ALBERT

Description: Abstract 4560 Introduction: About 15% of acute myelogenous leukemia (AML) patients will have disruption of the core binding factor (CBF) transcription factor as indicated by the detection of t(8;21) or inv(16) on metaphase cytogenetic analysis. In general, patients with CBF-AML are younger and regarded as having a favorable outcome when treated with anthracycline-based induction chemotherapy and multiple cycles of high-dose cytarabine consolidation. Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) are usually perceived as unnecessary in the management of CBF-AMLs. However, most data indicating the favorable prognosis of CBF-AML with non-HSCT management originates from young selected patients participating in clinical trials and information on relapse treatments is often lacking. We performed a retrospective analysis of consecutive patients diagnosed with CBF-AML at a regional leukemia center over the last twelve years to assess long term survival of unselected patients and the likelihood of therapeutic success without ever requiring HSCT. Methods: The study cohort was identified through a search of all AML reports issued by the institutional clinical cytogenetics laboratory since the introduction of electronic records (1998-2010). We subsequently reviewed the charts of all patients with CBF-AML (irrespective of other cytogenetic abnormalities) to extract demographic, treatment, and outcome information. Survival status and subsequent treatments in other institutions were determined by contacting the patient, attending physician or review of public death records. Data collection and analysis were approved by the Institutional Review Board. Results: Thirty patients with CBF-AML were identified, 14 with t(8;21) and 16 with inv(16) AML. Median follow up for survivors in this series is 35.3 months (range 6.4–117.4) with all survivors currently in remission. Median age at diagnosis was 43 years (range 18–69) with 10 (33%) patients older than 55. All patients initially received therapy with curative intent with anthracycline-based induction chemotherapy. Only 47% of the patients were treated on clinical trials. There was 1 death during induction therapy and 22/29 patients (73.3%) achieved a complete remission with initial induction therapy. Overall 13 patients (43.3%) have required some modality of HSCT. Six patients received HSCT in CR1 due to perceived high risk of relapse (5 autologous, 1 allogeneic). None of the 6 patients who underwent HSCT in CR1 (5 autologous, 1 allogeneic) have relapsed. Among the 16 patients receiving non-transplant consolidation in CR1, 6 have subsequently relapsed and required a HSCT (3 autologous, 3 allogeneic) and 3 of these patients are alive 20.9–117.4 months from the initial diagnosis. Seven patients received HSCT in CR2 or in relapse (4 autologous, 3 allogeneic) and 6 of these patients are long-term survivors. Estimated 5 year overall survival for the entire cohort is 58.8 +/− 10.8%, comparable to what has been described for younger patients entering clinical trials (Grimwade et al, 2010). However, the likelihood of survival at 5 years without requiring HSCT was only 28.1+/− 8.8% (Figure). Conclusions: The favorable outcome previously reported for CBF-AMLs was reproducible in unselected patients. However, only a minority of patients were long term survivors relying exclusively on conventional chemotherapy. In the near future, strategies for molecular risk stratification of CBF-AML patients need to be coupled with risk-adapted therapy, likely including early use of HSCT for high-risk patients. Disclosures: No relevant conflicts of interest to declare.

Description: Preclinical studies suggest that neoplastic cells may be particularly sensitive to simultaneous interruption of cell-cycle and survival signaling pathways. In accord with this concept, we have shown that flavopiridol (F), a CDK inhibitor, interacts with bortezomib (B), a proteasome inhibitor, to induce mitochondrial injury and apoptosis in human leukemia, myeloma, and lymphoma cells (Dai et al, Oncogene22:7108, 2003; Dai et al, Blood104:509, 2004). These actions were associated with inhibition of NF-kappaB DNA binding, increased expression of phospho-JNK, and downregulation of XIAP and Mcl-1. Based on these findings, a phase I trial has been initiated to identify appropriate doses of B+F for further investigation. Eligible patients (pts) include those with multiple myeloma or indolent B-cell neoplasms, and recurrent or refractory disease following at least 1 prior systemic therapy (excluding allogeneic stem cell transplantation). In the initial stage of the trial, pts received B (iv push) immediately followed by F bolus (1- hour infusion) on d1, 4, 8, and 11 out of a 21-day (d) cycle. Dose levels were, in mg/m2 (B/F): 1.0/15, 1.3/15, 1.3/22, 1.3/30, 1.3/40, 1.3/50, and 1.3/60. Subsequently, a “hybrid” F infusion schedule (30 minute load followed by a 4-hour infusion) was adopted based on evidence of activity of this schedule in chronic lymphocytic leukemia. With the hybrid schedule, all pts receive B (iv push) 1.3 mg/m2 on d1, 4, 8 and 11. Targeted F dose levels using the hybrid schedule are (Fload/Finfusion; mg/m2): 20/20 on d1 and 8; 30/30 on d1 and 8; 30/50 on d1 and 8; 30/30 on d1, 4, 8 and 11; 30/50 on d1, 4, 8 and 11. Dose limiting toxicity (DLT) is defined as NCI CTCAE grade 4 ANC/platelets for 〉 1 week or grade ≥ 3 non-heme toxicity. 38 pts have been enrolled. 29 pts were treated at 7 dose levels with the bolus schedule, after which development of the hybrid schedule was begun. With the hybrid schedule, 11 pts have been treated at 3 dose levels. To date, one DLT (grade 3 lower back pain) was observed at level 5 of the bolus schedule and one DLT (grade 3 fatigue) was seen at the 1st hybrid dose level. The MTD of the hybrid schedule has not been reached. Non-DLT toxicities include herpes zoster (2 disseminated), peripheral neuropathy, fatigue, postural hypotension, syncope, diarrhea and ≤ grade 3 cytopenias. Of 35 pts evaluable for response, there have been 2 complete responses (1 lymphoma and 1 mantle cell lymphoma), 7 partial responses (5 myeloma and 2 lymphoma), 3 minor responses (2 myeloma and 1 extramedullary plasmacytoma), 15 patients with stable disease (5 myeloma, 7 lymphoma, 1 Waldenstrom’s and 2 mantle cell lymphomas). Of the 3 pts who had received prior bortezomib, 2 had minor responses and 1 had disease progression. To date, hyperacute tumor lysis has not occurred with the hybrid schedule, but aggressive prophylaxis and monitoring are integral to the treatment plan. Correlative laboratory studies involving bone marrow CD138+ cells from patients with myeloma revealed a reduction in post-treatment NF-kappaB nuclear localization in 4 of 5 evaluable patients. Variable effects on myeloma cell expression of phospho-JNK, Mcl-1, and XIAP have been observed. Collectively, these findings indicate that a regimen combining bortezomib and flavopiridol, including the use of a hybrid flavopiridol schedule, is well tolerated in patients with progressive B-cell malignancies, and has clear activity in some patients refractory to standard therapy. Pending identification of the MTD and RPTD (recommended phase II dose), phase II evaluation of this therapeutic strategy should define its activity more definitively.

Description: VNP40101M (Cloretazine®) is a novel sulfonylhydrazine alkylating agent which preferentially targets the O6 position of guanine resulting in DNA cross-links. Data from a previously reported phase II multi-center single agent study (CLI-033) in patients ≥60 years old with newly diagnosed AML or high risk MDS showed an overall response rate of 31% after VNP40101M induction (Giles, 2007). Subgroup analysis showed significant activity in 54 elderly patients with de novo AML with 24 patients (45%) achieving a complete response (CR) or CRp (CI: 30.9;58.6). Subsequently a confirmatory phase II study of single agent VNP40101M was conducted in elderly patients with poor risk de novo AML (CLI-043). Patients received induction therapy with 600 mg/m2 VNP40101M as a 60-minute infusion on day 1. A second induction cycle could be administered to patients with a partial response or hematologic improvement. Patients with CR or CRp received consolidation with cytarabine 400mg/m2/day CIV for 5 days. Patients were eligible if they were ≥60 yrs and had one of the following poor risk factors: age ≥70 yrs, ECOG PS 2, unfavorable cytogenetics, or cardiac, pulmonary or hepatic dysfunction. Patients with a prior diagnosis of MDS or favorable cytogenetics were excluded. A 2-stage optimal minimax design was employed with a target response rate of 35%. The study proceeded to the 2nd stage when 〉8 responses were confirmed. At least 22 responses in 77 patients are required to accept the hypothesis of a 35% target response rate. Eighty-five patients were treated as of August 14, 2007. Median age (range): 73 yrs (61– 86 y); male: 59%. The majority of patients (79%) had 2 or more risk factors. The most common risk factors were age ≥70 (78%), unfavorable cytogenetics (45%, half with complex karyotype), ECOG PS 2 (41%) and cardiac dysfunction (38%). Thirty VNP40101M-related serious adverse events (SAE) have been reported to date in 22 of 85 patients. The most common SAEs are myelosuppression or complications thereof (pancytopenia (10%), infection (47%)). Non-hematologic SAEs consist of the following gr.3 events: left ventricular dysfunction (1), transaminitis (1), confusion (1), seizure (1), rash (1), hypokalemia (1), weakness (1) and hypoxia/pleural effusion (2). Seventy-nine patients are currently evaluable for early death analysis. Of these, 12 patients (15%) and 16 patients (20%) died at ≤30 days and ≤42 days from first induction therapy, respectively. The most common causes of induction death were progression of disease (6) and infection (6). Other causes were tumor lysis syndrome (1), acute renal failure (1), and respiratory failure (2). A confirmatory Phase II single-agent study of VNP40101M shows anti-leukemia activity in elderly patients with de novo AML and multiple poor-risk features. Major toxicities include myelosuppression. Severe drug-related non-hematological toxicity is uncommon. Patients continue in follow up, and additional safety and response data is pending.

Description: Combination therapy utilizing 2 novel agents with independent mechanisms of action and non-overlapping toxicities may be useful in the setting of advanced cancers. Tipifarnib (T) is an orally bioavailable farnesyltranferase inhibitor with documented single-agent activity in acute myeloid leukemia (AML). Bortezomib (B) is a broad inhibitor of proteasomal function, approved for treatment in multiple myeloma and mantle cell lymphoma. Preclinical studies indicated synergistic activity between these 2 agents for eliciting apoptosis within leukemia and myeloma cell lines and ex-vivo cells adhered to fibronectin. In this phase I combination trial, we studied the effect of combined effect of T plus B in patients with advanced acute leukemias. Objectives: The primary endpoint was toxicity assessment. Secondary endpoints included effect of combined therapy on signaling intermediates, including p-AKT, Bim, Bax, and NF-kB, as well as effects on farnesyltransferase (FT) and the proteasome activity. Eligibility: Patients with AML, ALL, or CML-BC who had received 〈 3 cycles of prior therapy were eligible. Methods: Patients received T on days 1–14 and B on days 1, 4, 8, and 11. Cycles were repeated every 21 days. Dose escalation occurred using cohorts of 3–6 patients. The starting dose was T: 300 mg/m2 and B: 1.0 mg/m2 Bone marrow aspirate was obtained at baseline, day 8, and between day 15 and the start of the next cycle. Measurement of signaling intermediates were performed in Ficoll-enriched leukemic marrow blasts using Western Blot (p-AKT, Bax, Bim) and ELISA (NF-kB). FT and proteasomal activity were directly measured within peripheral blood mononuclear cells (PBMC) using previously described methods. Results: To date, 27 patients have been enrolled at 3 centers. Four patients were ineligible after screening, and 23 patients have been treated. Median age was 69 years (range 48–84) Diagnosis: AML=25, ALL=1, MDS=1. Accrual to the 4th and final dosing cohort has occurred, without maximum tolerated dose being reached at the 4th and final planned dosing cohort (T: 600 mg/m2 and B: 1.3 mg/m2). Six patients received ≥ 2 cycles of treatment. Dose-limiting toxicities to date have included: nausea/diarrhea (1 patient), sensory neuropathy (1 patient), and fatigue (1 patient). Common drug-related (〉 10%) non dose-limiting toxicities included: infection/febrile neutropenia, diarrhea, nausea, vomiting, sensory neuropathy, and fatigue, most of which were grade 1 or 2. FTase inhibition within peripheral blood mononuclear cells (PBMC) was measured serially in 8 patients to date, with a median of 70% inhibition by day 8, and with 5 out of 6 evaluable patients having sustained inhibition at day 22. Proteasome function within PBMCs was reduced by a median of 44.3% in 7 patient samples pre-infusion and 1 hour post-infusion on day 8. Proteasome activity within PBMCs at day 22 was decreased from baseline in 5 out of 7 patient samples tested. Compared to baseline, NF-kB binding activity within leukemic blasts at day 8 was decreased by a median of 39% at in 10 out of 14 paired samples. No significant change in expression of p-AKT, Bax, or Bim, as measured by Western Blot, was detected at day 8. Two patients achieved clinical response; 1 patient had a complete response and another patient had complete response with incomplete count recovery. Four others had stable disease following cycle 1. Conclusion: combined therapy with T + B was well tolerated and demonstrated inhibition of several relevant target signals within leukemic blasts and PBMCs. In addition, clinical activity was seen in 2 patients to date. Accrual to the trial is ongoing and updated clinical and pharmacodynamic data will be presented.

Description: B-cell CLL is characterized by the accumulation of mononuclear B cells that are resistant to apoptosis as a result of bcl-2 oncogene overexpression. Nucleolin has recently been identified as a bcl-2 mRNA stabilizing protein that binds specifically to a 139 base AU-rich instability element (ARE) (Sengupta et al., J. Biol. Chem.279:10855–10863, 2004). Thus, studies were done to address the question whether the increased levels of bcl-2 mRNA in CLL are related to stabilization of bcl-2 mRNA by nucleolin. B cells were isolated from the blood of 9 patients with CLL and 5 normal volunteers by density gradient centrifugation followed by positive selection with CD19 immuno-magnetic microbeads. Flow cytometric analysis indicated that greater than 90% of the CLL and normal B cells were CD19 positive and CD3 negative. Western blotting revealed that cytoplasmic nucleolin and total cellular bcl-2 protein levels were elevated 18-fold (p

Description: Background: APL is a highly curable malignancy with reported survival above 90% in many large co-operative group studies. A recent study with use of ATRA/Arsenic versus ATRA/chemotherapy in low and intermediate risk patients showed an expected survival of 99% and 91% respectively. These spectacular results are not evident in the general population. A recent study from US SEER data showed that the 1 and 5 year relative survival in APL patients is 71% and 65%. Studies from Swedish Cancer Registry and Brazil showed that the early deaths (ED) can be approximately 30%. This is in contrast to observation in clinical trials where the early mortality is around 5%. The common causes of death are hemorrhagic complications (HC), infection, differentiation syndrome (DS) and multi-organ failure. It is now agreed that decreasing early deaths is a high priority at all leukemia treatment centers and will improve population wide survival. We report results of our prospective trial using a set of streamlined treatment guidelines along expert support that has been highly effective in reducing ED. Methods: The high ED rate in APL prompted us to develop a single page treatment algorithm with emphasis on quick diagnosis, prompt initiation of therapy and proactive and aggressive management of all the major causes of death during induction. More importantly we made our treatment protocol available to smaller outlying treatment centers and guided the treating oncologist/hematologist during induction. We were awarded a grant by the Leukemia Lymphoma Society (LLS) to implement this protocol in the states of Georgia and South Carolina to cover 15 million people over a 3 year period. We partnered with 3 other large leukemia treating centers and the study was approved by the respective institutional review boards. Aggressive outreach effort were made by visiting most of the leukemia treatment centers in both states to publicize the concept and educate the treating physicians about ED. Physicians called one of the leukemia treating physicians at the larger centers when a diagnosis of APL was suspected or confirmed and all patients were co-managed till the end of induction. Patients were consented using a telephone consent approved by the IRB for obtaining treatment information. There were no exclusion criteria but 3 patients were excluded for refusing transfusion support for religious reasons. Results: From 11/2010 to 06/2015, we treated a total of 106 patients. 40 patients were managed at large leukemia treatment centers and 66 were managed in the community at 18 practices spread across Georgia, South Carolina and neighboring states. Median age was 52 years (range 21-87 years) and 53% were males. Out of a total of 106 patients, there were 7 deaths (6.6%) with cause of death being bleeding due to DIC (n=3), multi organ failure and differentiation syndrome (n=3) and infection (n=1). 5/7 deaths were in patients older than 60 years with 3 being in patients above 70 years. Deaths occurred in both academic (2/40, 5%) and community centers (5/66, 7%). 3 patients died after induction from non APL causes which were metastatic colon cancer, infection not related to the APL treatments and another 87 year old patient who refused treatments and opted for hospice care. Conclusions: Our experience clearly shows that a streamlined treatment algorithm along with help from experts will result in better outcomes in this most curable hematological malignancy. A similar approach pioneered by investigators in Brazil (IC-APL consortium) confirmed this to be an effective intervention to decrease early deaths in APL. We believe our experience warrants large scale implementation of our protocol and is presently approved as an ECOG/ACRIN trial. Figure 1. Survival in APL patients treated using the algorithm and network of treatment centers. Figure 1. Survival in APL patients treated using the algorithm and network of treatment centers. Disclosures Jillella: Leukemia Lymphoma Society: Research Funding. Stuart:Novartis: Research Funding. Galipeau:Emory University: Patents & Royalties. Kota:Pfizer: Membership on an entity's Board of Directors or advisory committees; Leukemia Lymphoma Society: Research Funding.

Description: Abstract 1037 Poster Board I-59 Background: Voreloxin is a first-in-class anticancer quinolone derivative (AQD) that intercalates DNA and inhibits topoisomerase II, inducing apoptosis. Interim results of REVEAL-1, a Phase 2 (Ph 2) dose regimen optimization study of 3 schedules (sch) of single agent voreloxin in newly diagnosed elderly acute myeloid leukemia (AML) patients (pts), are reported. The initial dose regimen, voreloxin 72 mg/m2 qw x 3, was established in a Ph 1 dose-escalation study in relapsed/refractory leukemia pts (Lancet J et al., Proc ASH 2007). Overall remission rate (ORR = CR+CRp) was high (41%), but this regimen was less well tolerated in the frontline elderly population. The protocol explored 2 alternative voreloxin sch: 72 mg/m2 voreloxin qw x 2 and days 1 and 4 (d 1,4). A final cohort of pts is enrolling to the d 1,4 sch at 90 mg/m2. Dose escalation was based on safety data from the 72 mg/m2 cohort and from an ongoing Ph 1b/2 study of 90 mg/m2 voreloxin d 1,4 in combination with 1g/m2/d cytarabine x 5d (Lancet J, et al, ASCO 2009). Methods: Ph 2 study of 3 voreloxin sch (30 pts/sch): A 72 mg/m2 qw x 3 or B 72 mg/m2 qw x 2 or C 72 mg/m2 on d 1,4. C at 90 mg/m2 voreloxin is now enrolling to 20 pts. Eligibility: newly diagnosed AML (de novo or secondary AML), pts age ≥ 60 with ≥ 1 additional adverse risk factor (age ≥ 70, secondary AML, intermediate or unfavorable cytogenetics, or PS 2). PK were evaluated in a pt subset in cycle 1. Patient bone marrow aspirates (BMA) taken prior to dosing were tested ex vivo for extreme drug resistance (EDR®) to voreloxin. Results: To date, 105 pts have been treated. Preliminary safety and ORR are available for A, B and C at 72 mg/m2 voreloxin. Twelve pts in C at 90 mg/m2 are too early to evaluate (TETE). Overall incidence of infections and mucositis were reduced in B and C, sch with 2 voreloxin doses, relative to A which had 3 voreloxin doses. Voreloxin PK were similar to those in an earlier Ph 1 study in relapsed/refractory AML (Lancet J, et al., Proc ASH 2007). Pts whose BMA were inhibited 〈 48% by 1 μM voreloxin had a greater chance of treatment failure (p = 0.043) than those whose BMA were inhibited by ≥ 48%. Conclusions: In REVEAL-1, voreloxin demonstrates clinical activity with 3 dosing sch in previously untreated elderly (age ≥ 60) AML pts who are unlikely to benefit from standard chemotherapy. ORR across 3 sch was 35%; the majority (76%) were CR. Responses were seen in each risk factor category and with multiple risk factors. Of reinduced pts, 45% achieved CR(p). Durable remissions exceeding 6 months were observed in 50% (A) and 63% (B) thus far. C d 1,4 was selected for further development based on ORR (38%), 30 and 60 day all-cause mortality (7% and 14%, respectively) and an improved safety profile with lower rates of infection compared to previous schedules. Further accrual to C 90 mg/m2voreloxin d 1,4 is ongoing. Disclosures: Ravandi: Sunesis: sunesis study steering committee. Cripe:Sunesis: Research Funding. Chen:sunesis: Employment. Mahadocon:sunesis: Employment. Fox:Sunesis: Employment. Berman:Sunesis: Employment. Michelson:sunesis: Employment. Stuart:sunesis: sunesis study steering committee.

Description: Background: CD8+ T-cells in AML pts co-express multiple inhibitory receptors (IRs), including PD1, and IR expression increases with disease progression (Knaus et al, JCI Insight 2018). AZA upregulates pathways related to immunity and immune evasion in tumor cells, including PD-L1, (Wrangle et al, Oncotarget 2013) providing rationale for exploring AZA/Pembro combination in AML. Aims: To assess safety and response to AZA/Pembro after minimum 2 cycles of therapy in relapsed/refractory (R/R) (Cohort 1) and newly diagnosed (dx) older AML (Cohort 2). Methods: Cohort 1: Pts must have failed prior AML therapy. The first 6 pts (run in phase) received AZA 75 mg/m2 Days (D) 1-7 with Pembro 200 mg beginning on D8 and every (q)3 weeks (wks) thereafter. AZA cycles were repeated q4wks. No pts experienced dose limiting toxicity after minimum 3 cycles observation. After safety was established with the dosing schedule, patients with prior allogeneic stem cell transplant (alloSCT) were included and Cohort 2 started enrollment. Cohort 2: Pts ≥65 years (yrs) with newly dx AML and not candidates, or unwilling to receive, intensive chemotherapy. Other eligibility criteria (Cohort 1 and 2): ECOG PS 0-2 (changed to PS 0-1), adequate organ function, and no autoimmune processes requiring systemic immunosuppression. Results: Efficacy: Cohort 1 : 37 R/R pts have been enrolled. Baseline characteristics are summarized in Table 1A. 29 (78%) pts completed at least 2 cycles and are evaluable for response: 4 achieved complete remission (CR)/CR with incomplete hematologic recovery (CRi) (2/2) (14%) (Table 1B), 1 partial remission (PR) (4%), 4 hematologic improvement (HI) (14%), and 7 stable disease (SD) for at least 6 cycles (24%). The median # of cycles to response was 4 (range, 2-6). The 4- and 8-week mortality were 8% [all with rapidly progressive disease (PD): 2 received AZA for 3 and 5 days only] and 13%, respectively. With a median follow-up of 14.9 months (mos), the median overall survival (OS) for the whole cohort, responders + SD, and CR/CRi/PR is 10.8 mos (40% 1-yr), 13.9 mos (51% 1-yr), and 17.2 mos (75% 1-yr). The median event-free survival (EFS) is 6 mos, for all responders + SD 8.7 mos versus 2.6 mos for others (P

Description: Abstract 2230 Poster Board II-207 Background: Reduced intensity conditioning (RIC) for allogeneic hematopoietic stem cell (HSC) transplantation is a well established therapy for patients with advanced hematological malignancies who are not suitable candidates for fully myeloablative conditioning. The use of alemtuzumab as part of RIC has been associated with decrease in incidence and severity of graft versus host disease (GVHD), particularly in unrelated donor transplants. Methods: This is a single center, prospective study. Patients with relapsed or refractory hematological malignancies who were not candidates for fully myeloablative conditioning regimens received an non-alemtuzumab (nA) containing RIC regimen or an alemtuzumab-containing regimen (A) based on the use of a matched sibling or an allele-matched unrelated donor, respectively. Patients in the nA group were conditioned with either Fludarabine 30mg/m2/day for 5 days and total body irradiation 200cG or Fludarabine 25mg/m2/day for 5 days and Melphalan 70mg/m2/day for 2 days. Patients in the A group received alemtuzumab 20 mg/m2/day for 2 days, Fludarabine 30mg/m2/day for 5 days and Melphalan 70mg/m2/day for 2 days. All patients received peripheral blood HSC grafts. Prophylaxis against graft versus host disease with cyclosporine and mycophenolate mofetil as well as infectious disease prophylaxis and supportive care guidelines were standard across both groups. Results: From January 2003 to March 2009, 56 patients were enrolled in the study and 50 patients who actually received a HSCT are the subject of this analysis. Twenty nine patients were in group nA and 21 in group A. Median age of the patients in the entire cohort was 55 years (range 14-65). Eighteen patients had AML, 12 NHL, 8 MDS, 6 CML, 3 CLL and 3 MM. Twenty-three patients were considered to be at high-risk for post transplant relapse (45% of group nA vs. 47% of group A, P= 0.84). All patients in group nA had hematological engraftment while 2 patients in A (9.5%) failed to engraft. Despite the fact that all patients in group A received a transplant from an unrelated donor, the incidence of severe (grades C or D) acute GVHD was significantly higher in group nA (20.7% vs. 0%, P=0.03). Day 100 mortality was similar between the 2 groups (20.7% for nA vs 33.1% for A, P=0.31). Cumulative incidence of progression did not differ between the two groups (P=0.7) while the cumulative incidence of treatment related mortality was higher in group A (P=0.02, Figure 1). Both median overall survival (OS) (44.1 vs. 5.3 months; P=0.01, figure 2) and progression-free survival (PFS) (8.7 vs 5.3 months, P= 0.02) were superior in group nA. Cox regression analysis including conditioning regimen, age and risk of post-transplant relapse showed that conditioning with alemtuzumab was the only variable significantly associated with inferior OS (RR 2.8, P=0.009) and PFS (RR 2.42, P= 0.01). Group A had a higher incidence of late (after Day 100) infectious complications resulting in death (43% vs.10%, p=0.01). Conclusion: Even though alemtuzumab-based RIC in unrelated HSCT has a protective effect against acute GVHD and risk of D+100 TRM comparable with non-alemtuzumab containing RIC regimens in related donor transplant, its beneficial effect is overcome by excessive late infectious complications. Disclosures: Fouts: Genzime: Consultancy.