bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase III Clinical Study of Treatment of Patients with Chronic Lymphoproliferative Disorders (CLPD) with Fludarabine, Cyclophosphamide, and Rituximab (FCR) Combination.
Authors: Galanopoulos Athanasios G. , Tsakiridou Anastasia , Michalis Eurydiki , Marinakis Theodoros , Gortzolidis George , Zomas Athanasios , Xanthopoulos Vasilios , Savvidou Ioanna , Theodoropoulos George , Grigoraki Vasiliki , Anagnostopoulos Nikolaos I. 
Published: October 2019

Abstract
Background: The treatment of patients with chronic lymphocytic leukemia (CLL) with Rituximab in combination with fludarabine and cyclophosphamide was reported to be more efficacious, in terms of complete and molecular remission compared with historical data for fludarabine plus cyclophosphamide (S.O’Brien, Haematologica2002; 87:50–53).
Aims: Evaluation of the clinical efficacy and toxicity of the FCR combination in patients of our Haematologic Centre.
Methods: Seventeen patients, 8 males and 9 females with a median age of 69,5 years, with relapsed/refractory or de novo CLPD (9 CLL and 8 NHL patients) were enrolled in this study between February 2002 and August 2004. Fifty percent of CLL patients had Rai stage I/II and the rest 50% had Rai stage III/IV disease. Four NHL patients had an International Prognostic Index (IPI) 2, one patient IPI 3 and three patients IPI 4. All patients were treated with Rituximab 375 mg/m2 on day1 in combination with Fludarabine and Cyclophosphamide (25 mg/m2 and 250 mg/m2 respectively) for days 2 to 4, every 4 weeks, for 6 consecutive cycles. Nine patients had a history of a prior unsuccessful treatment.
Results: Overall, 14 out of 17 evaluable patients (82%) were responsive to the treatment [12 patients (70%) complete response (CR) and 2 patients (12%) partial response (PR)]. The remaining 3 patients had progressive disease (NR). Hematological toxicity was acceptable (grade 2–3 neutropenia in 6/17 patients, grade 2–3 anemia and thrombocytopenia in 2/17 patients). There were no septic episodes except one case with neutropenic fever. There were no adverse events like nausea or vomiting except one patient with a serious anaphylactic reaction due to Rituximab administration. Three CLL patients died because of progressive disease.
Summary/conclusions: this preliminary report suggests that the FCR regimen is an effective and safe treatment for CLPD patients, achieving higher CR rates than previous treatments. A longer follow up of a larger number of patients is required to confirm an improved survival in these patients.
Prospective Clinical Study of Surgical Resection Followed by CHOP in Localized Intestinal Lymphoma.
Authors: Lee Jeeyun , Kim Won Seog , Oh Sung Yong , Kwon Jung Mi , Kim Hyun Jung , Lee Hyo-Rak , Park Byeong Bae , Kim Kihyun , Jung Chul W. , Park Keunchil 
Published: October 2019

Abstract
Background: Due to the rarity of the disease, prospective clinical trials on optimal treatment of intestinal non-Hodgkin’s lymphoma have been scarcely performed.
Methods: Patients with; age > 18 years, pathologically proven diffuse large B cell lymphoma (DLBL), normal bone marrow, liver, renal and cardiac function were eligible. Patients with Burkitt’s lymphoma, lymphoblastic lymphoma, mantle-cell lymphoma, or infection with human immunodeficiency virus were excluded. All patients were staged after surgery according to the Ann Arbor classification modified by Musshoff et al. and Paris staging system (TNM system). Postoperative chemotherapy with CHOP regimen was administered for 6 cycles. CHOP consisted of cyclophosphamide 750 mg/m2 d1, doxorubicin 50 mg/m2 d1, vincristine 1.4 mg/m2 (max 2.0 mg/m2) d1, and prednisolone 100mg d1–5 repeated every 3 weeks.
Results: From 1999 to 2004, 41 patients were enrolled. The median age was 50 years (range, 26 – 84) and male:female ratio was 29:12. All patients had clinical stage I/IIE DLBL and underwent surgical resection. Of the 41 patients, 3 patients refused postoperative CHOP chemotherapy. The 5-year DFS and OS were 83.3% and 89.1%, respectively. Surgicopathologic staging of all patients according to the Ann Arbor classification revealed 34 patients with stage I, 11 patients stage II1, 1 patent stage II2 and 3 patients with stage IIE. The Ann Arbor stage significantly predicted the survival of intestinal DLBL (p = < 0.0001). The T staging according to Paris staging system did not correlate with survival (p = 0.1456) while the N staging showed significant predictability (p = <0.0001).
Conclusion: Surgical resection followed by 6 cycles of CHOP chemotherapy was a highly effective treatment scheme for localized intestinal DLBL patients. The Ann Arbor system seems to predict survival better than the TNM system.
Treatment of Primary Mediastinal Large B-Cell Lymphoma with Immunochemotherapy.
Authors: Tabacof Jacques , Yana Novis A.S. 
Published: October 2019

Abstract
Background: Primary mediastinal large B-cell (PMLBCL) non-Hodgkin’s lymphoma (NHL) is a relative rare disease and represents less than 2% of all newly diagnosed NHL. Analyses with DNA microarrays verified that primary mediastinal and diffuse large B-cell lymphomas are different diseases. The optimal treatment is still undefined. The aim of this study is to evaluate the response to immunochemotherapy in 10 cases of PMLBCL.
Patients and Methods: 10 previously untreated patients with confirmed diagnosis of PMLBCL were enrolled in 2 different institutions. All the patients were treated with rituximab (R) plus polychemotherapy. We retrospectively analysed their clinical data and response to immunochemotherapy.
Results: median age was 37 years-old (range 18 to 45 years), 5 were male and 5 were female, 6 had bulky disease, 4 had B symptoms and 4 presented HDL elevated. The immunochemotherapy regimens utilized for treatment were: 3 R+MACOP-B, 5 R+CHOP, 1 R+CBV and 1 R+MACOP-B+ICE+BEAM.
Complete remission was obtained in 9 patients (90%) and no relapse was observed in this group. One patient died 7 months after ABMT. Three out of 10 patients who were chemosensitive underwent Autologous Bone Marrow Transplantation (ABMT). Median disease free survival was 22 months. One patient got pregnant 4 months after the 8th cycle of R+CHOP, when she was in complete remission. The patient was delivered of a healthy child and is in complete remission for 34 months. It was observed toxicities related to chemotherapy. There was no report of toxicities during and after rituximab infusion.
Conclusion: the addition of rituximab to polychemotherapy may be a good strategy to the management of primary mediastinal large-B cell lymphoma. In this small series there was a high rate of complete sustained response. However, larger randomized studies are needed to confirm these findings.
Retreatment with Gemcitabine Still Hold Efficacy in Relapsed Lymphomas.
Authors: Jajeh Ahmad , Tamkus Diemanti , Menini Perry , Osafo David 
Published: October 2019

Abstract
Lymphomas are highly sensitive to chemotherapy. Approximately half of the patients with aggressive Non-Hodgkin’s Lymphoma will survive for five years. Patients with diffuse large B-cell type NHL have an expected five years survival( OS) rate of fourty five percent (45%). Approximately more than twenty five percent (25%) of NHL and ten percent 10% of Hodgkin’s Lymphoma HD are refractory to conventional front line therapy. Fifteen to twenty five percent of hodgkin’s lymphoma will relapse after therapy or will not achieve complete response CR. Salvage chemotherapy, radiation and high dose chemotherapy with stem cells collection can cure and achieve durable response in some refractory or relapsed patients. High dose chemotherapy and autologous stem cells transplant is not a feasible options for many of our patients due to lack of medical coverage and co-morbide status. Gemcitabine has been used either as a single agent or in combination at our institute in the treatment of variety of hematological malignancies that failed many lines of therapy. Forty patients were treated; twenty two (55%)NHL, nine patients(19%) with HD, three patients with visceral mycosis fungoides, three patients with advanced chronic lymphocytic leukemia in richter transformation and three with peripheral T cell NHL. Mean age of 45 years. Thirty two males and eight females. Eighty percent were african american. All patients had advanced stage III-IV disease. Complete respose CR and near complete response nCR was seen in eleven patients. Partial response PR seen in nineteen patients, stable disease in six. Total response rate of eighty percent. Five patients relapsed after a year (two 25 years old females with HD, three males with high grade NHL age 52, 60 and 70 respectively). Two patients recieved four cycles and three recieved six cycles. Each cycle constitute of 1 gram per meter square given IV weekly for three weeks and one week rest. All five patients had response, three CR and two PR. In conclusion retreatment with gemcitabine is a valid and safe option. None of the patients had grade 3 or 4 toxicity.
Treatment of Systemic Primary Cutaneous Anaplastic Large Cell Lymphoma with High-Dose Methotrexate and Leucovorin Rescue.
Authors: Batra Reema , Boyer James , O’Connor Thomas , Tabbara Imad 
Published: October 2019

Abstract
A 59 year-old Caucasian male with a history of hepatitis C infection, presented in October 2003 with a painless skin lesion on his back. Physical examination revealed a 3 cm lesion on the back that resembled a sebaceous cyst, with similar lesions on the anterior aspects of both legs. A right inguinal lymph node was palpated as well, measuring approximately 2 cm. A wide surgical resection was performed on the back lesion due to its extensive nature at the time of surgery. Pathologic evaluation revealed a primary cutaneous anaplastic large cell lymphoma, measuring 12 cm x 5 cm in size. Immunohistochemical staining showed reactivity for CD30, CD3, UCHL-1, CD43 and CD45. Despite being asymptomatic, the patient had widespread disease on CT/PET scans, including diffuse lymphadenopathy, bony disease, and lung lesions. The patient was treated with weekly high-dose methotrexate at 2 grams/m2 followed by leucovorin rescue for cycle 1 and dose-reduced for cycles 2 through 5 to 1 gram/m2 secondary to myelosuppression. For cycles 6 through 10, the patient was able to tolerate the original dose of 2 grams/m2. After eight cycles, the patient had complete resolution of all disease by clinical examination and by CT/PET scans, and has remained in complete remission since February 2004. The patient tolerated the chemotherapy well with myelosuppression being the most significant toxicity. He also had a transient increase in his liver enzymes after cycle 1 that resolved spontaneously. He is currently being treated for reactivation of hepatitis C with pegylated interferon and ribavirin. To the best of our knowledge, this is the first case of primary cutaneous anaplastic large cell lymphoma with systemic involvement being treated successfully with weekly high-dose methotrexate and leucovorin rescue with prolonged complete remission. Weekly high-dose methotrexate with leucovorin rescue is an active and well-tolerated regimen with limited side effects.
Rescue with Rituximab ® Monotherapy in Resistant T - Cell Rich B - Cell Lymphoma (TCRBCL).
Authors: Burgos Ruben A. , Hanono Isabel A. , Foncuberta Maria C. , Domenichini Enzo , Huertas Eduardo , Sanchez Avalos Julio C. , Tartas Norma E. 
Published: October 2019

Abstract
TCRBCL is a large B - cell lymphoma with a prominent reactive T cell proliferation. More common in males in the fourth decade of life, usual clinical presentation includes generalized adenopathies and bone marrow involvement. More localized presentation is frequently misdiagnosed as Hodgkin’s (HL) or T - cell lymphoma. Cases resistant to anthracyclines (A) pose a medical dilemma. We present here a patient initially misdiagnosed as HL who showed nodal relapse after ABVD and was resistant to conventional chemotherapy. Case report: CP is a 45 years old gentleman who presented with left axillaries adenophaties. A lymph node biopsy was diagnosed as lymphocyte predominant HL (LPHL) stage IA. Treated with 3 cycles of ABVD plus involved field radiation therapy, he relapsed in the margin of the radiation field soon after treatment was completed. A new biopsy showed TCRBCL. A review of the first biopsy was also consistent with TCRBCL. Treated with Promace/Cytabom the patient experience a spleen relapse which was resistant to ESHAP. With a gross hypo dense image in the spleen, treatment with R was started at a dose of 375 mg sqm2 weekly for four weeks. Disappearance of the splenic mass on the CT scan prompted us to perform a splenectomy. The pathologic study revealed a residual 8 mm lesion. The patient is currently without evidence of disease 40 months after the splenectomy. In total he received 6 doses of R. Interestingly an additional patient with TCRBCL originally misdiagnosed as ABVD resistant HL, showed a durable partial remission after treatment with R. In conclusion: due to our experience we think that it might be worth including R in the front line treatment of TCRBCL.
Blastic Mantle Cell Leukemia Maitaining Remission for 3 Years after the Treatment with Rituximab.
Authors: Tsuji Masanori , Akiyama Hideki , Kobayashi Takeshi , Sakai Miwa , Yamashita Takuya , Ohashi Kazuteru , Sakamaki Hisashi 
Published: October 2019

Abstract
[Introduction] Blastic mantle cell leukemia is defined as CD5-positive, CD23-negative, cyclin D1-positive mature B-lymphoid tumor characterized by leukemic presentation, blastic blood and bone marrow features with aggressive clinical behavior. Its prognosis is usually dismal and overall survival was reported to be 3 months. We present the case of blastic mantle cell leukemia treated with rituximab, enjoying complete remission for 3 years.
[Case presentation] A 68 year-old man was admitted because of leukocytosis. His CBC revealed WBC 31.0 x 10E9/L with 64% of blast. Hemoglobin level was 5.3 g/dl, and 78% of medium-sized blasts that were positive for CD5, CD19, CD20, and HLA-DR. Chromosomal study revealed normal karyotype. He was treated with adriamycin, vincristine, cyclophosphamide, and predonisone as for acute lymphoblastic leukemia, and then, with another two cycles of intensive chemotherapy including hyper-CVAD without any significant response.
He was transferred to our hospital for further treatment. The blastic cells showed bcl1/IgH re-arrangement on FISH analysis and bone marrow biopsy revealed CD23-negative and cyclin D-positive that confirmed the diagnosis of mantle cell lymphoma/leukemia. CT scan of the body showed no significant lymphadenopathy.
He was treated with fludarabine and idarubicin without any effect and then was treated with rituximab 375 mg/m2. After the initiation of rituximab treatment, blasts disappeared from peripheral blood within 24 hours completely and after 4 times of rituximab once per every week, CBC returned to normal and bone marrow examination revealed complete remission. He was treated with another 2 injection of rituximab and then followed without any further treatment. He has been in complete-remission status for 3 years since then.
[Discussion] Blastic mantle cell leukemia is usually chemotherapy-resistant as our case is and its prognosis is dismal. Our case represent the possibility that even in those patients, one may enjoy prolonged complete remission after the simple treatment with rituximab. This is, of course, only a single case experience and it is necessary to proceed for further investigation.
P210 Tyrosine Kinase Regulates the Expression of 14-3-3sigma in Hematopoietic Progenitors Expressing the bcr-abl Fusion Gene.
Authors: Santucci Maria Alessandra , Mancini Manuela , Zuffa Elisa , Brusa Gianluca , Barbieri Enza 
Published: October 2019

Abstract
The 14-3-3sigma is a member of a highly conserved family of acidic proteins that bind to serine/threonine-phosphorylated residues in a context specific manner analogous to the Src homology 2 (SH2)- and phospho-tyrosine- binding domains. Its central role in the subcellular distribution and transcriptional activity of partners molecules controlling cell cycle progression, survival, senescence, adhesion and metabolism made 14-3-3sigma isoform the most directly linked to cancer pathogensis and progression. Here we provide evidence for its involvement in deregulated proliferation and extended survival of Chronic Myeloid Leukemia (CML) hematopoietic progenitors. In LAMA cell line and CD34+ cells of CML patients at clinical diagnosis p210 bcr-abl dephosphorylation and enzymatic activity inhibition induced by in vitro exposure to 1 microM tyrosine kinase (TK) inhibitor Imatinib mesylate (IM) were associated with a significant reduction of 14-3-3sigma transcript and protein. 14-3-3sigma reduced expression arises from transcriptional mechanisms and involves epigenetic modifications of chromatin structure. In LAMA cell line PCR amplification of DNA from immunoprecipitated chromatin (ChIP) revealed histone H4 deacetylation at a discrete region of 14-3-3sigma promoter critical for gene transcription since 2nd up to 24th hour of IM treatment. Conversely, bisulfite-SSCP sequencing of PCR amplification of gene 5′ coding sequences encompassing the transcription start site did not show significant differences in CpG methylation status relative to p210 TK activity. Up-modulation and increased nuclear import of p27Kip1, downmodulation of cyclin D1 and Cdc25A levels, Bad dephosphorylation at Ser136 and Bax translocation to mitochondria proceeding from 14-3-3sigma reduction gave rise to cell cycle arrest in late G1-/early S-phase and committment to apoptotic death. Interestingly, higher levels of 14-3-3sigma protein were associated with the development of IM resistance in vitro and in vivo. To conclude, our study supports a role of 14-3-3sigma in the pathogenesis of CML hematopoiesis as well as in the disease progression towards a drug-resistant phenotype mostly due to its regulatory control on pro-apoptotic and growth-arrest proteins downstream of forkhead transcription factor Foxo3a and c-jun N-terminal kinase (JNK).
Inhibitory Effect of RNAi on Expression of bcr/abl Oncogene in K562 Cells.
Authors: Wang Chun , Ma Xiaoxia , Wei Ju , Qin Youwen , Yan Shike 
Published: October 2019

Abstract
The translocation t(9;22) can be found in 95% patients with chronic myeloid leukemia (CML). The resulting hybrid gene bcr/abl codes for a fusion protein with tyrosine kinase activity which activates signal transduction pathways, leading to uncontrolled cell growth. A promising anti-gene technology-RNA interference (RNAi) reported in recent years can disrupts the expression of the targeted cellular gene in a complicated manner in a variety of organisms and cell types.
To inhibit CML bcr/abl oncogene expression with RNAi, we used chemically synthesized anti-bcr/abl small interfering RNAs( siRNAs), mismatch control siRNAs having the three point mutations to transfect the K562 cells for different time through the electroporation. EGFP plasmid was used as a positive control and the amount of fluorescently stained cells was determined by FCM. Inhibitory effects of siRNAs were demonstrated by real-time quantitative RT-PCR and Western blots. Cell proliferation was measured by means of MTT assay and apoptosis was determined by Annexin V-FITC assay.
The transfection efficiency was about 70%. The synthesized siRNAs inhibited CML bcr/abl oncogene expression at both mRNA and protein levels. The anti-bcr/abl siRNAs reduced the bcr/abl mRNA level by 67%–72% without an obvious effect on abl mRNA levels. The K562 cells electroporated with anti-bcr/abl siRNAs contained less BCR/ABL protein than cells electroporated with mismatch control siRNAs or without any siRNAs. P210 was reduced to a very low level in Western blots, whereas the wild-type ABL protein was not influenced by the anti-bcr/abl siRNAs. Depletion of bcr/abl leading to increased apoptosis and reduction of cell viability. The flow cytometric analysis showed that the percentage of dead and apoptosic cells induced by anti-bcr/abl siRNAs for 24hrs and 48hrs were 42.10% and 53.33%, respectively, including 15.05% and 19.47% of the preliminary apoptosis cells, respectively. A significant induction of apoptosis was observed after transfection compared with untreated control(1.00%)and the mismatch control siRNAs (2.98%) (p<0.05). Anti-bcr/abl siRNAs inhibited cell growth of the K562 cells and the inhibitory rate was 47% and 56%, 24h and 48h after transfection respectively, whereas the mismatch control siRNAs had no such effect on K562 cells.
At the cell level, inhibition of CML bcr/abl oncogene expression by chemically synthesized siRNAs provides the new method for anti-leukemia study. Therefore, siRNAs may be potent tools for gene-specific modality against CML.
Effective Treatment of Basophilic Leukemia of the Central Nervous System in a CML Patient with the Combination of Imatinib Mesylate and Valproic Acid.
Authors: Nahajevszky Sarolta , Magocsi Maria , Mikala Gabor , Andrikovics Hajnalka , Adam Emma , Masszi Tamas 
Published: October 2019

Abstract
Imatinib is effective in all stages of CML but the level of the drug in the cerebral spinal fluid is two logs lower than in the plasma. In November, 2000 a 35 years old man in CML chronic phase was treated with interferon (10MU/day) and achieved complete hematologic remission. Two years later he progressed to myeloid blastic crisis. The patient was treated with an acute leukemia protocol (60mg/m2 daunorubicin days 1–3, 200 mg/m2 ara-C days 1–7). After hematological recovery 600 mg/day imatinib was administered continuously. 9 months later headache and vomiting indicated CNS involvement. In the CSF presence of Ph+ basophilic leukemia cells (1,27G/l) was proven by FISH. Although the patient was given intrathecal methotrexate(15mg), cytarabine(40mg) and dexamethasone(4mg), the headache was a permanent problem with persistent basophilia in the liquor. In vitro culture of his bone marrow cells at the time of the blastic phase was tested for drug sensitivity to different doses of imatinib alone or in combination with other antitumor drugs. In the in vitro growth assay 5 uM imatinib alone, 5mM valproic acid alone and 0,5uM imatinib + 5mM valproic acid together caused 15%, 33% and 80% decrease in cell survival, respectively, suggesting that combinations with valproic acid, (an anticonvulsive agent) would be more effective. Based on the results of our previous growth assay the therapy was supplemented with valproic acid (4x150mg/day). The meningeal leukemia resolved in 3 weeks and the patient had no complaint for 3 months with the same therapy.
We find it noteble that basophilic CNS blast crisis was exquisitely sensitive to the administration of imatinib in combination with valproic acid, an anticonvulsive agent with antitumor activity.