bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Results in Patients with Primary and Secondary Myelofibrosis Treated with Monthly Cycles of Oral Melphalan.
Authors: Carmosino Ida , Latagliata Roberto , Breccia Massimo , Cannella Laura , Vozella Federico , Volpicelli Paola , Santopietro Michelina , Spadea Antonio , Petti Maria Concetta , Alimena Giuliana 
Published: October 2019

Abstract
Abstract 4985
Prolonged continuous oral Melphalan treatment was successfully employed in patients with Idiopathic Myelofibrosis (IM); however, a high incidence of evolution into blastic phase (BP) was observed. In order to reduce the incidence of BP and other side effects, a different Melphalan schedule with intermittent monthly cycles was tested at our Institution. From 1/2003 to 2/2009, 24 patients (16 males and 8 females, median age 66.2 years, range 41.7 – 76.2) were enrolled into the study; 19/24 had primary IM while in 5 there was a previous history of Polycythemia Vera/Essential Thrombocythemia. Six patients (25%) had been pretreated with Hydroxyurea. A symptomatic splenomegaly was present in all patients, with median spleen enlargement below costal margin of 12 cm (range 7 – 22). Median WBC level was 11.6 × 109/l (range 3.6 – 63.6), with 11/24 patients having WBC > 12.0 × 109/l; in addition, 3 patients had PLT level > 500 × 109/l, 11 patients Hb level < 10 g/dl and 3 patients had transfusional requirement. Melphalan was administered orally at the dose of 8 mg/day for 5 consecutive days every month. Twelve patients (50%) had a reduction of spleen enlargement > 75%, 2 patients > 50% and 1 patient > 25%, with a global response rate of 15/24 patients (62.5%): the remaining 9 patients had no variation in spleen volume. Elevated WBC values reduced to normal in all but one patient, elevated PLT values reduced to normal in 2 out of 3 patients, transfusional requirement disappeared in 1 out of 3 patients. Median number of cycles to best response was 10 (range 2 – 30). As concerns hematological toxicity, 4 patients had Hb decrease < 8 g/dl, with 3/4 requiring transient transfusional support, and 1 patient had PLT decrease to < 50 × 109/l. One patient resistant to treatment died from broncopneumonia and 1 patient with normal PLT values died from cerebral hemorrhage; two patients had a grade 3 – 4 gastro-intestinal hemorrhage. Interestingly, only 2/24 patients (8.3%) had a BP evolution after 8 and 16 months from start of Melphalan, respectively. After a median number of treatment cycles of 18 (range 2 – 68), 12 patients are still in therapy and 12 discontinued Melphalan due to toxicity (4), resistance (3), relapse (3) or evolution to BP (2). In conclusion, the intermittent cyclic schedule of oral Melphalan seems capable to maintain a good response rate with reduction of symptomatic spleen enlargement in more than 50% of patients without excessive toxicity and with a lower rate of BP evolution, as compared to continuous Melphalan administration.

Disclosures
No relevant conflicts of interest to declare.
A Case of Massive Intracerebral Haemorrage in Advanced Myelofibrosis Due to Atypical Metaplasia.
Authors: Caramella Marianna , Gabutti Cristina , Del Curto Cecilia , Campidelli Cristina , Nador Guido , Pungolino Ester , Morra Enrica 
Published: October 2019

Abstract
Abstract 4988

BACKGROUND
Primary myelofibrosis is a chronic myeloproliferative disease characterized by connective tissue deposition in the bone marrow and extramedullary hematopoiesis commonly involving the liver and the spleen.

CASE REPORT
We report the case of a 60 year old patient with advanced Post Thrombocitemia Myelofibrosis extensively localized in almost all organs. He was referred to our Center in April 2008; clinical, radiological and haematological features suggested an evolution into Myelofibrosis. Molecular analysis for V617F JAK2 mutation was negative. Hemogram showed leukocytosis, mild anemia and normal platelet count. After few months of treatment with Danazol and Thioguanine, he was admitted for hemodynamic failure; echocardiography and chest X-ray were normal; abdomen CT scan confirmed important splenomegaly and didn't show any deep thrombosis. During hospitalization he developed massive intracerebral haemorrhage, cause of death. Post mortem histopatological examination documented osteomyelosclerosis and wide localization of extramedullary hematopoiesis. Morphological examination of the specimens showed an extensive dissemination of megakaryocytes, erythroid and myeloid precursors immunoreactive with factorVIII, hemoglobin, and myeloperoxidase respectively. We documented intravascular involvement of spleen, liver, lymph nodes, lungs, adrenal glands, myocardium, and central nervous system. Noteworthy fibrosis associated with haematopoietic cells were broadly distributed into retroperitoneal tissue.

CONCLUSIONS
Despite the massive myeloid metaplasia shown by the autopsy, general conditions of the patient until hospitalisation were good. Physical and radiological examination didn't reveal vascular and organ involvement. Although myeloid metaplasia is a possibility in advanced myelofibrosis, the assessment of cerebral and myocardial localization is difficult to find and standard radiological exams are not useful. In the subset of patients with Myelofibrosis and unexplained organ failure it could be interesting to look for an intravascular metaplasia throughout a multi-step approach: i) CD34+ peripheral cells count, since a very high count of these cells could suggest an extensive metaplasia; ii) high resolution pulmonary CT scan; iii) perfusional myocardial and/or pulmonary scintigraphy.

Disclosures
No relevant conflicts of interest to declare.
The Analysis of JAK2 and MPL Mutation as Well as JAK2 SNPs in MPN Patients by MassARRAY Assay.
Authors: Zhang Su-Jiang , Qiu Hongxia , Li Jianyong 
Published: October 2019

Abstract
Abstract 4989

Introduction
Recent studies have shown that JAK2 V617F, MPL W515L/K and JAK2 exon 12 mutations underlie the major molecular pathogenesis of myeloproliferative disorders (MPN).

Methods
To ascertain the real prevalence of these mutations and the influence of genetic susceptibility in Chinese MPN patients, we applied Allele-Specific Polymerase Chain Reaction (AS-PCR), directly sequencing and MassARRAY assay into our study.

Results
The positive rate of JAK2 V617F in polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) was 82.0%, 36.6% and 51.1% individually. We also found one ET patient, two PMF patients harboring MPL W515L mutation, and three PV patients harboring JAK2 exon 12 mutations. All of these patients were confirmed as JAK2 V617F negative. Moreover, clinical data demonstrated that PV patients with JAK2 exon 12 mutations had higher hemoglobin and lower age as well as WBC than PV patients with JAK2 V617F. In addition, through analysis of 4 polymorphic loci of JAK2 gene, no significant difference of distribution frequency was found among PV, ET and PMF patients. Distribution frequency of haplotype was not found to have significant difference among PV, ET and PMF patients either.

Conclusion
We conclude that JAK2 V617F is major molecular pathogenesis in Chinese MPN patients. MPL W515L mutation and JAK2 exon 12 mutations can also be found in JAK2 V617F negative MPN patients.

Disclosures
No relevant conflicts of interest to declare.
The Decrease of JAK2 V617F Allele Burden in Leukemia Transformation of An Elderly Patient with Myelofibrosis.
Authors: Zhang Su-Jiang , Li Jianyong , Xu Wei 
Published: October 2019

Abstract
Abstract 4990
Recently there were two different model about clone genesis of acute myeloid leukemia (AML) transformed from pre-existing JAK2 V617F positive myeloproliferative neoplasm (MPN). One model showed the leukemia cells were come from JAK2 V617F negative clone, however, the other indicated that the leukemia cells were still developed from JAK2 V617F positive clone. Here, we report a elderly AML patient who was developed from pre-existing myelofibrosis (MF) with homozygous JAK2 V617F mutation. In leuekmic transformation phase, heterozygous JAK2 V617F mutation was identified, supported the idea that the leukemia cells may be come from JAK2 V617F negative clone. Moreover, no other cytogenetic and molecular genetic abnormalities were further found. After one course of CAG regimen, complete remission was achieved. Further follow-up is still in progress.

Disclosures
No relevant conflicts of interest to declare.
FCγRIIa Polymorphism Is Not Associated with Overall Response in Diffuse Large B-Cell Lymphoma Treated with Rituximab.
Authors: Levy Debora , Oliveira-Souza, Pamela , Bellesso Marcelo , Maciel Felipe Vieira Rodrigues , Pereira Juliana , Bydlowski Sergio Paulo 
Published: October 2019

Abstract
Abstract 4994

Background
Low-affinity receptor for the Fc region of immunoglobulin G (IgG) (FcγR) is constitutively expressed on resting human neutrophils. These receptor, termed FcγRIIa display biallelic polymorphism which have functional consequences with respect to binding and/or ingestion of targets opsonized by human IgG subclass antibodies. Rituximab is a chimeric monoclonal antibody directed against CD20, an antigen found in most B-cell malignancies. Multiple mechanisms have been proposed for the activity of Rituximab, including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and a direct proapoptotic effect. F(ab')2 Rituximab homodimers were shown to be effective in inducing apoptosis of B-cell lymphoma cell lines in vitro. Recently, it have been established that ADCC is important as predominant mechanism of lymphoma cell clearance and that Fcγ receptors (FcγRs) are critical for the in vivo actions of Rituximab in non-Hodgkin lymphoma (NHL). A genomic polymorphism at amino acid 131 of FcγRIIA has been described whereby the presence of Histidine (H) rather than Arginine is associated with responses to the CD20-directed immunoglobulin G1 (IgG1) Rituximab among patients with indolent lymphoma. FcγRIIA genotype have been associated with a better clinical and molecular response in follicular lymphoma patients treated as first line therapy with Rituximab alone and in patients with diffuse large B-cell lymphoma (DLBCL) treated with the concomitant administration of Rituximab and CHOP (R-CHOP).

Methods
Here we analyzed the role of specific polymorphism of activating FcγRIIA in 42 patients with DLBCL treated with R-CHOP concerning prediction complete response (CR) using a polymerase chain reaction-restriction fragment length polymorphism method.

Results
The median age of the patients was 48 years (15 to 82). Out of the 42 patients 18 (42.8%) were stage III-IV and 17 (40.4%) had more than 2 factors of the International Prognostic Index. Thirty-seven (87.6%) had CR, 1 (2.3%) had partial remission (PR) and 4 (10.1%) had refractory disease (RD). Four ( 10.8%) of the patients that acquired CR relapsed. Deaths occurred in 3 (7.1%) patients with follow up of 2 years. Eight (19%) patients showed polymorphism HH, 21 (50%) HR and 13 (31%) RR. The univariate analysis did not show correlation between FcγRIIa H/H or R allele polymorphism and CR (p > 0.05).

Conclusion
Contrary to recent report we showed that FcγRIIa polymorphism is not associated to overall response in patients with DLBCL treated with Rituximab.

Disclosures
No relevant conflicts of interest to declare.
Plasmablastic Lymphoma – A Single Institution Experience.
Authors: Mohamed Zainab , Novitzky Nicolas , McDonald Andrew 
Published: October 2019

Abstract
Abstract 5003

Introduction
Plasmablastic lymphoma (PL) is a rare subtype of B-cell Non Hodgkin lymphoma that often involves the oral cavity of HIV-positive individuals but according to the WHO classification may occur in other sites.

Patients and Methods
A retrospective review of the charts of 25 HIV+ patients with PL who were seen from 2004 until 2008 was undertaken. Prognostic factors for outcome were determined by non parametric statistics. Survival was determined by the Kaplan and Meier method.

Results
Data from 12 male and 13 female patients with a median age of 35 years (30-57) were reviewed. Patients were mostly Ann Arbor stage 1 (44%) or stage 4 (40%). 92% of patients had extranodal involvement. The commonest extranodal site was the oral cavity, nasopharynx or maxillary sinus (32%), followed by bone (28%). Overall 76% presented with malignant lesions outside the oral cavity. At presentation median ECOG performance status and IPI was 1. Median LDH was 708 IU (310-17010). Median CD4 count was 63 ×106 /l (23-368). HIV infection was detected in 32% of patients at the time of lymphoma diagnosis; 20% had been on antiretroviral (ARV) therapy in excess of 6 months prior to presentation and 52% had been treated or continued treatment for tuberculosis (TB). Patients not yet on ARV were commenced on this treatment together with chemotherapy. All received anthracycline-containing (CHOP) chemotherapy and 19 had 4 or more cycles, while 5 were lost to follow up. 14 patients (56%) received radiotherapy either as palliation (6 patients) or involved field radiotherapy after achieving CR (8 patients). At median overall survival of 267 (27-1246) days 48% have achieved CR and 10 patients (40%) survive disease free for longer than 1 year. More favourable outcome was associated with any radiotherapy (p=0.01) and involved field radiotherapy (p=0.016).

Conclusions
In South Africa PL is associated with late HIV infection and frequently presents outside the oropharynx. The management is complicated by comorbidities, mainly TB infection. However, PL is responsive to chemotherapy and particularly involved field radiotherapy, which in some patients is associated with improved response and long term survival.

Disclosures
No relevant conflicts of interest to declare.
Clinical Outcome and Survival of EBV-Positive Diffuse Large B-Cell Lymphoma.
Authors: Beltran Brady , Quinones Pilar , Morales Domingo , Capellino Alex , Miranda Roberto , Bueso-Ramos Carlos E. , Sotomayor Eduardo M. , Castillo Jorge 
Published: October 2019

Abstract
Abstract 5005

Background
EBV-positive diffuse large B-cell lymphoma (DLBCL) is a new entity included provisionally in the most recent WHO Classification of lymphoid neoplasms. It usually affects elderly patients and has a poor survival. The goal of this study was to evaluate clinical characteristics and survival of EBV-positive DLBCL.

Methods
Between January 2002 and June 2008, twenty patients with EBV-positive DLBCL were deemed eligible for the study. Of those, eighteen cases were evaluable. All cases were positive for the presence of EBV-encoded RNA (EBER) by in situ hybridization, and CD20 and/or Pax-5 expression by immunohistochemistry (IHC). Clinical data were reviewed retrospectively and patient's biopsies were analyzed for the expression of bcl-6, CD10, CD30 and MUM-1 by IHC. The survival estimates were calculated using the Kaplan-Meier method and the log-rank test was used to compare the survival curves.

Results
The mean age was 72.7 years (range 34-95 years). B symptoms occurred in 6 patients (33%). Four patients (22%) presented with stage I, 4 (22%) with stage II, 5 (28%) with stage III and five (28%) with stage IV. The IPI risk score was low in 6 patients (33%), low intermediate in 2 (11%), high intermediate in 6 (33%) and high in 4 (22%). Extranodal disease occurred in 10 patients (55%); the most common extranodal sites were gastrointestinal tract (n=5), lung (n=3), suprarenal gland (n=1), bone (n=1), skin (n=1), tonsils (n=1) and bone marrow (n=1). Of 13 evaluated cases, eleven cases (83%) were of non-germinal center and 2 cases (17%) were of germinal center subtype. According to the Oyama score, 3 cases (17%) had 0 risk factors, 11 patients (61%) had 1 risk factor and 4 (22%) had 2 risk factors with median survival of 41, 11 and 1.5 months, respectively. Eight patients (44%) did not receive chemotherapy because they had a poor performance status. Ten patients (56%) received chemotherapy, eight received CHOP and two received R-CHOP. Overall response was 70% with a complete response in 7 cases and progressive disease in 3. No patients exhibited a partial response. Median survival for the entire group was 10 months; the median survival for the treated group was 17 months while for the untreated group was 2.5 months. The 2 patients treated with R-CHOP obtained a complete response.

Conclusions
EBV-positive DLBCL is an aggressive entity with frequent extranodal disease and a poor prognosis. The latter appears to be due to high IPI scores, non-germinal center immunophenotype and/or the presence of EBV. Although, EBV-positive DLBCL seems to respond well to R-CHOP, the survival remains dismal. Prospective studies are needed to validate EBV's prognostic, predictive and therapeutic value in DLBCL in the post-rituximab era.

Disclosures
No relevant conflicts of interest to declare.
Alcohol Drinking, Smoking, Past History of Gastroduodenal Ulcer, Height, and Risk of API2-MALT1 Fusion Positive and Negative Gastric MALT Lymphoma Among Japanese.
Authors: Kawase Takakazu , Matsuo Keitaro , Nakamura Tsuneya , Kanda Junya , Ito Hidemi , Hosono Satoyo , Watanabe Miki , Yatabe Yasushi , Morishima Yasuo , Tajima Kazuo , Seto Masao , Nakamura Shigeo , Tanaka Hideo 
Published: October 2019

Abstract
Abstract 5010
Extranodal marginal zone B-cell lymphoma of mucosaassociated lymphoid tissue (MALT Lymphoma) is low-grade extranodal lymphoma, and it comprises 7-8% of all B cell lymphomas, and up to 50% of primary gastric lymphoma. It is known that a preexisting chronic inflammation such as Helicobactoer pylori (H. pylori) gastritis can influence its development, however, some MALT lymphomas with no evidence of such inflammation are found. Protracted remissions may be induced by H. pylori eradication therapy, but cases with t(11;18)(q21;q21) appear to be resistant to the therapy. t(11;18)(q21;q21) has been observed in 25-50% of the cases and API2 at 11q21 and MALT1 at 18q21 are fused as a result of this translocation. Thus, API2-MALT1 fusion positive and negative MALT lymphoma may have different etiology, although histological features of both MALT lymphomas have not been clearly delineated. To clarify differences of epidemiological features between API2-MALT1 fusion positive and negative gastric MALT lymphoma, we conducted a case-control study of 61 newly and histologically diagnosed gastric MALT lymphoma cases (14 of API2-MALT1 fusion positive cases and 47 of negative cases) and 610 age and sex frequency-matched non-cancer controls. API2-MALT1 fusion was evaluated by a multiplex reverse transcription-polymerase chain reaction using formalin-fixed, paraffinembedded sections. We evaluated the association with alcohol intake (never drinkers, occasional drinkers, and frequent but moderate (<50 g/day of alcohol) and frequent and heavy drinkers (≥50 g/day of alcohol)), smoking (<5, 5-19, 20-39, ≥40 pack-years), past history of gastroduodenal ulcer, height, and risk of API2-MALT1 fusion positive and negative gastric MALT lymphoma. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using multinomial logistic models adjusted for potential confounders. A significant association was observed between past history of gastroduodenal ulcer and the risk only among fusion negative cases, with ORs of subjects with past history of gastroduodenal ulcer of 2.86 (95% CI, 1.31-6.14; p = 0.008) compared to subjects without past history of gastroduodenal ulcer. No clear associations were observed between alcohol intake, smoking, height and the risk irrespective of positivity of API2-MALT1 fusion. These findings suggest that past history of gastroduodenal ulcer, which may be due to H.pylori infection, does not associated with the carcinogenic mechanism of API2-MALT1 fusion positive gastric MALT lymphoma, and fusion positive and negative tumors have different etiology. Further investigations using large data sets are needed.

Disclosures
No relevant conflicts of interest to declare.
The Utility of Positron Emission Tomography (PET) with 18Fluorodeoxyglucose (18F-FDG) Compared to Standard Procedures in Detecting Bone Marrow Infiltration in Diffuse Large B-Cell Lymphoma in Developing Countries.
Authors: Bellesso Marcelo , Costa Renata Oliveira , Xavier Flavia Dias , Meneguetti José Claudio , Maciel Felipe Vieira Rodrigues , Steinbaun Daniel Salas , Hallack-Neto Abrahao Elias , Chamone Dalton Alencar Fisher , Pereira Juliana 
Published: October 2019

Abstract
Abstract 5015

Background
Computed tomography (CT) scanning and bone marrow biopsy (BMB) are the most used methods for initial staging in Diffuse Large B-cell Lymphoma (DLBCL) in developing countries. In the United States and Europe, 18-FDG PET has demonstrated to be an essential imaging modality for initial staging, early response and final therapeutic assessment in DLBCL patients. Afterward BM biopsy (BMB) is the gold standard to detect BM infiltration in lymphoma. However the ability of the FDG-PET to assess bone marrow (BM) positivity in DLBCL has been investigated and remains a controversial issue in the literature. For that reason we retrospectively compared the BM infiltration by bilateral BMB with FDG-PET at diagnosis in DLBCL patients.

Methods
We evaluated retrospectively 38 patients with DLBCL reporting the number of true-positive, false-positive, true-negative, and false-negative BM positivity by FDG-PET having the bilateral BMB as a reference standard.

Results
Out of 38, BM(+) was detected in 4 (10.5%) patients by BMB and in 14 (36.8%) patients by FDG-PET. The sensitivity and specificity of FDG-PET to recognize BM infiltration were respectively 100% and 71%. Negative and positive predictive values of the FDG-PET to identify BM(+) were respectively 100% and 28.5%. In negative-BMB patients, a positive FDG-PET BM was found in iliac 1 (10%), vertebra 5 (50%), sternum 2 (20%), scapula 1 (10%) and femur 1 (10%). The 18FDG mean maximum standardized uptake value (SUVmax) was 6.85 ± 3.9 in negative-BMB group and 9.77 ± 3.2 in positive-BMB group, p=0,208.

Conclusion
These results suggest that FDG-PET has a good sensitivity in detecting bone marrow infiltration in this type of aggressive lymphoma when compared to bilateral BMB to our knowledge the standard procedure to evaluate BM infiltration in lymphoma staging. Even though this study has several limitations such as one single center experience, a small number of patients and the lack of FDG-PET BM(+) confirmation by guided biopsy in previously negative-BMB patients, the majority of publications have been made in developed countries, and moreover we believe many issues still remain to be answered such as data regarding the FDG-PET cost-effectiveness out of clinical trails, specially in developing countries, in order to elucidate whether these results will be translated into a real benefit in overall survival for these patients.

Disclosures
No relevant conflicts of interest to declare.