There are no international guidelines on how the requirements for added clinical value (endpoints) should be prepared in terms of drug safety by entities performing health technology assessments (HTAs). The study aimed to review the Danish Medicines Council's drug safety endpointsSafety endpoints prepared by the Danish Medicines Council's expert committees were reviewed from their assessment reports for 50 treatments, of which 25 were for the treatment of cancer and 25 were for the treatment of other types of diseases. Similarities and differences were identifiedThe 139 endpoints for safety were grouped into 14 categories. The use of endpoints varied and all endpoints were based on an expert assessment. Serious adverse reactions/events were used as an endpoint in most of the cases: 43.2% (N=60)/15.8% (N=22), following treatment discontinuation based on four different causes 16.4% (N=32). A numerical grading scale for adverse events were predominately used for endpoints for cancer treatment (19.8%, N=20 vs. 2.1%, N=2)The variation in the use of endpoints reflects the complexity of safety assessments and the need for more standardization to promote stringency and transparency. The authors propose five recommendations for actions, which may promote more generalizability and transparency. International HTA entities and researchers are also encouraged to investigate the possibilities of establishing a universal grading system for adverse events and to develop international guidelines for safety assessment in HTAs.New medicines often have to be evaluated against the treatment already available in order to compare effectiveness, safety and price. If one treatment is superior, it will often be referred to as having added clinical value. This evaluation is known as a health technology assessment (HTA). All medicines can cause side effects and the assessment of safety in HTAS is therefore essential. No international guidelines for drug safety assessment in HTAs however exist. The requirements for safety prepared by the Danish Medicines Council's expert committees were therefore reviewed from their assessment reports for 50 treatments in order to present their approach to drug safety assessment. A total of 139 safety requirements, also referred to as endpoints, were identified. The use of endpoints varied which reflects the complexity of safety assessments and the need for more standardization to promote stringency. The authors propose five recommendations for actions, which may promote more generalizability and transparency in Denmark and internationally.

This study evaluated the in vitro activity of Ceftolozane/tazobactam (C/T) vs 10 comparator agents against Pseudomonas aeruginosa isolates obtained from clinical respiratory samples from pediatric patients with cystic fibrosis at three hospitals during 2015 to 2020. Antimicrobial susceptibility testing was performed using microbroth dilution technique with custom prepared Sensititre® MIC plates. MICs were determined via Sensititre Vizion® system and results were interpreted using current CLSI and EUCAST (2022) breakpoint criteria. C/T was the most potent agent as compared with other antipseudomonal drugs against 291 isolates with MIC50 = 1 μg/mL and MIC90 = 2 μg/mL with percent susceptibility as 95.2%. C/T remained active against majority of ß-lactam non-susceptible isolates; percent susceptibility ranging from 61.2% to 80% including 65.9% ceftazidime non-susceptible isolates. C/T had high activity against P. aeruginosa from 3 geographically diverse pediatric medical centers. Study results suggest that C/T may be used as a potential therapeutic option for treating pediatric patients with CF.

(R,R′)-4′-Methoxy-1-naphthylfenoterol (MNF) promotes growth inhibition and apoptosis of human HepG2 hepatocarcinoma cells via cannabinoid receptor (CBR) activation. The synthetic CB1R inverse agonist, AM251, has been shown to block the anti-mitogenic effect of MNF in these cells; however, AM251 is also an agonist of the recently deorphanized, lipid-sensing receptor, GPR55, whose upregulation contributes to carcinogenesis. Here, we investigated the role of MNF in GPR55 signaling in human HepG2 and PANC-1 cancer cell lines in culture by focusing first on internalization of the fluorescent ligand Tocrifluor 1117 (T1117). Initial results indicated that cell pretreatment with GPR55 agonists, including the atypical cannabinoid O-1602 and l-α-lysophosphatidylinositol, dose-dependently reduced the rate of cellular T1117 uptake, a process that was sensitive to MNF inhibition. GPR55 internalization and signaling mediated by O-1602 was blocked by MNF in GPR55-expressing HEK293 cells. Pretreatment of HepG2 and PANC-1 cells with MNF significantly abrogated the induction of ERK1/2 phosphorylation in response to AM251 and O-1602. Moreover, MNF exerted a coordinated negative regulation of AM251 and O-1602 inducible processes, including changes in cellular morphology and cell migration using scratch wound healing assay. This study shows for the first time that MNF impairs GPR55-mediated signaling and, therefore, may have therapeutic potential in the management of cancer.

Secondary acute myeloid leukemia (sAML) and AML with myelodysplasia-related changes (AML-MRC) both result in dismal outcomes. This retrospective study aimed to determine whether these features are poor prognostic factors independent of older age and adverse cytogenetics, which are commonly associated with a poor prognosis.The characteristics and real-world outcomes of sAML and AML-MRC from the Thai AML registry database were investigated.From a total of 992 newly diagnosed AML patients, 315 (31.8%) patients were classified into sAML or AML-MRC subtypes. Older age, low white blood cell (WBC) count, low bone marrow blast, and adverse cytogenetic risk were commonly present in sAML and AML-MRC compared to de novo AML. Complete remission after 7 + 3 induction therapy occurred in 42.3% of patients with sAML or AML-MRC and 62.4% of de novo AML (P < .001). The median overall survival (OS) of sAML, AML-MRC, and de novo AML were 6.9, 7.0, and 12.2 months, respectively (P < .001). The independent prognostic factors for inferior OS were older age, intermediate-risk or adverse-risk cytogenetics, WBC count > 100 × 109/L, poor performance status, and a subgroup of AML-MRC with the morphologic criteria of multilineage dysplasia (AML-MRC-M). In addition, sAML, AML-MRC, and a WBC count > 100 × 109/L were pre-treatment prognostic factors associated with poor relapse-free survival (P = .006, P = .017, and P < .001, respectively).Both sAML and AML-MRC are independently associated with poor outcomes in Thai patients. Our study supports AML-MRC-M as an adverse prognostic factor for OS.

Context Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for high-risk malignancies, although graft-versus-host (GVH) disease limits optimal outcomes. Post-transplant cyclophosphamide (PTCy) is an effective agent for the prophylaxis of GVH due to its functional inhibition of alloreactive T-lymphocytes and may enable GVH prevention while preserving the graft-versus-tumor effect. Additional data are needed to inform the use of PTCy when using fully matched donors. Objective To determine the rate of GVH, relapse, and overall survival following allogeneic HCT from fully matched donors using sirolimus/PTCy as GVH prophylaxis. Design Retrospective data were collected on 14 consecutive patients transplanted with a fully matched donor between November 2016 and June 2018 who received PTCy (day +3–4) and sirolimus (day +5) for GVH prophylaxis. Data collected included age, disease risk, HCT-CI, GVH incidence and grade, 1-yr overall survival, median survival, and GRFS. Patients or Other Participants 14 consecutive patients transplanted at BMDACC who received GVH prophylaxis with sirolimus and PTCy. All received thiotepa/fludarabine/melphalan conditioning. Results Disease risk index was intermediate (9), high (3), or very high (2). 7 with AML, 5 with MDS/MPN. Median age 69 yrs (39–81). Donor-related in 4, unrelated in 10, and all PBSC. Median days on sirolimus: 53 (5–238). Median overall survival was 908 days. 1-yr OS was 64%, and NRM was 28%. There was 1 case of VOD/SOS, 3 infectious deaths, and 1 due to CVA. Relapse-free survival median: 861 days (17–1362) and GRFS median: 565 days (17–1362). Incidence of all-grade GVH was 42%, with no grade 3/4 GVH and 7% cGVH. One patient relapsed. Seven of the 14 patients remain alive and disease-free at the time of this abstract, with a median follow-up of 3 yrs. Conclusions GVH prophylaxis with PTCy and sirolimus led to a low rate of grade 3/4 GVH and cGVH within this population. Relapse risk remained low, suggesting preserved graft-versus-tumor effect. Infectious deaths may be related to the timing of immune reconstitution following PTCy. Additional data are needed to inform the use of PTCy in the setting of fully matched donors. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for high-risk malignancies, although graft-versus-host (GVH) disease limits optimal outcomes. Post-transplant cyclophosphamide (PTCy) is an effective agent for the prophylaxis of GVH due to its functional inhibition of alloreactive T-lymphocytes and may enable GVH prevention while preserving the graft-versus-tumor effect. Additional data are needed to inform the use of PTCy when using fully matched donors. To determine the rate of GVH, relapse, and overall survival following allogeneic HCT from fully matched donors using sirolimus/PTCy as GVH prophylaxis. Retrospective data were collected on 14 consecutive patients transplanted with a fully matched donor between November 2016 and June 2018 who received PTCy (day +3–4) and sirolimus (day +5) for GVH prophylaxis. Data collected included age, disease risk, HCT-CI, GVH incidence and grade, 1-yr overall survival, median survival, and GRFS. 14 consecutive patients transplanted at BMDACC who received GVH prophylaxis with sirolimus and PTCy. All received thiotepa/fludarabine/melphalan conditioning. Disease risk index was intermediate (9), high (3), or very high (2). 7 with AML, 5 with MDS/MPN. Median age 69 yrs (39–81). Donor-related in 4, unrelated in 10, and all PBSC. Median days on sirolimus: 53 (5–238). Median overall survival was 908 days. 1-yr OS was 64%, and NRM was 28%. There was 1 case of VOD/SOS, 3 infectious deaths, and 1 due to CVA. Relapse-free survival median: 861 days (17–1362) and GRFS median: 565 days (17–1362). Incidence of all-grade GVH was 42%, with no grade 3/4 GVH and 7% cGVH. One patient relapsed. Seven of the 14 patients remain alive and disease-free at the time of this abstract, with a median follow-up of 3 yrs. GVH prophylaxis with PTCy and sirolimus led to a low rate of grade 3/4 GVH and cGVH within this population. Relapse risk remained low, suggesting preserved graft-versus-tumor effect. Infectious deaths may be related to the timing of immune reconstitution following PTCy. Additional data are needed to inform the use of PTCy in the setting of fully matched donors.

10046 Background: The SIPAT is used to assess psychosocial risk in solid organ transplants but data in HSCT is lacking. We examined if pre-HSCT SIPAT scores predict mortality, morbidity, length of stay (LOS) and number of hospitalizations over a 1 year period. Methods: 89 adult HSCT (59% autologous, 38% allogeneic) pts from an academic medical center underwent the SIPAT pre-HSCT. Additional data were obtained on Day 0, and 3-, 6-, and 12-months. Univariable Cox proportional hazards models assessed the instantaneous risk of mortality at any given time after Day 0 as a function of baseline pt characteristics and the SIPAT score. Results: TheSIPAT categorized 28%, 66% and 5.7% respectively of the pts as excellent (E), good (G), and high risk (HR) candidates. One year post HSCT, 76% of E, 72% of G, and 40% of HR candidates were alive. Higher SIPAT scores were a significant predictor of mortality. Compared to E candidates, the HR candidates were 5.94 (95% CI: 1.31-26.81) times more likely to die any time after Day 0 – even after controlling for pts’ comorbidity index ( p = .02). Similarly, compared to G candidates, HR pts were 4.81 (95% CI: 1.33-17.47) times more likely to die even after controlling for pts’ comorbidity index ( p = .01). There was no difference between the G and E candidates on univariable ( p = .75) or multivariable analysis controlling for comorbidity index score ( p = .72). For every 1 point increase in pts’ adherence score, the risk of death was expected to decline by approximately 14% ( HR = 0.86, 95% CI: 0.78 – 0.96; p = .01). SIPAT items that predicted mortality were depression ( p = .02), deceptive behavior ( p < .001) and moderate alcohol abuse ( p < .001). In linear regression analysis, higher SIPAT score was associated with longer LOS ( p = .04) but not infection ( p = .23), GVHD ( p = .40), or number of hospitalizations ( p = .73). Because there were only 18 mortality events, multivariable analyses were limited. Future research will examine the effect of SIPAT on time to death controlling for other pt comorbidities. Conclusions: We found the SIPAT was able to predict mortality and LOS in HSCT pts. This finding if validated in a multi-center manner could be an important tool for HSCT pt selection.

ASCT remains the standard of care for newly diagnosed MM. Recent studies have demonstrated that although STUR is improving across all ethnicities, it remains lowest in Black (B) and Hispanic (H) populations relative to Caucasians(C). New data suggests that the differences in utilization are not secondary to differences in outcome among different ethnicities. We reviewed our data on all patients seen in consult for a potential first transplant for MM, to attempt to understand why and where patients fail to undergo transplantation. From Nov 2011 to June 2016 we assessed 388 patients for consideration of an initial transplant for MM, 264 of whom (68%) proceeded to ASCT. Table 1 shows the transplant rate by ethnicity: 69% C, 72% H, 57% B, and 50% of Native Americans (NA) and the reasons for not proceeding to transplant. There is no obvious difference across groups. Table 2 shows the age and disease states for patients who underwent ASCT and for those who did not proceed. Although the numbers are small it does appear that a substantial number of the C patients who do not proceed are >70 years of age. For those who did proceed to transplant there also appears to be substantially more patients >70 in the C group.Table 1Reasons for Not Undergoing Transplant by Ethnicity (%)Ethnicity% Transplanted% Not Undergoing TransplantEarly DiseaseMedical Contra-IndicationProgressive DiseasePatient ChoiceNot SpecifiedCaucasian (n = 289)69 (n = 200)31 (n = 89)202116358Hispanic (n = 54)72 (n = 39)28 (n = 15)141426406Black (n = 35)57 (n = 20)43 (n = 15)401320270Native American (n = 10)50 (n = 5)50 (n = 5)02040400 Open table in a new tab Table 2Patient Characteristics: Proceeding to Transplant [T] versus Not Proceeding to Transplant [NT]EthnicityMedian Age (Range)% >70 y/oDisease Stages% Smoldering/1% 2A/2B% 3A% 3BTNTTNTTNTTNTTNTTNTCaucasian63 (33-80)68 (28-82)24421323221250511414Hispanic57.5 (39-74)63 (38-74)7131420141349532313Black60 (44-73)65 (31-80)152054015060472013Native American55 (51-56)57 (54-76)020000010010000 Open table in a new tab Our results suggest that once patients are seen at a transplant center, that there are no differences based on ethnicity regarding who proceeds to transplant. Additionally, there appears to be a tendency to see more C patients over the age of 70 for consideration of ASCT but the numbers for the comparison groups are small and make generalizations difficult. If these results can be verified at other centers, then the different STUR rates previously reported in minorities are more likely due to a referral bias or social factors rather than issues at the transplant center. Educational programs to overcome such obstacles, should be aimed at the primary oncologist to understand the differences in referral patterns across ethnicities and how to address these including referring more minorities over the age of 70 for consideration of transplant.

With the development of reduced intensity options, allogeneic transplant is increasingly being used in patients over the age of 60. Although early TRM has been decreased, there are still substantial complications with graft versus host disease (GVHD). Recent data with post transplant Cytoxan has been shown to allow safe transplant with substantially lower risks of GVHD in haplo-identical transplants. As part of a quality review we noted that our risks of GVHD and mortality in patients over the age of 60 was very high using standard dose tacrolimus and methotrexate (TM). We made a programmatic change incorporating post transplant Cytoxan in patients over the age of 60 as our new standard. In patients with a high risk of relapse the option remains to treat using TM. We now report on the patients treated to date, comparing our prior standard to our current protocol in consecutively treated patients. We retrospectively reviewed 31 patients, 16 that received standard TM and 15 that received post transplant Cy. Table 1 shows a comparison of the two groups. They appear well matched for graft source, age, disease and transplant preparative regimen. One patient who received TM after the change in policy due to refractory AML and 3 patients in the post transplant Cy are too early to evaluate (TETE) fully as they have not reached their 3 month follow up. Seven of the 14 (50%) evaluable patients in the TE group had early deaths (< 3months post transplant) and in 5 these were attributable to GVHD. The other two died from relapse and TRM. In the post Cy group 3 of 13 (23%) evaluable patients had an early death only 1 of which was attributable to GVHD. The other 2 deaths were from metapneumovirus and renal failure. An additional 3 patients in the post Cy group developed grade 3 GVHD but all responded and are currently well. It is difficult to make definitive conclusions based on the small sample size and the retrospective nature of the study. While not eliminating GVHD, there does appear to be a substantial decrease in the risk of death related to GVHD in patients over the age of 60 who receive post transplant Cy. Given our results, we believe this warrants additional studies to examine if there is a difference in GVHD rates and mortality attributable to GVHD in patients over the age of 60 with different GVHD prophylaxis regimens.Tabled 1GVHD ProphylaxisTM (N=15)Post HSCT CY (N=16)Donor SourceSibling66MUD910Median Age63 (60-70yrs)64 (60-74yrs)Preparative RegimenFlu/Mel1114Bu/Cy32Other1#DiseaseMDS65AML59Other4*2**TETE13Early Death7/14 (50%)1/13 (8%)GVHD Death5/14 (36%)1/13 (8%)#ATG/Cy/TBI*NHL (1), HD (1), AA(1),CLL(1)**NHL(1),ALL (1) Open table in a new tab #ATG/Cy/TBI*NHL (1), HD (1), AA(1),CLL(1) **NHL(1),ALL (1)

Autologous peripheral blood stem cell (PBSCT) transplant is considered standard therapy for Multiple myeloma (MM). GCSF started on day +1, historically had been used to expedite engraftment. More recent studies have demonstrated that initiating GCSF later during transplant does not delay engraftment and reduces transplant costs. As part of our QA policy we routinely look for cost savings and improvements to our clinical practice. One such potential enhancement was to determine in MM patients if we could safely discontinue G post transplant since these patients received peripheral blood stem cells collected after G CSF mobilization. We prospectively examined 10 consecutive patients MM treated with or without growth factor post transplant to see if there were differences in outcome. Table 1 shows the patient characteristics and outcomes. The two groups were well matched for patient age, disease stage or CD34/kg infused. Patients who did not receive G CSF post transplant engrafted a median of 2.5 days later to WBC and 1 day later to platelets. Despite the slower engraftment there were no differences in LOS, number of platelet transfusions, and there was a slight decrease in the readmission rate for those not receiving G CSF. There was one confirmed infection in each group. Additional antibiotic use was required in 4 patients who received G and 3 who did not. These observations have led us to discontinue routine G CSF use post PBSCT in patients with MM. Patients who require admission start G CSF to minimize hospital stay. We have subsequently treated an additional 30 MM patients without G CSF post transplant. The median time to ANC and Plt engraftment was 13.7 and 12.3 days (including 8 patients who did not require platelet transfusions). The mean LOS was 3.6 days. Twelve patients required readmission and received G CSF for a median of 4 days. We used these data to determine the potential cost savings. In the prior system each patient would use a median of 7 days of G CSF, now only 40% require any support for a median of 4 days. Thus the cost saving is the equivalent of 5.4 doses of G CSF/ patient which at our center would be 2500 dollars. In addition substantial numbers (26%) of patients did not require platelet transfusions which if confirmed would have even more potential cost implications. This data supports the notion that G CSF post transplant for patients with MM is no longer necessary as standard practice. Engraftment times are slightly slower, but there are no clinically relevant sequelae and there is the potential for significant cost savings.Tabled 1G post PBSCTNo G post PBSCTAge (median)62(42-77)58.5(44-73)Disease Stage2A/2B213A653B24Stem Cell Dose3.14X 106 CD34/kg (2.18-3.63)2.8X106CD34/kg (2.02-4.24)ANC>500 (for 3 consecutive days?)11.4 days (11-12)13.9 days (11-18)Platelet count>/=20k16.8 days (0-18)18 days (0-20)Median number of platelet transfusions11Median Length of stay3 days2 daysReadmission (%)5030 Open table in a new tab

Allogeneic transplant using reduced intensity conditioning is a therapeutic option for patients with Hodgkin lymphoma (HL) who relapse after an autograft. This was a prospective study of 31 consecutive eligible patients with HL who relapsed after an autograft and underwent an allograft using BEAM (BCNU, etoposide, cytarabine, melphalan) conditioning. At a median follow-up of 7 years the progression-free survival (PFS) was 36% (95% confi dence interval [CI] 19-54%) and overall survival (OS) was 42% (95% CI 23-59%). In multivariate analysis only residual disease at the time of transplant predicted outcome, with a 4-year PFS and OS of 62% and 75% for patients with minimal residual disease versus 8% and 8% for patients with gross residual disease, respectively ( p = 0.005 and p = 0.001, respectively). This benefit seemed to be irrespective of chemosensitivity, with an OS for patients with chemorefractory yet minimal disease of 71% at 4 years. BEAM allogeneic transplant is effective in producing long-term remissions after autograft failure. Regardless of chemosensitivity, minimizing tumor burden pre-transplant may improve long-term outcome.

Donor cell derived malignancies are a rare and interesting complication of allogeneic bone marrow transplantation. We present a case of a 56-year-old male with donor cell myeloid sarcoma of the stomach and myocardium.

Abstract Background Allogeneic hematopoietic stem cell transplantation (HDT) in the elderly patient with acute myeloid leukemia (AML) or myelodysplasia (MDS) continues to pose a challenge due to treatment failure and treatment related toxicity. TBI/Cy, allows for engraftment and tolerance while maximizing anti-tumor activity, but can be a difficult regimen in elderly patients due to its associated toxicity profile. The introduction of reduced intensity conditioning regimens (RIC) and improved supportive care has led to decreased mortality following HDT in the elderly. However, for patients at high risk for relapse, RIC may not achieve prolonged disease control. For these patients, an ablative HDT with reduced toxicity (RT-SCT) may be beneficial by controlling disease with acceptable toxicity while allowing a GVL effect. We evaluated a novel conditioning regimen in an open label phase II study consisting of Bu/Pent aimed at improving toxicity, relapse rate, and overall survival (OS) in elderly patients with AML or MDS, and compared them with an elderly group who received TBI/Cy. Methods We treated 54 patients with AML/MDS over the age of 55, who were recipients of HDT from fully matched related donor (MRD), umbilical cord donor, or matched unrelated donor (MUD). We defined elderly as greater than 55 years of age. The median age in the Bu/Pent group was 64, 61% had adverse prognostic features including cytogenetics, relapsed, treatment related or transformed disease, or high IPSS score, 39% were in the intermediate group. There were 60% MRD and 40% unrelated HDT. In the TBI group median age was 59, 48% had adverse features and 52% intermediate, 48% MRD and 52% unrelated HDT. The Bu/Pent group (n=23) was conditioned with intravenous busulfan 1.6mg/kg every 12 hours day -7 to -4 and pentostatin 4mg/m2 on day -3 and day-2 prior to SCT on day 0. GVHD prophylaxis was methotrexate 10mg/m2 on day 1 and 5mg/m2 on days 3 and 6. Tacrolimus was started on day -2 and tapered over 1 month after day +100. Relapse, survival and toxicity data was compared with a historical control group at our institution who received 12 Gy TBI/Cy (60 mg/kg x 2) (n=31). Controls were selected by retrospective chart review of patients with a diagnosis of MDS or AML who had received an allogeneic transplant with a TBI/Cy based conditioning regimen after the age of 55. There was no graft failure reported in either group. The OS at 100 days and 1-year post HDT was significantly better for the Bu/Pent group vs. TBI group (82.6% vs. 51.6% and 43.5% vs. 25.8% respectively; p value= 0.029). Progression free survival (PFS) was also significantly better in the elderly population receiving Bu/Pent; 43.5% at 1 year versus 22.6% in the TBI group with a p value of .021. The rate of relapse was comparable regardless of conditioning regimen with 34% in the Bu/Pent group (8/23) and 29% in the TBI/Cy group (9/31) relapsing. Transplant related mortality (TRM) accounted for 13% (3/23) of the deaths in the Bu/Pent group, and 38% (12/31) in the TBI/Cy group. Of the three deaths in the Bu/Pent group, 2 were due to GVHD and 1 was secondary to sepsis within 100 days. Other significant nonfatal toxicities such as mucositis and nausea/vomiting were medically managed and rates of GVHD were similar in the two groups; 10/23 (43%) in the Bu/Pent group and 14/31 (45%) in the TBI group. Of the 10 GVHD patients in the Bu/Pent group, 7 had chronic (cGVHD) (30%). None of the patients in the Bu/Pent group and 3/31 in the TBI group developed VOD. Upon sub-group analysis, elderly CIBMTR high-risk AML/MDS patients who received Bu/Pent had an 86% 100 day survival versus 60% in the TBI/Cy group; 1 year survival was 43% and 33% respectively. In the elderly CIBMTR intermediate risk group, Bu/Pent 100 day survival was 78% vs. 44% in the TBI group. At 1 year, patients in the intermediate group who received Bu/Pent had 45% survival vs. 19% in the TBI group. Conclusion We found that OS and PFS at 100 days and 1 year were significantly better in the Bu/Pent group due to a much lower TRM. The Bu/Pent based regimen appears to be superior for patients over the age of 55 with MDS or AML undergoing HDT when compared with TBI based regimens. With a low toxicity profile, Bu/Pent patients had a lower incidence of TRM when compared with a prospective study of patients receiving RIC-SCT busulfan/fludarabine (20%) and a lower incidence of cGVHD(53%) (Valcarcel et al). This regimen warrants further prospective evaluation. p value= 0.029 p value= 0.021 Disclosures: Smith: Seattle Genetics, Inc.: Research Funding; Spectrum: Consultancy; Cephalon: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; GlaxoSmith Kline: Speakers Bureau. Rodriguez:otsuka: Honoraria, Research Funding.

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin's lymphoma (NHL) characterized by the chromosomal translocation t (11;14) (q13;q32). It comprises approximately 6% of all NHL, but has a highly aggressive clinical course. While 60-90% of patients achieve complete remission (CR) with augmented induction regimens, approximately 85% will eventually relapse with a median overall survival (OS) of 3-4 years with less than 15% of patients alive at 5 years. Optimal initial therapy for this disease usually includes for those in first CR autologous hematopoietic stem cell transplant (HSCT), with allogeneic HSCT reserved for those who relapse. Patients who are non-responsive to first-line chemotherapy are increasingly being considered for an allogeneic HSCT.

Abstract Introduction Non-Hodgkin’s Lymphoma (NHL) is the most common hematologic malignancy in the United States with 69,700 new cases and 19,000 deaths predicted in 2013. The majority of patients diagnosed with NHL respond well to conventional chemotherapy, however, patients with relapsed or refractory NHL usually have poor long-term outcomes. While autologous stem cell transplantation (auto-SCT) is a mainstay for patients with relapsed or refractory disease that are chemotherapy-sensitive, allogeneic stem cell transplantation (allo-SCT) has been used to treat NHL in patients who have relapsed after auto-SCT, are chemotherapy-resistant, or have adverse risk factors. While some evidence has suggested that chemotherapy-resistant disease status prior to allo-SCT is associated with a poor prognosis, limited data exists to guide evidence-based transplant paradigms. We sought to determine if disease status prior to allo-SCT in patients with relapsed or refractory NHL impacts outcomes. Methods A retrospective chart review identified 154 patients diagnosed with relapsed or refractory NHL who underwent an allo-SCT at Loyola University Medical Center between January 1998 and January 2012. Fifteen patients were excluded for lack of data yielding 139 patients over a 14-year period. Of our patients with relapsed or refractory disease, chemotherapy-sensitive patients were defined as patients with partial or complete response to chemotherapy at time of transplant. Chemotherapy-resistant patients were defined as patients that either had progressive disease or were refractory to chemotherapy at time of transplant. Data on age, sex, type of NHL, stage at diagnosis, chemotherapy regiment, previous auto-SCT, disease status prior to allo-SCT, overall survival, and cause of death were collected. Results Of the 139 patients, the median age was 48 years with a male to female ratio of 1.4:1. The majority of patients had stage 3 or 4 disease (74%). Breakdown of NHL subtype revealed 31% diffuse large B-cell (DLBCL), 31% follicular, 13.7% mantle cell, 8% T-cell, 3.6% Burkitt’s, 2.1% marginal cell, and 10.7% other category that included small lymphocytic, anaplastic, natural killer cell, mixed cellularity, and unspecified NHL. A total of 44 patients (31%) underwent auto-SCT prior to allo-SCT. Subtypes of allo-SCT included matched sibling (45.3%), matched unrelated donor (MUD, 39.6%), and cord blood transplant (15.1%). Matched sibling allo-SCT had an improved 2 year overall survival of 57.1% when compared to MUD and cord allo-SCT (33% and 30%, respectively). Overall survival after allo-SCT for all patients was 41% at 3 years and 33.1% at 5 years. Disease status prior to transplant was divided into two categories: (1) chemotherapy-resistant (97 patients, 69.7%) and (2) chemotherapy-sensitive (42 patients, 30.2%). There was no statistical difference in overall survival between the chemotherapy-resistant and chemotherapy-sensitive groups at 6 months (60.8% and 78.5% respectively, p=0.066) and at 3 years (40.2% and 42.8% respectively, p=0.91). In a subgroup analysis, DLBCL patients with chemotherapy-resistant disease had similar 3 year survival as compared to patients with chemotherapy-sensitive disease (22.2% and 23%, respectively, p=0.93). Similar results were observed for both subgroups of patients with follicular lymphoma, with 55.2% survival in the chemotherapy-resistant group as compared to 64.2% in the chemotherapy-sensitive group at 3 years (p=0.81). Conclusion Our data suggest that disease status at the time of transplant does not impact survival outcomes in patients with relapsed or refractory NHL. This finding extended into a sub-group analysis of DLBCL, representative of an aggressive NHL subtype, and follicular cell lymphoma, representative of an indolent NHL subtype. We hypothesize that the comparable survival outcomes between chemotherapy-sensitive and chemotherapy-resistant disease states at transplant may be a result of graft versus lymphoma effect and use of a disease free graft. As no survival advantage was incurred in patients with chemotherapy sensitive disease, these data imply that the lymphoma burden at time of transplant is not prognostic. This potentially highlights the utility of earlier time to transplant in patients with chemotherapy-resistant disease, and perhaps suggest limiting the duration of attempted salvage chemotherapy after disease relapse. Disclosures: No relevant conflicts of interest to declare.

Abstract Background Progression free and overall survival (PFS/OS) for Multiple Myeloma (MM) have improved over the past 20 years largely as a result of ASCT as well as novel conventional dose therapeutic agents. However, since the 1990s improvements in PFS and OS due to ASCT have improved minimally due to continued reliance on single agent melphalan (MEL). In order to improve PFS and OS, better transplant regimens should be investigated. The combination of Busulfan (BU) and MEL delivers better PFS compared to MEL alone (Lahuerta, et al) with similar toxicity rates to MEL alone. Furthermore, in vitro and in vivo studies indicate synergy between MEL and proteasome inhibitors such as Botezomib (BTZ). Superior response rates and PFS were seen when BTZ is combined with MEL when compared with historical controls using MEL in a recent IFM study. (Roussel et al. Blood 2010). We hypothesize that IV BU and MEL followed by BTZ (BuMelVel) could be an effective preparative regimen with acceptable toxicity for patients with MM. Methods Between July 2009 and June 2013 57 patients with Multiple Myeloma who had already undergone induction therapy and were eligible for ASCT were enrolled. Patients received IV BU administered as a daily intravenous infusion for a total of 4 days with the first 2 days (day -6, -5) at fixed dose of 130 mg/m2 over 3 hours and the subsequent 2 doses (day -4, -3) adjusted to achieve a target area under the concentration-time curve (AUC) total of 20,000 mM* min. Pharmacokinetic (PK) analysis performed after the first dose of IV Bu was used to determine Bu AUC and individualized Bu PK-directed dosing for later doses (d-4 and -3). MEL was administered at 140 mg/ m2 IV over 15-30 minutes on D-2. BTZ 1.6 mg/m2 was administered IV push on D-1. Palifermin was given for mucoprotection at a dose of 6.25 mg IV for two consecutive days before the first busulfan dose (days -8 and -7). A third dose of 6.25 mg was give on day 0 after stem cell transplantation. Results Of the 57 patients enrolled 56 are evaluable for toxicity and 54 for response at D +100. Median age is 61 (31 - 72). 49 % of patients had received ≥ 2 induction regimens (range 1-4) and 69% were DS stage III. 38% of patients had achieved at least a VGPR after induction with 9% of those achieving a CR. After transplantation, 70% of patients had at least a VGPR including 37% CR or sCR. All but 4 patients had a PR or better to induction therapy (three had stable and one progressive disease). The most common grade ≥ 3 toxicities were neutropenic fever (n = 42) and mucositis (n=21). No VOD or treatment related deaths at D+100 were observed and all patients engrafted. Median time to engraftment was 10 days (range 10-12) and median hospital stay was 20 days ( 15-31). Median PFS at 2 years was 78%. Conclusion BuMelVel is an effective novel preparative regimen with ≥ VGPR and CR/sCR of 70% and 37% respectively which compare favorably to responses previously reported with MEL 200 alone (43% and 11%, respectively) by Roussel et al. At the time of reporting, 12 patients had relapsed; 2 and 3-year PFS rates were 78% and 60% respectively. The regimen of BuMelVel is well tolerated and may lead to improvements in PFS and OS in patients with multiple myeloma. Disclosures: Rodriguez: Otsuka: Research Funding; Millennium: Research Funding, Speakers Bureau; Celgene: Honoraria, Speakers Bureau.

An unusual case of cutaneous angiosarcoma clinically mimicking eczema is described. A 98-year-old Caucasian male presented with a 6-month history of a flesh-colored, subcutaneous nodule on his left forehead with contralateral facial erythema and scaling that had been previously diagnosed as eczema. Despite treatments with topical steroids and moisturizers, the condition did not resolve. At our clinic, excisional biopsy of the forehead lesion and scouting biopsies from the contralateral cheek were performed which revealed cutaneous angiosarcoma. The described case illustrates that dermatitis-like features should be considered as a rare clinical manifestation of cutaneous angiosarcoma. It also demonstrates that these lesions may respond well to radiotherapy as a single modality.

Sarcoma originating from the pulmonary veins represents one of the rarest subtypes of sarcoma. We report the case of a 52-year-old woman presenting with cough and scant hemoptysis and ultimately diagnosed with a primary intimal sarcoma of the left inferior pulmonary vein extending into the left lower lobe of the lung. To our knowledge, this is the first reported case of such pathology in the literature. We present the case and critically appraise the literature for sarcomas of the great vessels.

Abstract 3102 Identifying the optimal patients and timing for allogeneic hematopoietic stem cell transplant (HSCT) is an ongoing challenge for transplant centers that requires assessment of more than just the disease status and stage. Pre-existing co-morbidities also independently impact both 100 day and 1 year non-relapse mortality (NRM) as well as long term overall survival. Additionally, the CIBMTR has also shown that Hispanic patients have an inferior survival after allogeneic HSCT, although why ethnicity is linked to a higher mortality, e.g. is it higher risk/timing of transplant, lower socioeconomic status, increased co-morbidities, etc. however, is still undetermined. A survival analysis of allogeneic HCT outcomes that includes ethnicity, co-morbidity, insurance payor, as well as traditional risk factors such as age, disease risk at transplant, and remission status would be helpful to clarify the outcome disparities found in different ethnic subgroups and more importantly lead to strategies to minimize the effect. Methods: We performed a retrospective analysis of the outcome of 363 consecutive adult allogeneic transplants at Loyola University Hospital of whom approximately 10% were Hispanics (34) from January 1, 2003 to June 30, 2010. We use a focused approach to optimize care of non-English speaking Hispanics which involves native speakers at all levels, written materials in Spanish, and an IRB approved method to permit all non-English speaking patients to enroll in all clinical trials is present. Traditional prognostic data as well as the Sorror co-morbidity index and socioeconomic and ethnicity status were determined for each patient. The surrogate we used for socioeconomic status was insurance payor (i.e. indigent + Medicaid vs. third party insurance/Medicare). Survival analysis was calculated using Kaplan Meier plots considering each patient at 100 days, 1 year, and 3 years. Results: The median age for the 363 patients was 47.1 years with 48.7% being in the High Risk CIBMTR category, and 74.1% being in remission at transplant. The median co-morbidity index was 2.0. No differences were seen in remission status or the co-morbidity index for Hispanic vs. non-Hispanic patients, while fewer Hispanic patients were in the High CIBMTR Risk group (27.3 vs. 50.9%; p = .048). Survival for Hispanics (34) vs. non-Hispanics (329) showed no difference in overall survival at three years (42.1 vs. 42.8%). Based on payors, we found no statistical difference in 100 day overall mortality after HSCT for those with Medicaid (n = 35) vs. non-Medicaid (n = 328) payors with Hispanic non-Medicaid and non-Hispanic non-Medicaid survivals at 100 days of 82.8 and 87.9%. However despite the relatively small number, both the non-Hispanic and Hispanic patients with Medicaid showed a significantly decreased survival after 100 days with 3 year survivals of 20.0 and 30.0% for Hispanic and non-Hispanic Medicaid patients vs. 51.7 and 56.7% of the Hispanic and non-Hispanic non-Medicaid groups respectively (p = .002). Conclusions: Unlike prior reports, and perhaps by using a focused approach for our non-English speaking Hispanic patients, we found no difference in survival between Hispanics and non-Hispanics in our series of 363 consecutive allografts at 100 days, 1, or 3 years, although they may have been predicted to have had a slightly better prognosis based on a better Risk Group status. We did however find that payor was an important prognostic variable for outcome after the first 100 days regardless of ethnicity. Whether this is simply due to the financial toll of such a chronic illness and therapy remains to be seen, but this suggests that closer follow-up after day 100 may be of significant benefit for this subgroup of patents which may grow due to health care reform. Disclosures: No relevant conflicts of interest to declare.