ALBERT

Description: Abstract 3415 Poster Board III-303 High dose chemotherapy and SCT is an accepted treatment option for patients with relapsed lymphoid malignancies. Relapse remains a significant issue for patients with advanced disease. Predicting effective disease control with improved safety, we investigated the administration of intravenous (i.v.) busulfan (Bu) combined with melphalan (Mel) in patients with lymphoid malignancies undergoing ASCT. Patients and Methods Bu130 mg/m2 was infused daily for 4 days, either as a fixed dose per BSA (n=20), or to target an average daily AUC of 5,000 uMol-min ± 12% determined by a test dose of i.v. Bu at 32 mg/m2 given 48 hours prior to the high dose regimen (n=82), followed by a rest day, followed by two daily Mel doses at 70mg/m2. Stem cells were infused the following day. Dilantin was given for seizure prophylaxis. Results 102 patients (38 F/64 M) with non-Hodgkin's lymphoma (n=12), Hodgkin's lymphoma (n=49) and multiple myeloma (n=41) with median age 44 years (range 19-66) have been enrolled to date. The median number of prior chemotherapy regimens was 3 (range 1-6). At time of study entry, 88% of patients were in relapse (sensitive relapse n=70, refractory relapse n=19) and 12% were in second remission. The median CD34+ cell dose infused was 5.2 × 106/kg (range 0.7-12.5). Median days to ANC ≥ 0.5 × 109/L and platelet count ≥ 20 × 109/L were 10 (range 8-44) and 9 (7-141), respectively. There was no grade IV or V toxicity. The most commonly observed toxicities were grade I or II nausea and vomiting (77%), mucositis (67%), and diarrhea (55%)., Reversible grade III liver enzyme abnormalities were observed in 4% of patients; one patient developed reversible VOD. With a median follow-up of 2.1 years (range 0.2-4.3), the cumulative incidence of treatment-related mortality (TRM) at 100 days, 1 year, and 2 years was 1.0%, 3.1%, and 4.3%, respectively. Among patients with non-Hodgkin's or Hodgkin's lymphoma, the overall response rate was 90%, with 1- and 2-year PFS rates of 63% and 58%, respectively; 1- and 2-year OS rates were 90% and 82% respectively (Figure 1). PFS was significantly better in patients with chemo-sensitive lymphoma, 61% vs. 42% at 2 years, p=.03. Among patients with multiple myeloma, the overall response rate was 58%, with 1- and 2-year PFS rates of 67% and 44%, respectively; 1- and 2-year OS rates were 90% and 82%, respectively. Survival rates were not significantly different between the chemo-sensitive and chemo-refractory multiple myeloma patients. Conclusion Intravenous busulfan-melphalan is well-tolerated, and the individualized PK-directed dosing of i.v. busulfan likely contributes to the low toxicity profile of this regimen. The high response rate and disease control in patients with advanced disease is encouraging, and should be explored in larger phase II studies. Disclosures Andersson: Otsuka Pharmaceuticals: Consultancy.

Description: Abstract 3003FN2 Objective: Progressive disease (PD) remains the main cause of treatment failure following RIC allo-SCT in HL (Peggs KS et al, BJH 2008: 143; 468). We elected to explore the feasibility of adding gemcitabine (G), a highly active agent in relapsed/refractory HL (Santoro A et al, JCO 2000 :18; 2615), to our standard fludarabine (F) - melphalan (M) RIC in patients with relapsed and refractory HL undergoing allo-SCT, with the ultimate goal to augment cytoreduction and reduce the incidence of PD. Main G-associated non-hematologic toxicities include pulmonary, skin toxicities and mucositis. Patients and Methods: Between 8/07 and 3/11, fifteen consecutive HL patients (Unique Patient Number/UPNs 1–15) underwent an allo-SCT with the G-FM regimen. They had failed multiple conventional treatments (median prior chemotherapy regimens: 4; range 2–9), radiation therapy (6/15) and a prior auto-SCT (7/15). The median age was 33 years (range 20–46). Disease status at SCT was chemosensitive relapse (n=4), untreated relapse (n=1), induction failure chemosensitive (n=2), complete remission undetermined (CRU1 and CRU2) (n=8). The median time to PD after auto-SCT was 10 months (range 3–19). The donor was an HLA-identical sibling (n=10) or matched unrelated donor (MUD; n=5, with UPN 6 having a 9/10 match). The conditioning regimen was G 800 mg/m sq IV x1 at day -7 (two patients, UPN 6 and UPN 7 received G 1000 mg/m sq IV x2, day -5 and day -2 as part of a dose escalation attempt stopped for excess toxicity), F (32 mg/m sq IV x4, day -5 to day -2), M (70 mg/m sq IV x2, day -3 and day -2; total dose 140 mg/m sq). Thymoglobulin (4 mg/kg IV) was added in MUD allografts. Graft-vs-host disease (GVHD) prophylaxis included tacrolimus and mini-dose methotrexate (5 mg/m sq). Results: Myeloid recovery was prompt, with an absolute neutrophil count (ANC)〉500/mcL at day +12 (range 11–20). Median platelet recovery at 20K/mcL was at day +14 (range 9–26). Chimerism studies indicate 100% donor-derived engraftment in 13/13 evaluable patients (100%). Day 100/overall transplant-related mortality (TRM) were 2/15 (13%) and 2/15 (13%), respectively. Acute GVHD (grade II-IV) occurred in 8/14 evaluable patients, chronic GVHD in 7/13 evaluable patients (extensive in 7). Pulmonary toxicity was seen in four patients (26%). Grade 4 pulmonary toxicity was seen in UPN 6. Otherwise it was grade 1–2 (n=3). Cutaneous toxicity (skin rash, responsive to steroid therapy) was seen in five patients (33%: grade 3 n=1; grade 1–2 n=4). Mucositis was seen in nine patients (60%). It was grade 3 (n=1); grade 1–2 (n=8). Other organ toxicities were not seemingly markedly different from the ones seen with FM140 only. Three patients expired (graft rejection n=1, in UPN 6; CMV pneumonia n=1; PD n=1). Twelve patients are alive (ten progression-free, eleven in CR/CRU) with a median follow-up of 18 months (range 2–33). Actuarial rates of overall survival (OS) and progression-free survival (PFS) at 24 months are 87% (95% CI: 56–96) and 49% (95% CI: 18–74), respectively (see Figure). While a formal comparison with our historical experience with the FM140 regimen is clearly not possible, OS and PFS (actuarial estimates) at 24 months were 64% (95% CI: 49–76), and 32% (95% CI: 20–45), respectively (Anderlini et al, Haematol 2008; 93 :257). Conclusions: The addition of G to FM140 is feasible. Pulmonary, cutaneous toxicities, as well as mucositis, while clinically significant, were manageable and did not contribute to mortality in the patients treated with only one G dose. While quite encouraging, these data remain preliminary. The G-FM regimen deserves further study in a larger cohort of patients. Disclosures: Off Label Use: Gemcitabine, fludarabine and melphalan as part of conditioning regimen for allogeneic stem cell transplantation.

Description: Background: Ibrutinib has demonstrated efficacy in clinical trials for relapsed and refractory MCL and CLL. There is a paucity of information regarding its safety and efficacy after failing alloSCT. Clinical data suggest that B-cell dysfunction contributes to chronic graft-versus-host-disease (GVHD). It is speculated that this may be due to hyper-responsiveness of the B-cell receptor, which can be abrogated by disrupting the signaling downstream by the use of ibrutinib. Purpose: To study the safety, toxicity, survival rates and risk of GVHD in patients with CLL and MCL who relapsed post an alloSCT at our center. Methods: Retrospective review in MCL and CLL pts who received ibrutinib post alloSCT between 12-1-2011 and 12-1-2014. The study was approved by IRB. Results: We identified 22 pts with CLL (n=16) and MCL (n=6) who failed alloSCT with either nonmyelablative (n=17, 77%) or ablative (n=5, 23%) conditioning. Twelve (55%) received their transplants from HLA-compatible siblings and 10 (45%) from unrelated donors. Median time from alloSCT to progression was 12 months (range, 5-94 months). Ten (45%) failed to respond to donor lymphocyte infusion (DLI). The median time from progression post alloSCT and starting ibrutinib was 17 months (range, 0.5-88 months).When starting ibrutinib, median age was 63 (range, 47-73) years. Ten (43%) pts had bulky disease. Median β2-microglobulin was 4 mg/L (range, 2.7-10). Five (23%) CLL had 17p deletion. Median hemoglobin in CLL pts was 12.3 g/dL (range, 9.2-17.6), median platelets was 109,000/ µL (range, 8000-301,000), median absolute lymphocyte counts were 2,300/µL (range, 310-64,400). All MCL pts had elevated Ki-67 of 〉30% and 5 (83%) were blastoid. Median % of donor T cell (range, 27-100) and myeloid cells (range, 84-100) was both 100%. The ibrutinib starting dose was 420 mg in 12 (55%) and 560 mg in 10 (45%) pts. With a median follow-up time of 15 (range, 4-38) months, median overall survival (OS) was not reached for CLL, whereas this was of 17 months for MCL pts. Eighteen-month OS rate for CLL and MCL pts were 87% and 33%, respectively (P=0.08) and the 18-month progression-free survival rates were 87% and 33%, respectively (P=0.03). Survival rates were similar in CLL pts with or without 17p deletion. At the time of this analysis, 12 (75%) CLL pts (3 in CR, 4 in PR, 4 in stable disease and one with progressive disease) and 3 (50%) MCL pts (1 in PR, I in stable and 1 with progressive disease) remain alive. Ten episodes of grade 2 infection (3 of which were related to pneumonia) and one septic shock occurred during the course of ibrutinib treatment. Two of these infections occurred in the setting of severe neutropenia. One (5%) pt developed atrial fibrillation that required cardioversion. One (5%) pt experienced bleeding post a tooth extraction that required hospitalization and transfusions. With their prior alloSCT course and DLI, 8 (36%) pts had grade 1-2 acute GVHD, 3 (14%) had acute grade 3-4 GVHD and 7 (32%) had chronic GVHD. At the time ibrutinib was started, all pts were off immunosuppression and 3 had signs of limited chronic GVHD. At ibrutinib initiation, the 3 pts with limited chronic GVGD progressed to extensive GVHD at 43, 105 and 153 days respectively. All 3 had involvement of the mouth, skin (one with severe scleroderma) and 1 had acute gastro-intestinal diarrhea and bleeding. All responded to initiating tacrolimus, systemic steroids and reducing the ibrutinib dose. Conclusions: Our results show that the use of ibrutinib after alloSCT is safe in pts who do not have active GVHD. The treatment can improve OS especially in CLL pts. This warrants further studies incorporating the drug in an upfront transplant strategy. Disclosures No relevant conflicts of interest to declare.

Description: Background: Fluid retention/overload (FO) is common during hospitalization for allogeneic stem cell transplantation (ASCT) and is associated with weight gain (WG), edema, and other symptoms such as shortness of breath. It is unknown if symptomatic FO impacts transplant outcomes. We hypothesized that FO is associated with non-relapse mortality (NRM) and worse survival after ASCT. Methods: FO was scored by an independent team using the following criteria: grade 1 - asymptomatic weight gain 1.0 mg/dl in 16% of the patients. Median DLCO was 70 and EF was normal (〉40%) in all except 2 patients. Thirty patients (21%) developed ≥ grade 2 FO. Factors associated with Day100 NRM were ≥ grade 2 FO (HR 15, CI 4.2-55, p1 (HR 4.7, CI 1.6-14, p=0.005) and age〉55 (HR 4.5, CI 1.5-13, p=0.008) by univariate analysis. In multivariate analysis (MVA) factors that retained significance were FO ≥ grade 2 (HR 13.1, CI 3.4-50, p1 at study entry (HR 3.5, CI 1.1-11, p=0.03). We verified the prognostic value of FO in a separate cohort of HLA matched transplants [N= 449, 190 matched related donor (MRD) and 259 matched unrelated donor (MUD)] with AML/MDS treated with fludarabine and busulfan conditioning. The median follow-up for this group was 23 months. The median age was 58 years (range 18-77). 42% were in CR1/2 at transplant. 68% had a peripheral blood graft. Median weight was 81kg (47-170). Median creatinine at transplant was 0.8, 19% had 〉1 mg/dl. Median DLCO was 71 and EF was normal (〉40%) in all except 2 patients. Significant factors associated with Day100 NRM by univariate analysis, were FO ≥ grade 2 (HR 11, CI 4.5-25, p

Description: Background: Bendamustine is a novel active agent in CLL with favorable safety profile. We recently reported the preliminary results of allogeneic stem cell transplantation (alloSCT) in lymphoma/CLL patients (pts) after BFR conditioning (Khouri et al. Blood 2014; 124:2306). Herein, we report more mature outcomes in CLL pts. Results and safety were compared with a previous regimen using FCR (fludarabine, cyclophosphamide, rituximab). Patients and Methods: We studied 89 CLL pts treated on 3 trials (one includes FCR later changed to BFR) at our center. Twenty-six (29%) pts received BFR and 63 (71%) received FCR. The BFR regimen consisted of bendamustine 130 mg/m2 IV daily on days -5 to - 3 prior to transplantation, thus substituting the cyclophosphamide in the FCR regimen. The dose and schedule of fludarabine (30 mg/m2 IV daily on days -5 to -3) and rituximab (375 mg/m2 IV on day -13 and 1000 mg/m2 on days -6, +1, +8) were similar in both regimens. Tacrolimus and mini-methotrexate were used for GVHD prophylaxis. In addition, thymoglobulin 1 mg/kg IV was given on days -2, and -1 in patients receiving a matched unrelated donor (MUD) transplant. Results: Patient characteristics were similar in both groups. This included median age (58 years in both), sex distribution, and median number of prior therapies (3 in both), % pts with β2-microglobulin 〉3 mg/L at study entry, refractory disease (38% in BFR vs. 48% in FCR, P=0.4), presence of 17p deletion [27% in BFR vs. (8/33) 24% in FCR], unmutated status [19/21 (90%) of BFR vs 22/24 (92%) in FCR] and peripheral blood stem cell source (92% in BFR vs. 87% in FCR). Donor/recipient CMV and sex-mismatched distributions were not significantly different between the groups. However, more patients received their transplants from unrelated donors in the BFR group than the FCR group (54% vs. 32%, P=0.05). Ten (38%) BFR pts vs 2 (3%) FCR pts did not experience severe neutropenia (P 50 years (79% vs 50%), β2-microglobulin 〉3 mg/L (73% vs 45%), 〉3 prior lines of therapy (70% vs 43%) and recent years of transplant (82% vs 47%). Treatment-related mortality was 11% and 27% (P=0.05) at 2-year. The incidence of acute grade 3 GVHD was 4% and 10% in the BFR and FCR groups, respectively, despite the higher % of MUD transplants in BFR. Grade 4 acute GVHD was not observed in either group. The 3-year incidence of extensive chronic GVHD in BFR vs FCR was 45% vs 58% (P=0.01). This difference in GVHD incidence may in part be explained by a lower absolute blood level of CD8+ T cells in BFR patients compared to the FCR group at 6 months (median 343 vs 538, respectively) and 9 months (median 208 vs 406, respectively) post alloSCT. Conclusions: This is the first study to show that conditioning in alloSCT for CLL impacts outcomes with an improved survival after BFR when compared to the FCR regimen. Disclosures No relevant conflicts of interest to declare.

Description: Introduction Treatment outcomes for adult patients with relapsed ALL are limited. Allogeneic hematopoietic cell transplantation (HCT) is the only curative option in a small subset of patients. We sought to investigate the optimal extent of therapy required prior to proceeding to transplant in second complete remission (CR2). Methods 126 consecutive patients with ALL in CR2 underwent HCT at MD Anderson Cancer Center between January 2004 to December 2015. The patient and transplant characteristics are described in table 1. The probabilities of outcomes were calculated with the Kaplan-Meyer method. Variables found to be significant at the p45 (RR=2.06, CI=1.20-3.53, p=0.009), alternative graft sources (RR=1.81, CI=1.09-2.97, p=0.02) and Karnofsky 45 (RR=1.92, CI=1.15-3.20, p=0.01) and Karnofsky

Description: Introduction: Extra-nodal Natural Killer/T-Cell Lymphoma, Nasal Type (ENKL) is an aggressive, rare variant of non-Hodgkin lymphoma most frequently found in Asia, with 5-year survival estimates of 30-45%. The utility of stem cell transplant (HSCT) has been evaluated in a number of primarily small retrospective studies, almost exclusively from Asia, in which outcomes appear to be improved with HSCT by 10-20%. We conducted this study with the aim to determine the outcomes of autologous (AUTO) and allogeneic (ALLO) HSCT in patients with ENKL. Methods: This multi-center study was conducted in collaboration with 4 different centers, 3 in the United States, and 1 in Singapore. All patients with a diagnosis of ENKL who received either AUTO or ALLO HSCT after January 1, 2000 were eligible. Univariate probabilities of overall survival (OS) and progression-free survival (PFS) were estimated utilizing the Kaplan-Meier method using IBM SPSS version 22.0. Probabilities of non-relapse mortality (NRM) and relapse mortality (RM) were calculated by the cumulative incidence (CI) procedure to accommodate for competing risks utilizing EZR software. The log-rank test was used to assess for differences between groups in regard to OS and PFS, and the Fine-Gray analysis was performed to compare outcomes with competing risks. Results: Twenty-seven patients, with median age of 48 years (range 22-68), and a median of 2 prior chemotherapy lines (range 1-5) received HSCT for ENKL; 14 AUTO and 13 ALLO, of which 70% were performed at MD Anderson. Sixty-seven percent were male, 30% were not in complete remission (CR) at transplant, and 40% had an NK-IPI risk group of 3-4. Seventy-four percent of patients received myeloablative (MAC) conditioning, with the most common regimen being BEAM in 55% of ALLO and 65% of AUTO. All patients received peripheral blood as the stem cell source except one who received cord blood. With a median follow-up time of 11 years, OS and PFS for the entire group were 51% and 50%. The CI NRM was 19% at 1 and 2 years and the CI RM was 16% at 1 year, 26% at 2 years, and 40% at 11 years (Figure 1). Amongst ALLO recipients, there were 2 cases of grade II-IV acute GVHD (14% of ALLO) and 5 cases of chronic GVHD (1 limited, 4 extensive, 36% of ALLO). PFS was significantly better for patients in CR versus those not in remission at transplant (67% vs 13%, p=0.002). There was no impact of MAC vs non-MAC conditioning, disease stage at diagnosis (I-II vs III-IV), prior number of chemotherapy lines, comorbidity index, NK-IPI risk group 1-2 vs 3-4, age 〉50, sex, or race on PFS or OS. We did an exploratory analysis of transplant outcomes between the AUTO versus ALLO groups. More patients in the ALLO group (46% vs 17%, p=0.082) were not in CR at transplant, though other characteristics were balanced. PFS for AUTO versus ALLO was 67% vs 31% at 1 and 3 years (p=0.032), (Figure 2). OS for AUTO vs ALLO was 75% vs 54% at 1 year, and 64% vs 39% at 3 years, (p=0.146). One patient received an ALLO with progressive disease and survived. Additionally, 3 of 4 patients who received ALLO after prior AUTO survived, though one died of a second malignancy 11 years post-transplant. One of these patients received a prior AUTO but developed graft failure and subsequently received an ALLO and was counted in the ALLO group. CI NRM was higher in the ALLO vs AUTO group at 1 year (39% vs 0%, p=0.013). CI of RM was higher in the first year in the AUTO vs ALLO group at 1 year (26% vs 8%), though by 3-years this difference was not significant (36% vs 23%, p=0.472). Conclusion: Here we present the results of a multi-center study of patients who received a HSCT for ENKL. Our results are similar to those seen in Asian studies, with long-term PFS and OS of 50%, demonstrating that HSCT is an effective therapy for patients with ENKL. Patients in CR at transplant had better OS and PFS than those not in CR; therefore, complete remission should be the goal prior to HSCT for ENKL. ALLO is an effective treatment option for relapse post-AUTO or for progressive disease at transplant, with less relapse than AUTO, particularly within the first year. This is particularly interesting given that 46% of patients who received ALLO were not in remission at transplant, indicating a strong graft-versus-lymphoma effect. However, these results are limited by an increased NRM. Strong consideration for AUTO should be given to patients who are in CR at the time of transplant, and ALLO should primarily be reserved for refractory disease or relapse post-AUTO. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Brammer: Celgene: Research Funding. Fanale:Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Research Funding; Infinity: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Research Funding; Genentech: Research Funding; Medimmune: Research Funding; Novartis: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Molecular Templates: Research Funding; ADC Therapeutics: Research Funding; Onyx: Research Funding; Gilead: Research Funding. Maziarz:Novartis: Consultancy; Athersys: Consultancy, Patents & Royalties, Research Funding.

Description: Purpose: Rituximab (R) use can attenuate the risks of graft-versus-host disease (GVHD) after non-myeloablative allogeneic (NMA) alloSCT. There is a paucity of information on the impact of this strategy in patients receiving myeloablative (MA) conditioning. Experimental design: We compared the risk of GVHD after an NMA regimen of BFR (bendamustine, fludarabine, rituximab) (Khouri et al. Blood 20014;124:2306-12.) to the MA regimen of bortezomib-R-BEAM (carmustine, etoposide, cytarabine, melphalan) regimen in patients with relapsed lymphoma undergoing alloSCT. Patients were treated on 2 prospective trials at our center between 2009-2013 and 2007-2011, respectively. Patients were considered for NMA if they were not eligible for myeloablative chemotherapy. Primary GVHD prophylaxis consisted of tacrolimus and methotrexate. All patients received rituximab (375 mg/m2 intravenously on day -13 and 1000 mg/m2 on days -6, +1, and +8) as described previously. Patients in both groups also received thymoglobulin 1 mg/kg on days -2 and -1 if the transplant was from matched unrelated donor (MUD). In addition, the MA group received bortezomib (1 mg/m2 per dose) on days -13, -6, -1, and +2. Because the treatment groups were not randomized, we performed inverse probability weighting (Robins JM. Epidemiol. 2000; 11:550-60) to correct for potential bias in patients' selection for the comparison of GVHD. Results: The analysis included 95 patients (MA=39 and NMA=56). The majority of the patients were male (68%) with a median age of 58 years (range: 22-71). The most common histology was diffuse large B-cell lymphoma (26%), followed by chronic lymphocytic leukemia (23%), mantle cell lymphoma (19%), and follicular lymphoma (18%). Transplant characteristics included MUDs in 43 (45%) patients, 23 (24%) female-to-male donors, and 49 (52%) ABO-mismatched. In addition, CMV was reactive in 80% of patients/ and or donors. Most patients (95%) had alloSCT from peripheral blood. Significant differences between treatment groups were observed for patient age, histology, PET scan status, LDH, disease status, and prior number of chemotherapies. On average, patients receiving MA conditioning were younger (p=0.008) and had higher LDH (p=0.026) pre-transplant, compared with NMA group. In addition, a higher percentage of MA patients were diagnosed with diffuse large B-cell lymphoma (41% vs. 16%, p=0.003), had a positive PET scan (p 3 prior number of chemotherapies (p=0.007) compared with the NMA patients. The median follow-up duration for surviving patients was 64.8 and 62.1 months for the MA and NMA groups, respectively. The groups' weighted (adjusting for patient age, donor age, donor type, disease status, sex mismatch status, histology, PET scan status, LDH, and prior number of chemotherapies) cumulative incidences of grade II-IV acute GVHD was 63% and 10%, respectively (p

Description: Abstract 3072 Allogeneic hematopoietic stem cell transplantation (SCT) is the only effective treatment for high-risk or relapsed acute lymphoblastic leukemia (ALL). However, SCT carries high treatment-related mortality (TRM). There have been continuing efforts to refine criteria for patients who may benefit most from SCT. Minimal residual disease (MRD) at the end of induction or induction/consolidation therapy has emerged as the most significant risk factor for disease relapse in ALL patients, and has become an indicator for SCT or intensified chemotherapy. In addition, MRD prior to SCT is highly predictive for post-transplant relapse in the pediatric population. The significance of pre-SCT MRD in adult patients with ALL remains to be determined. Patients and methods: In this retrospective analysis, we examined the impact of MRD detected within one month prior to SCT on risk of disease progression in adult patients with ALL who were in complete remission, defined by less than 5% blasts in bone marrow by morphologic assessment and normal blood counts at time of SCT. MRD has been uniformly assessed in patients using multiparameter flow cytometry since 2004. Bone marrow aspirates were stained using a comprehensive panel of 〉=15 markers and 200, 000 cells were analyzed. MRD was scored as positive based on a distinct cluster of 〉=20 cells, showing a significant difference in the level of expression (〉=3-fold) of 〉=2 antigens, in comparison to the known phenotype of benign immature B-cell precursors. Disease progression (relapse) was defined as leukemic blast count 〉= 5%. Therefore, limiting our data set to transplants performed during February 2004 through May 2010 at MD Anderson Cancer Center, we identified 98 patients with median age 34 years (range 19–68) treated with a median of 2 lines of chemotherapy (range 1–6) who received a matched sibling (n=51), matched unrelated (n=36), haplo-identical family (n=3), or cord blood donor (n=8) transplant for ALL of B-(n=86) or T-lineage (n=12) in CR1 (n=52), CR2 (n=39) or CR3 (n=7) using a myeloablative non-TBI based (n=62) or TBI-based (n=36) transplant conditioning regimen. GVHD prophylaxis was tacrolimus-based for all patients. Among 88 patients with available cytogenetic data at diagnosis, 59% were considered high risk defined by the presence of the t(9;22), t(4;11), hypodiploid or complex cytogenetics, 2% were classified as good risk by the presence of hyperdiploidy, and the remaining 34% were intermediate risk. Results: Ninety-two patients were evaluable for response and all had sustained CR following transplant; 6 had early death. With a median follow-up of 33 months among survivors (range 5.8–80.7), patients transplanted without detectable MRD at time of SCT had a significantly lower cumulative incidence of relapse than those transplanted with MRD, 30% versus 70%, p=.004 (Figure 1). There was also a trend for better 3-year PFS in the MRD negative group, 38% versus 13%, p=0.1. Additional factors, including disease stage at time of SCT, cytogenetic profile at diagnosis, donor relation, and development of GVHD were evaluated in a univariate analysis for relapse rate, PFS, and overall survival. Only the presence of MRD remained a significant predictor for relapse. Conclusion: This study demonstrates that the presence of MRD prior to SCT in adult ALL patients is a significant predictor for relapse. Improvements in our current therapies are urgently needed to improve the outcomes for MRD positive patients.Figure 1.The cumulative incidence of disease progression in adult patients with ALL undergoing SCT in remission is stratified by MRD.Figure 1. The cumulative incidence of disease progression in adult patients with ALL undergoing SCT in remission is stratified by MRD. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4157 Background: We previously reported promising results with nonmyeloablative (NMA) allogeneic transplantation for indolent non-Hodgkin's lymphomas (NHL) (Khouri et al, Blood 2012; 119:6373). This strategy is however less effective in aggressive, bulky, chemoresistant, or heavily pre-treated lymphomas. The BEAM-rituximab is a commonly used regimen in transplantation for NHL. Bortezomib has synergistic activity with rituximab, is effective against many NHL subtypes with moderate non-hematologic toxicity; in addition, animal models suggest that pre-transplant bortezomib may reduce the risk of GVHD. We hypothesized that the addition of bortezomib to the conditioning would enhance initial disease control and that remission could be later sustained via the GVL effect of the graft, with lesser GVHD. Methods: We included pts up to 70 yrs, with relapsed/refractory NHL, acceptable organ function, having a matched donor, and who were not eligible for NMA transplantation. Bortezomib was designed to be given iv in an escalated dose of 1.0, 1.3, and 1.6 mg/m2 days-13, -6, - 1 and + 2. Rituximab was given at a dose of 375 mg/m2 on day -13 and 1000 mg/m2 on days -6, +1, and +8, as previously described. BEAM consisted of carmustine 300 mg/m2day-6, cytarabine 100 mg/m2 and etoposide 100 mg/m2 twice/day, days -5 to -2, and melphalan100 mg/m2 on day-1. Tacrolimus and methotrexate was used for GVHD prophylaxis. In addition, thymoglobulin of 1 mg/kg was given on days -2, and -1 in pts receiving an unrelated donor. Results: The study included 35 pts [Aggressive DLBCL=20, Indolent (CLL/FL with aggressive features =15)]. All pts had relapsed disease after the best conventional therapy (-ies) available. Median age was 53 (range, 22–65) years. Median prior treatments were 3 (range, 1–7). At transplant, 14 pts (51%) had refractory disease and 23 (66%) were PET+. Twenty-two pts (63%) received their transplants from HLA-compatible siblings (Sibs) and 13 (37%) from unrelated donors (MUDs). Bortezomib could not be escalated beyond the initial 1.0 mg/m2 per dose due to toxicity (2 of 3 pts treated at 1.3 mg/m2 died of sepsis related to C.Difficile; since then all pts received flagyl prophylaxis till engraftment). Blood was the source of donor graft in 97% of pts. All pts engrafted donor cells. Median donor T cells at day 30 were 100%. With a median follow-up time of 24.5 months (range, 5–49), the OS for the aggressive and indolent histologies were 58% and 44%, respectively (p=0.5); PFS rates were 32% in both. Determinants of outcomes were related to donor type, and age. In pts 50 yrs, the 2-years OS and PFS for sibs were 62% and 45%, respectively, vs 0% for the MUDs (Fig 1). There was no difference in pts and disease characteristics, or histology distribution between the 4 groups. In pts 〈 50 yrs, 2-year treatment-related mortality in Sibs and MUDs was 22% and 17% (p=0.9); whereas the incidence was significantly higher in 〉50 yrs pts receiving MUDs (62% vs 37%, p=0.03). This difference may be related to a higher incidence in acute 2–4 GVHD in 〉50 yrs pts receiving MUDs transplants (62% vs 33% in pts 〉50yrs receiving Sibs transplants). In 50 yrs, receiving an unrelated donor transplant. Results warrant further study and refinement. Disclosures: Khouri: Millenium Pharmaceuticals: Research Funding.