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• HCT outcomes in ALL patients after Flu/Mel conditioning & Tac/Siro GVHD prophylaxis. • OS and PFS at 4 years were 58% and 44%, respectively. • Cumulative incidences of relapse and NRM at 4 years were 34% and 22%, respectively. • Patients with Philadelphia chromosome–positive (Ph+) status had lower relapse. • This regimen had favorable outcomes in adult ALL patients with Ph+ status. Acute lymphoblastic leukemia (ALL) is associated with poor survival in older adults, and allogeneic hematopoietic cell transplant (HCT) with reduced-intensity conditioning (RIC) has been an increasingly used strategy in this population. At City of Hope we conducted a retrospective analysis of 72 patients who underwent allogeneic HCT with fludarabine and melphalan (FluMel) as the conditioning regimen between 2005 and 2018, from either a matched sibling or fully matched unrelated donor while in complete remission. Tacrolimus and sirolimus (T/S) were used as graft-versus-host disease (GVHD) prophylaxis. Overall survival and progression-free survival at 4 years post-HCT were 58% and 44%, respectively. The cumulative incidences of relapse/progression and nonrelapse mortality at 4 years were 34% and 22%, respectively. Patients with Philadelphia chromosome–positive (Ph+) ALL had a significantly lower cumulative incidence of relapse/progression (20% versus 48% for patients with Ph-negative status, P =.007). In conclusion, RIC HCT with FluMel conditioning and T/S GVHD prophylaxis was associated with favorable outcomes in patients with Ph+ ALL and should be considered as a viable consolidative therapy for adult patients with ALL. [ABSTRACT FROM AUTHOR]

ABSTRACT The current standard of care for patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) is high-dose conditioning followed by autologous stem cell transplantation (ASCT). For some patients (ie, those with highest-risk disease, insufficient stem cell numbers after mobilization, or bone marrow involvement) allogeneic hematopoietic cell transplantation (alloHCT) offers the potential for cure. However, the majority of patients undergoing alloHCT receive reduced-intensity conditioning as a preparative regimen, and studies assessing outcomes of patients after alloHCT with myeloablative conditioning are limited. In this retrospective study, we reviewed outcomes of 22 patients with recurrent and refractory NHL who underwent alloHCT with myeloablative BEAM conditioning and received tacrolimus/sirolimus as graft-versus-host disease (GVHD) prophylaxis at City of Hope between 2005 and 2018. With a median follow-up of 2.6 years (range, 1.0 to 11.2 years), the probabilities of 2-year overall survival and event-free survival were 58.3% (95% confidence interval [CI], 35.0% to 75.8%) and 45.5% (95% CI, 24.4% to 64.3%), respectively. The cumulative incidence of grade II to IV acute GVHD was 45.5% (95% CI, 23.8% to 64.9%), with only 1 patient developing grade IV acute GVHD. However, chronic GVHD was seen in 55% of the patients (n = 12). Of the 22 eligible patients, 2 had undergone previous ASCT and 2 had undergone previous alloHCT. Both patients with previous ASCT developed severe regimen-related toxicity. Patients who underwent alloHCT with chemorefractory disease had lower survival rates, with 1-year OS and EFS of 44.4% and 33.0%, respectively. In conclusion, alloHCT with a BEAM preparative regimen and tacrolimus/sirolimus-based GVHD should be considered as an alternative option for patients with highest-risk lymphoma whose outcomes are expectedly poor after ASCT. [ABSTRACT FROM AUTHOR]

High-dose therapy followed by autologous stem cell transplantation (ASCT) can improve outcomes for mantle cell lymphoma (MCL) but is associated with a high incidence of relapse. A retrospective study of 191 MCL patients who underwent ASCT at City of Hope was performed to examine prognostic factors for outcomes after ASCT. For all patients the 5-year overall survival (OS) was 71% (95% confidence interval [CI], 63% to 77%) and progression-free survival (PFS) was 53% (95% CI, 45% to 60%). The 5-year cumulative incidence of relapse was 41% (95% CI, 34% to 48%) with a continuous pattern of relapse events occurring at a median of 2.1 years (range, .2 to 13.4) after ASCT. In multivariate analysis, post-transplant maintenance rituximab was the factor most significantly associated with both OS (relative risk [RR], .17; 95% CI, .07 to .38) and PFS (RR, .25; 95% CI, .14 to .44). For the subset of patients who had positron emission tomography (PET) data available and were in a PET-negative first complete remission at ASCT (n = 105), maintenance rituximab was significantly associated with superior OS (RR, .17; 95% CI, .05 to .59) and PFS (RR, .20; 95% CI, .09 to .43). These results support a benefit with maintenance rituximab for all MCL patients treated with ASCT. [ABSTRACT FROM AUTHOR]

• Eculizumab given immediately post-allogeneic hematopoietic cell transplantation (HCT) as thrombosis prophylaxis is feasible. • Post-HCT eculizumab does not appear to delay engraftment. • Post-HCT eculizumab does not seem to increase infections due to encapsulated bacteria. Paroxysmal nocturnal hemoglobinuria (PNH) is frequently seen in the context of other aplastic anemia and myelodysplastic syndromes and is associated with hemolysis and increased thromboembolic events. Allogeneic hematopoietic stem cell transplantation (alloHCT) is the sole curative treatment but is associated with significant morbidity. The terminal complement inhibitor eculizumab reduces hemolysis and thromboembolic events and is the sole Food and Drug Administration-approved therapy for PNH. Prophylactic administration of this agent in the early post-transplantation setting to prevent hemolysis and thrombosis has not been described in the literature. We describe our institutional experience of 8 patients with PNH who underwent alloHCT and who received at least 1 dose of eculizumab within 30 days of alloHCT for prevention of thrombosis and hemolysis. One patient with underlying aplastic anemia who received bone marrow stem cells failed to engraft. Another patient experienced steroid-refractory grade IV acute graft-versus-host disease and died of a fungal infection. The other patients engrafted well; no hemolysis, thrombotic events, or infections associated with encapsulated bacteria occurred in any of the 8 patients. [ABSTRACT FROM AUTHOR]

Transformation from indolent non-Hodgkin lymphoma (NHL) to diffuse large B cell lymphoma (DLBCL) has historically been associated with a poor prognosis. A small series of autologous stem cell transplantation (ASCT) studies using conventional conditioning regimens has demonstrated durable progression-free survival (PFS) rates ranging from 25% to 47%, but data in the rituximab era are lacking. Here we report the results of a multicenter retrospective trial evaluating ASCT in patients with transformed lymphoma using the Z-BEAM conditioning regimen, which combines yttrium-90–labeled ibritumomab tiuxetan (Zevalin) with high-dose BEAM (carmustine, etoposide, cytarabine, melphalan) chemotherapy. Sixty-three patients from 4 institutions were treated between 2003 and 2011. Histological confirmation of transformation was required and defined as a diagnosis of DLBCL in patients with either a prior history or concomitant diagnosis of low-grade B cell NHL. Median patient age at ASCT was 59.5 years, median number of prior regimens was 2, and all patients were exposed to rituximab. Disease status at ASCT was as follows: first complete remission (CR) (n = 30), first partial remission (n = 11), first relapse (n = 14), and at least second CR (n = 8). The median time from diagnosis of histological transformation to ASCT was 7.5 months (range, 2.8 to 116). Two-year nonrelapse mortality was 0%. Median follow-up for living patients was 28 months (range, 5 to 103). Two-year PFS was 68% (95% confidence interval, 58% to 75%), and overall survival was 90% (95% confidence interval, 80% to 95%). In conclusion, the Z-BEAM conditioning regimen for ASCT is well tolerated by patients with transformed lymphoma and demonstrates encouraging clinical outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies demonstrate an increased risk of second primary malignancies (SPMs) in patients with multiple myeloma (MM) receiving maintenance lenalidomide after autologous stem cell transplantation (ASCT). We explored the possibility of other risk factors driving post-ASCT SPMs in patients with MM through analysis of our large transplantation database in conjunction with our Long-Term Follow-Up Program. We conducted a retrospective cohort study of 841 consecutive patients with MM who underwent ASCT at City of Hope between 1989 and 2009, as well as a nested case-control analysis evaluating the role of all therapeutic exposures before, during, and after ASCT. Median duration of follow-up for the entire cohort was 3.4 years (range, 0.3-19.9 years). Sixty cases with a total of 70 SPMs were identified. The overall cumulative incidence of SPMs was 7.4% at 5 years and 15.9% at 10 years when nonmelanoma skin cancers (NMSCs) were included and 5.3% at 5 years and 11.2% at 10 years when NMSCs were excluded. Multivariate analysis of the entire cohort revealed associations of both older age (≥55 years; relative risk, 2.3; P < .004) and race (non-Hispanic white; relative risk, 2.4; P = .01) with an increased risk of SPM. Furthermore, thalidomide exposure demonstrated a trend toward increased risk (odds ratio, 3.5; P = .15); however, an insufficient number of patients were treated with lenalidomide to allow us to accurately assess the risk of this agent. Exclusion of NMSCs retained the association with these variables but was accompanied by loss of statistical significance. This large single-institution analysis identified associations between race and older age and increased risk of developing SPM. The trend toward increased risk with thalidomide exposure suggests a class effect from immunomodulatory drugs that might not be restricted to lenalidomide. [Copyright &y& Elsevier]

Purpose: Approximately 50% of patients with relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) will relapse post-autologous stem cell transplant (ASCT), and the role of salvage therapy is not well defined. We examined radiation therapy (RT) as salvage treatment in this patient population.Materials and Methods: A retrospective review of patients with DLBCL who had an ASCT during 2004 to 2016 and subsequently relapsed was performed. Clinical and pathologic characteristics were collected, including detailed information regarding post-ASCT treatment. Response rates were tabulated and survival analysis was performed, stratified by salvage modality.Results: A total of 165 patients with R/R DLBCL who relapsed after ASCT were identified; 91 of these patients received salvage chemotherapy as their first line of relapse therapy, and 14 received salvage radiation. Median salvage RT dose was 36 Gy (range, 24-50). The objective response rate with salvage chemotherapy and RT was 53.0% and 78.5%, respectively (P = 0.07), and the complete response rate was 31.3% and 57.1%, respectively (P = 0.06). Median follow-up among living patients was 48.9 months (range, 4.8-136.17). Among patients with one site of relapse post-ASCT, median overall survival in patients who received salvage RT was significantly improved (P = 0.008) relative to chemotherapy (not reached [95% confidence interval {CI}, 8.4-not reached] versus 10.0 months [95% CI, 5.3-17.8]). Median progression-free survival in patients who received salvage RT was not significantly different (P = 0.16) relative to chemotherapy (8.4 months [95% CI, 2.5-47.7] versus 3.9 months [95% CI, 2.4-8.5]).Conclusions: Patients who received RT as first salvage therapy post-ASCT, particularly with localized disease, had favorable oncologic outcomes. Future studies are needed to understand which patients with R/R DLBCL who relapse after ASCT may benefit from early salvage RT versus chemotherapy. [ABSTRACT FROM AUTHOR]

• The combination of hypomethylating agents with the selective Bcl-2 inhibitor venetoclax (VEN-HMA) as a bridge to allogeneic hematopoietic cell transplantation (alloHCT) is associated with favorable HCT outcomes. • VEN-HMA could allow more patients of older age to proceed to potentially curative alloHCT. • AlloHCT outcomes are particularly good in patients who undergo HCT in complete remission after VEN-HMA therapy. The combination of hypomethylating agents with the selective Bcl-2 inhibitor venetoclax (HMA-VEN) has emerged as a highly active regimen in patients with acute myelogenous leukemia (AML) in both the upfront and relapsed/refractory (r/r) settings. We report our early experience with a cohort of patients who were able to proceed to allogeneic hematopoietic cell transplantation (alloHCT) after HMA-VEN therapy. Thirty-two patients with AML (19 r/r and 13 de novo) with a median age of 62 years underwent alloHCT after HMA-VEN therapy. Twenty-two (68.8%) were in complete remission (CR)/CR with incomplete count recovery at time of HCT. With a median follow up of 14.4 months, the 1-year overall survival (OS) was 62.5%, and disease-free survival was 43.8%. The 1-year nonrelapse mortality rate was 18.8%, and the cumulative incidence of relapse was 37.5%. Among patients who underwent alloHCT in CR, the 1-year OS was 77.3%, and the cumulative incidence of nonrelapse mortality was 9.1%. The cumulative incidence of grade II-IV acute graft-versus-host disease was 43.8%. We conclude that alloHCT after HMA-VEN is therapy associated with favorable allogeneic HCT outcomes in newly diagnosed older patients with AML, as well as those with r/r AML. [ABSTRACT FROM AUTHOR]

• HCT outcomes were analyzed in r/r ALL patients, after salvage with blinatumomab. • Pre-HCT blinatumomab was given for morphologic (n = 24) or MRD-positive disease (n = 11). • No unusual toxicities or delayed engraftment was observed post-HCT. • Subgroup analysis (MRD/cytogenetics) showed no significant difference in survival. • Blinatumomab may be considered as a safe and effective salvage therapy pre-HCT. Historically, outcomes of adult patients with relapsed acute lymphoblastic leukemia (ALL) who fail to enter remission with conventional chemotherapy are very poor. Blinatumomab, a bispecific CD3/CD19 antibody, has shown remarkable activity in relapsed/refractory (r/r) ALL. Although allogeneic hematopoietic cell transplant (HCT) is the recommended consolidation therapy for patients with r/r ALL who respond to salvage therapy, HCT and toxicity outcomes for those who received blinatumomab salvage and HCT remain largely unknown. We treated 89 patients with r/r ALL with blinatumomab, of whom 43 patients (48%) achieved remission. Here we describe our single-center experience in the subset of patients who responded to blinatumomab salvage therapy for eradication of either gross (n = 24) or minimal residual disease (n = 11) before HCT. Overall survival at 1 and 2 years after allogeneic HCT was 77% and 52%, respectively. Leukemia-free survival at 1 and 2 years were 65% and 40%, respectively. Additionally, with blinatumomab administration pre-HCT, no unusual toxicities such as delayed neutrophil/platelet engraftment or graft failure were observed. Acute grades II to IV graft-versus-host disease (GVHD) at day +100 post-HCT was at 43% and 2-year chronic GVHD was 36%, both comparable with historic control subjects. Finally, results of our subset analysis based on pre-HCT minimal residual disease (MRD) status indicated no significant difference in survival outcomes among patients undergoing transplant in MRD-negative status and the entire cohort. In conclusion, based on results of this study, blinatumomab may be considered as a safe and effective agent for r/r ALL patients before HCT. [ABSTRACT FROM AUTHOR]

• Fractionated total body irradiation-based myeloablative conditioning is well tolerated in young adults with acute myelogenous leukemia. • Tacrolimus/sirolimus graft-versus-host disease (GVHD) prophylaxis was associated with high rates of chronic GVHD (71%). • GVHD-free, relapse free survival at 2 years was low (39%), indicating the dynamic nature of chronic GVHD. • This regimen was associated with a low risk of long-term toxicities. Cyclophosphamide (Cy)/etoposide combined with fractionated total body irradiation (FTBI) or i.v. busulfan (Bu) has been the main conditioning regimens for allogeneic hematopoietic cell transplantation (alloHCT) for young patients with acute myelogenous leukemia (AML) eligible for a myeloablative conditioning (MAC) regimen. Recent data has suggested that i.v. Bu could be the preferred myeloablative regimen in patients with myeloid malignancies. However, Bu-based regimens are associated with higher rates of sinusoidal obstruction syndrome. Here we report long-term survival outcomes of patients with AML receiving FTBI combined with Cy or etoposide before undergoing alloHCT at City of Hope (COH). We obtained a retrospective review of a prospectively maintained institutional registry of clinical outcomes in 167 patients (median age, 41 years; range, 18 to 57 years) with AML in first or second complete remission who underwent alloHCT at COH between 2005 and 2015. Eligible patients received a MAC regimen with FTBI (1320 cGy) and Cy (120 mg/kg) for unrelated donor transplantation or etoposide (60 mg/kg) for related donor transplantation. Graft-versus-host disease (GVHD) prophylaxis was provided with tacrolimus and sirolimus. In this retrospective study, 6-year overall survival was 60% and nonrelapse mortality was 15%. The GRFS rate was 45% at 1 year and 39% at 2 years. We also describe late metabolic effects and report the cumulative incidence of secondary malignancies (9.5%). Overall, in this young adult patient population, our results compare favorably to chemotherapy-based (i.v. Bu) conditioning regimens without significant long-term toxicity arising from TBI-based regimens. [ABSTRACT FROM AUTHOR]

Clonal hematopoiesis (CH), characterized by the accumulation of acquired somatic mutations in the blood, is associated with an elevated risk of aging-related diseases and premature mortality in non-cancer populations. Patients who undergo autologous hematopoietic cell transplantation (HCT) are also at high risk of premature onset of aging-related conditions. Therefore, we examined the association between pretreatment CH and late-occurring (≥1 year) nonrelapse mortality (NRM) after HCT. We evaluated pathogenic and likely pathogenic CH variants (PVs) in 10 patients who developed NRM after HCT and in 29 HCT recipient controls matched by age at HCT ± 2 years (median, 64.6 years; range, 38.5 to 74.7 years), sex (79.5% male), diagnosis (61.5% with non-Hodgkin lymphoma, 18.0% with Hodgkin lymphoma, and 20.5% with multiple myeloma), and duration of follow-up. We analyzed mobilized hematopoietic stem cell DNA in samples collected before HCT using a custom panel of amplicons covering the coding exons of 79 myeloid-related genes associated with CH. PVs with allele fractions >2% were used for analyses. Cases were significantly more likely than controls to have CH (70% versus 24.1%; P =.002), to have ≥2 unique PVs (60% versus 6.9%; P <.001), and to have PVs with allelic fractions ≥10% (40% versus 3.4%; P =.003). Here we provide preliminary evidence of an association between pre-HCT CH and NRM after HCT independent of chronologic age. Integration of CH analyses may improve the accuracy of existing pre-HCT risk prediction models, setting the stage for personalized risk assessment strategies and targeted treatments to optimally prevent or manage late complications associated with HCT. • Pretransplantation clonal hematopoiesis (CH) is associated with nonrelapse mortality. • The association appears to be independent of chronologic age. • Studies are needed to determine the utility of CH in transplantation risk prediction. [ABSTRACT FROM AUTHOR]

Highlights • Semiablative melphalan-based conditioning regimen is safe for eligible elderly patients. • Rapid hematopoietic reconstitution after this regimen led to favorable survival outcomes. • Morbidity indicators (infection, etc.) were similar to younger patients undergoing same regimen. • This regimen is effective with promising relapse rate and minimal toxicities for patients > 70. Abstract Allogeneic hematopoietic stem cell transplantation (alloHCT) is offered increasingly to elderly patients with hematologic malignancies. However, outcome data in those who are 70 years or older are limited, and no standard conditioning regimen has been established for this population. In this retrospective study we evaluated the outcome of 53 consecutive patients aged 70 years and older who underwent alloHCT with melphalan-based reduced-intensity conditioning (RIC) at City of Hope. Engraftment was prompt, with median time to neutrophil engraftment of 15 days. More than 95% of patients achieved complete donor chimerism within 6 weeks from HCT, consistent with the "semiablative" nature of this regimen. With a median follow-up of 31.1 months, the 2-year overall survival (OS), progression-free survival (PFS), and nonrelapse mortality (NRM) were 68.9%, 63.8%, and 17.0%, respectively. Cumulative incidence of relapse at 1 and 2 years was 17.0% and 19.3%, respectively. One hundred–day cumulative incidence of grades II to IV acute graft-versus-host disease was 37.7% (grades III to IV, 18.9%), and 2-year cumulative incidence of chronic graft-versus-host disease was 61.9% (extensive, 45.9%). The only significant predictor for poor OS was high/very high disease risk index. Transplant-related complications and morbidities observed here did not differ from the commonly expected in younger patients treated with RIC. In conclusion, alloHCT with a melphalan-based conditioning regimen is associated with acceptable toxicities and NRM, lower incidence of relapse, and favorable OS and PFS in patients aged 70 years or older. [ABSTRACT FROM AUTHOR]

Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are associated with resistance to frontline and salvage immunochemotherapy, as well as autologous stem cell transplantation (SCT). We hypothesized that allogeneic SCT (alloSCT) could overcome the chemoresistance associated with DEL/DHL. We retrospectively studied the impact of DEL/DHL status in a multicenter cohort of patients who underwent alloSCT for relapsed/refractory (rel/ref) aggressive B cell non-Hodgkin lymphoma (B-NHL). Seventy-eight patients transplanted at 3 centers in whom tumor tissue was available for immunohistochemistry and fluorescence in situ hybridization were enrolled; 47% had DEL and 13% had DHL. There were no significant differences in 4-year progression-free (PFS) or overall survival (OS) between patients with DEL compared with patients without DEL (PFS 30% versus 39%, P  = .24; OS 31% versus 49%, P  = .17) or between patients with DHL compared with patients without DHL (PFS 40% versus 34%, P  = .62; OS 50% versus 38%, P  = .46). The lack of association between DEL or DHL and outcome was confirmed in multivariable models, although inadequate sample size may have limited our ability to detect significant differences. In our cohort alloSCT produced durable remissions in patients with rel/ref aggressive B-NHL irrespective of DEL and DHL status, justifying its consideration in the treatment of patients with rel/ref DEL/DHL. [ABSTRACT FROM AUTHOR]

Background Several organizations have developed frameworks to systematically assess the value of new drugs. These organizations include the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), the Institute for Clinical and Economic Review (ICER), and the National Comprehensive Cancer Network (NCCN). Objectives To understand the extent to which these four tools can facilitate value-based treatment decisions in oncology. Methods In this pilot study, eight panelists conducted value assessments of five advanced lung cancer drugs using the ASCO, ESMO, and ICER frameworks. The panelists received instructions and published clinical data required to complete the assessments. Published NCCN framework scores were abstracted. The Kendall's W coefficient was used to measure convergent validity among the four frameworks. Intraclass correlation coefficients were used to measure inter-rater reliability among the ASCO, ESMO, and ICER frameworks. Sensitivity analyses were conducted. Results Drugs were ranked similarly by the four frameworks, with Kendall's W of 0.703 ( P = 0.006) across all the four frameworks. Pairwise, Kendall's W was the highest for ESMO-ICER ( W = 0.974; P = 0.007) and ASCO-NCCN ( W = 0.944; P = 0.022) and the lowest for ICER-NCCN ( W = 0.647; P = 0.315) and ESMO-NCCN ( W = 0.611; P = 0.360). Intraclass correlation coefficients (confidence interval [CI]) for the ASCO, ESMO, and ICER frameworks were 0.786 (95% CI 0.517–0.970), 0.804 (95% CI 0.545–0.973), and 0.281 (95% CI 0.055–0.799), respectively. When scores were rescaled to 0 to 100, the ICER framework provided the narrowest band of scores. Conclusions The ASCO, ESMO, ICER, and NCCN frameworks demonstrated convergent validity, despite differences in conceptual approaches used. The ASCO inter-rater reliability was high, although potentially at the cost of user burden. The ICER inter-rater reliability was poor, possibly because of its failure to distinguish differential value among the sample of drugs tested. Refinements of all frameworks should continue on the basis of further testing and stakeholder feedback. [ABSTRACT FROM AUTHOR]

Identification of anti-apoptotic properties of the Bcl2 protein has offered novel treatment options in many malignancies including AML. Venetoclax, a Bcl2 inhibitor, has shown promising results as upfront therapy in elderly patients (pts) and relapse/refractory (R/R) AML, when combined with hypomethylating agents (HMA). Yet, due to the high relapse risk, allogenic HCT remains as the only curative option for these high risk populations. To date, outcomes of HCT after prior therapy with Venetoclax + HMA have not been described. Also, as Venetoclax induces aplasia of antigen presenting cells expressing Bcl2, we hypothesized that pre-HCT treatment with venetoclax may be associated with a lower risk for GvHD. We retrospectively analyzed 26 consecutive AML pts who underwent HCT at our institution from 2016 to 2018 with final line of systemic therapy of venetoclax + HMA. Pts were not eligible for upfront standard induction chemotherapy (n=8) or had R/R disease (n=18). Fifteen pts received ≥2 lines of therapy and 3 had previous HCT. CR/CRi was achieved in 62% (n=16), of which 3 pts had minimal residual disease and the rest (n=10) had persistent disease prior to HCT. Donors were matched related (n=8), matched unrelated (n=16), or haploidentical (n=2). Conditioning regimen was myeloablative (38.5%) or reduced intensity (61.5%). Most pts (n=24, 92.3%) received PBMCs as the graft source. Tacrolimus/Sirolimus (Tac/Sir) was administered in most pts (n=20, 77%) for GvHD prophylaxis. Descriptive statistics were used for baseline characteristics. Kaplan-Meier and cumulative incidence curves were constructed for overall survival (OS), progression-free survival (PFS), relapse, none-relapse mortality (NRM), and aGvHD. Median age at the time of HCT was 59 years (range: 18-73). Median time to neutrophil and platelet engraftment were 17 days (range: 14-20) and 20 days (range: 16-61), respectively. With a median follow up of 4.5 months (range: 1.4-18.6), 6 months relapse rate was 12% (95% CI: 0.16-0.54) and 100 day NRM was 4% (95% CI: 0.02-0.34). Grade II-IV aGvHD at 100 days was noted in 34% (95% CI: 0.15-0.51). One-year OS and PFS for all pts were 72% (95% CI: 0.43-0.88) and 40% (95% CI: 0.16-0.63), respectively. For patients in CR at the time of HCT, 1-year OS was 80% (95%CI: 37-95) and PFS was 38% (95%CI: 0.08-0.69) (Fig 1). Only one patient who had been treated with three lines of systemic therapy prior to HCT experienced veno-occlusive disease. Thus, administration of Venetoclax-based salvage regimen as a bridge to HCT is safe with no added immediate toxicities post-HCT. Our early outcome data are promising for this otherwise high-risk population. Our data also justify further studies on the role and impact of Venetoclax and its anti-Bcl2 properties as a component of the conditioning regimen or as post-HCT maintenance. [ABSTRACT FROM AUTHOR]

Historically, outcomes of adult patients (pts) with ALL who fail to enter remission with standard induction chemotherapy are very poor. Blinatumomab, a bispecific CD3/CD19 antibody, has shown remarkable activity in relapsed/refractory (r/r) ALL. While allogeneic HCT is the recommended consolidation therapy for r/r ALL pts who respond to salvage therapy, HCT and toxicity outcomes for those who received blinatumomab salvage and HCT remains largely unknown. A retrospective review of r/r ALL pts medical records, who received blinatumomab salvage therapy from 2012 to 2018 at our institution was obtained. Only pts who responded to blinatumomab and underwent HCT were included (n=29). Kaplan-Meier curves and the log-rank test were used to evaluate the overall survival (OS) and progression-free survival (PFS). Cumulative incidence (CI) curves and the Gray test were used to examine the differences in relapse rates and non-relapse mortality (NRM). The median age at the time of HCT was 29 years (range: 19-65), and 8 pts (28%) were over 50 years old. HCT was done in complete remission- (CR)-1 (n=14, 48%) or ≥CR-2, with 2pts receiving blinatumomab salvage after relapse from a prior HCT. Pts received transplant from a matched sibling (n=11), matched unrelated (n= 12), haploidentical donor (n=5) or double umbilical cord blood (n=1) after myeloablative (n=20, including TBI+VP16, n=15) or reduced intensity (n=9) conditioning. The graft source was PBSCs in 25 pts (86.2%). Graft-versus-host disease (GVHD) prophylaxis was tacrolimus/sirolimus-based (n=19, 66%), and post-HCT cyclophosphamide (n=5, 17%) for haploidentical transplants. At the time of salvage therapy initiation, pts had either gross residual (n=22) or minimal residual disease (MRD+) (n=7). Negative MRD remission status was achieved prior to HCT in 15 pts, including those who were MRD+ before blinatumomab salvage. With a median follow up of 21.7 months (mo) (range: 1.1-55.7) for all pts and 6.4 mo for surviving pts, the 1-year OS and PFS were 72.8% (95% CI: 48.5-87.0) and 63.0% (95% CI: 38.8-79.8), respectively (Fig 1). Causes of death post-HCT were GVHD (n=3); NRM (n=4; 3 sepsis and 1 regimen related toxicity) and relapse (n=3). The CI of relapse at 1 and 2 years were 24.9% (95% CI: 8.6-45.3) and 45.9%, (95% CI: 20.3-68.3), respectively. NRM at 100 days was 6.9% (95% CI: 1.2-20.0) and at 12 mo was 12.1% (95% CI: 2.7-29.0). The incidence of grades 3-4 acute GVHD and extensive chronic GVHD at 24 mo were 25.0% (95% CI: 8.7-45.5) and 38.8% (95% CI: 14.2-63.1), respectively. No cases of veno-occlusive disease post-HCT were reported. We present here, for the 1st time, detailed data showing the tolerability and efficacy of HCT following salvage therapy with blinatumomab. No unexpected toxicities were noted post-HCT and the study showed encouraging 1-year OS and PFS with. Longer-term follow-up is ongoing for these patients. [ABSTRACT FROM AUTHOR]

Peripheral T-cell lymphomas (PTCL) comprise 15-20% of adult non-Hodgkin lymphoma and have a poor prognosis; 5-year survival is less than 30% for the most aggressive subtypes. Allogeneic HCT (allo-HCT) is offered to eligible patients as a potentially curative modality in the salvage setting or in high risk patients to consolidate an initial response to frontline therapy. To report clinical outcomes derived from large sample size and long-term follow up data. We retrospectively reviewed medical records of 87 consecutive patients with PTCL who underwent allo-HCT at City of Hope from January 2000 to June 2018. Baseline patient demographic, treatment, and disease characteristics were summarized by descriptive statistics. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier curves and the log-rank test. Cumulative incidences of time to relapse and time to non-relapse mortality (NRM) were calculated with relapse and NRM as competing risks. Cumulative incidences of acute and chronic GVHD were calculated as time to onset of GVHD with relapse and death as competing events for GVHD. Median age at allo-HCT was 49 (range 2-70) years. Histologies were PTCL-NOS (n=21); transformed CTCL (n=19); NK TCL (n=17); AITL (n=15), ALCL (n=7); γδTCL (n=6) and other rare subtypes (n=2). No patients had a prior auto transplant. 42 patients (48%) had myeloablative conditioning; FTBI-based (n=39), or BEAM regimen (n=3). 45 patients (52%) had reduced intensity conditioning with a fludarabine/melphalan based regimen in 39. Sibling HCT was done in 47 (54%) patients. MUD HCT was done in 36 (41%); donors were fully HLA matched for 15 (17%) patients and mismatched in 21 (24%); 4 (5%) got haploidentical HCT. The most common GVHD prophylaxis was tacrolimus/sirolimus (n=54). Stem cell source was PBSC in 77 (88%), bone marrow in 5 (6%), and cord blood in 5 (6%) patients. At allo-HCT 25 (29%) patients were in complete remission, 25 (29%) in partial remission, 22 (25%) with induction failure and 14 (16%) with relapsed disease. The median follow-up among survivors was 6.9 years (range 1.1-15.5). The 5- and 10-year PFS was 47% (95% CI: 36%-58%) and 38% (95% CI: 26%-50%), respectively. The 5- and 10-year OS was 53% (95% CI: 41%-63%) and 42% (95% CI: 29%-54%), respectively (Fig.1). At day 100 after allo-HCT, the rate of acute GVHD grade II-IV was 41% (95% CI: 30%-51). Chronic GVHD rates at 3 years were 62% (95% CI: 51%-72%), with extensive GVHD of 55% (95% CI: 44%-65%). On univariate analysis, age (> 60 or not), sex, TBI-based conditioning, donor type, stem cell source or remission status prior to allo-HCT did not predict for OS. This large single-institution series with a long-term follow-up on allo-HCT outcomes in patients with high-risk, aggressive T-cell NHL shows encouraging survival outcomes for these patients with limited treatment options. [ABSTRACT FROM AUTHOR]

CMVi leads to significant morbidity in R+ HCT and preemptive therapy (PET) has been the standard of care. LTV was FDA-approved in Nov. 2017 for CMVi prevention in R+ HCT. Besides the clinical trials, there is are real world data on LTV. Upon IRB approval, we retrospectively studied consecutive R+ HCT pts with their first HCT between 1/1/2017 and 6/30/2018. LTV group included pts with HCT between 2/20/18 and 6/30/2018, who had LTV Px started within 28 days of HCT (n=59), and R+ HCT between 1/1/2017 and 2/19/2018 (n=307) served as control (ctrl). We compared CMVi rates in first 100 days of HCT, and time to engraftment between the 2 groups. Risk stratification: high risk - haplo/cord HCT & ATG use, low risk - all others. CMVi was defined as viral load (VL) of 625 IU/ml to 1250 IU/ml or higher (CMV assay conversion factor of 1 genomic copy/ml = 2.5 IU/ml). CMV VL less than 625 IU/ml is reported negative, VL between 625 and 1250 IU/ml is qualitative positive but numeric value is provided only for VL ≥ 1250 IU/ml. PET was recommended for VL >1250 IU/ml (500 copies/ml) in high risk and > 3750 IU/ml (1500 copies/ml) in low risk HCT (including those on LTV requiring PET). Descriptive statistics was done for baseline characteristics. Cumulative incidence curves were generated for CMVi within 100 days post-HCT and Gray's test was used to compare the difference between the 2 groups. In both groups, median age was 54 years and HCT indications were similar. Donor type in LTV/ Ctrl groups: MRD (27 vs 36%), MUD (44 vs 47%), haplo (27 vs 15%), cord (1.7 vs 1.6%). PBMC was graft source in 90% of both groups. Myeloablative conditioning: 40.7% in LTV and 35% in Ctrl. GVHD Px: Cellcept (32 vs 25%), methotrexate (7 vs 9%), tacro/siro (58 vs 65), and others (3.4 vs 0.3%) in LTV & Ctrl respectively. A majority (n=36) received both intravenous & oral LTV formulation while 23 received oral only. Median time from HCT to LTV start was 13 days (range: 4-26). LTV group had significant reduction in CMVi rate (22.4% [95%CI: 12.7-34.0]) compared with ctrl group (41.1% [95%CI: 35.4-46.7], p=0.008, Fig 1). In a subgroup of high-risk HCT LTV was significantly reduced CMVi rate (22.2%) compared with ctrl (62.8%, p=0.004, Fig 2) while statistical difference was not reached in low-risk HCT pts (22.8% vs. 35.6%, p=0.11). In the LTV Px, clinically significant (CS)-CMVi requiring PET occurred in 8.4% (n=5) and on excluding 2 pts who were not on LTV at the time of CMVi, the rate was 5% (Fig 1). CMVi cleared without PET in 8/13 LTV pts and LTV was continued; all pts had VL < 2500 IU/ml with 50% having VL <1250 IU/ml. There was no difference in time to WBC and platelet engraftment in 2 groups (Fig 3). LTV use in a real world setting is associated with significant reduction of CMVi and CS-CMVi without any discernible myelosuppression. The low level CMVi resolved spontaneously in majority with continued LTV Px and PET was not necessary. The high-risk HCT had most benefit with LTV Px. [ABSTRACT FROM AUTHOR]

Background AlloHCT is the only curative therapy for primary and secondary myelofibrosis (MF). Pulmonary arterial hypertension (PAH) can be seen in 30% of patients with MF. PAH can eventually lead to right heart failure and may be associated with complications after alloHCT. The primary objective was to determine the association of PAH with alloHCT outcome in patients with MF. Secondary objectives included the effect of HCT on the underlying PAH as well as incidence of specific transplant-related complications in these patients. Methods All patients with MF who underwent alloHCT from 2008 to early 2018 at the City of Hope Medical Center with evaluable pre-HCT echocardiography were considered for this retrospective analysis. Pre and postHCT echocardiograms were reviewed to evaluate the pulmonary arterial systolic pressure (PASP). Descriptive statistics were used for baseline patient and transplant related characteristics stratified by PAH. Paired t-test was used to detect the change in the pulmonary vascular pressure after HCT. Kaplan-Meier and cumulative incidence curves were constructed for OS and NRM), respectively. Log-rank test and Gray's test were used whenever appropriate. Results 65 patients with MF that met the inclusion criteria were studied. Median age at HCT was 61 years with 36 (55%) males. 39 (60%) patients had intermediate 2 or high DIPPS score at the time of HCT. 37 (57%) had JAK2 positive MF.. Median PASP was 37.0 mmHg (range: 16.0-57.9) prior to HCT with 37 out of 65 patients (57%) meeting the diagnostic criteria for PAH. With median follow-up of 35.0 months (range: 3.3 – 119.4), PAH was significantly associated with inferior OS (58.9% vs. 88.8%, p=0.025), primarily due to increased NRM (21.6% vs. 7.1%, p= 0.007). 57% of deaths (8 of 14) in patients with PAH occurred within day 100 after HCT. In patients with available post-HCT echocardiogram (n=33) eight patients (24%) had persistent PAH with the median pulmonary artery pressure of 30mmHg. Compared with pre-HCT values pulmonary arterial pressure was significantly reduced after HCT (p<0.001). Conclusion PAH is associated with inferior survival due to increased NRM in patients with MF undergoing alloHCT. About half of deaths in patients with PAH occurred within 100 days of HCT. PAH appears at least partially reversible after successful alloHCT. Based on our data, PAH should be considered a risk factor for early mortality after alloHCT and surveillance of pulmonary artery pressure in MF patients being considered for alloHCT may be useful. [ABSTRACT FROM AUTHOR]