Background

Objective: The hospitalization of the patient during the critical myelosuppressive period after chemotherapy is often complicated by infections caused by nosocomial pathogens, what is associated with a high antibiotics consumption and with prolongation of the period of hospitalization. These fi ndings have led many centres to change their policy from "in-hospital" to "out-hospital care". In this retrospective study we tried, on the basis of our experiences, to identify the feasibility and safety of this approach. Patients and methods: We studied 56 patients with the acute myeloid leukemia treated in our clinic with the consolidation chemotherapy. We compared two groups of patients. In the fi rst group, the patients were discharged upon completion of chemotherapy, consequently followed up as outpatients. Patients in the second group were observed in hospital during the entire nadir. Following 41 courses, patients were discharged and instructed to return immediately if fever or any other change of their clinical status occurred. Results: In 24 cases after chemotherapy, the patients returned to the hospital after a discharge (in 23 cases because of fever), in 17 cases of nadir periods the hospitalisation was not necessary at all. Seven patients were readmitted in septic shock, but rapidly recovered. Two other patients died, one due to an irreversible shock within 12 hours of readmission and one due to bacterial meningitis within 48 hours after readmission. In 10 cases of rehospitalization, patients responded to the fi rst line of antibiotics. In the second group of the patients, only 2 courses of consolidation from a total of 15 were not complicated. In contrast to the fi rst group, we detected only poor effectiveness of broad-spectrum antibiotics in the group of inpatients. Conclusions: For AML patients in a good clinical status without any complicating medical conditions, the early discharge is feasible, safe and cost saving option (Tab. 2, Fig. 2, Ref. 7).

Introduction:high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (autoHSCT) is widely used in the treatment of patients with haematological and non-haematological malignancies. One of the most common causes of mortality after HSCT is infection during the time of prolonged neutropenia. Prolonged neutropenia more than 7 days increase the risk of fungal infections and it is an indication for the use of antifungal prophylaxis. After hematopoietic SCT, G-CSF is commonly used to enhance stem cell engraftment to minimize the morbidity and mortality associated with prolonged neutropenia. However, there is no consensus on the optimal use of G-CSF after autoHSCT, most studies have been conducted on small numbers of patients and have varied significantly in patient’s demographics, G-CSF dosage regimen and other factors affecting outcomes. Objective:restrospective study to evaluate the efficacy of early vs. delayed initiation of G-CSF after autoHSCT in patients with lymphoid malignancies. Methods: between January 2009 and July 2014, 117 patients with lymphoid malignancies who underwent autoHSCT in the Department of Hematology and Transfusion medicine in Bratislava were included. The patients were divided into two groups; in the first group (43 patients), G-CSF (filgrastim, 5μg/kg s.c.) was applied late (on day 6.-8.) after autoHSCT. In the second group (74 patients), G-CSF (filgrastim, 5μg/kg s.c.) was applied early (on day 3.-4.) after autoHSCT. All patients received standard conditioning regimen for the underlying disease, and standard supportive treatment, including treatment of febrile neutropenia. Patient’s demographics are shown in table 1. Statistical analysis was performed using SPSS statistical software v. 20, with significant Pvalue of 0.05 (two-tailed). Results: sever neutropenia (ANC < 0.5 x 109) and very severe neutropenia (ANC < 0.1 x 109) for more than 7 days were recorded as following: in the first group (delayed G-CSF), 34/42 (81%) and 25/41 (61%) patients respectively. In the second group (early G-CSF), 11/66 (17%) and 2/52 (4%) patients respectively (RR = 4.8, 95% CI = 2.7 to 8.4 and RR = 15, 95% CI = 3.9 to 63). Median time to engraftment of leukocytes above 1, granulocytes above 0.5, and 0.1 x 109/l was 6, 5, and 4 days for patients who received G-CSF early and 7, 7 and 5 days for patients who received G-CSF late (P <0001). The median duration of hospitalization was 19 (15-28) days in the first group and 16 (11-23) days in the second group (P = 0.001, 95% CI =2.02-4.17). There was no significant difference in the rate of febrile neutropenia in both groups (P = 0.53), but the rate of fungal infection and the use of HRCT scan of the lung was higher in the group of patients who received delayed G-CSF than early G-CSF (19% vs. 3%, P=0.005) and (23% vs. 6%, P=0.007) respectively. Conclusion:early application of G-CSF (3rd-4th day) after autologous HSCT accelerates engraftment, shorten the duration of neutropenia, reduce the risk of infectious complications (especially fungal infections), reduce the use of antimicrobial drugs, shorten the hospital stay and overall costs. Table.1 Delayed application of G-CSF Early application of G-CSF Patient N. 43 74 Age, m edian(range) 60 (39-67) years 59 (33-68) years P = 0.694 Sex P = 0.079 Male, N (%) 16 (37%) 40 (54%) Female, N (%) 27 (63%) 34 (46%) CD34+cells x106/kg, m edian(range) 2.5 (1.3-5.6) 2.3 (1.3-4.5) P = 0.138 Diagnosis P = 0.855 Multiple myeloma, N (%) 41 (95%) 72 (97%) NHL, N (%) 2 (5%) 2 (3%) ECOG performance status P = 0.221 0 35 (82%) 53 (72%) 1 7 (16%) 18 (24%) 2 1 (2%) 2 (3%) 3 0 0 4 0 1 (1%) Engraftment , median(range) Leu. > 1 x 109/l 7 (4-12) days 6 (3-9) days P ≤ 0,0001 Neut.> 0.5 x 109/l 7 (5-9) days 5 (3-7) days P ≤ 0,0001 Neut. > 0.1 x 109/l 5 (3-6) days 4 (2-6) days P ≤ 0,0001 Hospitalization, median(range) 19 (15-28) days 16 (11-23) days P= 0,001 Sever neutropenia ≥ 7 days, N (%) 34/42 (81%) 11/66 (17%) RR = 4.8, 95% CI = 2.7 to 8.4 Very sever neutropenia ≥ 7 days, N (%) 25/41 (61%) 2/52(4%) RR = 15, 95% CI = 3.9 to 63 Febrile neutropenia, N (%) 40 (93%) 64 (88%) P = 0.531 Invasive fungal infection, N (%) 8/43 (19%) 2/73 (3%) P = 0,005 HRCT scan use, N (%) 10 (23%) 4 (6%) P = 0.007 Cost 3582 (787-18187) Eur. 1408 (263-2143) Eur. P=0,041 Disclosures No relevant conflicts of interest to declare.

Older patients with AML have poor prognosis after chemotherapy and allo-SCT was historically limited to the young patients. In the multicentre retrospective study we analyzed 96 consecutive AML patients ≥ 50 years allografted with related (n=59) or unrelated (n=37) donor. The 2-year OS and DFS rates were 45 % and 42 % for the whole group. The corresponding figures for related patients were 48% and 42% whereas for unrelated 42% and 42%, respectively (OS p=0,721, DFS p = 0,896). The cumulative incidences of relapse (28% of all patients) and NRM mortality (26%) were low with no significant differences among related and unrelated cohorts. Multivariate analysis revealed the only major independent variables associated with an inferior OS were unfavourable cytogenetics (RR 3.36; CI 1.66-6.83; p=0.001) and advanced disease status (RR 2.30; CI 1.21-4.37; p=0.011). Unfavourable cytogenetics (RR 3.00; CI 1.50-5.99; p=0.002) and advanced disease at SCT (RR 2.27; p=0.009) were also the only independent variables associated with inferior DFS. In conclusion, our analysis indicates that outcomes of allografted AML patients aged ≥ 50 years are determined by cytogenetic risk category and disease status at transplantation and not by the type of donor.

4272 Background: Early intensification of chemotherapy in the remission induction phase of patients with acute myeloid leukemia (AML) has been shown to improve the remission rate and long-term leukemia-free survival. Aim: This trail is designed to assess the role of etoposide in the induction remission schedules in younger patients with de novo AML. Methods: Newly diagnosed previously untreated younger patients (15–60 years) with AML were randomly assigned to 3 groups; group A received conventional treatment DA 3+7 [daunorubicin 60 mg/m2/day (days 1–3) and cytosine arabinoside (Ara-C) 200 mg/m2/day by continuous iv infusion (days 1–7)], group B received conventional treatment [ Ara-C 100 mg/m2/day by continuous iv infusion (days 1–10) + daunorubicin 50mg/m2/day (days 1,3,5)] + etoposide (50 mg/m2/day; days 1–5), and group C received high dose AraC (HD-AraC) 3g/m2/12 hrs. (days 1, 3, 5 and 7) + daunorubicin and etoposide in the same dose as above (as in group B). All patients were treated in the Department of Hematology, University Hospital, Bratislava. Informed consents were obtained. RT-PCR was done to determine the expression of topoizomerase I, II-alpha and II-beta genes in bone marrow samples at diagnosis. The data were analyzed using SPSS statistical software versions 16.0, 2008. Results: Between September 2000 and August 2011, 128 patients were recruited (group A = 27, group B = 57, and group C = 44). There was no statistically significant difference in age, sex, performance state, AML subtype (M4-5), WBC count and cytogenetic risk distribution in the 3 groups. Patients have been followed for a median of 92 months. After 1 course of induction the complete remission (CR) rate was 55.6%, 75.4% and 81.8% in group A, B and C respectively (P = 0.048). Group A vs. B (P = 0.025), group A vs. C (P = 0.027), group B vs. C (P = 0.81). Induction toxicity profile and grade was similar in all groups except for conjunctivitis grade 2 and 3 which was higher in group C. The 5 year’s overall survival (OS) was 17%, 41% and 33% (P = 0.36) and disease free survival (DFS) was 25%, 44% and 35% (P = 0.21) in group A, B and C respectively. There was statistically significant improvement in OS but not DFS in patient receiving etoposide (P < 0.00001). Overexpression of topoisomerase I and II genes were detected in 12/19 (63%) and 14/19 (74%) patients at diagnosis; respectively. Topoisomerase II-alpha and II-beta genes were increased by a median of 4.1 (range 1.7–27.3) and 2.9 (range 2.4–5.1) than normal; respectively. Conclusion: the addition of etoposide to standard treatment of AML can improve the rate of complete remission and outcome in adult de novo AML patients. The incorporation of etoposide to HD-AraC regimens during induction may further improve the rate of CR without effect on outcome (DFS and OS). Measurement of topoisomerase II gene expression at diagnosis can help in selecting patients who will benefit from the addition of etoposide. Disclosures: No relevant conflicts of interest to declare.