ALBERT

Description: Triplet regimens combining an immunomodulatory agent, a proteasome inhibitor (PI), and a steroid are used to treat newly diagnosed and relapsed multiple myeloma (MM). Although ixazomib (Ix), an oral PI with single agent activity, can be combined with lenalidomide (LEN), patients (pts) with relapsed/refractory (R/R) MM are often LEN-refractory. Pomalidomide (POM) has single agent activity in LEN-refractory disease, and both POM and Ix also show activity in poor cytogenetic risk pts. Methods: Primary objectives: 1) determine the maximum tolerated dose (MTD) of Ix in combination with standard dose POM and dexamethasone (DEX), and 2) evaluate the anti-tumor activity of the triplet. The treatment regimen included two dose levels (3 mg and 4 mg) of Ix on days 1, 8, 15; POM 4 mg days 1-21; and DEX 40 mg days 1, 8, 15, 22, of a 28 day cycle. Eligibility: R/R MM after 〉1 prior therapy, LEN-refractory, and ≤ grade(gr) 1 peripheral neuropathy (PN). Pts were treated until progression or unacceptable toxicity. Design: Phase I study utilizing a standard 3+3 design; dose limiting toxicities (DLTs) defined during cycle 1. Results: 32 pts treated, 31 evaluable for toxicity and response. Pts received a median 4 cycles (range 1-13); median follow-up is 5.5 months (range 1.8-21.1). Six pts treated on DL1, 25 treated on DL2, the MTD/Phase II dose (P2D). Median age: 62 years (range 38-84); median time from diagnosis: 3.7 years (range 1.0-8.9); median number prior therapies: 3 (range 1-5); prior transplant: n = 23 (74%); double (LEN/Bortezomib[BOR]) or triple (LEN/BOR/Carfilzomib[CFZ]) refractory: 19 (61%). Phase I: DL1 expanded to n=6 after 1/3 pts experienced DLT (gr3 lung infection); no further DLT seen on DL 1 or 2. Adverse events (AEs) related to POM and/or Ix: ANC decrease Gr1/2 n=11 (35%), Gr3/4 n=10 (32%), platelet decrease Gr1/2 n=9 (29%), lymphocyte decrease Gr1/2 n=8 (26%), Gr3/4 n=11 (35%), PN Gr1/2 n=9 (29%), no Gr3/4. Response: Phase I and II, n=31 pts treated. ORR: 45% (6 VGPR, 8 PR); Clinical Benefit Rate (CBR): 81% (6 VGPR, 8 PR, 3 MR, 8 SD). In the pts with high risk cytogenetics (7[23%] 1q, 3[10%] 17p, 2[6%] t(4;14)) an ORR of 58% (3 VGPR, 4 PR) was seen, and the CBR was 83%. In the double or triple refractory pts, an ORR of 26% and CBR of 79% (1 VGPR, 4 PR, 3 MR, 7 SD) were observed. Conclusions: Ix/POM/DEX is a well-tolerated oral combination therapy, and responses were seen even at DL1 and in high risk patients, including those with poor-risk cytogenetics or advanced refractory disease. Disclosures Kapoor: Celgene: Research Funding; Amgen: Research Funding; Takeda: Research Funding. Kumar:Millennium: Consultancy, Research Funding; AbbVie: Research Funding; Glycomimetics: Consultancy; Sanofi: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; BMS: Consultancy; Kesios: Consultancy; Onyx: Consultancy, Research Funding; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding. Lonial:Novartis: Consultancy; BMS: Consultancy; Janssen: Consultancy; Merck: Consultancy; Celgene: Consultancy; Onyx: Consultancy; Novartis: Consultancy; BMS: Consultancy; Celgene: Consultancy; Millenium: Consultancy; Janssen: Consultancy; Onyx: Consultancy. Nathwani:Carevive Systems, Inc.: Research Funding. Forman:Mustang Therpapeutics: Other: Construct licensed by City of Hope. Berdeja:Abbvie, Acetylon, Amgen, Bluebird, BMS, Calithera, Celgene, Constellation, Curis, Epizyme, Janssen, Karyopharm, Kesios, Novartis, Onyx, Takeda, Tragara: Research Funding.

Description: Allelic variants implicated in drug absorption, distribution, metabolism, and excretion (ADME) affect drug pharmacokinetic variability and have been increasingly recognized as important factors in medical therapy. In solid organ transplantation, certain ADME genes affect the blood level of immunosuppressants as well as clinical outcomes despite rigorous traditional therapeutic drug monitoring (TDM). The influence of ADME pharmacogenetics in Hematopoietic Stem Cell Transplantation (HSCT) has not been well studied, with few publications and none reporting the effects in the setting of the tacrolimus (TAC)/ sirolimus (SIR) GVHD-preventive combination. In this exploratory pilot study, the objective was to evaluate possible associations between ADME variants with TAC/SIR blood levels and clinical outcomes in the allogeneic HSCT setting. The primary focus was on 3 ADME genes [ABCB1 (MDR1), CYP3A4, and CYP3A5] known to influence TAC/SIR outcomes in solid organ transplant. Secondarily we explored associations with other gene variants on the ADME panel. We analyzed archived DNA samples from 179 HSCT recipients on the Sequenom MassARRAY® platform. This panel is based on the PharmADME Working Group core list and interrogates 184 allelic variants and 12 copy number variants and 4 gene conversions (in 36 pharmacogenetically relevant genes). Blood levels of TAC and SIR were collected for all patients at least once weekly for the first 100 days post-transplant. For this analysis, median blood levels of TAC and SIR were obtained for the first 7 and 14 days post-transplant. Conditioning regimens consisted of fludarabine/melphalan (n=106), total body irradiation (TBI)/cyclophosphamide (n=11), TBI/etoposide (n=46) and busulfan/cyclophosphamide (n=14). All patients received TAC/SIR-based GVHD prophylaxis according to Shayani et al. (Biol Blood Marrow Transplant 2013). No azoles were used as fungal prophylaxis. Of 179 samples genotyped, 178 showed high quality data. The average call rate for these samples was 98.85% over 200 assays, with a median call rate of 100%. Of these assays, 66 variants were identified that could be evaluated for association with TAC/SIR levels and clinical outcomes; other assays were excluded due to homozygosity or 〉10% missing data. In the setting of the TAC/SIR combination, the median SIR blood level over the first 14 days post-HSCT was higher in rs2032582 (ABCB1) T carriers vs other groups (p=0.01), as was the median concentration/dose (C/D) ratio (p=0.05) (Table). We also found that the median TAC blood level over the first 7 days post-HSCT was lower in the rs776746 ( CYP3A5) AA group compared to GG or GA groups (p

Description: Ruxolitinib (Rux), a potent JAK1/2 inhibitor, is the only FDA-approved drug for treatment of primary and secondary myelofibrosis (MF). Rux has been recently approved for treatment of steroid refractory acute graft-versus-host disease (GVHD), a major cause of non-relapse mortality (NRM) after allogeneic hematopoietic cell transplant (HCT). In MF patients proceeding with transplant, Rux is typically discontinued pre-HCT. Given the therapeutic, immunologic, and anti-inflammatory properties of Rux, we hypothesized that continuous peri-HCT administration of the drug is safe and can result in better transplant outcomes in MF patients. Here, we are reporting outcomes of our single arm, single center pilot study (NCT02917096) investigating the safety and efficacy of Rux administration in patients with primary or secondary MF undergoing HCT with fludarabine (125 mg/m2) and melphalan (140 mg/m2) as reduced intensity conditioning and sirolimus/tacrolimus (target levels: 5-10ng/ml for both) as GVHD prophylaxis. This pilot study is being conducted in MF patients with the goal of extending the therapy to other hematologic malignancies. The primary objective was to identify the maximum tolerated dose and recommended phase II dose. Rux was given at 2 dose levels (DL) of 5 and 10 mg BID, starting from day -3 pre-HCT until day +30 post-HCT, then tapered off by day +33. DLs were chosen based on previous retrospective studies identifying the drug dose for treatment of GVHD. Primary endpoint was safety. Dose limiting toxicity (DLT) was defined as grade 4 neutropenia associated with fever, infection, or engraftment failure or any grade ≥3 non-hematologic toxicities over 45 days. Key secondary endpoints were grade 2-4 acute GVHD, engraftment, infection, overall survival (OS), progression-free survival (PFS), NRM, relapse and chronic GVHD. So far, we have enrolled 12 patients: 6 for DL1 arm and 6 for DL2. Median age at the time of HCT was 53 years (range: 25-66) for DL1 and 68 years (range: 56-72) for the DL2 arm. Detailed patient/transplant characteristics are listed in table 1. One-year OS, PFS and NRM for all patients were 80% (95%CI: 39-95), 68% (95%CI: 30-89) and 21% (95%CI: 3-50), respectively. All patients engrafted (n=12), with the median time to neutrophils engraftment of 19 days (range: 13-23) for DL1 and 16 days (range: 12-22) for the DL2 arm. Hematologic DLTs were not observed in patients at either dose level. At DL1, by day +60, grade ≥3 toxicities were cardiac (n=1), pulmonary (n=1) and gastrointestinal (n=1). Only one case of grade ≥3 pulmonary toxicity was observed in patients at DL2. After median follow-up time of 373 days (range: 365-744) in DL1 and 98 days (range: 30-379) for DL2, there were two deaths; one due to respiratory failure in DL1, and another due to acute GVHD at DL2. Median time of acute GVHD onset was 20 days (range: 19-35) in DL1 and 51 days (range: 26-76) in DL2. Grade III-IV acute GVHD was seen in only 1 out of 12 patients and grade 1 acute GVHD was seen in 4 patients. One patient in DL1 relapsed at 9 months and re-entered remission with post-HCT treatment. CMV infection was seen in only 1 patient at DL2. Pharmacokinetics (PK) studies were done for five patients at DL1 and all patients at DL2. PK was dose-proportional, in which doubling of the dose corresponded to the twice greater Cmax and AUC. The half-lives and oral clearances were not different between the two DLs. The Cmax and AUC were lower in our patients compared to a previously published report in healthy volunteers. Furthermore, the elimination half-life was similar to the published data, indicating that the lower drug exposures measured on the current trial is most likely due to decreased oral absorption. Lastly, GVHD biomarkers and inflammatory cytokines levels were not different between patients receiving Rux at DL1 and DL2. In conclusion, early results of this pilot study indicate that Rux administration at 10 mg BID in MF patients undergoing HCT is safe and feasible, with 100% engraftment and low rate of acute GVHD. We are currently accruing an expansion cohort of 6 patients at DL2. Results of our PK studies indicated a direct correlation between Cmax and AUC and that higher oral clearance compared to previous study is most likely due to poor GI absorption of the drug in HCT patients. More follow up is needed to see the impact of this combination on incidence of chronic GVHD. This regimen may also be useful for patients undergoing HCT for other hematologic malignancies. Disclosures Palmer: Gilead Sciences: Consultancy. Salhotra:Celgene: Other: Research Support; Kadmon Corporation: Other: Non paid consultant. Mei:Seattle Genetics, Inc.: Research Funding. Nakamura:Celgene: Other: support for an academic seminar in a university in Japan; Alexion: Other: support to a lecture at a Japan Society of Transfusion/Cellular Therapy meeting ; Merck: Membership on an entity's Board of Directors or advisory committees; Kirin Kyowa: Other: support for an academic seminar in a university in Japan.

Description: Since NHL is radiosensitive, total body irradiation (TBI) has been used as part of HDT and ASCT for NHL. However, due to short-term and long-term toxicity associated with TBI, alternative regimens have been developed. We have reported that Zevalin at conventional and high doses can be given in combination with HDT and ASCT in patients (pts) with poor-risk or relapsed B-cell NHL without additional toxicity. Given the efficacy of Zevalin in FL and DLBCL, we retrospectively evaluated the outcome of HDT and ASCT in pts with FL and DLBCL who received Zevalin-based HDT regimens (Z-ASCT) and compared to those receiving TBI-based regimen (TBI-ASCT)Between 1/2000 to 1/2006, 187 pts with FL grade I/II (30), FL grade III (20) and DLBCL (137) underwent HDT and ASCT, 62 received Z-ASCT while 125 received TBI-ASCT. For Z-ASCT, pts 〈 60 years old without prior radiotherapy (RT) received high-dose Zevalin in combination with high-dose etoposide and cyclophosphamide while pt 〉 60 yrs or with prior RT received conventional dose Zevalin plus high-dose BEAM. TBI-ASCT was performed during the same period for the following reasons: ineligible for Z-ASCT, pt refusal, physician preference and protocol closure. The pt characteristics between the two groups were similar with respect to histology, disease status, prior regimens, bulky disease, B symptoms and performance status. However, the median age was younger for TBI-ASCT (49 vs. 53, p=0.01) and there were more chemo-resistant pts in the Z-ASCT group (p=0.01). Results: At a median follow-up of 28 months (range 2–64) for Z-ASCT and 38 months (range 1–78) for TBI-ASCT, the 2-year overall survival (OS) and disease-free survival (DFS) were 91% (95% CI, 82–96) and 74% (95% CI, 64–82), respectively for Z-ASCT, and 76% (95% CI, 69–80) and 72% (95% CI, 65–77), respectively for TBI-ASCT(Figure 1). OS remained significantly different when first complete remission pts were excluded from analysis (p=0.019). Multivariate models were generated for the primary endpoints of the study (OS and DFS). The results of these analyses showed that the risk of death and/or relapse was less among the Z-ASCT pts after adjusting for baseline differences (ie. Age, performance status and chemosensitivity status at transplant), and other factors (i.e., disease status at transplant, number of previous chemotherapies) previously shown to be associated with survival/disease free survival post transplant (OS: p

Description: Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative treatment for patients (pts) with myelofibrosis (MF). Outcomes utilizing fully myeloablative conditioning regimens have been disappointing in large part due to transplant related mortality in this generally older pt population. Recently, there have been encouraging results reported with reduced intensity conditioning (RIC) regimens followed by allogeneic HCT. Most of the reports have focused on HLA matched siblings as the stem cell donors. We have treated nine patients with MF (7 idiopathic, 1 secondary to essential thrombocythemia, 1 secondary to polycythemia vera) with RIC HCT utilizing matched unrelated donors (MUD) for 7 of the 9 patients, and sibling donors for 2 patients. The median age was 54 yrs (range 46 to 68); 4 female and 5 male. (See Table) The time interval from diagnosis to HCT ranged from 8 to 156 mos (median 41 mos). By the Lille classification, 4 pts were characterized as high risk, 4 as intermediate, and 1 as low risk. All 9 pts had significant splenomegaly, and 5/9 underwent splenectomy prior to HCT. Eight of the nine pts had ≥ 1% blasts in the PB at the time of HCT; 3 pts had abnormal cytogenetics (although none had +8 or 12p-); and 4 pts had constitutional symptoms. Seven of the 9 pts were RBC transfusion dependent. The RIC regimen consisted of fludarabine (Flu) and a single dose of total body irradiation (TBI) for Pt 1, and Flu/melphalan (Mel) for the subsequent 8 pts. G-CSF primed peripheral blood stem cells (PBSC) were used for all patients, except for Pt 6 who received a total of 3 products because of graft failure. The number of CD34+ cells X 106 /kg ranged from 0.97 to 17.1 (median 2.8). Prophylaxis against graft vs. host disease (GVHD) consisted of cyclosporin/mycophenolate +/− methotrexate. Seven pts successfully engrafted WBC with ANC 〉 500 by a median of day +15 (range 10 to 21). Pt 6 never engrafted WBC, and the nadir for Pt 1 was 〉500. Five pts achieved platelet engraftment (〉25k) from 15 to 594 days (median 32), 3 pts never engrafted platelets (Pts 2,6,7), and the nadir for Pt 1 was 〉25k. At the time of the latest FISH and/or STR analysis, 8/9 pts were chimeric with 96 to 100% donor cells and/or DNA. All but 1 pt developed acute GVHD that was ≥ grade III in 4/8 pts. Four of 6 evaluable pts had extensive chronic GVHD. Six of the 9 pts are alive at the time of last contact with follow-up for the living pts ranging from 3.4 to 48.5 mos (median 11.8). The 3 deaths were from: septic shock due to primary graft failure on day +125 (Pt 6), sepsis related to severe acute GVHD on day + 51 (Pt 4), and sepsis with secondary graft failure related to severe acute GVHD on day +45 (Pt 2). The probability of overall and disease free survival was 64.8% (30.8 to 88.4%, 95% CI). These results demonstrate that MUD HCT utilizing PBSC can be an effective treatment for older pts with MF. Treatment Summary Pt Number Age/Gender Dx Donor Cell Material Regimen GVHD Prophylaxis 1 68/M MF MUD PBSC Flu/TBI CSA/MMF 2 58/F MF MUD PBSC Flu/Mel CSA/MMF 3 54/F MF MUD PBSC Flu/Mel CSA/MMF 4 64/F ET to MF Bro PBSC Flu/Mel CSA/MMF 5 46/M MF MUD PBSC Flu/Mel CSA/MMF/MTX 6 53/M MF MUD #1 BM Flu/Mel CSA/MMF/MTX 6 MUD #1 PBSC Flu/ATG 6 MUD #2 BM Flu/Mel 7 63/M PV to MF MUD PBSC Flu/Mel CSA/MMF/MTX 8 54/M MF Bro PBSC Flu/Mel CSA/MMF 9 63/F MF MUD PBSC Flu/Mel CSA/MMF/MTX

Description: The reported incidence of t-MDS/t-AML following traditional ASCT for lymphoma ranges between 0–12%. Previously identified risk factors include older age, prior alkylator therapy and use of radiation either prior to ASCT or as part of the preparative regimen. It is unclear whether novel conditioning regimens for ASCT that utilize targeted RIT with the potential to deliver higher radiation doses to the marrow are associated with a higher risk of t-MDS/t-AML. We identified a case-series of 83 pts who underwent RIT based ASCT between 06/00 and 01/06 to evaluate the incidence of t-MDS/t-AML; Forty-one pts received standard dose 90Y ibritumomab tiuxetan (0.4mci/kg: median dose 32.9 mci (range 20–40)) in combination with high dose BEAM (BCNU 450mg/m2, etoposide 800mg/m2, cytarabine 800mg/m2, melphalan 140mg/m2) and 42 pts received high dose 90Y based on dosimetry (median 70.8 mci range 36–105) in combination with etoposide 60mg/kg plus cyclophosphamide 100mg/kg. Pts were followed prospectively post ASCT with serial bone marrow biopsies approximately annually. The median age at ASCT was 54 years (range 19–78). Disease histology included diffuse large cell n=40, follicular NHL n=17, mantle cell n=21, transformed n=4, SLL n=1. Disease status at ASCT was 1st CR n=17, 1stPR n=14, induction failure n=14, 1st relapse or greater n=38. With a median follow-up of 39 months (range, 1.4–83), three patients (3.61%) have developed t-MDS/t-AML. The three pts also had associated complex chromosomal abnormalities including de1(13q), del(5q), del (20q). The median time to t-MDS/t-AML was 2.63 years (range, 1.51 – 8.41) post NHL diagnosis and 1.99 years (range, 0.56 – 5.10) post ASCT. The cumulative incidences of t-MDS/t-AML at 1 and 2 years were 1.20% (95%CI, 0.17– 8.1%) and 2.60% (95%CI 0.64–9.9%). None of the potential risk factors including age(〉50 at ASCT) (p=0.33), prior radiotherapy (p=0.99), number of prior regimens (p=0.5) and 90Y dose (p=0.99) were statistically significant by univariate analysis. As 82/83 pts had received prior alkylator therapy this was not analyzed as a separate risk factor. Two year overall survival for the entire cohort is 90% (95%CI 83–95). Although the follow up is relatively short, the incidence of t-MDS/t-AML is consistent with our previous institutional experience in ASCT patients who received non-RIT based conditioning (Krishnan et al. Blood 2000) and with the 2.5% incidence of t-MDS/t-AML observed in pts receiving 90Y in registration and compassionate use trials (Czuczman et al JCO 2007 in press). In conclusion RIT based conditioning does not appear to confer an increased risk of t-MDS/t-AML above what has been previously reported with traditional ASCT preparative regimens. Incidence of t-MDS/t-AML Incidence of t-MDS/t-AML

Description: Background: 90Y ibritumomab tiuxetan (Zevalin®) has been shown to be an effective therapy for patients with both follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). We have previously reported the feasibility of adding high-dose 90Y ibritumomab tiuxetan to high-dose VP-16 and CY followed by AHSCT without additional toxicity. Herein, we reported longer follow-up results of this high-dose regimen. Methods: Patients undergo dosimetry study (day-21) with 5 mCi 111In-ibritumomab tiuxetan following 250 mg/m2of rituximab, followed by 90Y ibritumomab tiuxetan (day-14) to deliver a target dose of 1000 cGy to highest normal organ and then VP-16 (day-4), and CY (day-2). Bone marrow biopsy is done on day-7 to estimate the radiation dose. Stem cells are re-infused when the radiation dose to re-infused stem cells is estimated to be 500/μl and platelet〉20,000/μl was 10 days (range 8–17) and 12.5days (range 8–123), respectively. The transplant-related mortality (TRM) at day 100 was 2%. There were 8 deaths due to relapse (3), second malignancies (2), graft failure (1), alcohol induced liver failure (1) and sudden death (1). Secondary malignancies occurred in 3 (7%) heavily pre-treated FL: pancreatic cancer at 3.8 yrs, acute myeloid leukemia at 5 years and one with abnormal chromosome but without morphologic evidence of MDS at 1 year. At a median follow-up of 55 months (range, 25–84) for the surviving patients, the 4-year estimated overall survival (OS) and disease-free survival (DFS) is 81% (95% CI, 67–89%), and 65% (95% CI, 54–74%), respectively (figure.1). The 4-year estimated DFS for FL, DLBCL and MCL is 71% (95% CI, 51–85%), 67% (95% CI, 49–79%) and 47% (95% CI, 29–63%), respectively. Conclusion: Our long-term results suggest that the combination of high-dose 90Y ibritumomab tiuxetan and high-dose VP-16 and CY is an effective high-dose regimen, especially for FL and DLBCL. Short term toxicities appear comparable to other conventional high-dose regimens. Further prospective studies are ongoing to determine the curability and long term toxicities of this preparative regimen. Overall Survival and Disease-Free Survival Sample Size: 42 patients Treated with RIT in 98153 Run Date: August 15, 2007 Overall Survival and Disease-Free Survival Sample Size: 42 patients Treated with RIT in 98153 Run Date: August 15, 2007

Description: The majority of patients (pts) with PTCL present with advanced stage with high-intermediate or high-risk IPI and their prognosis are poor with current standard induction chemotherapy. HDT followed by ASCT has been shown to be effective therapy for relapsed and refractory PTCL, although the outcomes of transplant varied depending upon the histologic subtype, disease status and IPI at transplant. Given the poor outcome with current treatment approach, HDT and ASCT as consolidative therapy during first remission are being investigated in pts with PTCL. We performed retrospective analysis of all pts with T-cell, NK cell and null cell lymphomas who underwent HDT and ASCT between 2/1991 to 6/2005. We analyze the outcome based on disease status at transplant and the subset of PTCL. There were 57 pts (35 male, 22 female) with a median age of 45 years (range 5–68). Histology included 6 (10.5%) angioimmunoblastic T-cell lymphoma (AILD), 26(46%) Anaplastic large cell lymphoma (ALCL), 22 (39%) PTCL, unspecified (NOS), 1 panniculitis like T-cell, 1 NK-T, and 1 adult T-cell lymphoma. Twelve (21%) were transplanted during first remission; 11 were high intermediate-high risk IPI, and 1 for histology NK-T. Twenty-eight (49%) were transplanted during relapse or ≥second remission and 17 (30% ) induction failure or primary refractory disease. Twenty-one (37%) had advanced stage III-IV at transplant. The median number of chemotherapy regimens was 2 (range 1–5). For ALCL subtype, 9 were anaplastic lymphoma kinase (ALK) positive, 9 ALK negative, 8 unknown. Results: At a median follow-up of 22 months (range 0.5–179), 29 are alive in remission, 25 relapsed and 3 died from transplant related mortality. One patient developed therapy induced myelodysplasia at two years post ASCT and is alive in remission after allogeneic stem cell transplant. The 2 years overall survival (OS) and disease-free survival (DFS) for the whole group were 53% (95% CI 46–60), and 45% (95% CI 39–50), respectively. The OS and DFS were significantly better for pts. who were transplanted in first complete remission (Figure1). The 2-year OS and DFS were both 83% (95% CI 55–94) for pts. transplanted in first remission compared to 45% (95% CI 38–52%, p=0.03) and 35% (95% CI 30–40, p= 0.006), respectively for those transplanted beyond first remission. Univariate models showed that the risk of death and/or relapse was significantly less among the pts. transplanted in first complete remission (OS, DFS and time to relapse: p 〈 0.05). When compared the outcome among the 3 subtypes, AILD, ALCL and PTCL NOS, there were no significant differences in survival or relapse among the 3 groups. Conclusion: our results suggest that HDT and ASCT can improve prognosis and survival of pts. with PTCL. The outcome of ASCT is best when performed during first complete remission. The role of HDT and ASCT during first remission should be further investigated in larger multi-center studies. In contrast to other reports, the prognosis of pts. with ALCL is similar to other PTCLs. Disease-Free Survival: ASCT for PTCL
 Startified by Disease Status: 1CR (n=12) vs. 〉 1CR (n=45) Disease-Free Survival: ASCT for PTCL
 Startified by Disease Status: 1CR (n=12) vs. 〉 1CR (n=45)

Description: Brentuximab vedotin induces an overall response rate of 75% in patients with relapsed/refractory Hodgkin lymphoma, but its impact on future allogeneic transplantation (allo-HCT) is not known. We retrospectively examined the records of 18 patients with relapsed/refractory Hodgkin lymphoma who were treated on brentuximab vedotin clinical trials to evaluate the efficacy and safety of subsequent reduced-intensity allo-HCT. Seventeen patients had previous autologous transplant; 6 were in complete remission, and 8 were in partial remission before allo-HCT with 12 grafts from unrelated or mismatched donors. The 1-year overall survival was 100%, progression-free survival was 92.3%, and nonrelapse mortality was 0% (median follow-up, 14 months). The incidence of acute GVHD was 27.8% and chronic GVHD was 56.3%. Brentuximab vedotin before reduced-intensity allo-HCT does not appear to adversely affect engraftment, GVHD, or survival and may provide sufficient disease control to enable reduced-intensity allo-HCT.

Description: Current CGVHD prognostic and staging systems are still undergoing development and have identified plt count; CGVHD types progressive(P), quiescent(Q), de novo(DN); KPS, and GI involvement as significant risk factors affecting outcome. A simple reproducible staging system such as used for AGVHD to apply in clinical trials is still lacking. We evaluated whether the PSE dose required to control CGVHD at 3 months from diagnosis would have a prognostic effect on survival and in and of itself serve as a criteria for secondary intervention or investigational therapy. We hypothesized that by 3 months from start of treatment patients would be on the lowest dose dictated by medical necessity rather than by physician driven dose preference. A retrospective analysis of charts from 109 patients diagnosed with CGVHD between 6/2000 and 6/2003 was done. Data collected included age, donor type(mud/sib), plt count, CGVHD type(P/Q/DN), KPS, GI involvement. Outcome analysis included survival and cause of death. PSE dose was calculated in mg/kg at 3 months from first diagnosis of CGVHD. With a median follow up of 47.2 months(range 6.6–67.2) relapse censored survival of patients on a 3 month PSE dose of more than .3 mg/kg was 53% compared to all lower doses 86%(P.03). In a univariate analysis only PSE dose (P .05) and KPS (P