFR 677TT was associated with increased risk. To evaluate the association between the MTHFR C677T and MTR A2756G polymorphisms and risk of non-Hodgkin’s lymphoma, large-scale population-based case-control study was conducted in Chonnam University Hwasun Hospital between March 1997 and June 2005. Three hundreds sixty-five patients with histologically comfirmed lymphoma and 1,162 controls were evaluated. Genotyping was done using PCR-RFLP. The cases consisted of 203 diffuse large B-cell lymphomas(DLBCL), 77 T-cell lymphomas, 62 other B-cell lymphomas, and 23 unclassifiable lymphomas. The MTHFR 677CT and 677TT genotypes were inversely associated with NHL and DLBCL, respectively. Using subjects with the MTHFR 677CC as reference group, the odds ratio of MTHFR 677CT and 677TT were (0.70, 95% CI 0.54–0.90) and (0.46, 95% CI 0.32–0.68) for NHL. The association was more evident for DLBCL (OR 0.56, 95% CI 0.40–0.78 for 677CT; OR 0.40, 95% CI 0.24–0.65 for 677TT). Dose-response effect was evident for the MTHFR T-allele (p < 0.01). There was no significant association of MTR A2756G with NHL. These results suggest that the MTHFR polymorphism may play an important role in the pathogenesis of NHL, particularly DLBCL.
Favorable Outcomes with CHOP Therapy in Plasmablastic Lymphoma in HIV Positive Patients.
Authors: Javidan Masumeh Rafati , Amin Alpesh J. , Guron Gunwant 
Published: October 2019

Abstract
Plasmablastic lymphoma (PBL) is a rapidly progressive variant of diffuse large-cell lymphoma predominantly diagnosed in HIV positive patients. It is frequently associated with latent EBV infection and is often lacking expression of CD20 and CD45. A retrospective study of HIV positive patients diagnosed with PBL to determine outcomes after CHOP therapy. Two HIV positive patients diagnosed with PBL and treated with CHOP were identified. The first patient is a 48 year old male with CD4 count of 80 cells/mm3 on HAART, who presented with a rectal mass. Pathologic exam revealed granulation tissue with marked inflammation. A second colonoscopy because of ongoing rectal bleeding was done. Histologic exam was interpreted as infiltrating poorly differentiated carcinoma. The third biopsy obtained via colonoscopy (after developing bowel obstruction) was reported as a high grade tumor with neuroendocrine features. The patient received one dose of cisplatin 60 mg/m2 and irinotecan 60 mg/m2 and radiation therapy. Patient underwent a diverting colostomy. The immunohistochemical exam of the tissue was negative for CD20, CD3 and positive for CD 138, suggestive of the diagnosis of plasmablastic lymphoma. In situ hybridization for EBV was positive. The patient received 6 cycles of CHOP (cytoxan 750 mg/m2, vincristine 1.4 mg/m2, doxorubicine 50/m2 and prednisone 100 mg) chemotherapy and 6 more cycles of radiation therapy. He is in complete remission 16 months after the diagnosis, and continues to be followed. The second patient is a 44 year old female on HAART with CD4 count of 415 cells/mm3, who presented with the swelling of the right jaw for three weeks. The histologic exam of the tissue, obtained by the incision biopsy of the mass, favored plasmablastic lymphoma. Immunohistochemical analysis tested positive for CD3, CD138 and CD45. In situ hybridization for EBV RNA was positive. Patient received 3 cycles of CHOP regimen and radiation to the jaw. She has not shown any evidence of relapse and is in complete remission 22 months after diagnosis, and continues to be followed. Durable remissions, 16 and 22 months, were achieved with CHOP therapy in HIV positive patients with PBL. This study supports the use of CHOP as an effective treatment of PBL in HIV positive patients.
Ki-1 Positive Anaplastic Large Cell Lymphoma Due to Immune Deficiency.
Authors: Chang Monique , Kujawa Jennifer , Garrison Michael , Hindenburg Alexander 
Published: October 2019

Abstract
Cases of Ki-1 positive anaplastic large cell lymphoma (ALCL), including ALK (t 2,5) positive and negative expression, have largely been associated with immunosuppressed transplant recipients, human immunodeficiency virus (HIV) positive patients and patients with a prior history of a lymphoproliferative disorder. We reviewed the literature and found cases of secondary Ki-1 positive ALCL in immunocompromised patients including patients with a prior history of lymphoid malignancy. Some of these latter cases may have been diagnosed initially as Hodgkin’s disease and later reclassified as Ki-1 positive ALCL. In post-transplant and HIV positive patients, severe and prolonged immunosuppression likely led to the development of Ki-1 positive ALCL. We postulate that although rare, the occurrence of Ki-1 positive ALCL in patients previously treated for a lymphoid malignancy is possible due to a pre-existing immune deficiency state. We report a case of ALK- ALCL occurring 10 years following treatment of HCL with persistent depressed T4/T8 ratio one year after achieving a complete remission of the ALCL.
Secondary Cases of Ki-1 Anaplastic Large Cell Lymphoma Cases of Post-transplant Ki-1 Positive Anaplastic Large Cell Lymphoma Allograft # of Case Reports ALK (t 2,5) Renal 16 12 unknown, 4 positive Cardiac 3     1 negative, 2 positive Liver 1 1 positive Cases of Ki-1 Positive Anaplastic Large Cell Lymphoma in Patients With HIV or Treated with Immunosuppressants for Non-Malignant Disorders Cause of Immune Deficiency # of Case Reports ALK (t 2,5) HIV + 10 10 unknown Immunosuppressive tx for Evan’s syndrome 1 negative Azathioprine for Crohn’s Dz. 1 unknown Cases of Secondary Ki-1 Positive Anaplastic Large Cell Lymphoma in Patients Treated for Malignancy Primary Malignancy # of Case Reports ALK (t 2,5) Hodgkin’s Disease 3 3 unknown Hairy Cell Leukemia 2 1 unknown, 1 negative Mycosis Fungoides 2 2 unknown
R-CHOP vs R-mini-CEOP in Elderly Patients with Diffuse Large B Cell Lymphoma: An Interim Report from Intergruppo Italiano Linfomi (IIL).
Authors: Merli Francesco , Vitolo Umberto , Luminari Stefano , Mazza Patrizio , Stelitano Caterina , Rossi Giuseppe , Baldini Luca , Ilariucci Fiorella , Levis Alessandro 
Published: October 2019

Abstract
Objectives: CHOP plus Rituximab (R-CHOP) is considered the standard treatment for elderly patients affected from Diffuse Large B Cell Lymphoma (DLCL). The primary objective is to compare in an intent to treat analysis the Event Free Survival (EFS) between R-CHOP and a regimen especially devised for elderly (R-mini-CEOP). Secondary objectives are:
to verify the feasibility of a multidimensional score for excluding the frail patients from the study to demonstrate that Rituximab could improve the result of a regimen different from CHOP.
Patients and methods: Patients were previously submitted to 4 multi-item scales: Activities of Daily Living scale (ADL), Instrumental Activities of Daily Living Scale (IADL), comorbidity scale and geriatric scale. The patients who got over were randomised between R-CHOP (day 1:Rituximab 375/m2; Cyclophosphamide 750 mg/m2; Doxorubicin 50 mg/m2; Vincristine 1,4 mg/m2; days 1–4: Prednisone 60 mg/m2) and R-mini-CEOP (day 1: Rituximab 375 mg/m2; Cyclophosphamide 750 mg/m2; Epidoxorubicin 50 mg/m2; Vinblastine 5 mg/m2; days 1–4: Prednisone 60 mg/m2). Both regimens recycled at 21 days and scheduled G-CSF in the days 2–7. An intermediate restaging was scheduled after the first 3 courses.
Results: From March 2003 until July 2005 19 patients were classified “frail”, while 133 patients coming fom 21 Hematology/Oncology Departments were enrolled into the trial. Most of these patients had a severe clinical presentation. Median age was 73 years old. LDH upper than normal value was found in 56% of this group of patients. 72% were in stage III-IV. 25% presented a bulky disease at diagnosis. The two different treatment group were well balanced for number and clinical charatheristics. 72 patients (37 treated with R-CHOP and 35 with R-mini-CEOP) completed the chemotherapy and were assessed for the response. CR rate was 82%. PR rate was 13 %. Five percent progressed during treatment or had no response to the chemotherapy. The overall survival estimated at 13 months was 81 % versus 34 % in frail group (p=0.0001). Despite the use of G-CSF the more frequent side effect was a leucopenia of grade 3–4, which occurred in the 37% of the patients. Severe infections (grade 3–4) occurred in 7% of the patients and in one case was lethal. Toxic deaths were 2%.
Conclusions: The results in terms of CR and feasibility are encouraging. Events which suggest to stop the randomisation have not occurred. The multidimensional score system seems a good tool to identify the patients who are able to tolerate a full dose regimen.
Treatment of Hematological Malignancies in Central Nervous System with Idarubicin and Teniposide Containing Regimens.
Authors: Wang Chun , He Xiaojun , Cai Qi , Zhu Jun , Bai Haitao 
Published: October 2019

Abstract
Background: The prognosis of central nervous system(CNS) involvement in hematological malignancies remains poor. Clinical investigation for better protocols is mandatory. Some reports from small samples of clinical trials suggested that the systemic chemotherapy with the agents that better cross the blood-brain barrier may result in disease remission in some patients with CNS lymphoma. Based on the pharmacokinetic properties of each drug, we have developed and evaluated the chemotherapy regimens for patients with hematological malignancies involving central nervous system.
Objective: To evaluate a idarubicin (IDA) and teniposide based regimen in the treatment of hematological malignancies with CNS involvement.
Patients and Methods: From April 2003 to July 2005, fourteen patients were enrolled onto the study. There were 8 male and 6 female, with a median age of 53(22–75) years. Three patients with primary CNS lymphoma (PCNSL) and 5 patients with secondary CNS lymphoma (SCNSL) were treated with the combination regimen of IT, including idarubicin(8mg/m2/d×3) and teniposide (75mg/m2/d×3). Six cases of acute myeloid leukemia with both bone marrow and CNS relapse, including 2 patients with acute promyelocytic leukemia and 4 patients with acute monocytic leukemia, were treated with the combination regimen of ITA, including IT and conventional cytosine arabinoside. The cycles were repeated at 3-weekly intervals. Patients were followed carefully for evaluation of toxicity and response to treatment.
Results: Of the 8 patients with CNS lymphoma, three cases achieved complete remission(CR), four cases achieved partial remission(PR) after 2 cycles of IT regimen. Only one case died of cerebral hemorrhage two days after the delivery of chemotherapy. Among the 6 patients with CNS leukemia, four cases achieved CR and 2 cases achieved PR after 1 cycle of ITA regimen. Three cases achieved CRs of both CNS and bone marrow, which indicates that the regimen may be effective for concurrent relapse of both CNS and bone marrow. Of the 5 patients in coma, all of them regained consciousness during the course of chemotherapy. Rapid effect and well tolerance were observed, which made the following comprehensive treatment possible and were especially valuable for the patients in coma. Although the study was not primarily designed to investigate long term outcomes, the first patient treated with IT regimen remained CR for 26 months at the last follow-up.
Conclusion: The promising efficacy of idarubicin and teniposide containing regimens was observed in the treatment of hematological malignancies in central nervous system, indicating that the regimens may be the first line option as primary or salvage therapy in hematological malignancies in central nervous system.
Accelerated R-COP:A Pilot Study for the Treatment of Follicular Lymphoma.
Authors: Bertino Joseph R. , Roger Strair , Arnold Rubin , Mecide Gharibo , Dale Schaar 
Published: October 2019

Abstract
To test the hypothesis that dose intensity/dose density treatment may improve the complete response rate and remission duration in patients with follicular lymphoma (grades I and II, ECOG performance 0–2, Stages III and IV, progressive disease), a combination of known effective agents were administered as follows: rituximab,375 mg/m2; cyclophosphamide, 1000 mg/m2; and vincristine, 2mg (cap), IV every two weeks. Prednisone, 50 mg, was given p.o., every other day for 30 days then tapered over the next 30 days. G- CSF was administered days 7–10 following each treatment. Patients were evaluated for response after 5 and 10 cycles, that included imaging with CT and PET scans. Toxicity was mild to moderate, consisting mainly of paresthesias, requiring attenuation of the vincristine dose in some patients. There were no instances of neutropenic fever requiring hospitalization. In this pilot study, 6 of 7 patients previously untreated achieved a CR, and none have relapsed to date (6+ to 20+ months after completion of treatment). Two heavily treated patients, including relapse from agents used in this regimen, had PRs, lasting 2 and 8+ months. This program is well tolerated with a high CR rate, and may serve as a basis for future trials.
HuMax-CD20, a Novel Fully Human Anti-CD20 Monoclonal Antibody: Results of a Phase I/II Trial in Relapsed or Refractory Follicular Non-Hodgkins’s Lymphoma.
Authors: Hagenbeek A. , Plesner T. , Johnson P. , Pedersen L. , Walewski J. , Hellmann A. , Link B. , Robak T. , Wojtukiewicz M. , Pfreundschuh M. , Kneba M. , Engert A. , Sonneveld P. , Petersen J. , Radford J. 
Published: October 2019

Abstract
The fully human monoclonal IgG1 antibody HuMax-CD20 targets a novel epitope of the CD20 molecule on B-cells. HuMax-CD20 stops growth of engrafted B-cell tumors in SCID mice more efficiently and exerts stronger complement activation than Rituximab. HuMax-CD20 kills Rituximab-resistant cells expressing low levels of CD20. Data are presented from an ongoing, open label, dose-escalation, multicenter clinical trial in patients with relapsed or refractory CD20+ follicular non-Hodgkin’s lymphoma. Four cohorts of 10 patients were treated with 4 weekly i.v. infusions of 300, 500, 700 or 1000 mg. The endpoints are adverse events, CT verified tumor response (central review) according to the Cheson criteria, B-cell depletion, time to next anti-lymphoma treatment, duration of response, BCL2 conversion and pharmacokinetics. Fourty patients have been treated. Mean age was 57 years; median number of prior treatment regimens was 2; 15 patients were previously treated with Rituximab. Rapid, efficient and sustained peripheral B-cell depletion was observed in all dose groups. No dose limiting toxicity has been reported. Only 8 short lasting episodes of grade 3 CTC were observed. Hematological toxicity was low and confined to 6 events of grade 1 neutropenia; no cases of thrombocytopenia were reported. The following pharmacokinetic parameters were derived (medians per dose group): Cmax 129, 185, 380 and 610 μg/ml, T½ 447, 245, 322 and 621 hr, Cl 9, 19, 10 and 7 ml/hr/kg and AUC 75000, 51000, 185000 and 326000 hr *μg/ml, for the 300, 500, 700 and 1000 mg dose groups, respectively. No correlation between pharmacokinetics and response was found. Objective responses (CR, CRu, PR) have been elevated in 36 patients and were obtained in all 4 dose groups; 4 CR + 1 CRu/8 (300mg), 1CR + 2 PR/9 (500mg), 2PR/10 (700mg) and 1 CRu + 4 PR/9 (1000mg). Objective responses were achieved in 8 of 14 (57%) evaluable patients previously treated with Rituximab, i.e. 3CR, 1 CRu and 4 PR. In total 18 patients showed stable disease; progression was observed in only 3 patients. Data on duration of response will be presented. In conclusion, this preliminary analysis demonstrates a favorable safety profile and encouraging efficacy of HuMax-CD20 in patients with follicular NHL. Objective responses were achieved in all dose groups with response rates up to 63% including a 57% response rate in patients previously treated with Rituximab.