ALBERT

Description: BACKGROUND AND OBJECTIVES. Post transplantation High dose Cyclophosphamide (PTCY) used in haploidentical hematopoietic transplantations, has a high effectivity in acute Graft versus Host Disease (aGVHD), and chronic Graft versus Host Disease prophylaxis (cGVHD), however it is associated with high relapse rates. On the other hand, Anti-T-Lymphocyte Globulin (ATG-Fresenius ®) is also effective as immunosuppressive (IS) drug, but its benefit on Overall Survival (OS) and Relapse Free Survival (RFS) is unclear. The aim of this study was to compare the effectiveness of two GVHD prophylaxis regimes used in high risk transplantation: PTCY used in Haploidentical transplantation and ATG used for peripheral blood, non-related, related and mismatched donors. The primary endpoint was to evaluate the incidence of aGVHD and cGVHD, and its severity in both groups. As secondary endpoints we analyse the OS, RFS and GRFS (recorded adverse events include grade 3-4 aGVHD, systemic therapy-requiring cGVHD, relapse or death during median follow-up). We also consider transplantation related mortality (TRM) and post-transplantation complications. PATIENTS AND METHODS. We retrospectively analyse 111 allo-transplantations performed at our institution between 2012 and 2017. We analyse two cohorts: 49 haploidentical transplantation with PTCY (50 mg/kg, on day +3, +4) followed by Tacrolimus and Mycophenolate; and 62 peripheral blood related, non-related and mismatched with low dose ATG Fresenius (7mgr/Kg on days -3, -2, -1) associated with Tacrolimus/Cyclosporine starting on day -1 with a short course Methotrexate (on day +1, +3, +6) or Mycophenolate. Mycophenolate was stopped on day +28 and Cyclosporine or Tacrolimus were tapered on day +50. RESULTS. There were no differences in patients' age (49 vs 51), sex or pre-transplantation HCTI-score ≥ 3 (30 vs 26) between PTCY and ATG groups. We found differences between diagnosis (lymphoproliferative disorders (16 vs 4, p= 0.003), high DRI-score (18 vs 11, p = 0.04), number of previous transplantations (12 vs 5, p= 0.02), reduced intensity conditioning regimen (36 vs 20, p 〈 0.001) and bone marrow as stem cells source (38 vs 9, p 〈 0.001) between PTCY and ATG groups. The median time to neutrophil engraftment (〉500/uL) was similar: 17 days [13-34] for PTCY and 16 days [9-33] for ATG. Median time to platelet recovery was higher in PTCY cohort (33 vs 18 days, p= 0.016). There were 3 secondary graft failures in PTCY group vs 4 graft failures in ATG (3 primary, 1 secondary). The were no differences in grade 2 - 4 aGVHD incidence between groups (PTCY:30.6% vs ATG:36.4%), but we found differences in grades 3 - 4 aGVHD (PTCY:4.1% vs ATG: 9%, p=ns). The global incidence of any NIH grade cGVHD was 56.1% in PTCY vs 66% in ATG group. Mild, moderate and severe cGVHD incidence were 31.7%, 19.5% and 4.8% for PTCY vs 28%, 26% and 12% in ATG (p=ns). The median duration of IS in alive patients with cGVHD was 6.5 months [3-19] in PTCY patients and 10 [3-34] in ATG group. Among moderate and severe forms, the median IS duration was 10 and 5 months in PTCY group vs 13 and 12 months in ATG respectively. PTCY cohort developed more non-infectious complications, especially, cardiac, lung, digestive and neurologic complications, (p=0.086), however there were not differences in infectious complications (Table 1). TRM was similar between groups, 18.4% for PTCY vs 22.5% for ATG, (p=0.250). We didn´t find differences in early toxic mortality (

Description: INTRODUCTION: Neurological complications (NC) are frequently reported after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but their incidence, characteristics and impact on the overall survival are not well defined. For this reason, we retrospectively analyzed our experience. PATIENTS AND METHODS: A retrospective study of 506 allo-HSCTs performed in our center from January 2000 to September 2013, including 336 myeloablative and 170 non-myeloablative, 280 sibling and 226 unrelated, and 397 matched and 109 mismatched. All neurological complications, according to NCCN classification, were included. RESULTS: Seventy seven patients developed neurological complications. Their median age was 48 years (5-70) and 43 (56%) were male. Underlying diseases were Acute Leukemia (34), Myelodysplastic Syndrome (11), Multiple Myeloma (9), Non-Hodgkin Lymphoma (7), Myeloproliferative disease (7), Bone marrow Aplasia (5), Hodgkin Lymphoma (2) and other (2). Thirty eight patients (49.4%) were in CR, 14 (18.2%) in PR, 16 (20.8%) had a refractory disease and 9 (11.7%) had a stable disease. Median preceding treatments were 2 (0-10), including in 24 (31.2%) a preceding HSCT (19 autologous and 5 allogeneic). Fifty seven patients (74%) had received a myeloablative (MA) regimen (14 TBI and 43 chemotherapy). Stem cell source was bone marrow, peripheral blood and umbilical cord blood in 53, 20 and 4 patients, respectively. The donor was unrelated in 47 patients (61%) and mismatched in 25 (32.5%). A calcineurin inhibitor (Cyclosporine or Tacrolimus) was included in all cases as GVHD prophylaxis, combined with Methotrexate (37), Mycophenolate (35) and Prednisone (5). Seventy seven patients developed 81 NC (74 central and 7 peripheral). The global incidence was 16%, being more frequently reported in unrelated (21.4% vs. 11.4%, p=0.002) or mismatched (24.5% vs. 13.5%, p=0.007) allo-HSCT. Within the group who developed central NC, 48 patients (65%) had an early onset (less than 100 days after HSCT), which consisted of impairment of consciousness (36 patients), focal syndrome (22 patients) or seizures (16 patients). The etiology was toxic-metabolic in 32 patients (posterior encephalopathy in 10 cases), infectious in 21 (viral 10, fungal 6, bacterial 5), vascular in 12 (Thrombotic Thrombocytopenic Purpura 6, hemorrhagic 4, ischemic 2) and relapse in 9. Within the group who developed peripheral NC, 5 patients (71.5%) had a late onset, which consisted of polyneuropathy. The etiology was infectious in 2 cases (viral) and immune in 5 cases. Twenty four patients are alive (31.2%) with a median follow-up of 10 months (0-110). Excluding relapses, NC was a direct or indirect cause of death in 24 patients (54.5%), due to viral (9) and fungal (8) infections, above all. The development of a NC, specially in the central nervous system, had a negative impact on the overall survival (17 months vs. 40 months; p=0.001) (figure 1) CONCLUSIONS: In our series, the incidence of NC in the setting of allo-HSCT was 16%, being more frequently found with unrelated and mismatched donor. They were associated with high mortality, having a negative impact on the overall survival and becoming a direct or indirect cause of death in more than half of cases. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Background Patients undergoing hematopoietic stem cell transplantation (HSCT) are at high risk of multiple complications being graft versus host disease (GvHD) one of the most concerning. Addition of anti-T-lymphocyte globulin (ATG-Fresenius ®) reduces the incidence of acute and chronic GvHD however, optimal dose has not yet been established. Standard dose (60 mg/kg) has shown a significantly lower moderate-severe cGvHD yet its effect in Progression Free Survival (PFS) and Overall Survival (OS) is contradictory. Our primary objective was to analyze the efficacy of low ATG dose (21 mg/kg) in the prophylaxis of acute and chronic GvHD. As secondary objective we analyzed non-relapse mortality (NRM), infectious and non-infectious complications, GvHD and relapse free survival (GRFS), overall survival and progression free survival in high risk patients undergoing HSCT. Patients and methods We retrospectively analyzed 57 patients who underwent HSCT in our center from 2012 to 2017, receiving a total dose of 21 mg/kg (7 mg/kg on day -3, -2 and -1) of ATG as part of the GvHD prophylaxis, associated to cyclosporine/tacrolimus and MMF/short course-MTX. The conditioning regimen were myeloablative in 42 patients (73.7%). The donor was unrelated in 46 cases (80.7%). Seventeen (29.9%) had a mismatch (16 unrelated, 1 sibling). Stem cell source was peripheral blood in 51 patients (89.4%). Forty six (80.7%) patients were positive for CMV, from these 17 (36.9%) were paired with seronegative donors. The median age was 57 years old (18-70), 38(66.7%) were males. The most frequent diagnosis were Acute Myeloblastic Leukemia (40.4%), myelofibrosis (17.5%) and myelodisplastic syndrome (14%); 28 (49%) had a HCTI score ≥ 3 and 16 (29%) a high risk DRI score. Thirty patients (52.6%) were in complete remission at the moment of HSCT. (Table 1) Results Hematopoietic engraftment was observed in 54 patients (94.7%). The median neutrophil and platelet engraftment were 14 (10-34) and 15 (9-28) days, respectively. Primary graft failure occurred in 3 patients (2 myelofibrosis, 1 AML). Twenty (39.2%) out of 51 evaluable patients developed grade 2-4 acute GvHD. The cumulative incidence of grade 3-4 aGvHD was 8.8% (95% CI, 3.2-17.9%). Skin was the most affected organ (62%). We found a cumulative incidence of moderate to severe cGvHD of 35.2% (95% CI 22.7-47.9%), only 5 cases (10.6%) were severe, with a median onset at day 177 (57-893). The median duration of immunosuppresive systemic therapy was 488 days (207-2046) in the group of patients with moderate to severe cGvHD. Twelve patients died due to transplant related events, 7 were reported before day 100, all of infectious etiology. The NRM at two years was 21.9% (95% CI, 12-33.7%). Eleven patients (19.2%) had at least two episodes of CMV reactivation and one had cytomegalic gastrointestinal disease. One patient developed postransplantation lymphoproliferative disorder associated to Epstein Barr virus. Twenty patients (35%) developed noninfectious complications, being hemorrhagic diathesis, hepatotoxicity and severe mucositis the most frequents. With a median follow up of 28 months in alive patients (3-67), the GRFS at one year, OS and PFS at two years were 47.6% (95% CI, 42.8-52.2%), 59% (95% CI, 54.5-63.2%) and 52% (95% CI, 46.9-56.5%), respectively. The relapse incidence at two years was 26.3% (95% CI 14.7-39.4%). Conclusions In our center, the use of low ATG doses is protective against severe forms of acute GvHD, offering also a moderate protection against chronic GvHD in a cohort with high prevalence of mismatched unrelated donors, high median age and high risk DRI and HCTI. This approach doesn't seem to have a significant negative impact neither in GRFS, OS and PFS at two years. Disclosures No relevant conflicts of interest to declare.