bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flow Cytometric Detection of Liposomes in the CSF of Patients with NHL/ALL, Treated with Intrathecal Liposomal Cytarabine: Synonymous of Toxicity?
Authors: Peñalver Francisco Javier , Pilar Martínez-Barranco , Villalón Lucía , Barón Manuel , Martín L , Ricard Pilar , Arribalzaga Karmele , Garcia Bueno María José , Orfao Alberto 
Published: October 2019

Abstract
Objectives
Patients with aggressive non-Hodgkin’s lymphoma (NHL) and acute lymphoblastic leukemia (ALL) with high risk of CNS infiltration or recurrence may receive prophylaxis or be treated with intrathecal injections (IT) of liposomal cytarabine (LC) once every 2 weeks (due to its sustained release of cytarabine).
Sequential flow cytometric studies in patients with CNS involvement and treated with LC, allow to detect tumor cells as well as LC liposomes (LCL) in the CSF. The true meaning of the presence of these liposomes during the treatment with LC is still unknown.
Patients and Methods
In this study, we aimed to investigate the presence of LCL detected by Flow Cytrometry (FC) among 166 CSF samples of 69 patients treated with LC. Samples were taken before each administration of intrathecal LC and centrally processed.
Results
Results are shown in the below table. Abstract 5444. Table 1Patients with NHL/ALL, treated with Intrathecal Liposomal CytarabineNPatients69Samples166Liposomal Cytarabine Liposomes (LCL) in CSFN%Patients1319%DLBCL646%LLT215%ALL215%MCL18%MM18%CLL18%Samples2616%Males862%2616%Age66 years[33-84]LCL in CSF of patients receiving Liposomal CytarabinePROPHYLAXISNToxycityTotal nº of IT LC dosesPatients7nº of IT LC doses*3 (2-5).LCL7After 1st dose5After 2nd dose21 LLT patient: arachnoiditis, high intrathecal pressure, papillitis, without sequelae5After 3rd dose2After 5th dose1LCL in CSF of patients receiving Liposomal Cytarabine leptomeningeal disease TREATMENTNTumor: ToxycityTotal nº of IT LC dosesPatients6nº of IT LC doses*6 (4-7)LCL6After 1st dose31 DLBCL patient: Headache, dizziness and instability51 MM patient: Headache, dizziness and instability4After 3rd dose2After 5th dose11 ALL patient: Headache, dizziness and instability7 * Median [range]
The thirteen patients were simultaneously treated with LC and IT + IV dexamethasone. It was found no relationship between the amount of LCL and toxicity.
Conclusions:
Presence of LCL in CSF is detected in 15-20% of patients receiving IT LC as prophylaxis / treatment and it does not show a direct relationship with presence of toxicity.
Although the true clinical significance of the presence of LCL in CSF remains unknown, their monitoring could be useful to individualize the treatment with CL IT (dose and time between doses).

Disclosures
Off Label Use: Liposomal cytarabine is not approved for prophylaxys of lymphomatous meningitis..
Pediatric Hodgkin Lymphoma-Treatment Outcome with COPDac/ABVD Combination Chemotherapy – Single Institution Experience
Authors: Ahmed Mehboob , Riaz Shazia , Abbas Syed Nasir , Rehman Fahim 
Published: October 2019

Abstract
Background:
We describe single center experience of using ABVD/COPDac . This regimen was adapted due to perceived excessive toxicity with OEPA/COPDac by treating physicians. Hodgkin lymphoma is being treated with multiple treatment regimens single agent or in combination. MOPP (mechlorethamine, vincristine, procarbazine and prednisolone) has been standard treatment for almost two decads. But it had significant toxic effects including infertility in both genders, myelosuppression and second malignancies . ChlvPP( chlorambucil, vincristine, procarbazine and prednisolone ) has comparable efficacy and toxicities to MOPP . ABVD( Adriamycin, bleomycin, vincristine and doxorubicin ) was mostly used as second line with high activity without permanent male sterility, myelodysplasia or risk of leukemia.
Objective :
We describe single center experience of using ABVD/COPDac . This regimen was adapted due to perceived excessive toxicity with OEPA/COPDac by treating physicians.
Results
62 patients out of 301( 20.6%) with age range of 2-18 years were treated with COPDac/ABVD alternating courses depending on the treatment group from 2012 to date. Out of this 62, 49 (79%) are on follow up and are free from disease relapse or recurrence. Mean duration of follow up is 12 months with a range of 8-16 months. No patient lost to follow up. No death reported due to any cause during or after completion of treatment till last follow up. 9 out of 62 has had progression of disease while on this treatment protocol (15%) and 4 out of 62(6%) has had relapse after completion of the therapy.
Conclusion
In our single center experience of ABVD/COPDac as first line therapy seems effective and safe when compared with historical published literature.

Disclosures
No relevant conflicts of interest to declare.
FCR (Fludarabine, Cyclophosphamide, Rituximab) Followed By 90yttrium Ibritumomab Tiuxetan for the Treatment of Relapsed Grades 1 and 2 Follicular Lymphoma. Long Term Efficacy and Safety Results of 9 Cases
Authors: Pisani Francesco , Dessanti Maria Laura , Giannarelli Diana , Kayal Ramy , Marchesi Francesco , Sciuto Rosa , Rea Sandra , Maini Carlo Ludovico , Marino Mirella 
Published: October 2019

Abstract
Background: This retrospective analysis is focused on the efficacy and safety of radioimmunotherapy (RIT) with Zevalin® in nine patients with recurrent follicular lymphoma (FL) who were treated in a consolidation setting after having achieved complete remission or partial remission with FCR.
Methods: The median age was 63 years (range 46-77), all patients were relapsed with histologically confirmed CD20-positive (grade 1 or 2) FL, at relapse they received FCR every 28 days: F (25mg/m2x 3 days), C (1gr/m2 day 1) and R (375mg/m2 day 4) for 4 cycles. Who achieved at least a partial remission, with<25% bone marrow involvement, was treated with 90Yttrium Ibritumomab Tiuxetan 11.1 or 14.8 MBq/Kg up to a maximum dose 1184 MBq, at 3 months after the completion of FCR. The patients underwent a further restaging at 12 weeks after 90Y-RIT with total body CT scan, FDG-PET/CT and bilateral bone marrow biopsy.
Results: Nine patients have completed the treatment: FCR followed by 90Y-RIT (6 patients at 14.8 MBq/Kg, 3 patients at 11.1 MBq/Kg). After FCR 7 patients obtained CR and 2 PR; after 90Y-RIT two patients in PR converted to CR 12 weeks later. With median follow up of 86 months (range 20-107) since FCR and 79 months (range13-97) since RIT, 3 deaths were observed not related to lymphoma: one for acute renal failure, one for ictus cerebri and one for sepsis; all three deceased patients obtained CR before 90Y-RIT and died still in CR. The median overall survival (OS) and progression free survival (PFS) have not been reached , current analysis has shown that either OS or PFS are 67% at 7 year. The most common grade 3 or 4 adverse events were hematologic, one patient developed herpes zoster infection after 8 months following valacyclovir discontinuation; another patient developed fungal infection.
Conclusions: These results confirm the long term efficacy and safety of 4 cycles of FCR followed by consolidation with 90Y-RIT in patients relapsed with grades 1 and 2 FL and suggest that this regimen could be an option to be used for treatment in this setting of patients, specially at age of 60-75 with no unexpected toxicities.
Figure 1. Progression free survival from RIT Figure 1. Progression free survival from RIT

Disclosures
No relevant conflicts of interest to declare.
Clinical Research on Burkitt Lymphoma—a Single-Center Report in China
Authors: Jiang Meng , Niu Ting 
Published: October 2019

Abstract
Objectives
To analysis the clinical characteristics and discuss the factors that influence the treatment efficacy and prognosis of the patients with Burkitt lymphoma (BL).
Patients and Methods
A retrospective study was performed to collect the clinical characteristics and follow-up data of the patients with BL from January 2004 to December 2014 in West China Hospital.
Results
A total of 42 patients with BL included 32 male patients and 10 female ones,with a median age at diagnosis of 45 yr (range: 13 to 74 yr) old. In the whole cohort, 66.67% of the patients had an Ann Arbor stage III`W. Patients with B symptoms accounted for 50.00%. Gastrointestinal discomfort and axillary, jugular and mandibular mass were the main complaints.
Twenty patients received Hyper-CVAD/HD-MTX-Ara-C regimen (Hyper regimen), while the other 22 patients received non-Hyper regimen, which included CHOP/CHOP-like, CODOX-M/IVAC regimen and others. The 42 cases showed an overall response of 59.52%, with a complete response (CR) rate of 57.14% (24/42).
With univariate analysis: the CR rates of the patients received Hyper regimen and non-Hyper regimen were 75.00% and 40.91%, respectively, indicating a statistical significance between the two groups (P=0.027); the CR rate of the patients with elevated LDH was higher than the patients with normal LDH; the CR rate of patients with ECOG PS of 0`2 was higher than the patients with PS 3`4; the CR rate of the patients with IPI of 0`2 was higher than the patients with IPI of 3`5; for the patients whose LDH increased, the CR rate of the patients received Hyper regimen was higher than the patients with non-Hyper regimen. The OS of the patients who received Hyper regimen was better; the OS of the patients with ECOG of 0`2 was superior to that with ECOG of 3`4; the OS of the patients with IPI of 0`2 is better than that of 3`5; the OS of the patients with Ann Arbor stage of ±`II was higher than that of III`W; the OS of the patients who acquired CR was better than that did not; the OS of the patients without bone marrow involvement was superior to that with it.
In multivariate analysis: treatment regimen was of significance in predicting the probability of CR, whereas treatment regimen and IPI score were confirmed as being highly predictive for OS.
The main side reactions of the 20 cases who accepted Hyper regimen were hematologic toxicity of III`W degree, gastrointestinal discomforts and infections, and there was no treatment-related mortality occurred.
Conclusions:
Hyper regimen could improve the CR rate and prolong the survival of BL patients, and the adverse reactions could well be tolerated.

Disclosures
No relevant conflicts of interest to declare.
Bing-Neel Syndrome: A Rare Complication of Waldenstrom’s Macroglobulinemia
Authors: Sanchez-Guerrero Sergio A. , Treon Steven P. , Guevara-Arnal Luis , Darwich Akram , Cardenas-Ortega Andrea , Castillo Jorge J. 
Published: October 2019

Abstract
A sixty-one year-old Hispanic female with Waldenstrom’s Macroglobulinemia diagnosed in 2011 and successfully treated with 6 monthly cycles of Cyclophosphamide, Rituximab and Dexamethasone (CDR) from 12/11 through 5/12 was then put on a two-year maintenance scheme with Rituximab every three months. In February, 2014 (six months before the end of the planned treatment), she came to the ER complaining with severe headache, aphasia and blurred vision. A stroke was initially ruled out and she received Paracetamol with partial improvement. Nonetheless, symptoms re-appeared accompanied with disorientation and agitation. Antipsychotic medication was given with no improvement. On PE she was disoriented with aphasia, paraparetic and neck stiffness suggestive of meningitis. Blood tests, a MRI and lumbar puncture were performed showing leptomeningeal hyperintensity with no signs of encephalitis (Figure 1).
Figure 1 Leptomeningeal reinforcement as seen in MRI. Figure 1. Leptomeningeal reinforcement as seen in MRI.
CSF analysis showed WBC 64 cells/µL, (95% MNC), glucose= 9.8 mg/dL and proteins= 110 g/dL. Gram dye was negative. A geneXpert for Tuberculosis was negative. CSF cytology showed an infiltration of lymphoid neoplastic cells confirmed by cytochemistry (Figures 2a and 2b).
Figure 2a: CD 20+ and 2b: kappa + neoplastic cells in CSF Figure 2a:. CD 20+ and 2b: kappa + neoplastic cells in CSF Figure 3 Figure 3.
With these results a Bing Neel syndrome was diagnosed and IT Methotrexate was given for a total of 6 doses resulting in a nice reduction of the neoplastic cells. However, she relapsed in April/2014 and IV Fludarabine was started. We are planning to add IT liposomal Cytarabine. Additionally, MYD 88 gene mutation was detected.
DISCUSSION: There are only 33 reported cases of Bing-Neel syndrome in the medical literature for the last 80 years and this one has been confirmed with the newest tools such as: MRI, cytochemistry and gene mutation.
CONCLUSION: Bing-Neel syndrome should be suspected in every patient with Waldenstrom’s Macroglobulinemia and CNS impairment.

Disclosures
No relevant conflicts of interest to declare.
Establishment of a Therapeutic Anti-Pan HLA-Class II Monoclonal Antibody That Directly Induces Lymphoma Cell Death Via Large Pore Formation
Authors: Matsuoka Shuji , Ishii Yasuyuki , Nakao Atsuhito , Masutani Hiroshi , Takahashi Satoshi , Nakauchi Yusuke , Hino Okio 
Published: October 2019

Abstract
To develop a new therapeutic monoclonal Antibody (mAb) for Hodgkin lymphoma (HL), we immunized a BALB/c mouse with live HL cell lines, alternating between two HL cell lines. After hybridization, we screened the hybridoma clones by assessing direct cytotoxicity against a HL cell line not used for immunization. We developed this strategy for establishing mAb to reduce the risk of obtaining clonotypic mAb specific for single HL cell line. A newly established mouse anti-human mAb (4713) triggered cytoskeleton-dependent, but complement- and caspase-independent, cell death in HL cell lines, Burkitt lymphoma cell lines, and advanced adult T-cell leukemia cell lines. Intravenous injection of mAb 4713 in tumor-bearing SCID mice improved survival significantly. mAb 4713 was revealed to be a mouse anti-human pan-HLA class II mAb. Treatment with this mAb induced the formation of large pores on the surface of target lymphoma cells within 30 min. This finding suggests that the cell death process induced by this anti-pan HLA-class II mAb may involve the same death signals stimulated by a cytolytic anti-pan MHC class I mAb that also induces large pores formation. This multifaceted study supports the therapeutic potential of mAb 4713 for various forms of lymphoma.

Disclosures
No relevant conflicts of interest to declare.
Using HDAC Inhibitors to Eradicate Adult T-Cell Leukemia-Lymphoma
Authors: Pimentel Agustin , Reis Isildinha , Toomey Ngoc , Diaz Luis , Ruiz Phillip , Taylor Graham , Ramos Juan Carlos 
Published: October 2019

Abstract
Adult T-cell leukemia-lymphoma (ATLL) is an aggressive malignancy with a poor prognosis caused by HTLV-I, which is endemic in Japan, the Caribbean, and South America. ATLL cannot be cured with conventional chemotherapy thus urging the development of new therapeutic strategies. Histone deacetyalse (HDAC) inhibitors are broadly active anti-neoplastic agents, which have shown efficacy in T-cell lymphomas. At our institution we encounter a relatively high number of ATLL cases as compared to other regions in the U.S. We have conducted a pilot trial using AZT/interferon-α(IFNα) plus the HDAC inhibitor valproic acid (VPA) during maintenance therapy in acute (leukemia-type) ATLL. We hypothesized that VPA would reactivate HTLV-I leading to a cytotoxic T-cell immune response followed by reduction of residual blood circulating ATLL clones that normally persist during AZT/IFNα therapy despite its suppressive effects. Supporting this notion, the addition of VPA to AZT/IFNα resulted in reduction of HTLV-I proviral loads in treated patients and a sustained molecular response in one subject who is still alive >4.5 years later. More recently, we have tested newly available and more potent HDAC inhibitors using fresh primary leukemic ATLL cells and low-passage cell lines. Through HDAC inhibition, these agents reactivated HTLV-I Tax gene expression and induced apoptosis in a dose-dependent manner. Belinostat, which is currently FDA-approved for the treatment of relapsed or refractory peripheral T-cell lymphoma, augmented ATLL cell death when added to AZT/IFNα at nanomolar concentrations. Therefore, we have proposed a new pilot clinical trial using belinostat for the treatment of ATLL during post-induction therapy. The role of HDAC inhibitors in ATLL, pre-clinical laboratory studies involving these agents, and clinical trial design will be discussed at the meeting

Disclosures
Off Label Use: The use of HDAC inhibitors in adult T-cell Leukemia-lymphoma.
Induction of Na+-H+ Ion Exchanger 1 Protein By Heme Oxygenase-1 Plays a Crucial Role in Imatinib-Resistant Chronic Myeloid Leukemia Cells Via p38/MAPK Signaling Pathway
Authors: Wang Jishi , Ma Dan 
Published: October 2019

Abstract
Background: Resistance toward imatinib (IM) and other BCR/ABL tyrosine kinase inhibitors(TKI) remains an increasing clinical problem in the treatment of advanced stages of chronic myeloid leukemia (CML). Heme oxygenase-1 (HO-1), as a Bcr/Abl-dependent survival molecule in CML cells, is important to resist against TKI in patients with freshly diagnosed CML or IM-resistant CML. However, the resistant mechanism on HO-1 up-regulation was still unclear.
Objective: In this study, our findings indicated that over-expression of Na+-H+ion exchanger 1 protein (NHE1) companied with HO-1 up-regulation in CML patients’ mononuclear cells who resisted with IM, while not in whom was sensitive to IM. Therefore, we explored the difference in the signaling pathway related to HO-1 and NHE1 in IM-resistant or sensitive CML cell lines.
Method: CCK-8 kits was used to determine the proliferation inhibition of cells. Flow cytometry was used for analyzing cell proliferation rate and apoptosis. Real-time PCR Array was used to search the relative pathway. Apoptosis relative factors expression were detected by real-time transcription and Western blot.
Result: As a result, we found that up-regulation of NHE1 after transfection of K562 cells line with lentivirus vector, lenti-TOPO-EGFP-HO-1. However, this effect disappeared when HO-1 expression was inhibited by transfection with lenti-U6.2-EGFP-siHO-1. Then, the relationship between HO-1 and NHE1 was detected by qPCR array, activation of p38/MAPK pathway mediated by protein kinase C-β II(PKC-β II) was found. NHE1 wasn’t up-regulated as PKC-β was blocked as well as p38/MAPK pathway was inhibited by SB203580 in K562/IM cells. Meanwhile, the apoptotic rate of the IM-resistant cells line K562 was increased by silencing HO-1, or treatment with SB203580, Enzastaurin, and Cariporide alone.
Conclusion: In this study, we demonstrated that HO-1 relative IM-resistance in CML was involved in the regulation of NHE-1 phosphorylation, which mediated by p38/MAPK signaling pathway activated by PKC-β.

Disclosures
No relevant conflicts of interest to declare.
“FLAG” Regimen Induces Deep, Although Short-Term, Responses in Patients Resistant to Tyrosine Kinases Inhibitors in BP CML.
Authors: Romanova Ekaterina , Girshova Larisa , Siordia Nadia , Goriunova Elena , Motorin Dmitry , Lomaia Elza , Konopleva Marina 
Published: October 2019

Abstract
Background:
Currently the main potential treatment for chronic myeloid leukemia (CML) blast phase (BP) are tyrosine kinase inhibitors. The aim of our study is to try to find any therapy in TKI resistant patients in CML BP.
Material and methods:
The patients were 5 male and one female (age range from 28 to 45 years old). 4 patients progressed to BP from chronic phase (CP), there was rapid progression from AP in other two pts (4 lymphoid, 1 myeloid, 1 undifferentiated). The pts were unresponsible to one or two second generation TKI treatment in BP (dasatinid, nilotinib). Two patients were also failed to respond to high dose cytarabine and methotrexate treatment after TKI failure. Chemotherapy «FLAG» (fludarabine, cytarabine high dose, G-CSF) was used to induce of CP.
Results:
Five of six pts achieved the second CP and deep response (1- CcyR, 3- MMR, and one BCR/ABL reduction to 0,371%).Two of these pts obtained deep response (CCyR, and bcr/abl reduction to 0.371% after unsuccessful treatment with dose mono cytarabine and methotrexat treatment. The response was short, the longest MMR duration is 48 days (patient is being prepared for ASCT).
Conclusion:
FLAG can induce deep molecular responses in BP pts resistant to TKIs. This regimen seems to be more effective than HDAC and HD MTX. The response is of short duration. Thus, in case of absence of relative sibling, haploidentical ASCT with unmanipulated bone marrow and posttransplantation cyclophosphamide could be the optimal treatment choice. The protocol for FLAG induced remission followed haploidentical ASCT is prepared.

Disclosures
No relevant conflicts of interest to declare.
A Phase 2 Study of Bendamustine Plus Melphalan Conditioning for Second Autologous Stem Cell Transplantation in "De-Novo" Multiple Myeloma Patients in a Tandem Transplant Strategy
Authors: Martino Massimo , Giuseppe Messina , Fedele Roberta , Irrera Giuseppe , Giuseppe Console , Gallo Giuseppe Alberto , Vincelli Iolanda Donatella , Ronco Francesca , Gentile Massimo , Morabito Fortunato 
Published: October 2019

Abstract
Background:
High-dose melphalan (HDM) is the standard therapy for autologous stem cell transplantation (ASCT) in multiple myeloma (MM), although the optimal conditioning regimen remains yet to be identified. Bendamustine (BENDA) has a proved activity in hematological malignancies including both first line and relapsed MM.
Methods:
We conducted a phase II trial, adding BENDA to HDM before second ASCT, in a tandem ASCT strategy, in 32 patients with "de-novo" MM. All patients received a bortezomib-based induction therapy. High-dose cyclophosphamide (CY) and G-CSF were used to mobilize stem cells. Four to 6 weeks after the administration of CY, patients received HDM (200 mg/mq), followed by ASCT. Three to 6 months after the first transplantation, patients received a second ASCT with BENDA (200 mg/m2) to HDM (140 mg/m2) as conditioning regimen (BM).
Results: The median age was 56 years (range 40 to 66). Overall, there was no transplant related mortality. The incidence of neutropenic fever and mucositis (grade 1-2) was 46.9% and 81.2%, respectively. No mucositis grade 3-4 was observed. Median number of days to neutrophil and platelet engraftment were 11 and 12, respectively. After the second transplantation, the complete response (CR) improved to 62.5%. Overall response rate was 90.6%. After a median follow-up of 18,2 months, 4 patients had progressed and 1 died. Median progression free survival (PFS) was not reached and actuarial 2-year PFS and OS was 78% and 90%, respectively.
Conclusion: Bendamustine plus melphalan is feasible as conditioning regimen for second ASCT in MM and should be explored for efficacy in a phase III study. Longer follow-up is needed to evaluate conversion rate and survival.

Disclosures
No relevant conflicts of interest to declare.