bluuebunny/crossref_metadata_2025_split huggingface dataset:
Penumbra Encodes a New Tetraspanin Critical to Effective Erythropoiesis.
Authors: Cao Thai M. , Heikens Marc J. , DeHart Sarah L. , Morita Chikako , Tsai Schickwann 
Published: April 2020

Abstract
To search for new genes that might be involved in the regulation of erythropoiesis, we performed cDNA representational difference analysis on a multipotent murine hematopoietic cell line, EML C1. Penumbra was identified based on its predominant, high-level expression in TER119+ erythroblasts. It is not expressed or is expressed at very low levels in Gr1+ or CD3+ or B220+ or CD11c or NK1.1+ bone marrow or spleen cells. The full-length murine Penumbra mRNA contains 2017 nucleotides and encodes a new membrane protein characterized by four transmembrane domains, a small extracellular domain between the first and second transmembrane domains and a large extracellular domain between the third and fourth transmembrane domains. It is a member of the evolutionarily conserved tetraspanin membrane protein superfamily that includes CD63, CD81, CD151 and Peripherin. Using the murine Penumbra as a probe, we identified the human Penumbra from a human bone marrow cDNA library. The human Penumbra also encodes a protein of 283 amino acids and is 97% identical to the murine Penumbra. The human Penumbra gene is mapped to chromosome 7q32, a hotspot for interstitial deletions in myelodysplastic syndromes and acute myelogenous leukemias. Immunofluorescence microscopy indicated that Penumbra is targeted to the cell surface. Immunoprecipitation-Western analysis showed that Penumbra formed disulfide bond-linked homodimers. To study the possible effects of Penumbra deletions, a knockout mouse model was created by homologous recombination. To avoid any pathology that might result from the Neo selectable marker, the targeting vector employed a self-excising Cre-Neo cassette driven by a testis-specific promoter. At 3 months of age, Penumbra−/− mice had similar numbers of RBC, hematocrits, WBC and platelets as the WT littermates. At 1 year of age, Penumbra−/− mice as a group had significantly lower RBC numbers and hematocrits than the WT littermates. Furthermore, about 40–60% of the Penumbra−/− mice had increased percentages of basophilic or polychromatophilic macrocytic RBC. As a group, these mice had even lower numbers of RBC (6.24 ± 1.87 vs. 8.88 ± 0.51 x 106/microliter in WT; p = 0.0002) and hematocrits (36.63 ± 8.28 vs. 46.21 ± 3.62% in WT; p = 0.002). Many such mice had massive splenomegaly due to increased extramedullary hematopoiesis. A multipotent hematopoietic cell line, EMX, was established from the bone marrow of a Penumbra−/−- mouse. EMX exhibits ineffective erythropoiesis in response to erythropoietin, a defect that is reversed by re-expression of Penumbra. These findings indicate that Penumbra plays an important role in erythropoiesis and suggest that Penumbra may be one of the genes that are often deleted during the evolution of myelodysplastic syndromes and acute myelogenous leukemias.
Dexamethasone, Etoposide, Ifosfamide and Cisplatin (DVIP) as Salvage Therapy in Non-Hodgkin’s Lymphoma and Hodgkin’s Disease.
Authors: Chubar Yevgene , Gavish Israel , Yegena Shay , Bennett Michael 
Published: April 2020

Abstract
26 patients (16 male, 10 female; median age 53 years, range 18–77) with relapsed Non-Hodgkin’s Lymphoma or relapsed Hodgkin’s Disease were treated with DVIP combination chemotherapy from July 1999 until February 2006. This consisted of 4 consecutive days of Dexamethsone 20 mg IV twice a day, Etoposide 75mg/m2 IV daily, Ifosfamide 1.2 gm/m2 IV daily with Mesna and Cisplatin 20 mg/m2 IV daily. Cycles were repeated every 3 weeks. 14 (53%) of the patients had an aggressive lymphoma (11 diffuse large B cell lymphoma, 2 anaplastic large T cell lymphoma, 1 immunoblastic lymphoma). 7 (26%) patients had an indolent lymphoma (5 Follicular Lymphoma, 2 splenic lymphoma with villous lymphocytes of which one had a blastic transformation). 5 (19%) patients had Hodgkin’s Disease. 19 (73%) patients received DVIP as a second line of therapy, 5 (19%) as third line therapy and one after 5 previous regimes. The median number of cycles given was 3 (range 1–6).
There was a total response rate of 54% (14) : CR 35% (9) and PR 19% (5). In 11 (42%) of the remaining patients stable disease was documented and one had disease progression with this therapy. 7 of the 9 in CR underwent successful PBSC mobilization and then received consolidation with high dose chemotherapy (HDCT) and autologous stem cell support. All of these are alive and in CR at a median of 55 months (range 2 – 80 months) post DVIP therapy. One patient in PR who underwent this procedure died 12 months later from disease progression.
Overall mean survival (OS) of all 7 patients who achieved CR was 70 months (95%CI = 53-87 months). A significantly lower mean OS of 13.5 months (95%CI = 3.4-23.6) was observed in those who did not achieve CR (p=0.001).
Hematological toxicity such as grade II/IV neutropenia was found in 23 (88%) of patients.
Conclusion : DVIP is an active regimen in relapsed aggressive and indolent non-Hodgkin’s lymphoma and relapsed Hodgkin’s disease. It can be used as cytoreductive treatment prior to PBSC collection and HDCT with autologous stem cell support. Further studies in combination with Rituximab in suitable patients are warranted.
CHOP Every 14 Days in Naïve Patients with Diffuse B-Large Cell Lymphoma.
Authors: Rubio-Martinez Araceli , Palomera Luis , Gonzalez Nicolas , Domingo Jose A. , Arguinano Carlos , Puente Fernando , Perella Matilde , Angos Jose A. , Sancho Ignacio , Herrera Pilar , Recasens Valle , Giraldo Pilar 
Published: April 2020

Abstract
Introduction: Some studies have shown that patients with aggressive lymphoma may benefit from dose intensified schedules as CHOP-14. The addition of rituximab ® improves response rate and survival. The support with G-CSF in dose intensification regimes may provide a good complementation of courses and advantage compared with schedules standard-dose as R-CHOP.
Purpose: To evaluate the efficacy of R-CHOP-14 in naïve patients with diffuse B- large cell lymphoma (DBLC) (REAL classification).
Design: observational, prospective and multicentric in a consecutive and previously untreated patients diagnosed of DBLC CD20+. Exclusion criteria: HIV positive, other malignancies and CNS involvement.
Patients and methods: Since June 2003 to June 2006, 56 patients were included in an R-CHOP regimen administered every 14 days (8 courses). At baseline assessment: clinical and physical exam, blood counts, serum and urine biochemistry, albumin, β2-microglobuline and LDH level, body scan, bone marrow biopsy. Patients were classified according ECOG, clinical stage and IPI. All patients have received prophylaxis with G-CSF. Re-staging studies were performed every 4 cycles. Responses were classified as complete remission (CR), partial remission (PR), and non response (NR).
Statistical analysis: Overall survival (OS), relapsed free survival (RFS). Survival analysis was performed using Kaplan-Meier and Cox regression.
Results: Mean age 50.13 years (20–78), 19M/37V. ECOG 0(24), 1(18), 2(3), 3(11). B symptoms 30 patients (53.5%). IPI score 0–1(21), 2(12), 3(8), 3 4 (15), stage I(4), II(9), III(13), IV(30). Extranodal location 33 (59%): bone marrow 13, lung 8, liver 6, CNS 4. After 4 cycle: 50 evaluable patients; response: 50 (91%), 15 CR (27%), 35 PR (64%), 5 NR. After 8 cycle: 40 valuables patients, 38 CR (95%), 2 PR. 5 patients have relapsed and 12 died (progression 6, infection 6: 5&gt; 70 years). Adverse events 187 episodes: neutropenia III-IV 107 (72%), thrombocytopenia III-IV 21(16%), infection 22 (11.7%): pneumonia 8(4.3%), neutropenia febrile 5(2.7%), gastrointestinal 5 (2.7%). Mean OS was 34.3 months and mean RFS 38.9 months.
Conclusions: A high response rate to R-CHOP 14 in adult’s naïve DBLC patients was observed in this study with acceptable toxicity. No differences in response were observed according to age groups but higher myelotoxicity and adverse events was present in older than seventy
Clinical Features and Treatment Outcomes of Primary Testicular Lymphoma.
Authors: Park Byeong-Bae , Kim Jong Gwang , Eom HyeonSeok , Kim Hyo Jin , Kwon Hyuck Chan , Oh Sung Yong , Kang Jung Hun , Oh Suk Joong , Shin Ho-Jin , Suh Cheolwon , Kim Jung Han , Kim Ho Young , Lee Sang Cheol , Kim Kihyun , Jung Chul W. , Kim Won Seog 
Published: April 2020

Abstract
We investigated clinical features and clinical outcomes of patients with primary testicular non-Hodgkin lymphoma (NHL) between 1996 and 2006. Thirty-eight cases were identified from clinical records. The median age was 59 years (range 41–81). Disease was classified as stages I in 13 cases, stages II in 15 and stages III-IV in 10. Diffuse large B-cell lymphoma was diagnosed in 92% of cases. All patients received orchiectomy. Twenty-three (61%) had orchiectomy and chemotherapy, 13 (34%) had orchiectomy, chemotherapy and involved field radiotherapy. All chemotherapy regimens which were used to patients in this study contained an anthracycline. Central nervous system (CNS) prophylaxis was performed in 6 (16%) patients and 10 (26%) patients were received prophylactic irradiation or surgery on the contralateral testis. In 33 evaluable patients, 4 (12%) had immediate disease progression following orchiectomy or on systemic treatment. A complete response was seen in the remaining 25 (76%) patients, irrespective of treatment modality. The median duration of follow-up was 25 months (range 2.5–122). Recurrence occurred in 18 patients and the most frequent site (45%) was the CNS: 4 in brain parenchyma, 3 in meninges, and 1 in both. Nine (36%) patients relapsed following a complete response and median time to relapse was 10 months. Overall median progression free survival (PFS) was 21 months. Twelve (32%) patients were died during follow-up: 10 died of causes related to their lymphoma and 2 were treatment-related mortality. Estimated median overall survival (OS) was 45 months for the entire patients. Significant survival differences between low/low intermediate and high intermediate/high risk of IPI were observed in OS (p=0.001). Primary testicular NHL was frequent in older patients, and has a poor prognosis although large proportion of this disease was loco-regional stage. Most of patients have died of disease related causes and their frequent relapse site was brain or meninges. Therefore, additional CNS prophylaxis including cranial irradiation and intrathecal chemotherapy to chemotherapy and involved field irradiation after orchiectomy should be considered as an effective treatment modality for improving survival.
Pediatric Hodgkin Lymphoma Patients Treated with ABVD Chemotherapy with or without Low-Dose Radiation Therapy.
Authors: Al-Kofide Amani , Belgaumi Asim F. , Khafaga Yasser , Joseph Nicey , Malik Rubina J. , Mourad Waleed , Mohamed Gamal-Eldin H. , Sabbah Rajeh S. 
Published: April 2020

Abstract
The ABVD protocol is probably the most effective chemotherapy (CTX) regimen for the treatment of Hodgkin Lymphoma (HL), however the dose and volume, and indeed the need for radiation therapy (XRT) in combination remains uncertain. Pediatric patients (0–14 years) at our institution have been treated with ABVD either with or without XRT, based on the treating physician’s decision. Patients receiving XRT were usually given one or two cycles less of CTX than those without. Since 1998 we have used 1500cGy as the dose of XRT, however the field was determined by the radiation oncologist. Between 1990 and 2003, 152 patients were treated according to the ABVD protocol. Of these, 64 were treated with CTX alone, while 88 also received radiation as consolidation therapy (Combined modality therapy; CMT). Of those who received XRT 63 were administered a dose of 1500cGy. The remaining 25 received various higher doses (1655cGy: 1, 2400cGy: 9, 2500cGy: 10, 3500cGy: 3, 3680cGy: 1, 3980cGy:1). Patients who were treated with CMT were older (mean age 9.2 v. 7.4 years; p&lt;0.05), had less B-symptoms (10.2% v. 26.6%; p&lt;0.05), but not more bulky disease (43.2% v. 34.4%; p=0.2). CTX group had more patients with stage III and IV disease, while CMT group had more stage II disease (p&lt;0.05). With a median follow-up of 4 years, the actuarial overall survival (OS) and event free survival (EFS) at 5 years for all the patients is 97.3% and 88.0%, respectively. The OS and EFS for the patients treated with CTX and CMT were 95.3% v. 98.8% (p=0.4) and 85.1% v. 90.2% (p=0.3), respectively. We next looked at the patients who received only 1500cGy of radiation therapy. Of the 63 patients, 29 received extended field radiation (EFXRT) and 34 involved field radiation (IFXRT). Patients who received radiation were administered a median of two cycles of ABVD less than those who did not (median 4 v. 6 cycles; mean 4.3 v. 5.1, p&lt;0.05). OS at 5 years for the patients treated by CTX v. CMT/EFXRT v. CMT/IFXRT is 95.3%, 96.6% and 100%, respectively (p=0.3). The EFS for the same groups is 85.1%, 86.2% and 90.1% (p=0.4).
Conclusion: Pediatric patients with HL can be treated successfully with minimal or no XRT. These results need to be confirmed in a prospective clinical trial.
Prognostic Factors in Hodgkin’s Disease - Analysis of 211 Patients from a Single Institution.
Authors: Grudeva Janet G. , Nenova Ivanka , Mateva Nonka , Ananoshtev Nikola 
Published: April 2020

Abstract
The treatment adaptation to individual risks of patients with Hodgkin’s disease is closely connected to the prognostic factors identification. The goal of the study was to identify prognostic factors related to survival of patients with Hodgkin’s disease in the population of Plovdiv district (South Bulgaria).
Patients and methods: The retrospective study involved 151 patients with Hodgkin’s disease, diagnosed and treated in the University Clinic of Hematology, Plovdiv, Bulgaria, from 1995 to 2005. The prognostic value of several pretreatment parameters with regard to the survival time was analyzed:
Sex, Ann-Arbor clinical staging, ECOG Performance status, Histological type, Extranodal localization, Systemic B symptoms, Abdominal lymphadenopathy and Infradiaphragmatic disease.
The patient’s survival was analyzed by using the Kaplan-Meier method. The log-rank test was used to compare cumulative survival functions.
Results: The mean survival period of patients was 13,35 years (95% C.I. 10,35–16,36). The most important prognostic factors for survival were: ECOG Performance status (P&lt;0,001), Ann-Arbor clinical stages (P=0,0046), extranodal localization (P=0,0009), abdominal lympadenopathy (P=0,0025), B symptoms (P=0,0145) and histological type (P=0,02). The factors with negative impact on survival time were: advanced III/IV clinical stage; poor ECOG performance status 3/4; mixed cellularity/lymphocyte depletion histological type; presence of abdominal lymphadenopathy and B symptoms and more than one extranodal localization. There is a tendency of poorer survival in patients in clinical stage I/II and infradiaphragmatic initial presentation of disease (P=0,185).
Conclusion: Prognostic factors identified in the present study can be easily applied in the routine clinical practice and may be used as a basis for mathematical prognostic models.
Treatment of Peripheral T-Cell Lymphoma (PTCL) with High-Dose Chemotherapy and Autologous Stem Cell Transplantation (ASCT).
Authors: Kim Min Kyoung , Kim Shin , Lee Seoung Sook , Sym Sun Jin , Lee Dae Ho , Kim Sang We , Jang Seongsoo , Park Chan Jeong , Chi Hyun Sook , Huh Joo Ryung , Suh Cheolwon 
Published: April 2020

Abstract
Objectives: Although CHOP-type chemotherapy has been the mainstay of therapy, outcome of PTCL has been uniformly disappointing. Despite the poor outcome after conventional chemotherapy, the impact of high-dose chemotherapy (HDCT) and ASCT is not well defined in these patients. The purpose of this study is to evaluate the efficacy of ASCT and the prognostic factors in PTCL with ASCT.
Patients and Methods: We performed a retrospective analysis of 40 PTCL patients from the Asan Medical Center treated between January 1995 to December 2005 with HDCT and ASCT.
Results: A total 40 patients were enrolled. Median age was 39 years (range 18–63). Twenty patients had PTCL-U, 10 extranodal NK/T cell lymphomas, 5 anaplastic large cell lymphomas, 3 angioimmunoblastic, one hepatosplenic γσ T cell lymphoma, and one disseminated mycosis fungoides. Disease status at transplant were CR1 in 3, CR2 or more in 8, partial remission in 25 (PR1 in 8 and PR2 in 17), and refractory in 4 patients.Three (7.5%) therapy-related mortalities occurred. A median follow-up of 16 months (range, 5 to 135 months) for surviving patients, the median overall survival (OS) was 11.5 months and the 1-year probability of survival was 41.5%. Ten patients (25%) were alive without evidence of disease. The median OS of 11 patients with CR at ASCT were not reached and of these, 7 patients (63.6%) were alive with CR. In multivariate analysis, CR status at HDT and BM involvement at ASCT was the most important prognostic factor for event free survival (P=0.032, P=0.031, respectively). A pretransplant IPI ≤1 and infused CD34+ cell dose ≥5×106/kg were the prognostic factors for an improved overall survival (P = 0.04 and P = 0.025, respectively).
Conclusion: The results of HDT with ASCT for the patients with PTCL who did not achieve a CR to first line or salvage chemotherapy are not satisfactory. The patients who did not achieve CR at ASCT and patients with low infused CD34+cell dose, BM involvement or high IPI score at ASCT have poor outcome.
Incidence and Outcome of T-Cell Lymphomas in Malaysia.
Authors: Chang Kian Meng , Lau Ngee Siang , Chew Lee Ping , Tan Sen Mui , Jameela S. , Puru V. 
Published: April 2020

Abstract
The T- and NK-cell neoplasms are a heterogenous group and are relatively uncommon. From the International Non-Hodgkin’s Lymphoma classification study, precursor T-lymphoblastic lymphoma and the mature T- and NK-cell lymphomas account for 1.7% and 12% of all NHLs. T-NHL are in general more common in Asia. The outcome of this disease is poorer with a 5-y overall survival of 20% (excluding anaplastic NHL). Hospital Kuala Lumpur is the major hematology referral centre in Malaysia. A total of 414 new cases of lymphoma was seen during 2000–2005. The majority were DLBCL 46% and follicular grade I/II lymphomas 15.8%. Only 48 cases (12%) were T-NHL. These were PTCL 19 (5%), anaplastic T-NHL 9 (2.2%), cutaneous T-NHL Stage IV 9 (2.2%), T/NK-NHL 5 (1.2%) and angioimmunoblastic NHL 3 (0.7%). Between 2002–2005, 15 patients were treated with HyperCVAD regimen alternating with Mtx/Ara-C. Three had T-lymphoblastic lymphoma, 7 had PTCL and 5 had T/NK cell. The complete remission was 40% with two proceeding to stem cell transplant. One received local DXT. The median duration of remission was 18.5mths(10–30mths) with median follow-up of 30mths(25–35mths). Alemtuzumab(Campth-1H) is a humanised monoclonal antibody that targets the CD 52 antigen including the T-cell. We combined HyperCVAD with Alemtuzumab 30mg sc on day 1 of every chemotherapy cycle. Four patients with relapsed/refractory T-ALL and 1 patient with T/NK NHL were treated. Two patients, one who relapsed six months after chemotherapy and the other after allogeneic transplant achieved complete remission. The patient with T/NK who had progressive disease with enlarging hepatosplenomegaly after 1 pair of HyperCVAD achieved remission after the addition of Campath. The median duration between each chemotherapy cycle was 25 days(23–26d). One patient had CMV reactivation with no evidence of disease. All patients are still undergoing treatment. The addition of Campath 30mg on day 1 of each chemotherapy cycle appears to be a viable option to try to improve the results in aggressive T-NHL. In view of these preliminary findings, we are starting a study protocol using Campath plus HyperCVAD in aggressive T-cell disease.
A Report of AIDS-Related Lymphoma (ARL) in Korea.
Authors: Kim Jin-Soo , Kim Seok Jin , Kim Jin Seok , Min Yoo Hong , Lee Moon Hee , Bang Soo-Mee , Kim Jeong A. , Chi Hyun-Sook , Jang Seong Soo , Park Chan Jeoung , Suh Cheolwon , Kim Chul Soo 
Published: April 2020

Abstract
The prevalence of ARL is thought to be on increase in Korea. The aim of this study is to review cases of ARL in Korea from August 1998 through July 2006. A total of 16 cases of ARL were reported from 6 institutions in Korea. The patients consisted of 14 males and 2 females at a median age of 41 (range, 30–68) on diagnosis of AIDS. ARL developed at their median age of 43 (range, 32–69). The histologic diagnosis was diffuse large B cell lymphoma (n=9), Burkitt lymphoma (n=1), peripheral T cell lymphoma (n=1), NK/T cell lymphoma (n=1), primary CNS lymphoma (n=1), primary effusion lymphoma (n=1), Hodgkin lymphoma (n=1), or plasmablastic lymphoma (n=1). The disease extent was unknown in 4, stage I in 3, stage II in 4, stage III in 1, stage IV in 5. B symptom was noted in 5 at presentation. Seven of 16 (43.8%) was receiving highly active anti-retroviral therapy (HAART) before the diagnosis of ARL. All the patients were given HAART after the diagnosis of ARL. The response to HARRT was evaluable in 9 patients based on CD4+ cell count and HIV viral load, among which 8 (88%) responded. Four of 16 patients did not receive chemotherapy against medical advice. The chemotherapy regimen included CHOP (n=6), CEOP-B (n=3), m-BACOD (n=2), or CODOX-M/IVAC (n=1). Four patients who refused chemotherapy were lost to follow up. Of 12 patients treated with chemotherapy, 7 were alive in remission, 1 alive in disease, 1 died of treatment related complication, 1 died of progressive lymphoma, 2 died of AIDS related causes. The response to chemotherapy included CR in 7 (70%), PR in 2 (20%) and PD 1 (10%). The median follow-up duration was 15.2 months (range, 0.5–53.2) and the median survival time 43.9 months.