bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dasatinib Compared with Imatinib In Newly Diagnosed Chronic Myelogenous Leukemia In Chronic Phase (CML-CP):Results of Japanese Subset Analysis In DASISION Trial.
Authors: Ogura Michinori , Nakamae Hirohisa , Fujisawa Shin , Ishizawa Kenichi , Taniwaki Masafumi , Utsunomiya Atae , Matsue Kosei , Tamura Kazuo , Usuki Kensuke , Tanimoto Mitsune , Ishida Yoji , Akiyama Hideki , Sakai Rika , Kasai Masanobu , Hino Masayuki , Ueda Kyoji , Seriu Taku , Bradley-Garelik M. Brigid , Zhu Chao 
Published: October 2019

Abstract
Abstract 4484

Background:
Dasatinib is a highly potent BCR-ABL kinase inhibitor. The previous report from the global DASISION trial showed dasatinib 100 mg once daily resulted in significantly higher and faster rates of complete cytogenetic response (CCyR) and major molecular response (MMR) compared with imatinib; both treatment arms were well-tolerated (N Engl J Med. 2010;362:2260-70). The objective of this subset analysis was to assess the efficacy and safety of dasatinib compared with imatinib in the Japanese population.

Methods:
Forty-nine Japanese patients (total 519 pts) with newly diagnosed CML-CP were randomly assigned to receive dasatinib 100 mg QD or imatinib 400 mg QD. Confirmed CCyR (cCCyR; CCyR on 2 consecutive assessments at least 28 days apart) was the primary efficacy endpoint with MMR as an important secondary endpoint. The safety profiles were also evaluated.

Results:
Minimum follow-up time and median treatment duration were 12 months and 15 months, respectively. Twenty-six patients with median age 56 (range, 21–70) years were treated with dasatinib and 23 patients with median age 52 (range, 22–77) years were treated with imatinib. Overall 89% of patients receiving dasatinib and 83% of patients receiving imatinib continue to receive treatment. The cCCyR rate by 12 months (primary endpoint), CCyR rate by 12 months and MMR rate at any time in dasatinib arm were higher than those in imatinib for Japanese patients (96% vs 70%, 96% vs 78%, and 73% vs 48%, respectively). Grade 3/4 cytopenias in dasatinib arm and imatinib arm were as follows: anemia (8% vs 4%), neutropenia (27% vs 39%), and thrombocytopenia (8% vs 9%). Non-hematologic and drug-related adverse events occurring in ≥10% of patients are shown as Table. No deaths were reported in either group. Drug-related serious adverse events were rarely reported and all events were not severe (Grade 1–2, including vomiting, hypoxia and cardiomyopathy in dasatinib arm).

Conclusion:
Dasatinib showed higher rates of cCCyR and MMR compared with imatinib. Both treatments were well tolerated. Given the predictive value of 12 months cCCyR, dasatinib may improve long-term outcomes in Japanese patients with newly diagnosed CML-CP.

Disclosures:
Ueda: Bristol-Myers K.K.: Employment. Seriu:Bristol-Myers K.K.: Employment. Bradley-Garelik:Bristol-Myers Squibb: Employment. Zhu:Bristol-Myers Squibb: Employment.
Pregnancy out Come In the Perspective of Chronic Myeloid Leukemia Patient on Imatinib Therapy: An Experience From India.
Authors: Mukhopadhyay Soma , Mukhopadhyay Ashis , Dasgupta Swati , Dey Subhasish , Majumdar Deboshree , Sarkar Sanjoy , Gharami Firoj , Konar Sukanta , Ray Ujjal 
Published: October 2019

Abstract
Abstract 4493

Objective:
Now that imatinib is being used to treat thousands of chronic myeloid leukemia (CML) patients for more than 10 year it is highly probable that many patients will get pregnant during its use. Company warns against any such use. But the fact remains that there is need for planned pregnancies in indicated cases. So we selected few cases both male and female for such pregnancies by interrupting treatment and following the pregnancy closely. Their outcome was studied so that we have an idea about what best could be suggested in such instance.

Patients and Methods:
From November 2002 to May 2010, 634 patients with CML in any stage of the disease were treated with imatinib at our tertiary cancer research institute. Among them 274 were female and 221 were of 17 to 50 years age group. We report information of 8 accidental pregnancies and 10 planned pregnancies involving 18 patients (10 females and 8 males) where pregnancy had occurred while receiving imatinib for the treatment of CML.

Observations:
Among 10 pregnancies reported in female sufferers there were two spontaneous and one elective abortion all in unplanned group and seven live births including one twin. There was one case of hypospadius which could be surgically corrected. Among the eight male patients whose wives conceived four pregnancies were planned, there was one spontaneous abortion, two elective abortions. The conceptions resulted in the birth of five healthy babies (two females). There was no other identifiable congenital anomaly.

Conclusion:
In the patients, who do become pregnant while on treatment, balancing the risk to the fetus of continuing imatinib versus the risk to the mother of interrupting treatment remains difficult. From the fetal perspective, imatinib should be discontinued due to the potential risk of serious developmental abnormalities; from the maternal perspective also there is chance of drug interruption induced cytogenetic relapse. CML patients, in the child bearing age group can do bear children. There was no major foetal anomalies which was documented. In the case of female patients the drug was withheld during the first trimester for concerns regarding potential teratogenecity. In both male and female, in the case of a planned pregnancy the drug should preferably be stopped one month before the time of expected conception.

Disclosures:
No relevant conflicts of interest to declare.
Relapse of Lymphoma After Allogeneic Hematopoietic Cell Transplantation: Management Strategies and Outcome.
Authors: Wudhikarn Kitsada , Cao Qing , Brunstein Claudio , Bachanova Veronika , Burns Linda J , Weisdorf Daniel J. 
Published: October 2019

Abstract
Abstract 4503

Background&Objective:
The management of lymphoma which has relapsed after allogeneic hematopoietic cell transplantation (HCT) is difficult. Therapeutic options may include donor lymphocyte infusion (DLI), withdrawal of immunosuppression, rituximab, chemotherapy, radiation, immunotherapy and experimental treatments, but response and survival are uncertain.

Result:
We analyzed 72 patients with relapsed or progressive lymphoma after allogeneic HCT (1991-2007); 44 non-Hodgkin's lymphoma (7 mantle cell, 5 indolent, 19 diffuse large B [DLBCL], and 13 T/NK cell) and 28 Hodgkin's lymphoma (HL). At HCT, 62 patients (86%) were in remission (22 CR, 40 PR); nine (13%) had progressive disease and one had stable disease. Conditioning was myeloablative (n=17) or reduced intensity conditioning (RIC) (n=55). Relapse or progression occurred at a median of 99 days (0-1898 days; 25–75% 43–194 days). At relapse, 41 (57%) had extensive nodal disease and 56 (78%) had extranodal organ involvement. Management of relapse included: no therapy (n=5, 7%), reduction of immunosuppression (RIS) (n=58, 81%), chemotherapy alone (n=14, 19%), immunotherapy alone (n=20, 28%), combined chemo-immunotherapy (n=7, 10%) donor lymphocyte infusion (DLI) (n=7, 10%), second allogeneic HCT (n=2, 3%), radiation (n=23, 32%) and other therapy (n=7, 8%). Twenty-four patients achieved a remission (15 CR, 9 PR) to the initial salvage therapy: RIS (n=13), combined chemo-immunotherapy(n=5), chemotherapy alone (n=2), radiation (n=3) or DLI (n=1). Overall, 40 (56%) patients responded (30 CR, 8 PR, 2 stable disease) with a median post-relapse overall survival of 28 months (range 0–147 months). At 3 years following relapse, 44% (95% CI, 32–56%) survive. Favorable prognostic factors for improved 3-year survival after relapse include stage I-III at relapse, single site of relapse and most importantly, later relapse (>100 days after HCT [3 year survival 53% vs. 36%, p=0.02]).

Conclusion:
The overall prognosis of relapsed lymphoma after allogeneic HCT differs based upon extent of disease at relapse and time of relapse. Appropriate therapeutic approaches (RIS, combined chemo-immunotherapy, radiation or DLI) in these high risk, post transplant relapsed patients can yield promising outcome. Prospective study of post-relapse therapy to determine the most effective management strategies are warranted.

Disclosures:
No relevant conflicts of interest to declare.
CMV Specific T Cells Prevent Progression From Low to High Level Viremia In D+R+ but Not D-R+ Patients.
Authors: Hoegh-Petersen Mette , Roa Lina , Liu Yiping , Zhou Feng , Ugarte-Torres Alejandra , Louie Polly , Fonseca Kevin , Khan Faisal , Storek Jan 
Published: October 2019

Abstract
Abstract 4532

Background.
Cytomegalovirus (CMV) reactivates (becomes detectable in blood) in most seropositive hematopoietic cell transplant (HCT) recipients. In some reactivating patients, low level viremia (<50,000 DNA copies/ml plasma, ie, less than our institutional threshold for preemtive therapy) progresses to high level viremia or CMV disease, which is potentially fatal. We hypothesized that low level viremia progresses in patients with low specific T cell counts and spontaneously resolves in patients with high specific T cell counts.

Methods.
In 30 CMV seropositive HCT recipients monitored weekly for reactivation by real-time PCR, blood was drawn for specific T cell counts within 4 days from the first episode of low level viremia. Fourteen patients received grafts from seropositive donors (D+R+), and 16 patients from seronegative donors (D-R+). Mononuclear cells were stimulated overnight with CMV lysate, pp65 overlapping peptides, no stimulus (negative control) or staphylococcal enterotoxin B (positive control). T cells producing IFNγ, TNFα and/or IL2 were enumerated by flow cytometry.

Results.
Among D+R+ patients, counts of CMV lysate and pp65 specific CD4 T cells producing IFNγ and TNFα (and not IL2) were higher in patients with spontaneous resolution than patients with progression (p=0.02 for CMV lysate, p=0.004 for pp65). Also, there was an inverse correlation between pp65 specific CD8 T cells producing IFNγ and TNFα and peak viremia (r=-0.94, p=0.005) in D+R+ patients who progressed to high level viremia/disease. In contrast, among D-R+ patients, CMV lysate and pp65 specific T cell counts were similar in patients with spontaneous resolution and patients with progression, and there was no correlation between specific T cell counts and peak viremia.

Conclusion.
CMV specific T cells play a role in preventing progression from low to high level CMV reactivation/disease in D+R+ patients. Other immune mechanisms (eg, NK cells?) play the role in D-R+ patients.

Disclosures:
No relevant conflicts of interest to declare.
Transient but Reversible Activation Defect of T-Cell Responses Against Cytomegalovirus and Adenovirus through Immunosuppresion with Calcineurin Inhibitors.
Authors: Neinhaus Cornelia , Opherk Kathrin , Kayser Simone , Leibold Joseph , Feucht Judith , Lang Peter , Handgretinger Rupert , Feuchtinger Tobias F. 
Published: October 2019

Abstract
Abstract 4542
Immunosuppressive treatment is widely used, especially after allogeneic stem cell transplantation (HSCT) to prevent or treat graft versus host disease (GvHD). Common drugs are Ciclosporin A or Tacrolimus in combination with steroids. However, immunosuppressive treatment and the underlying conditions are associated with an increased risk of viral reactivations with persistent pathogens like cytomegalovirus or adenovirus. In the absence of a protective immune response, virus infection remains a life-threatening complication after HSCT. Here we investigated the antiviral T-cell response (n=12) after ex vivo exposition with Ciclosporin A, Tacrolimus, Prednisolone or Mycophenolate at time of immunosuppression, 24 hours and 72 hours later. Analysis has been done with IFNgamma Elispot assays, confirmed by intracellular cytokine staining in flow cytometry and analysis of T-cell proliferation detected by CFSE. The antiviral T-cell response is suppressed after 24 hours using normal serum concentrations (100-200ng/ml) of cyclosporine A. T-cell annergy, induced by cyclosporine, could be reversible, after 72 without immunosuppression. Tacrolimus has a stronger immunosuppressive effect on T-cell activation within the same time and even low levels of 1ng/ml induce T-cell suppression after 72 hours. Peak levels of calcineurin inhibitors even suppressed the T-cell response to superantigens like staphylococcal antigen B or PHA. As expected, Prednisolone had a short and dose dependend effect on T-cell activation. Mycophenolate has a mild effect on the activation of virus-specific T-cells. However, all three drugs induced a significant reduction in Ag-specific T-cell proliferation. In conclusion, Interferonγ detection in virus-specific T-cells is a good diagnostic tool for clinicians to monitor the risk of viral complications in immunosuppressed patients. Tacrolimus, Cyclosporin A, Prednisolone and Mycophenolate induce an activation defect in Ag-specific T-cells with decreasing severity. The effect is reversible and corresponds to high or low serum levels.

Disclosures:
No relevant conflicts of interest to declare.
Thoax CT Scan as Invasive Fungal Infection (IFI) Screening In Neutropenic Patients, a Prospective-Retrospective Experience of It Impact on Therapeutic Intervention.
Authors: Sevilla Sebastian , Kusminsky Gustavo Daniel , Damiano Mario Atilio , Rizzo Miguel , Trucco Jose 
Published: October 2019

Abstract
Abstract 4554

Introduction:
Persistent fever in high risk neutropenic patients (HRNF) after day 5 of empiric treatment is a sign of high susceptibility for IFI with elevated morbidity and mortality. Diagnostic tools in this setting are inaccurate to determine the occurrence of IFI and most patients start with empiric antifungal agents. Drugs are usually associated with increasing costs and toxicity. It is challenging to establish the population of patients in whom in spite of persistent fever and neutropenia, avoidance of antifungal treatment is a reasonable strategy.

Methods:
We have prospectively allocated 229 HRNF patients in different empiric antimicrobial regimens over a 4.5 year period. In a retrospective revision, there were 33 patients with persistent fever on day 5 of empirical antimicrobial treatment and no evident new infection episode or clinical impairment. In 28 patients, a thorax CT scan was performed as part of the evaluation of persistent fever. The clinical outcome was evaluated regarding the presence or absence of pulmonary infiltrates in the CT scans. Initial empiric antifungal treatment, transfusions, days in hospital, days with neutropenia, antimicrobial treatment, and days with fever were evaluated.

Results:
Nineteen patients (68%) of 28 presented with pulmonary infiltrates. All of them received antifungal treatment. In 9 patients with normal CT scan antifungal treatment was deferred. The difference of the decision in not giving antifungals according CT scans was highly significant (p <0,0001). Transfusions of red blood cells and platelets were significantly less in the group of normal scans (p 0,0004 and 0,005 respectively). Antimicrobial treatment, days in hospital and days with fever were not significantly different in both groups. There was one death in the normal scan group due to relapse. Mortality was not significantly different in both groups.

Conclusion:
In HRNP, normal thorax CT scan changed the clinical decision in not starting antifungal treatment in spite of persistent fever. There was no difference in mortality with patients under antifungal treatment, allowing continuing with this strategy in more patients in the future.

Disclosures:
No relevant conflicts of interest to declare.
Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation for Low Grade Non Hodgkin's Lymphoma: Preliminary Results at Hospital De Clínicas De Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
Authors: Araujo Beatriz Stela Gomes de Souza Pitombeira , Paz Alessandra Aparecida , Ferreira Clarissa Barros , Boffo Manoela Santos , Ottoni Erica Lammerhirt , Fischer Gustavo Brandão , Daudt Liane Esteves , Silla Lucia 
Published: October 2019

Abstract
Abstract 4557

INTRODUCTION:
Advanced low grade non-Hodgkin Lymphomas have many and varied treatment options. For patients with relapsed or refractory disease, outcome following only chemotherapy protocols remains poor. The standard Conditioning Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) might be an alternative for relapsed low grade non-Hodgkin lymphomas, but its high Transplant Related Mortality (TRM), varying from 24% to 54%, accounts for a lower overall survival in this group. Reduced Intensity Conditioning (RIC) HSCT has been shown to be a good alternative to myeloablative regimens, with lower TRM, Graft versus Lymphoma Effect, and appears to be associated with improved outcome, presenting a 3 years disease free survival and overall survival from 32% to 66% and from 32% to 73%, respectively, depending on factors such as disease stage before transplantation.

PATIENTS, METHODS AND RESULTS:
Sixteen heavily pretreated patients with low grade non-Hodgkin Lymphoma (NHL) were submitted to RIC HSCT with matched related donors at the Bone Marrow Transplantation Unit at HCPA between the period of September 2002 to October 2009. The mean age was 43 years and were 7 patients male and 9 female. Fifty percent (8) of the patients had refractory disease pre-HSCT, 43.8% (7) were at third complete remission (CR) and 6.2% (1) at second CR. Median of CD34/kg infused was 10.7 × 106 and the median of days for engraftment was 14.53. Conditioning regimens were Fludarabine + Cyclophosphamide in 3 patients, Fludarabine + Melphalan in 7, Fludarabine + Cyclophosphamide + Rituximab in 2, Fludarabine + Cyclophosphamide + Melphalan in 1, Cyclophosphamide + Total Body Irradiation (TBI) in 1 and Fludarabine + Cyclophosphamide + TBI in 2. Acute Graft versus Host Disease (aGVHD) occurred in 50%, with 37.5% of those were steroids resistant; and 62.5% of the patients evolved to chronic GVHD, with 80% of them classified as extensive. Chimerism from 9 patients was analyzed, and 89% of them were complete. Mean overall survival was 2.95 years; 62.5% of patients were alive within 1 year and 40% within 3 years. TRM was 6.66%. Eight patients died, five of them were transplanted with refractory disease. Only 2 patients died of relapse, 5 of infections and 1 of aGVHD.

CONCLUSION:
Low grade NHL patients treated at HCPA with RIC HSCT had an overall survival and TRM comparable to the observed at other centers, appearing as a good alternative for this heavily treated group of patients with less toxicity than myeloablative regimens.

Disclosures:
No relevant conflicts of interest to declare.
The Effect of KIR B/X Genotype and Missing KIR Ligands In Haploidentical Hematopoietic Stem Cell Transplantation.
Authors: Sun Aining , He Jun , Zhou Lina , Depei Wu , Li Weiyang , Bao Xiaojing 
Published: October 2019

Abstract
Abstract 4578

Objective:
To study the prognostic impact of missing ligands for inhibitory killer-immunoglobulin receptor(KIR) and donor KIR genotype in haploidentical hematopoietic stem cell transplantation(HSCT).

Methods:
HLA genotype of 14 patients (ALL 8 cases, AML 3 cases, CML 1 cases, NHL 1 cases and granulocytic sarcoma 1 case) and their donors was determined by polymerase chain reaction sequence oligonucleotide probes (PCR-SSOP) and sequence specific primers (PCR-SSP). The KIR genotype was determined by PCR-SSP.

Results:
1. Donors were divided into those with (n=9) KIR B/X and those with (n=5) KIR A/A. We found that the 2-year OS rate was higher with KIR B/X versus KIR A/A donors (33.3% vs 20%, P=0.308). Of the B/X group, most donors (77.8%) expressed activated KIR (aKIR) with 2DS4 or 2DS1. The 2-year OS rate was higher for those (n=5) with 1–2 aKIR than those (n=4) with 3–4 aKIR group (40% vs 25%). The GVHD incidence was slightly lower with 1–2 aKIR versus 3–4 aKIR donors (40% vs 50%).
2. Patients were divided into those with (n=11) and those without (n=3) missing 1 or more HLA class I ligands for donor inhibitory KIR. The 2-year OS rate for patients with and without missing KIR ligands was 36.4% and 0%,respectively(P=0.680)

Conclusion:
In haploidentical HSCT, donor and recipient should be performed the high resolution HLA-Cw genotyping and KIR genotyping (A/A and B/x). Using donors with KIR B/X genotype or missing KIR ligands may be associated with improved OS and decreased GVHD.

Disclosures:
No relevant conflicts of interest to declare.
The Use of Double-Unit Umbilical Cord Blood Transplantation In Adults with Hematologic Disease.
Authors: Ma Xiao , Depei Wu , Sun Aining 
Published: October 2019

Abstract
Abstract 4579

Objective:
In this study, we explored the efficiency and toxicity of 38 cases of double-unit umbilical cord blood transplantation (CBT) in adults with hematologic disease.

Methods:
The tolerance; transplant related complications; survival rate and disease free survival rate were observed and analyzed. A nonmyeloablative conditioning regimen included cyclophosphamide, fludarabine and 2Gy TBI. Cyclosporine combined mycophenolate mofetil and ATG were used to prevent graft versus host disease (GVHD).

Results:
All these 38 patients tolerated the therapy well while two patients had graft failure. Severe acute GVHD was presented in 6 patients. Chronic GVHD was occurred in 16 patients. Fatal infection complications were occurred in 5 patients (including CMV idiopathic pneumonia in 2 patients) and 4 patients relapsed after transplantation. Neutrophil engraftment obtained on day +17 and platelet reconstitution occurred on day +42 on median. In the follow-up duration of 17 months on median, the expected 2-year relapse mortality was 17.95%; non-relapse mortality was 25.90%; overall survival was 60.80%, and disease free survival was 52.11%. Compare with 39 cases of haplo-identical HSCT in our department, significant delays in engraftment and lower severe GVHD occurred after CBT. There was no apparent difference between the risk of relapse and DFS in both groups.

Conclusion:
The use of double-unit CBT after reduced intensive conditioning therapy in adults with hematologic disease is an effective and safe treatment. Fatal infection and relapse are the main reasons of failure.

Disclosures:
No relevant conflicts of interest to declare.