Victoria Otero

Safety of Bendamustine for the Treatment of Patients with B-Cell Non-Hodgkin Lymphoma, a Retrospective Cohort Study

S292 We chose a common therapeutic agent, fludarabine, a purine analog, which does not require any dose adjustment for hepatic impairment on FDA approved labeling. Notably our patient did achieve a partial response to FR and a concurrent improvement in liver enzymes after one cycle of combination fludarabine and rituximab. Fludarabine, with or without rituximab has been used effectively as a first line regimen in patients with chronic lymphocytic leukemia, eliciting significant complete responses and has also been extensively used in low-grade B-cell lymphoma. Concerns have been raised about the tolerability and long-term toxicity of fludarabine. An alternative purine analog, pentostatin, purports advantages including improved tolerability and less myelosuppression. With limited available data regarding appropriate frontline therapy for patient with aggressive NHL and severe hepatic dysfunction, purine analogs provide a practical treatment approach either as a first line regimen or as a bridging therapy.

Progression Free Survival at 24 Months in Patients with Diffuse Large B-Cell Lymphoma, an Argentinian Retrospective Cohort Study

S290 by the release of danger signals, including ATP. The purinergic P2X7 receptor is an ATP-gated cation channel expressed by hematopoietic as well as by many tumor cells. Basal activation of P2X7 is beneficial for tumor growth, but strong stimulation of P2X7 can kill tumor cells. Little is known about the role of P2X7 in the context of chemotherapy. We therefore studied the effects of P2X7 stimulation on Doxorubicin (DOX) toxicity in lymphoma cell lines. Objective: To evaluate a possible role of P2X7 as a therapeutic target to improve cancer therapy. Study Design: In this study we tested the interaction between P2X7 and DOX in different murine lymphoma cell lines: Yac-1 (T cell lymphoma) and A20 (B cell lymphoma, Cell death and pore formation were monitored by DAPI uptake and cell death assays. Pre-apoptosis by phosphatidyl-serine exposure and translocation of calreticulin to the cell surface were monitored by flow cytometry. Results: P2X7 stimulation synergistically enhanced the sensitivity to DOX in Yac-1 lymphoma cells that express P2X7 endogenously. Transient exposure to extracellular ATP (eATP) + DOX for one hour was sufficient to induce cell death after overnight culture. Mechanistically, gating of P2X7 augmented the initial uptake of DOX into cells. However, enhanced cell death was also observed when DOX was washed away before exposure to eATP, suggesting that the synergism resulted from an interaction of downstream signaling pathways. The synergistic effect was dependent on P2X7 as it was completely blocked by a P2X7 inhibitory nanobody, while an agonistic P2X7 nanobody further enhanced the effect. Sensitization to DOX by eATP was also observed after retroviral transduction of P2X7 into A20 lymphoma cells that do not express P2X7 endogenously. In these experiments we observed that sensitization to DOX by ATP was linked to a specific splice variant (k) of P2X7. Conclusion: Our results suggest that expression of P2X7 by tumor cells may contribute to their sensitivity to chemotherapeutic drugs.

CNS Relapse in Patients with Diffuse Large B-Cell Lymphoma, an Argentinian Retrospective Cohort Study

S290 by the release of danger signals, including ATP. The purinergic P2X7 receptor is an ATP-gated cation channel expressed by hematopoietic as well as by many tumor cells. Basal activation of P2X7 is beneficial for tumor growth, but strong stimulation of P2X7 can kill tumor cells. Little is known about the role of P2X7 in the context of chemotherapy. We therefore studied the effects of P2X7 stimulation on Doxorubicin (DOX) toxicity in lymphoma cell lines. Objective: To evaluate a possible role of P2X7 as a therapeutic target to improve cancer therapy. Study Design: In this study we tested the interaction between P2X7 and DOX in different murine lymphoma cell lines: Yac-1 (T cell lymphoma) and A20 (B cell lymphoma, Cell death and pore formation were monitored by DAPI uptake and cell death assays. Pre-apoptosis by phosphatidyl-serine exposure and translocation of calreticulin to the cell surface were monitored by flow cytometry. Results: P2X7 stimulation synergistically enhanced the sensitivity to DOX in Yac-1 lymphoma cells that express P2X7 endogenously. Transient exposure to extracellular ATP (eATP) + DOX for one hour was sufficient to induce cell death after overnight culture. Mechanistically, gating of P2X7 augmented the initial uptake of DOX into cells. However, enhanced cell death was also observed when DOX was washed away before exposure to eATP, suggesting that the synergism resulted from an interaction of downstream signaling pathways. The synergistic effect was dependent on P2X7 as it was completely blocked by a P2X7 inhibitory nanobody, while an agonistic P2X7 nanobody further enhanced the effect. Sensitization to DOX by eATP was also observed after retroviral transduction of P2X7 into A20 lymphoma cells that do not express P2X7 endogenously. In these experiments we observed that sensitization to DOX by ATP was linked to a specific splice variant (k) of P2X7. Conclusion: Our results suggest that expression of P2X7 by tumor cells may contribute to their sensitivity to chemotherapeutic drugs.

Características clínicas y mortalidad de pacientes adultos con síndrome hemafagocítico, estudio de cohorte retrospectiva.

Background: Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome of excessive immune activation Aim: To describe the clinical characteristics, causes and survival associated with HLH. Material and methods: Review of medical records of patients with HLH attended between 2004 and 2016. They were classified according to their probable cause in: associated with immunosuppression, cancer, post-infectious or idiopathic. Kaplan-Meier survival analysis was performed. Results: Twenty seven patients with HLH aged 18 to 87 years (59% men), were detected. Fourteen (52%) were secondary to immunosuppression, six (22%) were post-infectious, five (18%) were associated with cancer and two (7%) were of unknown cause. There were no significant differences in clinical or laboratory features between these etiologies. Within the immunosuppressed group, 12 (86%) were patients with oncologic or hematologic diseases or bone marrow transplantation. Associated cancers were mostly oncohematologic diseases. Thirty-day mortality was 53.4% (95% confidence intervals (CI) 32.7 - 70.3%), despite the treatment. Mortality was significantly associated with the presence of renal failure with a hazard ratio (HR) of 3.4 (95% CI of 1.2 - 9.9, p=0.025). Treatment of the underlying disease proved to be protective against mortality with an HR of 0.3 (95% CI 0.1 to 0.98, p= 0.046). Conclusions: The prognosis of HLH could be related to the treatment of the underlying disease. The study of the pathophysiology of this syndrome will allow a better understanding and treatment.BACKGROUND Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome of excessive immune activation Aim: To describe the clinical characteristics, causes and survival associated with HLH. MATERIAL AND METHODS Review of medical records of patients with HLH attended between 2004 and 2016. They were classified according to their probable cause in: associated with immunosuppression, cancer, post-infectious or idiopathic. Kaplan-Meier survival analysis was performed. RESULTS Twenty seven patients with HLH aged 18 to 87 years (59% men), were detected. Fourteen (52%) were secondary to immunosuppression, six (22%) were post-infectious, five (18%) were associated with cancer and two (7%) were of unknown cause. There were no significant differences in clinical or laboratory features between these etiologies. Within the immunosuppressed group, 12 (86%) were patients with oncologic or hematologic diseases or bone marrow transplantation. Associated cancers were mostly oncohematologic diseases. Thirty-day mortality was 53.4% (95% confidence intervals (CI) 32.7-70.3%), despite the treatment. Mortality was significantly associated with the presence of renal failure with a hazard ratio (HR) of 3.4 (95% CI of 1.2-9.9, p =0.025). Treatment of the underlying disease proved to be protective against mortality with an HR of 0.3 (95% CI 0.1 to 0.98, p = 0.046). CONCLUSIONS The prognosis of HLH could be related to the treatment of the underlying disease. The study of the pathophysiology of this syndrome will allow a better understanding and treatment.

Promyelocytic Blastic Crisis in Chronic Myeloid Leukemia During Imatinib Treatment.

An 82-year-old woman was admitted to our hospital presenting with febrile neutropenia. She had been diagnosed with chronic myeloid leukemia 2 years ago and had been on imatinib treatment since [1]. A month before admission she presented with malaise, anemia, and mild leukopenia; a bone marrow aspirate and biopsy performed 20 days before admission showed no alterations. Imatinib dosing was adjusted but mild cytopenia persisted. The patient presented with acute abdominal pain, fever, and shaking chills to the emergency department. On physical examination the patient was awake and appeared uncomfortable. She had pain in the left lower abdominal quadrant. Petechiae were evident on the lower limbs. Complete blood count revealed anemia, severe neutropenia, and thrombocytopenia (Table 1). Overt disseminated intravascular coagulation was present. Abdominal computed tomography showed acute diverticulitis. The patient was started on broad-spectrum antibiotics. Informed consent was obtained. Table 1 Results of laboratory testing. A peripheral blood smear revealed more than 30% circulating promyelocytic blasts. A bone marrow aspirate and biopsy showed hypercellular marrow with myeloid hyperplasia and more than 90% myeloblasts (Figure 1). The blasts displayed hypergranular cytoplasm with bundles of Auer rods. PML/RAR-α was positive according to real-time PCR of the bone marrow. A diagnosis of promyelocytic blastic crisis was made [2,3,4,5]. Figure 1 Leukemic cell morphology of bone marrow aspiration specimen (May-Grunwald-Giemsa).