Pretransplant Positron Emission Tomography Research Articles

Comparative Effectiveness of PET and SPECT MPI for Predicting Cardiovascular Events After Kidney Transplant.

Advanced chronic kidney disease is associated with high cardiovascular risk, even after kidney transplant. Pretransplant cardiac testing may identify patients who require additional assessment before transplant or would benefit from risk optimization. The objective of the current study was to determine the relative prognostic utility of pretransplant positron emission tomography (PET) and single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) for posttransplant major adverse cardiovascular events (MACEs). We retrospectively followed patients who underwent MPI before kidney transplant for the occurrence of MACE after transplant including myocardial infarction, stroke, heart failure, and cardiac death. An abnormal MPI result was defined as a total perfusion deficit >5% of the myocardium. To determine associations of MPI results with MACE, we utilized Cox hazard regression with propensity weighting for PET versus SPECT with model factors, including demographics and cardiovascular risk factors. A total of 393 patients underwent MPI (208 PET and 185 SPECT) and were followed for a median of 5.9 years post-transplant. Most were male (58%), median age was 58 years, and there was a high burden of hypertension (88%) and diabetes (33%). A minority had abnormal MPI (n=58, 15%). In propensity-weighted hazard regression, abnormal PET result was associated with posttransplant MACE (hazard ratio, 3.02 [95% CI, 1.78-5.11]; P<0.001), while there was insufficient evidence of an association of abnormal SPECT result with MACE (1.39 [95% CI, 0.72-2.66]; P=0.33). The explained relative risk of the PET result was higher than the SPECT result (R2 0.086 versus 0.007). Normal PET was associated with the lowest risk of MACE (2.2%/year versus 3.6%/year for normal SPECT; P<0.001). Kidney transplant recipients are at high cardiovascular risk, despite a minority having obstructive coronary artery disease on MPI. PET MPI findings predict posttransplant MACE. Normal PET may better discriminate lower risk patients compared with normal SPECT, which should be confirmed in a larger prospective study.

Impact of Early Post-Transplant 5-Point Deauville Scale (18)F-FDG-PET Status on Survival Outcomes after Allogeneic Transplantation for Lymphoma

Background: Conversely to what has been reported for autotransplant,most studies have shown that pre-transplant Fluorine-18-fluorodeoxyglucose (FDG)-positron emission tomography (PET) status does not appear to predict survival after allogeneic stem cell transplantation (Allo-SCT) for lymphoma patients. However it is less clear what is the impact of early FDG-PET status on outcomes after Allo-SCT, especially when using Deauville 5-point scale (DS) which has become a standard of care for staging and re-staging of FDG-PET.Methods: This retrospective study included all lymphoma patients who underwent FDG PET before and/or early after Allo-SCT in our institution and who were alive at least 3 months after the graft. The primary objective was to study the impact on OS and LFS of pre-transplant (within 1 month) and early post-transplant (+3 months and within +6-9 months) FDG PET in these patients. All FDG-PET were reviewed by a nuclear medicine expert and restaging was performed according to 5-point DS. Two thresholds of positivity were used: a score of at least 3 (DS3, i.e. scores 3 - 5) and a score of at least 4 (DS4, i.e. score of 4 or 5).Results: Between April 2005 and December 2015, 103 patients fulfilled the inclusion criteria. There were 69 males (66%) and the median age was 51.6 years old (range: 22-67). Forty-seven patients had high-grade non-Hodgkin lymphoma (NHL), 6 low-grade NHL, 34 T-cell lymphoma and 16 Hodgkin lymphoma. Most patients were considered in complete remission at the time of transplant (n=56) and received a reduced-intensity conditioning regimen (n=90). The numbers of patients with available FDG PET before transplant, at 3 months and between 6-9 months post-transplant were 81, 93 and 61, respectively. Deauville FDG PET staging identified 29 DS3 and 20 DS4 patients before transplant, 28 DS3 and 20 DS4 at 3 months, and 25 DS3 and 18 DS4 between 6-9 months post-transplant, respectively.With a median follow-up of 49.5 months (range: 6-140.5) for alive patients, 3-year OS and LFS were 81% (71-87) and 65% (54-74) for the whole cohort, respectively. Twenty-six patients relapsed at a median time of 4.5 months (range: 2.9-15.9) from Allo-SCT.In univariate analysis, only the post-transplant FDG-PET status influenced outcomes. Factors associated with a lower OS were DS3 and DS4 scores at 3 months (HR: 2.25; 95%CI: 0.93-5.44, p=0.07 and HR: 3.00; 95%CI: 1.22-7.36, p=0.01, respectively) and a DS3 score between 6-9 months post-transplant (HR: 4.08; 95%CI: 1.00-16.55, p=0.04). Factors associated with a lower LFS were DS3 and DS4 scores at 3 months (HR: 2.64; 95%CI: 1.30-5.39, p=0.007 and HR: 3.86; 95%CI: 1.86-8.02, p=0.0003, respectively) as well as between 6-9 months (HR: 4.20; 95%CI: 1.26-13.98, p=0.01 and HR: 2.72; 95%CI: 0.86-8.60, p=0.08) post-transplant.In multivariate analysis, DS4 FDG-PET at 3 months was the only independent factor associated with lower OS (HR 2.8; 95%CI: 1.13-6.97), p=0.0269) and LFS (HR 2.44, 95%CI: 0.94-6.33, p=0.06).Total body CTscan evaluation was performed in 16/28 and 14/25 DS3 patients at 3 months and between 6-9 months post-transplant, respectively. At 3 months, all CT-scans were considered normal while 4/14 were considered positive between 6-9 months. Lymph nodes biopsies were performed for 8/25 DS3 patients at 3 months showing 6 lymphoma relapses (75%) and for 7/25 DS3 patients between 6-9 months post-transplant showing 2 lymphoma relapses (29%). Six patients received donor lymphocyte infusion between 3 to 9 months post-transplant, only 2 being guided by FDG-PET.Conclusion: A DS4 FDG-PET status at 3 months is highly predictive of survivals in lymphoma patients receiving an Allo-SCT and may help to guide strategies to prevent relapse. These results have to be validated prospectively. DisclosuresTouzeau:AbbVie: Research Funding. Moreau:Bristol-Myers Squibb: Honoraria; Onyx Pharmaceutical: Consultancy, Honoraria; Millennium: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene, Janssen, Takeda, Novartis, Amgen, Roche: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Celgene: Consultancy, Honoraria; Amgen: Honoraria; Novartis: Consultancy, Honoraria.

Diagnostic Accuracy of Advanced Imaging in Cardiac Sarcoidosis

Background The diagnostic yield of cardiac sarcoidosis (CS) by endomyocardial biopsy is limited. Fluorodeoxyglucose (FDG) positron emission tomography (PET) and cardiac magnetic resonance imaging (MRI) may facilitate noninvasive diagnosis, but the accuracy of this approach is not well defined. We aimed to correlate findings from FDG PET and cardiac MRI with histological findings from explanted hearts of patients who underwent cardiac transplantation. Methods We analyzed the explanted heart histology for all patients who underwent cardiac transplant at our center from April 2008 to July 2018 and had pretransplant FDG PET (n=18) or cardiac MRI (n=31). The likelihood of CS based on FDG PET or cardiac MRI was categorized in a blinded fashion using a previously published method. RESULTS: Using a CS probable cutoff for FDG PET resulted in a sensitivity of 100.0% (95% CI, 54.1%-100.0%) and a specificity of 33.3% (95% CI, 9.9%-65.1%). Three of the 9 CS probable by FDG PET cases were found to be arrhythmogenic cardiomyopathy. The test characteristics of cardiac MRI are more challenging to comment on using our data as there was only one confirmed case of CS on post-transplant histological assessment. Of the 8 CS highly probable or probable cases by cardiac MRI, 3 were found to be dilated cardiomyopathy, and 2 were found to be end-stage hypertrophic cardiomyopathy. Conclusions FDG PET and cardiac MRI can help facilitate the diagnosis of CS in patients with advanced heart failure with a high degree of sensitivity but lower specificity.

Post-Transplant Radiation Had No Impact on Survival in Patients with Refractory or Relapsed Diffuse Large B-Cell Lymphoma

IntroductionHigh-dose chemotherapy followed by autologous hematopoietic cell transplantation (AHCT) offers cure for appropriate patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) sensitive to chemotherapy. Post-AHCT consolidative radiation therapy (RT) has been associated with improved outcomes in R/R DLBCL patients with bulky [based on computed tomography (CT)] disease after AHCT. We and others have demonstrated that patients with a Deauville score 4-5 (high-risk) on pre-AHCT FDG positron emission tomography (PET) have significantly worse outcomes as compared to those with Deauville 1-3 (low risk). We here examined the impact of consolidative post-AHCT RT in R/R-DLBCL patients with high-risk functional imaging based on Deauville score) on pre-transplant FDG PET scan on AHCT outcomes. Therefore, we retrospectively studied the effect of post-ASCT RT within 6 months after ASCT on survival in patients with R/R-DLBCL with high-risk pre-ASCT PET scans.MethodsWe retrospectively studied 193 consecutive adult patients with R/R-DLBCL identified from the Cleveland Clinic and University of Minnesota who had available pre-transplant FDG PET scans and adequate clinical follow-up. PET scans were re-reviewed and scored Deauville 4-5 were considered high risk. Patients that died within 6 months of ASCT (n=20) were excluded from the final survival analyses. Univariate analysis was performed using the Kaplan-Meier method, and the log-rank test was used to compare the subgroups.ResultsThe mean (SD) age of diagnosis was 54 (11) years and 61% patients were male. The mean follow-up for alive patients was 43 (32.6) months. We identified 69 patients with pre-transplant Deauville scores 4 (n=41) or 5 (n=28). Seventeen (25%) received RT at median 58 days post AHCT (IQR 39-79 days). Receiving post-ASCT RT did not impact overall survival in univariable (Figure 1) or multivariable analyses adjusted for age and gender.ConclusionWithin the limits of the study design, we did not observe a benefit to RT on overall survival in patients with RR-DLBCL with high-risk pre-AHCT PET scans. Alternative treatment approaches for high risk patients based on pre-transplant PET should be investigated in prospective clinical trials. High-dose chemotherapy followed by autologous hematopoietic cell transplantation (AHCT) offers cure for appropriate patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) sensitive to chemotherapy. Post-AHCT consolidative radiation therapy (RT) has been associated with improved outcomes in R/R DLBCL patients with bulky [based on computed tomography (CT)] disease after AHCT. We and others have demonstrated that patients with a Deauville score 4-5 (high-risk) on pre-AHCT FDG positron emission tomography (PET) have significantly worse outcomes as compared to those with Deauville 1-3 (low risk). We here examined the impact of consolidative post-AHCT RT in R/R-DLBCL patients with high-risk functional imaging based on Deauville score) on pre-transplant FDG PET scan on AHCT outcomes. Therefore, we retrospectively studied the effect of post-ASCT RT within 6 months after ASCT on survival in patients with R/R-DLBCL with high-risk pre-ASCT PET scans. We retrospectively studied 193 consecutive adult patients with R/R-DLBCL identified from the Cleveland Clinic and University of Minnesota who had available pre-transplant FDG PET scans and adequate clinical follow-up. PET scans were re-reviewed and scored Deauville 4-5 were considered high risk. Patients that died within 6 months of ASCT (n=20) were excluded from the final survival analyses. Univariate analysis was performed using the Kaplan-Meier method, and the log-rank test was used to compare the subgroups. The mean (SD) age of diagnosis was 54 (11) years and 61% patients were male. The mean follow-up for alive patients was 43 (32.6) months. We identified 69 patients with pre-transplant Deauville scores 4 (n=41) or 5 (n=28). Seventeen (25%) received RT at median 58 days post AHCT (IQR 39-79 days). Receiving post-ASCT RT did not impact overall survival in univariable (Figure 1) or multivariable analyses adjusted for age and gender. Within the limits of the study design, we did not observe a benefit to RT on overall survival in patients with RR-DLBCL with high-risk pre-AHCT PET scans. Alternative treatment approaches for high risk patients based on pre-transplant PET should be investigated in prospective clinical trials.

PRE-Transplant Positron Emission Tomography (PET) Predicts Outcomes of Patients with Hodgkin disease Undergoing Reduced Intensity Conditioning Haploidentical Transplant

Background. In recent years, the number of Hodgkin Lymphoma (HL) patients submitted to reduced intensity haploidentical allogeneic transplant (RIC haplo SCT) consistently increased. [Sureda et al. Curr Treat Options Oncol 2014] However, with a post alloSCT relapse rate so high as 40-60%, disease control after autoSCT relapse remains a clear unmet medical need. In respect of improving transplant outcome identification of factors influencing outcomes are warrantedMethods.We reviewed outcomes obtained in 44 consecutive HL patients who received RIC haplo SCT between September 2009 and June 2015 at our institution. The donor was haploidentical relative in all cases. All patients had received at least 3 conventional chemotherapy lines before RIC haplo SCT; most of them (72%) were refractory to front-line chemotherapy and all but one had received an autologous SCT. All patients received the same reduced intensity conditiong regime, and GvHD prophilaxis with post-transplant cyclophosphamide (Raiola et al. BBMT 2008). The median age was 31years (range 18-60). Deauville five-points scale were used to interpretate the results of pre-transplant positron-emission tomography (PET) studies, with a threshold of 4 or above considered positive. Survival curve and GvHD incidence were calculated with the method of Kaplan and Meier. Cox regression model was performed to identify pre-transplant factors influencing outcomes.Results. All patients engrafted but 1 who showed autologous recovery. The median day for 500 neutrophils was 15 days (13-23). Three patients died in remission at 8 (cGvHD), 16 (myocarditis) and 51(pneumonia) months from SCT, respectively. Three years non relapse mortality = 8%. Risk of grade II-IV acute GvHD and 3-year chronic GvHD were 22 and 21%, respectively. With a median follow-up for surviving patients of 38 months (range 13-83), 21 relapsed (47%). All relapsed patients were treated with further therapy, mainly immuno-chemotherapy and donor lymphocyte infusion (DLI). The 3-year overall (OS) and progression free survival (PFS) were 77% and 39%, respectively. Pre-transplant PET status was the only factor influencing outcomes of the procedure (OR 5.4; 95% CI 1.7 - 16.6). In the 41 patients with available pre-transplant PET status, 19 were positive and 22 negative. Outcomes accordingly to pre-transplant PET status are shown in the following table.Conclusions.Pre-transplant PET status is a factor influencing outcomes of relapsed/refractory HL submitted to RIC haplo SCT. Grade II-IV aGvHD was markedly reduced in patients with metabolic remission at time of transplantation. [Display omitted] DisclosuresAngelucci:Novartis oncology, celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Early detection of disseminated tuberculosis after cord blood transplantation: role of pre-transplant positron emission tomography

Early detection of disseminated tuberculosis after cord blood transplantation: role of pre-transplant positron emission tomography

Prognostic Value of FDG PET/CT before Allogeneic and Autologous Stem Cell Transplantation for Aggressive Lymphoma

To determine the prognostic value of performing fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) before allogeneic and autologous stem cell transplantation (SCT) in patients with aggressive lymphoma. A HIPAA-compliant retrospective review was performed under institutional review board waiver. Patients with aggressive lymphoma underwent allogeneic or autologous SCT between January 2005 and December 2010. FDG PET/CT was performed within the 3 months prior to transplantation. PET/CT images were evaluated for lesions with FDG avidity greater than that of the background liver. The relationship between pretransplantation PET and progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) was assessed with Kaplan-Meier curves and a corresponding log-rank test for categorical variables and Cox regression for continuous variables. A total of 175 patients were identified, of whom 73 underwent FDG PET/CT before allogeneic SCT and 102 underwent FDG PET/CT before autologous SCT. Before allogeneic SCT, 23 of 73 patients (32%) had FDG-avid lesions, and before autologous SCT, 11 of 102 patients (11%) had FDG-avid lesions. For allogeneic SCT, the 2-year PFS estimate was 68% (95% confidence interval [CI]: 56%, 82%) in patients without FDG-avid lesions, but only 35% (95% CI: 20%, 61%) for patients with FDG-avid lesions (P = .014). For autologous SCT, the 2-year PFS was 72% (95% CI: 64%, 82%) in patients without FDG-avid lesions, but only 18% (95% CI: 5%, 64%) for patients with FDG-avid lesions (P < .0001). Similar differences were seen in OS and DSS. The risk for posttransplantation recurrence correlated with higher lesional maximum standardized uptake values: for PFS, P < .0001 to P = .01; for DSS, P < .0001 to P = .002; and for OS, P < .0001 to P = .015. Performing FDG PET/CT before SCT in patients with aggressive lymphoma has prognostic value. For patients with aggressive lymphomas, the presence of FDG-avid lesions at PET/CT performed before allogeneic and autologous SCT indicates a lower likelihood of SCT success.

Impact of Pretransplantation 18F-fluorodeoxy Glucose–Positron Emission Tomography Status on Outcomes after Allogeneic Hematopoietic Cell Transplantation for Non-Hodgkin Lymphoma

Assessment with 18F-fluorodeoxy glucose (FDG)–positron emission tomography (PET) before hematopoietic cell transplantation (HCT) for lymphoma may be prognostic for outcomes. Patients with chemotherapy-sensitive non–Hodgkin lymphoma (NHL) undergoing allogeneic HCT reported to the Center of International Blood and Marrow Transplantation Registry between 2007 and 2012 were included. Pre-HCT PET status (positive versus negative) was determined by the reporting transplantation centers. We analyzed 336 patients; median age was 55 years and 60% were males. Follicular lymphoma (n = 104) was more common than large cell (n = 85), mantle cell (n = 69), and mature natural killer or T cell lymphoma (n = 78); two thirds of the cohort received reduced-intensity conditioning; one half had unrelated donor grafts. Patients underwent PET scanning a median of 1 month (range, .07 to 2.83 months) before HCT; 159 were PET positive and 177 were PET negative. At 3 years, relapse/progression, progression-free survival (PFS), and overall survival (OS) in PET-positive versus PET-negative groups were 40% versus 26%; P = .007; 43% versus 47%; P = .47; and 58% versus 60%; P = .73, respectively. On multivariate analysis, a positive pretransplantation PET was associated with an increased risk of relapse/progression (risk ratio [RR], 1.86; P = .001) but was not associated with increased mortality (RR, 1.29, 95% confidence interval [CI], .96 to 1.7; P = .08), therapy failure (RR, 1.32; 95% CI, .95 to 1.84; P = .10), or nonrelapse mortality (RR, .75; 95% CI, .48 to 1.18; P = .22). PET status conferred no influence on graft-versus-host disease. A positive PET scan before HCT is associated with increased relapse risk but should not be interpreted as a barrier to a successful allograft. PET status does not appear to predict survival after allogeneic HCT for NHL.

Cytochrome P450 2B6*5 Increases Relapse after Cyclophosphamide-Containing Conditioning and Autologous Transplantation for Lymphoma

Cyclophosphamide (Cy) is a prodrug that depends on bioactivation by hepatic cytochrome P450 (CYP) enzymes for its cytotoxicity. We evaluated the influence of single nucleotide polymorphisms (SNPs) of CYP enzymes on the efficacy of autologous hematopoietic cell transplantation (HCT) for lymphoma. SNPs of 22 genes were analyzed in 93 patients with Hodgkin (n = 52) and non-Hodgkin lymphoma (n = 41) treated with high-dose Cy followed by autologous HCT between 2004 and 2012. Preparative regimens contained Cy (120 mg/kg) combined with carmustine/etoposide (n = 61) or Cy (6000 mg/m2) with total body irradiation (n = 32). Lack of complete remission as measured by pretransplant positron emission tomography was the sole clinical factor associated with increased risk of relapse (HR, 2.1). In genomic analysis, we identified a single SNP (rs3211371) in exon 9 (C > T) of the CYP2B6 gene (allele designation 2B6*5) that significantly impacted patient outcomes. After adjusting for disease status and conditioning regimen, patients with the CYP2B6*1/*5 genotype had a higher 2-year relapse rate (HR, 3.3; 95% CI, 1.6 to 6.5; P = .041) and decreased overall survival (HR, 13.5; 95% CI, 3.5 to 51.9; P = .008) than patients with the wild-type allele. Two-year progression-free survival for patients with 2 hypofunctional CYP2B6 variant genotypes (*5 and *6) was only 11% (95% CI, 1% to 39%) compared with 67% (95% CI, 55% to 77%) for patients with the wild-type CYP2B6*1 allele in exon 9. Our results suggest that CYP2B6 SNPs influence the efficacy of high-dose Cy and significantly reduce the success of autologous HCT for lymphoma patients with the CYP2B6*5 variant.

Extended Ischemia Times Promote Risk of HCC Recurrence in Liver Transplant Patients.

There is increasing evidence that ischemia-reperfusion injury (IRI) promotes vasculogenesis and tumor outgrowth in the liver. Hepatic IRI is exaggerated by prolongation of ischemia times. The aim of this retrospective analysis was to assess the impact of ischemia times on risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). Subgroup analysis focused on patients with (18)F-fluoro-deoxy-glucose ((18)F-FDG)-avid HCC on pretransplant positron emission tomography (PET). A total of 103 liver transplant patients with HCC were included in this study. The impact of cold (CIT), warm (WIT), and total ischemia times (TIT) along with other prognostic variables on posttransplant outcome was analyzed in uni- and multivariate analysis. Twenty-four patients (23.3 %) developed tumor relapse after LT. Mean durations of CIT (468.0 vs. 375.5 min; P = 0.001), WIT (58.4 vs. 45.7 min; P = 0.001), and TIT (525.8 vs. 422.0 min; P < 0.001) were significantly longer in patients with compared to those without HCC recurrence. In multivariate regression analysis, (18)F-FDG-avid HCC (odds ratio [OR] 73.4), WIT >50 min (OR 52.5), alpha-fetoprotein level >400 IU/ml (OR 11.1), and Milan Out status (OR 7.4) were identified as independent predictors of HCC recurrence. In the subgroup of patients with PET-positive HCC, WIT remained the only independent variable to predict HCC recurrence (OR 15.5). Prolongation of ischemia times promotes the risk of HCC recurrence after LT, especially in patients with unfavorable tumor biology on PET imaging.

Pre-Transplantation FDG-PET Predicts Early but Not Late Survival Outcomes Following Allogeneic Transplantation in Chemo-Sensitive Hodgkin Lymphoma

Positron emission tomography (PET) is increasingly employed both to guide response-adjusted therapeutic strategies and to provide prognostic information in patients with Hodgkin Lymphoma (HL). The presence of residual [18-F]FDG-avid lesions prior to autologous stem cell transplantation (ASCT) confers a poor prognosis in terms of relapse risk and event-free survival outcomes, even when analysis is restricted to those with chemo-sensitive disease. The prognostic power of PET in the setting of allogeneic SCT remains more contentious, with relatively little data currently published. Information is particularly sparse in terms of outcomes relating to specific histological subtypes of lymphoma.We identified 160 patients transplanted for HL at four UK transplant centers using T-cell depleted conditioning regimens, based either on fludarabine-melphalan-alemtuzumab (FM-C) or the BCNU-etoposide-cytarabine-melphalan-alemtuzumab (BEAM-C) backbone, in whom pre-transplantation PET data were available. These represent the primary data set. Median age was 30 (12-66) years; 59 had failed a prior ASCT and these patients more commonly received FM-C (56/59 vs 26/101, p<0.001); median number of prior lines of treatment was 4 (2-10); median follow-up was 3.1 years in patients remaining alive. A Deauville score could be assigned according to a visual analysis 5-point scale in 137 cases following central review of digital file data; D1-2 (metabolic complete response) n=54, D3 n=13, D4 n=36, D5 n=34. Of those with a D5 score, 18 were non-progressive, and 16 progressive (D5p) prior to transplant. Overall survival (OS) was significantly worse in the D5p subset (19% [0-41%] at 4 years, p=0.001); it did not differ significantly between D1-2 vs D3-5 (78%[66-90%] vs 67%[54-80%], p=0.626), although the OS curves demonstrated early divergence from years 1-4 followed by convergence at later time points (Figure). The worse OS in the D5p cohort related both to a higher non-relapse-related mortality (NRM)(29%[12-65%] at 1 year) and a higher relapse risk (RR)(38%[19-76%] at 4 years). The latter were equivalent for the D1-2 vs D3-5 cohorts (NRM 17%[9-31%] vs 17% [10-30%] at 1 year; RR 23%[13-40%] vs 24% [15-38%] at 4 years respectively)(Figure). Interestingly the kinetics of relapse differed between the latter 2 groups, with relapse occurring later in the D1-2 cohort, again illustrated by early divergence (RR 16%[9-31%] vs 24%[15-38%] at 2 years) followed by later convergence from year 4. Progression free survival was also equivalent (57%[43-72%] vs 54%[41-67%] at 4 years respectively, p=0.347). Although the number of patients with non-progressive D5 scores was relatively small, exploratory analyses revealed no significant differences in survival outcomes between those with D4 vs D5 scores. Analysis of survival outcomes of D1-3 vs D4-5 also revealed no statistically significant differences.In summary, these data from a large cohort of patients with HL undergoing T-cell depleted allogeneic SCT illustrate inferior outcomes in those with progressive disease prior to transplantation, an altered kinetic of relapse and early survival advantage for those with Deauville 1-2 PET scores compared to those with non-progressive Deauville 3-5 PET scores, but no statistically significant differences in longer term outcomes including relapse risk, PFS and OS. Importantly, these data suggest that the allogeneic graft-versus-tumor activity likely overcomes the poor prognostic impact that has been demonstrated with residual metabolically active disease in the context of conventional dose escalation and ASCT, supporting further exploration of response-adjusted transplantation algorithms. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Extended Postinterventional Tumor Necrosis—Implication for Outcome in Liver Transplant Patients with Advanced HCC

BackgroundLocoregional interventional bridging therapy (IBT) is an accepted neoadjuvant approach in liver transplant candidates with hepatocellular carcinoma (HCC). However, the prognostic value of IBT in patients with advanced HCC is still undefined.AimThe aim of this trial was to evaluate the impact of postinterventional tumor necrosis on recurrence-free long-term survival after liver transplantation (LT) in patients with HCC, especially focusing on those exceeding the Milan criteria on pretransplant radiographic imaging.Patients and MethodsA total of 93 consecutive liver transplant candidates with HCC were included in this trial. In 36 patients, tumors were clinically staged beyond Milan criteria prior LT. Fifty-nine patients underwent IBT by transarterial chemoembolization or radiofrequency ablation pretransplantation. Postinterventional tumor necrosis rate as assessed at liver explant pathology was correlated with outcome post-LT.ResultsThere was no significant difference in 5-year tumor-free survival rate between the IBT- and the non-IBT subpopulation (78% versus 68%, P = 0.25). However, tumor response following IBT (≥50% tumor necrosis rate at explant pathology) resulted in a significantly better outcome 5 years post-LT (96%) than tumor non-response to IBT (<50% tumor necrosis rate at explant pathology; 21%; P<0.001). Five-year recurrence-free survival rate was 80% in Milan Out patients with extended post-IBT tumor necrosis versus 0% in Milan Out patients without tumor response to IBT (P<0.001). None of macromorphological HCC features, but only the absence of increased 18F-fluoro-deoxy-glucose (18FDG) uptake on pretransplant positron emission tomography (PET) was identified as independent predictor of postinterventional tumor response (P<0.001).ConclusionOur results implicate that extended postinterventional tumor necrosis promotes recurrence-free long-term survival in patients with HCC beyond standard criteria. Pretransplant PET assessment may identify those patients with advanced HCC that will benefit from post-IBT tumor response and may, thereby, achieve excellent posttransplant outcome.

Postinterventional Tumor Necrosis Predicts Recurrence-Free Long-Term Survival in Liver Transplant Patients with Advanced Hepatocellular Carcinoma on Clinical Staging

Background: There is some evidence that a subset of patients with advanced HCC on clinical staging may, nonetheless, benefit from liver transplantation. The role of pretransplant interventional bridging treatment (IBT) for identifying adequate liver transplant candidates with HCC beyond the Milan criteria is still undefined. The aim of this trial was, therefore, to evaluate the value of IBT induced tumor necrosis on recurrence-free long-term survival in liver transplant patients with advanced HCC. Furthermore, we aimed at identifying pretransplant available clinical parameters that may predict histopathological response to IBT, and thereby, be useful for selecting adequate liver transplant candidates. Patients and methods: A total of 93 patients with HCC were included in this trial. 18F-FDG positron emission tomography (PET) has been performed in all of them pre-LT, classifying patients in PET− (no increased FDG tumor uptake on PET) and PET + (increased FDG tumor uptake on PET). If being eligible, patients underwent pretransplant IBT by transarterial chemoembolization (TACE) or radiofrequency ablation (RFA). Clinical response to IBT was assessed by repeat CT scans (RECIST criteria). Macromorphologic tumor staging was based on CT/MRI. Explant livers were histopathologically examined to determine variables of macromorphology, vascular and lymphatic invasion invasion, grading and grade of post-IBT tumor necrosis. Patients with a 50%-100% tumor necrosis were defined to be histological responders, while tumor necrosis rate < 50% indicated histological non-response to IBT. The impact of clinical and histopathologic parameters on clinical outcome was evaluated in uni- and multivariate analysis. Results: Current overall follow-up is ranging between 5 and 162 months posttransplantation (mean: 64.3 ± 44.2 months). Finally, 59 liver transplant patients (63.4%) have received IBT, predominantly TACE. Overall, 21 patients developed tumor recurrence post-LT (22.6%), 11 patients in the IBT-group (18.6%) and 10 patients in the non-IBT-population (29.4%). Histologic responders had a significantly better recurrence-free survival rate after 5 years than histologic non-responders (96% versus 21%; P < 0,001). Histologic response to IBT resulted in a 5-year recurrence-free survival of 80% in Milan Out patients, which was comparable to Milan In recipients (87%), but significantly better than in histologically non-responding Milan Out recipients (0%; P < 0,001). In multivariate analysis, histologic response to IBT was identified as the only independent predictor of recurrence-free long-term survival (hazard ratio 53.3; P < 0.001). In multivariate logistic regression, pretransplant PET- status was assessed as the only independent clinical parameter predicting histologic response to IBT (odds ratio 12.4; P < 0.001). Conclusion: Data of our trial indicate that liver transplant patients with HCC should undergo pretransplant IBT, if being eligible, aiming at extended tumor necrosis. Patients with advanced HCC on clinical staging may, thereby, achieve excellent recurrence-free lomg-term survival. Pretransplant PET evaluation is useful for identifying those patients that may undergo successful IBT. This could be useful for a reasonable extension of liver transplant criteria.

The Role of F18-fluorodeoxyglucose Positron Emission Tomography in the Management of Relapsed or Refractory Hodgkin’s Lymphoma

Positron emission tomography (PET) is widely used in the diagnosis and response assessment after first-line treatment of Hodgkin’s lymphoma (HL). For the approximately 30 % of patients who relapse or have refractory disease, PET can provide valuable prognostic information during second-line therapy, at the time of autologous stem cell transplant (ASCT). Retrospective studies performed over the past decade have consistently found a significant association between a positive PET scan after salvage chemotherapy for HL and progression-free and overall survival after ASCT. In fact, the predictive value of pre-transplant PET appears higher than that of more traditional clinical risk factors. Unfortunately, there is little data to recommend the best treatment course for patients who have a positive pre-ASCT PET, and few studies have addressed the role of PET in other relapsed/refractory HL settings.

Patients with non-[18F]fludeoxyglucose-avid advanced hepatocellular carcinoma on clinical staging may achieve long-term recurrence-free survival after liver transplantation

There is increasing evidence that a relevant number of patients with hepatocellular carcinoma (HCC) exceeding the Milan criteria may benefit from liver transplantation (LT). We retrospectively analyzed the prognostic significance of [(18) F]fludeoxyglucose ([(18) F]FDG) positron emission tomography (PET) for identifying appropriate LT candidates with advanced HCC on clinical staging. Between 1995 and 2008, 111 patients with HCC were listed for LT. All underwent a pretransplant PET evaluation. LT was performed for 91 of these patients. The tumor recurrence rate after LT was 3.6% for patients with non-[(18) F]FDG-avid (PET(-) ) tumors, but it was 54.3% for patients with [(18) F]FDG-avid (PET(+) ) tumors (P < 0.001). The 5-year recurrence-free survival rates were comparable for patients with tumors meeting the Milan criteria (86.2%) and patients with PET(-) HCC exceeding the Milan criteria (81%) at LT, but these rates were significantly higher than the rate for liver recipients with [(18) F]FDG-avid advanced HCC (21%, P = 0.002). In a multivariate analysis, negative PET findings (odds ratio = 21.6, P < 0.001), an alpha-fetoprotein level <400 IU/mL (odds ratio = 3.3, P = 0.013), and a total tumor diameter <10 cm (odds ratio = 3.0, P = 0.022) were identified as pretransplant prognostic variables for recurrence-free survival. A PET(+) status was assessed as the only independent clinical predictor of tumor-related patient dropout from the waiting list (hazard ratio = 5.7, P = 0.01). Patients with non-[(18) F]FDG-avid HCC beyond the Milan criteria according to clinical staging may achieve excellent long-term recurrence-free survival after LT.

Pre-transplant positron emission tomography in patients with relapsed Hodgkin lymphoma

This retrospective study evaluated the secondary clinical risk score at relapse, the prognostic significance of pre-transplant positron emission tomography (PET), and complete remission (CR) assessed by computed tomography (CT) after salvage chemotherapy before autologous stem cell transplant (ASCT) in 76 patients with relapsed/refractory Hodgkin lymphoma (HL). Median follow-up after ASCT was 23 months. Overall 11/20 PET-positive and 14/56 PET-negative patients relapsed after ASCT. In univariate analysis, only PET negativity before ASCT was significantly associated with better 2-year progression-free survival (PFS) (72.7 ± 6.3% vs. 36.1 ± 11.6%, p = 0.01) and 2-year overall survival (OS) (90.3 ± 4.1% vs. 61.4 ± 11.6%, p = 0.009). Other factors were not significant. In multivariate analysis, none of the evaluated factors were significant for PFS and OS. However, positive pre-transplant PET identified a population with worse PFS and OS at least in univariate analysis.

18F-deoxyglucose PET: useful in the management of patients with stem cell transplantation for lymphoma?

Evaluation of: Lambert JR, Bomanji JB, Peggs KS et al. Prognostic role of PET scanning before and after reduced-intensity allogeneic stem cell transplantation for lymphoma. Blood 115(14), 2763–2768 (2010).18F-deoxyglucose (FDG) positron emission tomography (PET) and more recently FDG PET/computed tomography (CT) has become an important tool in the management of patients with Hodgkin and non-Hodgkin lymphoma. It adds metabolic and functional information to conventional anatomical imaging, mainly assessed by CT. Especially for the detection of early response to treatment and prognostic considerations, this type of information seems better suited than anatomical information. Consequently, the ability of FDG PET to predict the outcome in patients with stem cell transplantation (SCT) for lymphoma has been tested in several studies. Results in patients with autologous SCT have been promising, and pretransplant FDG PET is likely to become routine in this group of patients. The evaluated study investigates, for the first time, the predictive value of pretransplant FDG PET in allogeneic SCT, as well as the utility of FDG PET for the follow-up of these patients. All 80 patients included in the prospective study had reduced-intensity conditioning. In contrast to FDG PET before autologous SCT, there was no correlation at all between pretransplant FDG PET results and the outcome after allogeneic SCT. This reflects the fact that other or additional reasons, especially the graft-versus-leukemia effect, are substantial for the outcome of allogeneic SCT in comparison with autologous SCT. Follow-up with FDG PET after reduced-intensity allogeneic SCT was significantly more sensitive than CT to detect disease progression or relapse, and was useful in guiding treatment in the situation of disease relapse.

Prognostic role of PET scanning before and after reduced-intensity allogeneic stem cell transplantation for lymphoma

AbstractAllogeneic stem cell transplantation (SCT) is an established therapy for patients with relapsed lymphoma, but the role of positron emission tomography (PET) scanning preallogeneic and postallogeneic SCT is uncertain. We investigated whether pretransplantation PET status predicted outcome after allogeneic SCT and whether PET surveillance after transplantation provided additional information compared with computed tomography (CT) scanning. Eighty consecutive patients with lymphoma who received a reduced-intensity allogeneic SCT were entered onto a prospective trial. PET and CT scans were performed before transplantation and up to 36 months after transplantation. Forty-two patients were PET-positive before transplantation. Pretransplantation PET status had no significant impact on either relapse rate or overall survival. Thirty-four relapses were observed, of which 17 were PET-positive with a normal CT scan at relapse. Donor lymphocyte infusion (DLI) was administered in 26 episodes of relapse and was guided by PET alone in 14 patients. These findings suggest that, in contrast to autologous SCT, pretransplantation PET status is not predictive of relapse and survival after allogeneic SCT for lymphoma. Posttransplantation surveillance by PET detected relapse before CT in half of episodes, often allowing earlier administration of DLI in patients with recurrent lymphoma, and permitted withholding of potentially harmful DLI in those with PET-negative masses on CT scans.

Pretransplantation positron emission tomography scan is the main predictor of autologous stem cell transplantation outcome in aggressive B‐cell non‐Hodgkin lymphoma

Limited data exist about the role of second-line chemotherapy response assessed by positron emission tomography (PET) as a prognostic factor in patients with aggressive non-Hodgkin Lymphoma (NHL) who undergo autologous stem cell transplantation (ASCT). The objective of this analysis was to investigate the main determinants of prognosis in patients with aggressive B-cell NHL who undergo ASCT, focusing on the impact of pretransplantation PET, secondary age-adjusted International Prognostic Index (sAA-IPI) score, histology, and previous response to first-line chemotherapy. Seventy-five patients with diffuse, large B-cell lymphoma or grade 3 follicular lymphoma who were treated at the author' institution with second-line chemotherapy (combined ifosfamide, etoposide, and epirubicin [IEV]) followed by ASCT between September 2002 and September 2006 were included. All patients were evaluated by PET after 1 to 3 courses of IEV chemotherapy before ASCT, and all patients received a conditioning regimen of combined carmustine, etoposide, cytosine arabinoside, and melphalan. The prognostic impact of pretransplantation PET, sAA-IPI score, histology, and previous response to first-line chemotherapy was evaluated by univariate and multivariate analyses. Seventy-two of 75 patients underwent ASCT. In a univariate analysis for progression-free survival (PFS) and overall survival (OS), a significant association was observed with pretransplantation PET (PFS, P< .00001; OS, P< .01) and previous first-line response (PFS, P= .02; OS, P= .04). In the multivariate framework, pretransplantation PET was identified as the only independent prognostic factor (PFS, P< .001; OS, P= .01). The current data indicated that pretransplantation PET is the main prognostic predictor in patients with aggressive B-cell NHL who are scheduled for ASCT.

Positron emission tomography using F-18 fluorodeoxyglucose pre- and post-autologous stem cell transplant in non-Hodgkin's lymphoma

Positron emission tomography (PET) utilizing fluorodeoxyglucose (FDG) has an ever-increasing role in the management of numerous malignancies. FDG PET in lymphoma is being incorporated into the response assessment in lymphoma as published by the Imaging Subcommittee of International Harmonization Project in Lymphoma. The exact role of FDG PET in non-Hodgkin's lymphoma (NHL) associated with autologous stem cell transplant (ASCT) is unclear. Numerous studies have identified pretransplant PET scans as being highly prognostic with regard to overall and PFS after ASCT. Many included a wide range of histologies, including Hodgkin's lymphoma and NHL. In studies with mixed histologies, PFS at 2 years has been improved by as much as 82% in patients with negative pre-ASCT PET scans. In studies incorporating only patients with NHL, improvements in failure-free survival have been reported as high as 43% for patients with negative pre-ASCT PET imaging. Limitations have included inclusion of many histologies, different reported time points, small retrospective studies and variation in the interpretation of a positive PET. Validation is ongoing in larger prospective trials. Future directions include the potential incorporation of post-ASCT therapy, such as radiation therapy or maintenance antibody therapy, for patients with positive pre-ASCT PET scans.