ALBERT

Description: Background: Post-remission treatment for AML is very aggressive and many times a SCT is needed. Comparisons between Allo-SCT and Auto-SCT ve always shown more Transplant Related Mortality (TRM) but less Cumulative Incidence of Relapse (CIR) in the first group. Our study describes, not only the long-term survival outcomes, but also the quality of life in long survivors. Methods: Retrospective study of 274 patients diagnosed with non-promyelocytic AML who underwent SCT between 1982 and 2011 in our center. Characteristics in the 162 Allo-SCT and the 112 Auto-SCT groups of patients were respectively: median age of 38 and 45 years old, secondary AML in 20% and 10%, refractory to Induction AML in 16% and 3%, pre-SCT status different from Complete Remission (CR) in 13% and 3% and year of SCT before 2005 in 53% and 86%. No significant differences between both groups were found in other risk factors as hyperleucocytosis at diagnosis or adverse cytogenetics. Results: With a median follow-up of 55 months [2-316], Overall Survival (OS) until 1997 in Allo-SCT and Auto-SCT were respectively, 40% and 61% at 1 year and 28% and 45% at 5 years (figure 1), but from 1997, 66% and 70% at 1 year and 47% and 48% at 5 years (figure 2). Disease Free Survival (DFS) until 1997 in Allo-SCT and Auto-SCT were respectively, 50% and 65% at 1 year and 38% and 46% at 5 years, but from 1997, 67% and 63% at 1 year and 52% and 47% at 5 years. In the last 15 years, no differences were found between both groups in OS nor DFS. CIR in Allo-SCT and Auto-SCT were respectively, 18% and 32% at 1 year and 24% and 50% at 5 years, without dependence on year of SCT. No relapse was observed later in any group. TRM until 1997 in Allo-SCT and Auto-SCT were respectively, 30% and 7% at 1 year and 35% and 9% at 5 years, but from 1997, 16% and 2% at 1 year and 25% and 4% at 5 years. Multivariable analysis showed that the only risk factor with a negative impact on OS was not having achieved CR at the time of SCT. Other variables as older age, hyperleucocytosis at diagnosis, adverse cytogenetics, secondary AML or sooner year of SCT lost their univariable analysis significance. Allo-SCT: From the 162 patients, 72(44%) are alive by this moment, 43(60%) with ECOG 0, 21(29%) with ECOG 1 and the other 8(11%) with ECOG 2, basically because of graft versus host disease (GVHD in 39 patients, 21 steroid-dependent and 3 refractory to any treatment). All of them have been in CR during the last 2 years of follow-up. In contrast, 90(56%) patients have died: 52(58%) because of SCT complications (20 infections, 16 GVHD, 8 toxicity and 8 mixed causes), 33(37%) because of disease and 5(5%) because of other causes. With a median follow-up of 43 months [2-316], there have been 4 secondary neoplasm, all of them solid ones, which appeared with a median of 242 months [179-311] from SCT. None of them had previously received radiotherapy. Auto-SCT: From the 112 patients, 43(38%) are alive by this moment, 32(74%) with ECOG 0 and the other 11(26%) with ECOG 1. All of them have been in CR during the last 2 years of follow-up. In contrast, 69(62%) patients have died: 45(65%) because of disease, 14(20%) because of SCT complications and 10(15%) because of other causes. With a median follow-up of 93 months [5-230], there have been 6 secondary neoplasm, 5 of them hematologic ones, which appeared with a median of 90 months [76-115] from SCT. None of them had received radiotherapy, but previously treated hematopoietic stem cells. Only one is alive at the time of last follow-up. Conclusions: In one hand, despite the high incidence of relapse in Auto-SCT in any period, OS is lower in Allo-SCT during the first years [1982-1996], although it has a tendency towards OS in Auto-SCT from 1997 because of the decrease in TRM, which is more significative in Allo-SCT. In the other hand, DFS is slightly higher in Allo-SCT during the last years [1997-2011], although the quality of life in long survivors is worse, basically because of GVHD. In summary, we have not really found differences between Allo-SCT and Auto-SCT in terms of OS and DFS in our series, so both procedures are efficient to treat AML (near 50% of the patients in both groups are alive at 5 years from SCT in recent years). The decrease in TRM until 4% at 5 years in Auto-SCT makes it a good choice, particularly for older patients without risk factors. However, the development of secondary hematologic neoplasms is a relevant fact, with an incidence of 11% and a high late mortality. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 3831 Background: Controversy exists regarding optimal treatment for pts with MDS with low blast percentages. Benefits of early transplant versus transplant-related morbidity and mortality have been debated. With increased time to transplant, MDS pts are more likely to undergo increased numbers of blood transfusions, experience more cytopenias, and are at risk of disease progression. Transplant offers a cure for MDS, and advances in supportive care during and after transplantation have afforded better outcomes and increased numbers of older pts to undergo transplant. Depletion of mature T cells from allogeneic HSCTs decreases the incidence of GvHD and its associated morbidity and mortality. This study therefore evaluated outcomes of pts with refractory cytopenias with less than 5% marrow blasts, who underwent T-cell depleted HSCTs from matched or mismatched, related or unrelated donors at a single center. Patients and Methods: Between February 1982 and May 2010, 44 pts with refractory cytopenias(marrow blasts 500cells/uL at a median of 11d (range: 9–22). Two pts had primary graft failure, and 3 had secondary graft failure. Four of these pts underwent second transplants. Acute GvHD, grade 1–2, developed in 3 pts. Three additional pts developed grade 3 GvHD, 2 after DLI given for refractory opportunistic infections and 1 after a second unmodified transplant for graft failure. Chronic GvHD occurred in 3 pts, one of whom had received a second unmodified transplant for graft failure. As of May 2011, 16 pts have expired. Causes of death included: GvHD (5, including post DLI), infections (5), graft failure/poor graft function (3), regiment-related toxicity (2), and late death due to lung cancer (1). Twenty-eight pts are alive and doing well with a median survival of 2.8 years (range: 0.5–21.43). The 2-year and 5-year survivals are: 70.1% and 63.3%. Younger recipient age (60% of pts beyond 5 years, with a low incidence of acute and chronic GvHD. These findings support early transplant in the treatment of MDS with refractory cytopenias, especially in younger pts. Disclosures: Small: Pfizer, Inc: Equity Ownership, family member employed by Pfizer, Inc.

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: Abstract 3099 Background: Despite the fact that allogeneic SCT currently offers patients with high risk AML the best chance of cure, we've aimed to investigate the outcome of AML patients who have undergone ASCT in our center, considered as one of spanish reference hospital in SCT, and the parameters that have been able to influence in relapse rate (RR), overall survival (OS) and relapse free survival (RFS). Methods: Retrospective study in 121 AML patients who have undergone ASCT between 1988 and 2010. The analysis has been performed in 95 patients (50 male and 45 female) by excluding 26 acute promyelocitic leukemias (APL): 62 patients until 1999 and 33 since 2000. Median age was 45 [18–74] and median lecocyte count, 17250/μL [1000–318000]. 90% were “de novo” AML and 92% were in first complete remission (1°CR). Cytogenetic risk was as follows: 64% intermediate, 29% high and 7% low. Conditioning regimens were oral BuCy (62%), CyTBI (24%) and intravenous BuCy (12%). Stem cell source was bone marrow (BM) in 46 patients (48%), but the use of peripheral blood (PB) was generalized since 1997. Colony-stimulating factors were used in 52% of total patients. Median time from last treatment was 94 days [30–285]. Results: The median follow-up of this study was 125 months [0–216]. OS at 1, 3 and 5 years were 59%, 46% and 44%. RFS at 1, 3 and 5 years were 60%, 49% and 48%. There was no relapse after 5 years from ASCT. Early mortality (before day +100) was 12% (9 in 11 patients between 1988 and 1999) and late mortality was 47% (34 in 45 patients because of relapse, with no significant difference between 1988–1999 and 2000–2010). Secondary malignancies incidence was 13% (5 in 6 patients suffered from haematologic neoplasms: 4 MDS at 43, 89, 90 and 97 months and 1 Follicular Lymphoma at 50 months), median age of these patients was slightly higher (53, 5 years old) and none of them had received TBI. Multivariable analysis showed that RFS at 5 years was influenced by: disease status at ASCT (55% if 1°CR vs 0% if ≥2°CR/PR/refractory disease, p

Description: Abstract 4498 Background: Giving the fact that allo- SCT currently offers patients with high risk AML the best chance of cure, we`ve aimed to investigate the outcome of AML patients who have undergone allo-SCT in our center, considered as one of spanish reference hospital in SCT, and the parameters that have been able to influence in relapse rate (RR), overall survival (OS) and relapse free survival (RFS). Methods: Retrospective study in 192 AML patients who have undergone allo-SCT between 1982 and 2010. The analysis has been performed in 171 patients (85 male and 86 female) by excluding 21 acute promyelocitic leukemias (APL): 65 patients until 1999 and 106 since 2000. Median age was 37 1874 and median lecocyte count, atchmode documentclass[fleqn,10pt,legalpaper]{article} usepackage{amssymb} usepackage{amsfonts} usepackage{amsmath} pagestyle{empty} egin{document} (13400/hbox{ L }frac{470}{250000}) end{document}. 82 were de novo AML and 87 were in morfologic complete remission (70 in first CR). 14 patients had received a previous SCT. Cytogenetic risk was as follows: 55 intermediate, 34 high and 11 low. Conditioning regimen was ablative in 162 patients: CyTBI (36), BuCy (31), BuFlu (30) and others (3). 130 patients (76) underwent a related allo-SCT (95 of them were matched) and 41 patients (24), an unrelated allo-SCT (64 of them were matched). Stem cell source was bone marrow (BM) in 146 patients (85) and only 3 patients received umbilical cord (UC). Graft versus host disease (GvHD) prophilaxis was based on Ciclosporine in 150 patients (88). Median time from last treatment was 73 days 12268. Results: The median follow-up of this study was 61 months 1317. OS at 1, 3 and 5 years were 57, 44 and 40. RFS at 1, 3 and 5 years were 62, 50 and 45. Early mortality (before day 100) was 26 (43 until 1999 and 15 since 2000, p0,0001): 18 patients because of infections, 10 because of toxicity, 9 because of disease and 7 because of EICH. Late mortality was 27 (more than the half because of relapse, with no significant difference between 19881999 and 20002010). Cumulative relapse incidence at 5 years was 35, with a median time of relapse of 4 months. Secondary malignancies incidence was 5. Multivariable analysis showed that Transplantation Related Mortality (TRM) was influenced by: year of allo-SCT (OS at 5 years of 49 if 20002010 vs 28 if 19821999, p0,0001), late engraftment (p0,002) and severe acute GvHD (OS at 5 years of 45 if no evidence/grade I-II vs 25 if grade III-IV, p0,071). The other important parameters which lost its univariable analysis significance were donor type, recipient age and conditioning regimen. No difference was found in case of HLA and ABO discordance or donor/recipient CMV status. Multivariable analysis also showed that RR and RFS at 5 years was influenced by: disease status at allo-SCT (50 if 1CR vs 0 if 2CR/PR/refractory disease, p0,002), chronic GvHD (67 if present vs 41 if absent, p0,035) and leucocyte count at diagnosis (54 if 20000/ L vs 37 if 20000/ L, p0,038). The other important parameters which lost its univariable analysis significance were cytogenetic risk, initial induction response and positive minimal residual disease (MRD) before allo-SCT. No diference was found in case of ethiologic classification or stem cell source. Conclusions: Allo-SCT is a curative procedure in AML patients (global RFS of 50 at 3 years), specially when disease is under control and patient develops chronic GvHD. In the last decade, there have been important improvements in the procedure which have led to a significant decrease in TRM, and consequently, a significant increase in OS. Disclosures: No relevant conflicts of interest to declare.