scholarly journals Acute Leukemia and High-Risk Myelodysplastic Syndromes in HIV-Positive Patients: 25-Years' Experience of the Rete Ematologica Lombarda (REL)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3603-3603 ◽  
Author(s):  
Chiara Cattaneo ◽  
Massimo Bernardi ◽  
Valentina Mancini ◽  
Chiara Pagani ◽  
Monica Fumagalli ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Hiv Infection ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Hiv Positive ◽  
Complex Karyotype ◽  
Advisory Committees

Introduction. Acute leukemia (AL) and high-risk myelodysplastic syndromes (HR-MDS) are relatively uncommon among HIV-positive (HIV-pos) patients (pts) and epidemiologic studies are very limited. A dismal outcome for these patients has been reported in the past; however more recently an improvement of prognosis was observed using intensive approaches, such as allogeneic stem cell transplantation (alloSCT) (Kwon, AIDS 2019). In order to better define the clinical characteristics of AL/HR-MDS HIV-pos pts, the feasibility of any specific treatment and the outcome in this setting, we evaluated all HIV-pos AL and HR-MDS pts diagnosed at 5 Hematology Centers participating to Rete Ematologica Lombarda (REL). Patients and Methods. We asked to the Centers to retrospectively report all cases of HIV-pos adult pts with AL or HR-MDS. We sent a database asking information about the characteristics of hematological disease, HIV infection, therapy, toxicities and outcome of pts. AL and MDS were classified according to WHO classification. The response to therapy was defined by European Leukemia Net criteria. Results. Between 1994 and 2019, 23 pts have been retrieved: 3 affected by HR-MDS, 15 by acute myeloid leukemia (AML) and 5 by acute lymphoblastic leukemia (ALL). Median age at AL/MDS diagnosis was 49y (range 28-67), M/F ratio 17/6. Median CD4 count was 336/mcl (range 50-2048). HIV infection was antecedent to AL/MDS diagnosis in 20/21 evaluable cases, with a median duration of 115 months (range 0-396); these pts were already on HAART at AL/MDS diagnosis. In 6 (29%) pts AIDS was also documented (1 Kaposi sarcoma, 1 P. jirovecii pneumonia and 4 non Hodgkin B-cell lymphoma). Six (30%) of the 20 evaluable cases had an adverse cytogenetics (complex karyotype), while only 1 pt showed a favorable karyotype (inv16). NPM1 mutation was observed in 2 AML cases, FLT3 ITD and p53 mutation in 1 case each. No bcr/abl rearrangement was observed in ALL cases. Three pts (13%) did not receive any treatment due to poor performance status (1 ALL, 2 AML) and died of progressive disease after a median of 2 months (mo, 0.5-2). Two HR-MDS pts received azacytidine but they rapidly progressed after 2 courses and died at +7 and +8mo respectively. Eighteen pts were treated with intensive therapy: 17 underwent induction chemotherapy (cht) and 1 alloSCT upfront. All the pts received HAART during AL/MDS treatment. Eleven out of the 17 pts (65%) receiving induction cht achieved a complete remission (CR); 4 pts received further induction cht, which was successful in 2/4 (50%) the overall CR rate being therefore 76.5%. A further pt received venetoclax+azacytidine as fourth-line treatment and achieved a morphological CR. Ten pts (9 AML and 1 HR-MDS) underwent stem cell transplantation at first-line: 3 autologous (ASCT) and 7 allogeneic. Overall 5 out of 13 (38%) pts achieving CR after induction cht relapsed; only one of the 5 receiving salvage treatment achieved a durable CR and proceeded to salvage alloSCT. Five pts (22%) died of toxicity: 2 (1 P, jirovecii pneumonia and 1 septic shock) during induction cht (2/17, 12%), 1 during aplastic phase after ASCT (hemorrhagic stroke), 2 after alloSCT (1 aGVHD, 1 infection); overall, SCT therapy-related morality was 3/10 (30%). After a median follow up of 21mo, 10 pts are alive in CR, with a median overall survival (OS) of 17mo and a 2y OS of 41.2±22.7SEM. A trend for a better OS was observed in pts with AL/HR-MDS diagnosis in the last years (2y OS: 2011-2019: 64.2% vs 1994-2010 27.3%, p=0.12) (Fig.1), even if median age was significantly higher in the second period (55.5y vs 44.5y, p=0.02). A complex karyotype was predictive of poor outcome in pts evaluable for cytogenetics (45% vs 10%, p=0.04), whereas no correlation between age, CD4 count, HIV duration and OS was observed. Conclusions. Intensive chemotherapy and stem cell transplantation are feasible and effective in AL/HR-MDS HIV-pos pts, with an acceptable toxicity profile, similar to the HIV-neg counterpart. The more frequent curative intent approach to AL HIV-pos pts is probably the main responsible for the improved survival in the last years also in the elderly; antiviral, antibiotic and antifungal prophylactic strategy, together with a prompt diagnosis and a careful management of infectious events, should be carefully considered in this setting of pts. HIV infection responsive to HAART should no longer be considered a contraindication to standard AL/HR-MDS treatment. Disclosures Rossi: Sandoz: Honoraria; Daiichi-Sankyo: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Mundipharma: Honoraria; BMS: Honoraria.

scholarly journals Feasibility and Outcomes of T-Cell Depleted Hematopoietic Stem Cell Transplantation in Patients with Relapsed or Refractory AML and High Risk MDS

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3324-3324
Author(s):  
Satyajit Kosuri ◽  
Sang Mee Lee ◽  
Hongtao Liu ◽  
Mylove Mortel ◽  
Lucy A Godley ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Advisory Committees

Background: Survival in patients (pts) with relapsed/refractory (R/R) acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS) is dismal. Treatment options are limited; however, a proportion of these individuals can be rescued by allogeneic stem cell transplantation (allo-SCT). Historically, allo-SCT, especially for R/R myeloid diseases, has used myeloablative regimens and no T-cell depletion (TCD) to maximize graft-versus-leukemia effect, often restricting this approach to younger and fit pts with matched donors. The aim of this study was to investigate outcomes of in vivo T-cell depleted stem cell transplantation (TCD-SCT) in a high-risk AML and MDS population. Methods: We performed a retrospective analysis of 141 patients with R/R AML (n=108)/high risk MDS (RAEB or CMML, n=33) who received TCD-SCT at our center from 2002-2015. Median age was 55 years (18-71) with 37 (26%) pts older than 60. Patients underwent in vivo TCD with alemtuzumab or ATG and 117 (88%) received reduced-intensity conditioning (RIC). Alemtuzumab was generally given as 100 mg total divided over 5 days whereas rabbit ATG dosing included days -1, - 3, -5 (+/- on day -7). Alemtuzumab usually partnered with matched related (n=65; 46%) or unrelated (n=53; 38%) peripheral blood stem cell (PBSC) grafts whereas ATG mostly was a component of umbilical cord grafts combined with a CD34 selected haploidentical donor (haplo-cord) (n=23; 16%). Prognostic factors such as age, HCT-CI, CIBMTR score (Duval 2010), revised disease risk index (R-DRI), donor type and pre-transplant disease status were analyzed. Multivariate cox regression models were considered from forward selection for factors with a p value <0.1 in univariate analysis. Results: Table 1 summarizes baseline characteristics. Among the 141 R/R AML or high risk MDS pts, AML predominated (77%). Sixty six (47%) pts had primary induction failure (PIF), 42 (37%) had relapse and 33 (23%) had high risk MDS. Eighty three pts (59%) had peripheral blasts at time of TCD-SCT. Cumulative incidence (CI) of relapse for all pts was 53% and non-relapse mortality was 28% at 2 yrs. Two and 5 yr PFS rates for the group were 19% and 11%, respectively. Two and 5 yr OS rates for the group were 30% and 18%, respectively. Figure 1 shows OS by disease type. Day 100 mortality was 18%. Twenty one percent developed Grade 2-4 acute GVHD (aGVHD) (6% Grade 3-4), and only 5% developed chronic GVHD (cGVHD) requiring therapy. Figure 2 shows CI of cGVHD amongst disease types. Differences in 2yr survival outcomes were not significant among prognostic factors. Specifically, age 60+ vs younger was not prognostic (PFS 24% vs 17% p=0.4, OS 29% vs 29% p=0.7). Likewise, haplo-cord did not differ relative to matched donors in outcomes (PFS 18% vs 26% p=0.2, OS 35% vs 29% p=0.5). Conclusions: Although novel therapeutic approaches are emerging for R/R AML and high risk MDS, allo-SCT remains an established option for long-term disease control. In our analysis, outcomes after in vivo TCD-SCT in R/R AML and high-risk MDS pts treated with RIC mirror published historical results (Duval 2010, Schlenk 2010) but with low rates of cGVHD. The lack of significant difference in survival outcomes amongst age groups and donor sources suggests RIC with in vivo TCD can also be utilized as a platform in older individuals and those with alternative donors. With high relapse rates in this population, better pre-transplant disease reduction, minimal residual disease monitoring and post-transplant maintenance will be critical to increase long-term cures. Disclosures Liu: Agios: Honoraria; Arog: Other: PI of clinical trial; BMS: Research Funding; Karyopharm: Research Funding; Novartis: Other: PI of clinical trial. Larson:Novartis: Honoraria, Other: Contracts for clinical trials; Agios: Consultancy; Celgene: Consultancy. Odenike:Oncotherapy: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Astra Zeneca: Research Funding; Astex Pharmaceuticals: Research Funding; NS Pharma: Research Funding; Gilead Sciences: Research Funding; Janssen Oncology: Research Funding; Agios: Research Funding; CTI/Baxalta: Research Funding. Stock:Kite, a Gilead Company: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Daiichi: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; UpToDate: Honoraria; Research to Practice: Honoraria. Kline:Merck: Honoraria; Merck: Research Funding. Riedell:Bayer: Honoraria, Speakers Bureau; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding. Van Besien:Miltenyi Biotec: Research Funding. Bishop:Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno: Consultancy, Membership on an entity's Board of Directors or advisory committees; CRISPR Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Artz:Miltenyi: Research Funding.

scholarly journals Post-Transplant Cyclophosphamide in Acute Leukemia Patients Receiving More Than 5/10 HLA-Mismatched Allogeneic Stem Cell Transplantation: A Study on Behalf of the ALWP of the EBMT

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3890-3890
Author(s):  
Michele Wieczorek ◽  
Myriam Labopin ◽  
Luca Castagna ◽  
Eolia Brissot ◽  
Gerard Socié ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Median Time ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Advisory Committees ◽  
Free Survival

Abstract Background Post-transplant cyclophosphamide (PTCy) is a powerful strategy to prevent occurrence of graft-versus-host disease (GvHD) following allogeneic hematopoietic stem cell transplantation (HSCT). Initially developed in the setting of haploidentical HSCT, PTCy has been increasingly used for fully HLA-matched transplants with favorable results. The purpose of this retrospective multi-center study is to evaluate PTCy-based GvHD prevention for patients with acute leukemia receiving a traditionally prohibitive highly mismatched HSCT and to describe their outcome. Methods This is a registry-based study employing the data set of the Acute Leukemia Working Party (ALWP) of the European Society of Blood and Marrow Transplantation (EBMT). We retrospectively assessed the outcome of adult patients with acute myeloid or lymphoblastic leukemia (AML/ALL), transplanted between 2010 and 2020 with grafts from HLA-mismatched donors with more than 5/10 mismatches using PTCy-based GvHD prophylaxis. Results The study cohort consisted of 59 patients, with a median time of follow up of 20 (95% CI, 14-39) months. The median age was 47 (range, 18-69) years. Forty-four patients had a diagnosis of AML, 14 of ALL and one case of mixed phenotype acute leukemia. At time of transplant, 39 (66%) were in first or second complete remission, 4 (7%) were in later remission and 16 (27%) had active, relapsed or refractory, disease. Conditioning regimens were myeloablative for 54% of cases and peripheral blood was the preferred source of stem cells (64%). All donors were related. Most patients (85%) received a 4/10 HLA-matched transplant, the most commonly mismatched loci were C and DQB1, often with a double mismatch involving the same locus. Two cases of fully mismatched donors were also recorded. PTCy was always associated with other immunosuppressive treatments, especially with the standard combination of calcineurin inhibitors and mycophenolate mofetil. In only 8 cases in vivo T-cell depletion was realized with anti-thymocyte globulin. A large proportion of patients (86%) attained engraftment with a median time of 19 (range, 11-37) days. Only 8 patients did not reach engraftment and all of them died of infection or disease relapse in the first one-hundred days (range, 6-99) after HSCT. Thirty-three patients (58%) did not present any sign of acute GvHD (aGvHD). Cumulative incidence of grade II-IV and grade III-IV aGvHD at day 180 were 30.3% and 14.3%, respectively. At 2 years, the cumulative incidence of chronic GvHD (cGvHD) was 21%, and 7% for extensive cGvHD. Twenty-four patients died during the study period, mostly because of leukemia progression (n=13, 54%), infectious complications (n=6, 25%) and interstitial pneumonia (n=2, 8%). Other causes of death were hemorrhage, GvHD, and another non HSCT-related that accounted for one case (4%) each. At 2 years, the overall survival (OS), leukemia-free survival (LFS), and a GVHD and relapse free survival (GRFS) were 56%, 54% and 47% respectively. Rates of relapse incidence and non-relapse mortality were 28% and 19%, respectively. Conclusion According to this preliminary data overview, transplantation in a highly mismatched framework is possible, without unfavorable OS, LFS and GVHD rates. Despite the important limitation of the retrospective non-controlled nature of this analysis, these findings suggest that PTCy-based strategies could help overcome the barrier of HLA-matching and configure a new setting of transplantation, encouraging more in-depth investigations. Figure 1 Figure 1. Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Angelucci: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene BSM: Honoraria, Other: DMC; Blue Bird Bio: Honoraria, Membership on an entity's Board of Directors or advisory committees; Menarini-Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: steering commitee, Speakers Bureau; Vertex Pharmaceuticals: Honoraria, Other: DMC; Crispr therapeutics: Honoraria, Other: DMC; Glaxo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria. Mohty: Takeda: Honoraria; Jazz: Honoraria, Research Funding; Gilead: Honoraria; Adaptive Biotechnologies: Honoraria; Sanofi: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Amgen: Honoraria; Astellas: Honoraria.

Phase I/II Study of the Deacetylase Inhibitor Panobinostat As Maintenance Therapy after an Allogeneic Stem Cell Transplantation in Patients with High-Risk MDS or AML: The Panobest-Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4344-4344 ◽  
Author(s):  
Gesine Bug ◽  
Andreas Burchert ◽  
Eva-Maria Wagner ◽  
Nicolaus Kroeger ◽  
Zuzana Jedlickova ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Research Funding ◽  
Hematologic Toxicity ◽  
Advisory Committees ◽  
One Year

Abstract Background: Leukemic relapse and graft-versus-host disease (GvHD) remain major obstacles after an allogeneic stem cell transplantation (HSCT). Panobinostat is a potent inhibitor of class I, II and IV deacetylases and has shown antileukemic as well as immunomodulatory activity. The hypothesis of our phase I/II PANOBEST trial was that panobinostat can effectively prevent relapse in patients (pts) with high-risk (HR) myeloid diseases while simultaneously reducing GvHD. We aimed to determine dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of panobinostat in adult pts with HR acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) in complete hematologic remission (CR) after a reduced-intensity HSCT. Secondary objectives were evaluation of safety and tolerability of panobinostat, and overall (OS) and disease-free survival (DFS) at 1 and 2 years after HSCT. Methods: In two sequential schedules, panobinostat was administered orally thrice weekly, (TIW), either every week (A) or every other week (B). In schedule A, panobinostat was started at a dose of 10 mg TIW and escalated to 30 mg TIW using a 3+3 design; in schedule B, panobinostat was given at doses of 20-40 mg TIW. Panobinostat was initiated between day +60 and +150 after HSCT and given for up to 1 year. Eligibility criteria included: ANC ≥ 1,000/μL, platelets ≥ 75,000/μL, adequate organ function and no severe GvHD. DLT was defined as prolonged G4 hematologic toxicity or any non-hematologic toxicity ≥ G3 unrelated to disease progression or intercurrent illness within 28 days of the first panobinostat dose. Results: 42 pts (37 AML, 5 MDS) were enrolled, with a median age of 52 years (range, 21-71). Cytogenetics were classified as low (n=6), intermediate-1/2 (n=20) or adverse risk (n=16) according to ELN criteria. Panobinostat was started a median of 98 days (range, 60-147) after HSCT from a matched related (n=9), matched unrelated (n=24), mismatched unrelated (n=6) or haploidentical donor (n=3). The majority of patients (n=28, 67%) were transplanted with active disease (bone marrow blasts 0-80%, median 21%, 1 pt. with extramedullary AML), 9 in CR1 (21%) and 5 in CR2 (12%). Patient and transplant characteristics were equally distributed between schedules A and B. Of 42 pts, 22 (54%) have completed one year of panobinostat, 1 remains on treatment and 19 (46%) discontinued prematurely after a median of 70 days (range, 12-342) due to adverse events (AEs) (n=10), relapse (n=6), patient decision (n=2) or prohibited comedication (n=1). To date, 24 out of 42 patients experienced panobinostat-related grade 3/4 AEs (schedule A: n=14, 67%; schedule B: n=10, 48%). The most common AEs were hematologic toxicity (G3: 14 pts, 33%; G4: 2 pts, 5%), constitutional (G3: 7 pts, 17%) and gastrointestinal symptoms (G3: 5 pts, 12%). Neurological AE and pain (G3, 2 pts each, 5%) as well as metabolic/laboratory alterations (G3: 3 pts., 7%) and renal toxicity (G3, 1 pt, 5%) were also reported. AEs were fully and rapidly reversible after interrupting panobinostat (n=24); 14 patients needed dose adjustment and no study-related deaths occurred. The RP2D was 20 mg TIW in arm A and 30 mg TIW every other week in arm B based on 5 DLTs: fatigue G3 at 20 mg, colitis and nausea/emesis G3 each at 30 mg (arm A), diarrhea and headache G3 at 40 mg each (arm B). Prophylactic or preemptive donor lymphocyte infusions (median 2, range, 1-6) were administered to 10 pts (42%, median 1.5x106 CD3+ cells/kg) in arm A and 8 pts (33%, median 0.5x106 CD3+ cells/kg) in arm B. Cumulative incidence (CI) of moderate (n=8) or severe (n=2) chronic GvHD was 24±0.4% at one year after HSCT and did not differ between both arms. There was no evidence of impaired immune reconstitution. To date, median OS and DFS have not been reached after a median follow up of 22 months (range, 6-57). At two years after HSCT, 5 patients have died from relapse (n=3), sepsis (n=1) or sudden death (n=1 at 3.5 months after study discontinuation) and CI of relapse was 21±0.5%, resulting in probabilities for 2-year OS and DFS of 88±5% and 74±7%, resp. Discussion: Panobinostat maintenance following HSCT for high-risk AML or MDS is feasible with a RP2D dose of 20 mg TIW weekly or 30 mg TIW every other week and associated with a low relapse rate. This provides a rationale for a prospective randomized trial of panobinostat as post-transplant intervention. Disclosures Bug: NordMedica: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Other: Travel grants, Research Funding; Novartis Oncology: Honoraria, Other: Travel grants, Research Funding; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Astellas: Other: Travel grant; TEVA Oncology: Other: Travel grant; Gilead: Honoraria. Off Label Use: Panobinostat has not been approved for maintenance therapy after an allogeneic stem cell transplantation in ANL and MDS patients . Burchert:Bristol Myers Squibb: Honoraria. Bader:Neovii: Other: Institutional grants; Medac: Other: Institutional grants; Amgen: Consultancy; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy; Riemser: Other: Institutional grants. Ottmann:Ariad: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Outcomes of Salvage Stem Cell Transplantation in Hodgkin Lymphoma in a Single Institution in the Modern Era

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5500-5500
Author(s):  
Tatyana Feldman ◽  
Larysa Sanchez ◽  
Lina Starovoitova ◽  
Ewelina Protomastro ◽  
Yucai Wang ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Salvage Therapy ◽  
Brentuximab Vedotin ◽  
Advisory Committees ◽  
Significant Difference

Abstract Background: Though overall Hodgkin lymphoma (HL) carries one of the best outcomes among lymphoma, about 40% of patients relapse and/or fail to respond to initial therapy. Out of those about half can be cured with salvage therapy followed by high dose therapy and autologous stem cell transplantation (ASCT) while eligible patients who fail and/or relapse after HDT-ASCT are offered nonmyeloablative stem cell transplantation. Achieving a negative PET response prior to ASCT correlate with superior outcome in HL regardless of their clinical presentation. More recently novel therapies have emerged in the field from brentuximab vedotin approved in r/r setting in HL as well as checkpoint inhibitors currently in trials with very promising results. This study analyzed a cohort of HL pts transplanted at our institution over the last 5 years to identify potential new patterns in the evolving landscape of HL. Methods: We performed a retrospective analysis of r/r HL pts referred to our center for salvage therapy at our institution between 2009 and 2014 using the Blood and Bone marrow transplant database at HUMC. Results: A total of 66 patients with r/r HL transplanted at HUMC were identified. Baseline characteristics were as follows: male 57%, female 43%, median age 36.8y (range 16-66), Frontline therapy was ABVD in all but one pt who received Gemzar, Vinorelbine, Doxil; and 27% pts received consolidation w/ radiation. Median time to relapse was 7mo (range 0.93-87mo), stage at first relapse I-0, II-33%, III-20%, IV-23%, NA 24%. The salvage regimen used was ICE in 54 pts, brentuximab vedotin in 8 pts and HCVAD in 4 pts. Involved field radiation was used in 10% at salvage prior to HDT-ASCT. Responses after first salvage were as follows: PET-CR 59%, CT-CR 5%, PR-14%, PD-12%, NA-10%. As per our practice, pts not in CR after first salvage continue to the next salvage until they reach a CR. Pts not in CR after 2 lines of salvage were considered for allogeneic stem transplantation (alloSCT). Conditioning regimen was BEAM prior to ASCT, reduced intensity (fludarabine-based) prior to alloSCT. Source of allo stem cells was: MRD in 7 pts, MUD in 3 pts, haploidentical donor in 2 pts. A total of 59 pts had ASCT, 6 pts had alloSCT as first transplant (primary refractory), while 6 pts underwent alloSCT for relapse after ASCT. Disease status post first transplant was as follows: PET-CR 76%, CT-CR 17%, PR-1%, PD-6%. All 6 alloSCT pts are alive in remission, while 13 out of 59 ASCT pts have relapsed, 7 relapses occurred within the first year, 3 within the second year post ASCT. Out of 6pts with alloSCT after ASCT relapse, 4 pts are alive in CR, one died from PD, one died from PTLD (in CR from HL). After a median follow up of 24.5 mo (3.7-70), the 3y PFS and OS are 73% and 95% respectively. For CR and PR after first salvage to SCT pts, median PFS and OS has not been reached. For SD/PD after first salvage therapy pts median PFS is 14.5mo, median OS 47mo. No significant difference in mPFS and mOS is seen in pts who received one vs more than one salvage therapy prior to ASCT or had radiation as part of frontline or salvage therapy. Conclusion: We report on a consecutive series of high-risk r/rHL. Our results demonstrate an improved outcome compared to historical data. Pts requiring more than one salvage prior to SCT while having mPFS of only 14.5 mo, have prolonged survival at median 47 mo. While the number is small, selected young pts with high risk relapsed HL may benefit from alloSCT. Strategy of requiring CR prior to SCT, and alloSCT (instead of ASCT) in pts requiring more than 2 consecutive salvage regimens, availability of novel agents, diminishing use of RT may have contributed to observed improved outcomes. Disclosures Feldman: Pharmacyclics/JNJ: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau. Vesole:Idera Pharmaceuticals: Research Funding; Celgene Corporation: Speakers Bureau. Skarbnik:Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Speakers Bureau; Gilead Sciences: Honoraria, Speakers Bureau. Goy:Acerta: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/JNJ: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

scholarly journals Multicenter Analysis of Treatment and Outcomes for Patient with TP53 Mutated AML in the Era of Novel Therapies; Significant Impact of Allogeneic Stem Cell Transplantation on Survival

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 797-797
Author(s):  
Talha Badar ◽  
Mark R. Litzow ◽  
Rory M. Shallis ◽  
Jan Philipp Bewersdorf ◽  
Antoine Saliba ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Research Funding ◽  
Univariate Analysis ◽  
Advisory Board ◽  
Novel Therapies ◽  
Advisory Committees ◽  
Tp53 Mutations

Abstract Background: TP53 mutations occur in 10-20% of patients with AML, constitute high-risk disease as per ELN criteria, and confer poorer prognosis. Venetoclax combination therapies and CPX-351 were recently approved for AML treatment and lead to improved outcomes in subsets of high-risk AML, however the most effective approach for treatment of TP53-mutated (m) AML remains unclear. In this study we explored the clinical outcome of TP53m AML patients treated over the last 8 years as novel therapies have been introduced to our therapeutic armamentarium. Methods: We conducted a multicenter observational study in collaboration with 4 U.S. academic centers and analyzed clinical characteristics and outcome of 174 TP53m AML patients diagnosed between March 2013 and February 2021. Mutation analysis was performed on bone marrow specimens using 42, 49, 199, or 400 gene targeted next generation sequencing (NGS) panels. Patients with an initial diagnosis of AML were divided into 4 groups (GP) based on the progressive use of novel therapies in clinical trials and their approvals as AML induction therapy during different time periods: 2013-2017 (GP1, n= 37), 2018-2019 (GP2, n= 53), 2019-2020 (GP3, n= 48) and 2020-2021 (GP4, n= 36) to analyze difference in outcome. Results: Baseline characteristics were not significantly different across different GP, as shown in Table 1. Median age of patients was 68 (range [R], 18-83), 65 (R, 29-88), 69 (R, 37-90) and 70 (R, 51-97) years in GP1-4, respectively (p=0.40). The percentage of patients with de novo AML/secondary AML/therapy-related AML in GP1-4 was 40/40/20, 36/29/24, 37.5/37.5/25 and 28/52/20, respectively (p=0.82). The proportion of patients with complex cytogenetics (CG) was 92%, 89%, 96% and 94% in GP1-4, respectively (p=0.54). The median TP53m variant allele frequency (VAF) was 48% (range [R], 5-94), 42% (R, 5-91), 45% (R, 10-94) and 60% (R, 8-82) in GP1-4, respectively (p=0.38). Four (11%), 13 (24.5%), 10 (21%) and 9 (25%) patients had multiple TP53 mutations in GP1-4, respectively (p=0.33). The proportion of patients who received 3+7 (30%, 16%, 6% & 8%; p=0.01), HMA only (11%, 18%, 2% & 8%; p=0.06), venetoclax-based (2.5%, 12%, 48%, & 61%; p &lt;0.01) and CPX-351 induction (16%, 40%, 28% & 5%; p&lt;0.001) were varied in GP1-4, respectively. The rate of CR/CRi was 22%, 26%, 28% and 18% in GP1-4, respectively (p=0.63). Treatment related mortality during induction was observed in 3%, 7%, 10% and 17% of patients in GP1-4, respectively (p=0.18). Overall, 28 (16%) patients received allogeneic hematopoietic stem cell transplantation (alloHCT) after induction/consolidation: 22%, 15%, 17% and 11% in GP1-4, respectively (p=0.67). In subset analysis, there was no difference in the rate of CR/CRi with venetoclax-based regimens vs. others (39% vs 61%, p=0.18) or with CPX-351 vs. others (25% vs 75%, p=0.84). The median progression-free survival was 7.7, 7.0, 5.1 and 6.6 months in GP1-4, respectively (p=0.60, Fig 1A). The median overall survival (OS) was 9.4, 6.1, 4.0 and 8.0 months in GP1-4, respectively (p=0.29, Fig 1B). In univariate analysis for OS, achievement of CR/CRi (p&lt;0.001) and alloHCT in CR1 (p&lt;0.001) associated with favorable outcome, whereas complex CG (p=0.01) and primary refractory disease (p&lt;0.001) associated with poor outcome. Multiple TP53 mutations (p=0.73), concurrent ASXL1m (p=0.86), extra-medullary disease (p=0.92), ≥ 3 non-TP53m mutations (p=0.72), TP53m VAF ≥ 40% vs. &lt; 40% (p=0.25), induction with CPX-351 vs. others (p=0.59) or venetoclax-based regimen vs. others (p=0.14) did not show significance for favorable or poor OS in univariate analysis. In multivariable analysis, alloHCT in CR1 (hazard ratio [HR]=0.28, 95% CI: 0.15-0.53; p=0.001) retained an association with favorable OS and complex CG (HR 4.23, 95%CI: 1.79-10.0; p=0.001) retained an association with dismal OS. Conclusion: We present the largest experience with TP53m AML patients analyzed by NGS. Although outcomes were almost universally dismal, alloHCT appears to improve the long-term survival in a subset of these patients. Effective therapies are warranted to successfully bridge patients to alloHCT and to prolong survival for transplant ineligible patients. Figure 1 Figure 1. Disclosures Badar: Pfizer Hematology-Oncology: Membership on an entity's Board of Directors or advisory committees. Litzow: Omeros: Other: Advisory Board; Pluristem: Research Funding; Actinium: Research Funding; Amgen: Research Funding; Jazz: Other: Advisory Board; AbbVie: Research Funding; Astellas: Research Funding; Biosight: Other: Data monitoring committee. Shallis: Curis: Divested equity in a private or publicly-traded company in the past 24 months. Goldberg: Celularity: Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Aprea: Research Funding; Arog: Research Funding; DAVA Oncology: Honoraria; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Prelude Therapeutics: Research Funding; Aptose: Consultancy, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Atallah: BMS: Honoraria, Speakers Bureau; Takeda: Consultancy, Research Funding; Amgen: Consultancy; Abbvie: Consultancy, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Research Funding. Foran: revolution medicine: Honoraria; gamida: Honoraria; bms: Honoraria; pfizer: Honoraria; novartis: Honoraria; takeda: Research Funding; kura: Research Funding; h3bioscience: Research Funding; OncLive: Honoraria; servier: Honoraria; aptose: Research Funding; actinium: Research Funding; abbvie: Research Funding; trillium: Research Funding; sanofi aventis: Honoraria; certara: Honoraria; syros: Honoraria; taiho: Honoraria; boehringer ingelheim: Research Funding; aprea: Research Funding; sellas: Research Funding; stemline: Research Funding.

scholarly journals Outcome of Autologous Stem Cell Transplantation in Waldenström's Macroglobulinemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2149-2149
Author(s):  
Romil Patel ◽  
Neeraj Y Saini ◽  
Ankur Varma ◽  
Omar Hasan ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Advisory Committees ◽  
First Remission ◽  
Relapsed Disease

Abstract Introduction: The role of autologous hematopoietic stem cell transplantation (auto-HCT) in the management of patients with Waldenström Macroglobulinemia (WM), a rare, indolent lymphoma, has not been established. We had previously published our experience with auto-HCT in a small cohort of WM patients1. Here, we present an updated analysis of auto-HCT with a larger cohort of WM patients. Methods and study population: The study cohort was comprised of 29 patients who underwent high-dose chemotherapy and auto-HCT at MD Anderson Cancer Center (MDACC). The Kaplan-Meier method was used to create survival curves. Overall survival (OS) was defined as the duration from date of transplant to death or last date of follow-up in living patients. Progression-free survival (PFS) was defined as the duration from date of transplant to either progressive disease or death, whichever occurred first. Results: Median age at auto-HCT was 60 (range, 43-75 years). Eight patients (28%) had concurrent light chain amyloidosis (AL). Of the five patients who had MYD88 testing completed, 3 were positive for the MYD88 mutation. Additionally, of these 3 patients, 2 were also positive for CXCR4 mutation. Patients received a median of 2 lines (range 1-6) of therapy prior to auto-HCT; 3(10%) patients had primary refractory disease, 8(28%) were in first remission, and 18 (62%) had relapsed disease. Median time from transplant to last follow-up for the surviving patients was 5.3 years. Preparative regimens received by the patients were: Melphalan (n=20), BEAM-R (n=2), Busulfan/Melphalan (n=1), Cyclophosphomaide/Etoposide/total body irradiation (n=1), Thiotepa/Busulfan/Cyclophosphamide (n=1), and Carmustine/Thiotepa (n=1). Three patients further went on to receive allogeneic transplant either after relapse from auto-HCT or due to disease transformation to aggressive lymphoma. Twenty-eight patients achieved engraftment with a median time to neutrophil engraftment of 11 days (range, 10-15 days). One patient suffered primary graft failure due to progression of disease and died 84 days after transplant. Non-relapse mortality was 3.4% at 1 year. All patients were eligible for response evaluation. The median OS from diagnosis was 12.2 years. Overall response rate was 96%: complete response (n=8, 27.6%), very good partial response (n=5, 17.3%), partial response (n=15, 51.7%), and progressive disease (n=1, 3.4%). PFS and OS at 5 years were 43.3% and 62.9%, respectively. Median PFS and OS from auto-HCT were 4.1 and 7.3 years (Fig. 1A). The median OS from auto-HCT in first remission + primary refractory and relapsed disease was 8.2 years and 4.1 years, respectively.16 patients were alive at the time of censoring while 13 patients had died. Causes of death include relapsed disease (n=6), secondary malignancy (n=2), infection (n=1), chronic graft-versus-host disease (n=1), and unknown (n=3). 8 patients (28%) were positive for concurrent AL amyloidosis. The sites of amyloid involvement were kidneys (n=2), lungs (n=1), bone marrow (n=1), heart(n=1), lymph nodes(n=1), gastrointestinal tract (n=1) and subcutaneous fat aspirate(n=5). The median overall survival for patients with amyloid involvement (n=8) was 12 years. On univariate analyses, the number of chemotherapy regimens prior to transplant (≤ 2 vs >2 lines) was the strongest predictor of overall survival (p=0.03, HR 0.3, CI: 0.09-0.9, log-rank) and PFS (p=0.001, HR 0.24, CI: 0.07-0.85, log-rank). The median PFS in patients with ≤ 2 lines and > 2 lines of therapy was 71 months versus 19 months, respectively (Fig. 1B). Conclusion: Auto-HCT is safe and feasible in selected patients with WM, with a high response rate and durable remission even in patients with relapsed or refractory disease. References: Krina Patel et.al. Autologous Stem Cell Transplantation in Waldenstrom's Macroglobulinemia. Blood 2012 120:4533; Disclosures Thomas: Celgene: Research Funding; Bristol Myers Squibb Inc.: Research Funding; Acerta Pharma: Research Funding; Array Pharma: Research Funding; Amgen Inc: Research Funding. Lee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Orlowski:Takeda: Consultancy; Celgene: Consultancy; Spectrum Pharma: Research Funding; Janssen: Consultancy; Kite Pharma: Consultancy; Sanofi-Aventis: Consultancy; BioTheryX: Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy. Champlin:Otsuka: Research Funding; Sanofi: Research Funding. Patel:Poseida Therapeutics, Inc.: Research Funding; Takeda: Research Funding; Abbvie: Research Funding; Celgene: Research Funding.

Phase I Trial of High-Dose Clofarabine and Busulfan as a Myeloablative Regimen Prior to Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Relapsed or Refractory Acute Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 198-198 ◽  
Author(s):  
Sherif Farag ◽  
Lisa L Wood ◽  
Jennifer E. Schwartz ◽  
Shivani Srivastava ◽  
Robert P. Nelson ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Phase I ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Phase I Trial ◽  
High Dose ◽  
Dose Levels

Abstract Abstract 198 Fludarabine in combination high-dose busulfan (Bu) is an effective myeloablative preparative regimen for allogeneic stem cell transplantation. At doses used, however, fludarabine has only modest anti-leukemic activity. Clofarabine (Clo) is a second-generation purine nucleoside antimetabolite with significant single agent activity in patients with AML and ALL. The novel combination of Clo with Bu may provide improved disease activity safely. Therefore, we conducted a phase I trial to determine the maximum tolerated dose (MTD) of Clo in combination with Bu in patients with high-risk acute leukemia. Patients received i.v. Bu (Busulfex) 0.8 mg/kg q 6 hrs on days −6 to −3 and Clo at 30–60 mg/m2/day on days −6 to −2 in successive cohorts. Stem cells were infused day 0. GvHD prophylaxis included sirolimus plus tacrolimus starting day −2 to day 100, tapering to day 180. Patients were eligible if they were 18–60 years, had primary refractory or relapsed and refractory AML or ALL, or were in CR2 or higher, had Karnofsky performance status ≥70%, and adequate organ function. Donors were HLA-matched related (5/6 or 6/6 antigen-matched) or unrelated (10/10 allele-matched). Toxicity was scored using the Common Terminology Criteria for Adverse events, version 3.0. Dose limiting toxicity (DLT) was defined as any grade 3–4 non-hematologic toxicity that did not resolve to grade 2 or less by day 30. A total of 15 patients were treated at 4 Clo dose levels, 30 (n=3), 40 (n=3), 50 (n=3), and 60 mg/m2 (n=6). Seven males and 8 females of median age 48 (30–58) years, with AML (n=13) or ALL (n=2) were treated. At transplant, leukemia was relapsed and refractory (n=8), primary refractory (n=6), or in CR2 (n=1). Median number of lines of treatment failed before transplant was 2 (1–3). Median marrow blasts at transplant was 12% (3%–83%). Hematopoietic cell transplants were from related (n=9) and unrelated (n=6) donors. All patients engrafted. Median time to neutrophils >0.5×109/l was 16 (12–20) days, and to platelets >20×109/l was 15 (10–42) days. One patient treated at the 30 mg/m2 dose level failed to achieve platelets > 20×109/l. No DLT was observed. Transient Grades 3–4 non-hematological toxicities were evenly distributed across all 4 dose levels, and included vomiting (n=3), mucositis (n=9), hand-foot syndrome (n=1), and elevation of AST/ALT (n=10). Grades 3–4 elevation of AST/ALT occurred in 2 of 3 patients treated at 30 mg/m2, 3 of 3 at 40 mg/m2, 2 of 3 at 50 mg/m2, and 3 of 6 patients at 60 mg/m2 dose levels. AST/ALT peaked at day −1 or 0 and returned to baseline in all patients by day 10, with no long-term sequelae. There was no correlation between Clo dose and peak AST/ALT. One patient developed acute renal failure at the 60 mg/m2 dose on day +12 in association with elevated tacrolimus levels, although the creatinine subsequently normalized. Two patients, both at the 30 mg/m2 dose, developed mild veno-occlusive disease of the liver which was self-limiting. One treatment-related death due to sepsis was observed at day +104 in a patient treated at the 30 mg/m2 dose. Thirteen of 15 patients were in CR by day 30; 2 patients, treated at 40 mg/m2 and 50 mg/m2, respectively, failed to achieve CR. Day 100 mortality was 0. With a median follow-up of 313 days, the 1-year relapse-free survival was 51% ± 15%, and the 1-year overall survival was 61% ± 14%. Clo at doses as high as 60 mg/m2/day × 5 days in combination with Bu 3.2 mg/kg/day × 4 days is well tolerated and demonstrates promising efficacy in a very-high risk acute leukemia population. The MTD has not been reached. We recommend Phase II testing of Clo 60 mg/m2/day × 5 days in combination with high-dose Bu as a myeloablative regimen for allogeneic stem cell transplantation in patients with acute leukemia. Disclosures: No relevant conflicts of interest to declare.

Effectiveness of Reduced Toxicity Conditioning Regimen with Intravenous Busulfan Plus Pentostatin (BUPENT) in Patients Older Than 50 Years with Advanced Hematologic Malignancies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3331-3331
Author(s):  
Tulio E. Rodriguez ◽  
Mala Parthasarathy ◽  
Scott E. Smith ◽  
David H. Vesole ◽  
Zachary M. Earley ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Graft Failure ◽  
Conditioning Regimen ◽  
Advisory Committees ◽  
Reduced Toxicity

Abstract Abstract 3331 Poster Board III-219 Introduction Current data suggests that recipient age above 50 is associated with an inferior outcome after myeloablative allogeneic stem cell transplantation (SCT). Overall survival (OS) of 31%, and transplant related mortality (TRM) of 17% at 100 days have been reported in this population (Ditchkowski, et al 2005; Yanada, et al. 2004). Encouraging results are observed with non-myeloablative conditioning regimens. However, for patients with a high relapse risk, this approach may not be sufficient to achieve long term disease control. In these cases, a reduced toxicity, yet ablative stem cell transplantation (RT-SCT) may give adequate time to the transplanted cells to mature and mount an immune-mediated antitumor response. This study evaluated the outcome after RT-SCT using a conditioning regimen consisting of intravenous busulfan (Bu) and pentostatin (Pent). Methods Consented adult patients up to 70 years with a fully-matched related (MRD) or unrelated donor (MUD) were screened for enrollment. Conditioning consisted of Bu 1.6 mg/kg every 12 hours days -7 to -4, and Pent 4 mg/m2 on day -3 and -2 prior to stem cell infusion on day 0. GVHD prophylaxis was methotrexate 10 mg/m2 on day 1, and 5 mg/m2 on days 3, and 6. Tacrolimus was started on day -2, and then tapered over 1 month after day +100. Characteristics Twenty six patients were analyzed. Male to female ratio was 1:1. Stem cell source was from MRD in 15 patients and MUD in 11. Median age was 62, with 92% of patients being older than 50 years. Indications for treatment were AML (35%), MDS (42%), Refractory CLL (23%), Relapsed NHL (12%), and Philadelphia (+) ALL (4%). All AML patients were high risk either due to poor cytogenetic, transformation, or relapse and only two of them were transplanted in first complete remission. MDS patients were RAEB (36%), secondary MDS (36%), or multilineage dysplasia (18%). Two patients had prior autologous transplants. Results No graft failure was observed. All patients achieved neutrophil (NEU) engraftment. Two patients expired prior to platelet (PLT) engraftment. Median engraftment days for NEU and PLT were 13 days. At a median follow up of 25 months, the OS and progression free survival for the entire group was 40% and 38% respectively. The OS in the MRD group was 58%. TRM at 100 days was seen in one patient (4%) due to veno-occlusive disease (VOD). Limited chronic GVHD was the most common observed toxicity (54%), followed by diarrhea (30%) and mucositis (23%). Mucositis was mainly grade 1 (8%) and grade 2 (8%). No grade 3 mucositis was observed. There was only one case of VOD and one case of acute GVHD. Conclusion To our knowledge, this is the first report of a RT-SCT using BuPent. This study demonstrates the efficacy of the regimen in patients older than 50 years. No graft failure was observed and the regimen related toxicity was acceptable in this high-risk population. The overall survival of 40% at a median follow up of 25 months compares favorably with prior reports of myeloablative allogeneic stem cell transplatation in patients older than 50 years. This regimen provides an exciting opportunity to extend the benefits of allogenic transplant to an older population, and warrants replication with larger controlled trials. Disclosures Rodriguez: Otsuka: Membership on an entity's Board of Directors or advisory committees, Research Funding. Vesole:Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau; Millenium: Speakers Bureau; Centocor Ortho Biotech: Speakers Bureau.

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