scholarly journals Chronic GVHD risk score: a Center for International Blood and Marrow Transplant Research analysis

Blood ◽  
2011 ◽  
Vol 117 (24) ◽  
pp. 6714-6720 ◽  
Author(s):  
Mukta Arora ◽  
John P. Klein ◽  
Daniel J. Weisdorf ◽  
Anna Hassebroek ◽  
Mary E. D. Flowers ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Score ◽  
Chronic Gvhd ◽  
Disease Status ◽  
Risk Groups ◽  
Marrow Transplant ◽  
Karnofsky Score ◽  
Blood And Marrow Transplant ◽  
Gvhd Prophylaxis ◽  
Research Analysis

Abstract Several risk factors are associated with increased mortality in patients with chronic graft-versus-host disease (cGVHD), but there is considerable variability in the reported factors. Therefore, we evaluated patient, transplantation, and cGVHD characteristics to develop a risk score in 5343 patients with cGVHD. Ten variables were identified as being significant in multivariate analysis of overall survival and nonrelapse mortality (NRM): age, prior acute GVHD, time from transplantation to cGVHD, donor type, disease status at transplantation, GVHD prophylaxis, gender mismatch, serum bilirubin, Karnofsky score, and platelet count. These 10 variables were used to build a cGVHD risk score, and 6 risk groups (RGs) were identified. The 5-year NRM was 5% (1%-9%) in RG1, 20% (19%-23%) in RG2, 33% (29%-37%) in RG3, 43% (40%-46%) in RG4, 63% (53%-74%) in RG5, and 72% (59%-85%) in RG6. The 5-year overall survival was highest at 91% (95% confidence interval [CI]:85%-97%) in RG1, followed by 67% (65%-69%) in RG2, 51% (46%-55%) in RG3, 40% (37%-43%) in RG4, 21% (12%-30%) in RG5, and 4% (0%-9%) in RG6 (all P < .01). This analysis demonstrates the usefulness of data from a large registry to develop risk-score categories for major transplantation outcomes. Validation of this cGVHD risk score is needed in a different population to ensure its broad applicability.

scholarly journals Reduced-Intensity Transplantation for Lymphomas Using Haploidentical Related Donors Versus HLA-Matched Sibling Donors: A Center for International Blood and Marrow Transplant Research Analysis

2016 ◽  
Vol 34 (26) ◽  
pp. 3141-3149 ◽  
Author(s):  
Nilanjan Ghosh ◽  
Reem Karmali ◽  
Vanderson Rocha ◽  
Kwang Woo Ahn ◽  
Alyssa DiGilio ◽  
...  
Keyword(s):  
Overall Survival ◽  
Calcineurin Inhibitor ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Marrow Transplant ◽  
Free Survival ◽  
Blood And Marrow Transplant ◽  
Gvhd Prophylaxis ◽  
Matched Sibling ◽  
Reduced Intensity

Purpose Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. Materials and Methods We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versus-host disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor–based GVHD prophylaxis. Results Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). Conclusion Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD.

Umbilical Cord Blood (UCB) Transplantation in Children with Acute Leukemia: Impact of Conditioning Regimen on Transplant Outcomes

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1231-1231 ◽  
Author(s):  
Mary Eapen ◽  
Joanne Kurtzberg ◽  
Mei-Jie Zhang ◽  
Adam M. Mendizabal ◽  
Ka Wah Chang ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cord Blood ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Survival Rates ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Marrow Transplant ◽  
Blood And Marrow Transplant ◽  
Hematopoietic Recovery

Abstract The Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0501; NCT00412360) randomized children with hematologic malignancy to one or two cord blood unit transplantation between December 2006 and February 2012. While the trial concluded that survival was similar regardless of number of units infused, results were generally better than those previously reported after single UCB transplant. The apparently improved survival in recipients of BMT CTN 0501 compared to prior studies in children transplanted with a single UCB unit prompted a comparison of trial versus non-trial treatment outcomes to determine 1) the generalizability of trial results and 2) whether survival was better for patients treated with the trial regimen. Using data reported to the Center for International Blood and Marrow Transplant Research during the trial period, 396 recipients of one UCB unit transplant met the broad eligibility criteria for BMT CTN 0501 (i.e. aged 1- 21 years, high-risk acute leukemia, performance score ≥70). Trial and non-trial patients were comparable in their HCT-CI score. Trial patients (n=100) received total body irradiation (TBI) 1320 cGy, cyclophosphamide 120 mg/kg, and fludarabine 75 mg/m2 (TCF). Non-trial patients either received the same regimen as in the trial (N=62; non-trial TCF) or an alternative regimen (N=334; non-trial non-TCF regimen). Excluded were 13 patients on BMT CTN 0501 randomized to receive a single UCB unit for malignant diseases other than acute leukemia. Patient and disease characteristics of those treated on BMT CTN 0501 and others were similar except that those who received non-trial TCF regimen were more likely to report performance scores of 80 or 70 (24% versus 11%, p=0.04) and transplanted in relapse (18% vs. 5%, p=0.02) and those that received non-TCF regimens were more likely to 1-10 years of age (76% versus 53%, p<0.0001). Sixty-three percent of non-trial non-TCF regimens included TBI (≥1000 cGy) and the predominant non-TBI regimen was busulfan and cyclophosphamide. All patients received a calcineurin inhibitor for graft-versus-host disease (GVHD) prophylaxis. Donor-recipient HLA-match, median infused total nucleated cells and median follow up times were similar across the groups. Three-year survival rates were similar between patients receiving TCF regimen either on (A) or off trial (B), Figure1A, p=0.83. Similarly, there were no differences in hematopoietic recovery, relapse or non-relapse mortality between trial and non-trial TCF. However, compared to TCF on trial (A), overall survival rates were significantly lower with non-TCF non-TBI (C) and TBI (D) containing regimens after adjusting for age, CMV serostatus, disease and disease status; Figure 1B, 68% versus 55% (p=0.001) and 68% versus 50% (p=0.04), respectively. Results of multivariate analysis are shown in Table 1. Compared to patients treated on trial (TCF regimen; 20% at 3-years) relapse rates were higher with non-TCF non-TBI (42%, p=0.003) but not TBI-containing regimens (25%, p=0.38) after adjusting for age, disease, disease status and CMV seropositivity. Among non-TCF patients, relapse risk was higher for non-TBI compared to TBI-containing regimens (hazard ratio [HR] 1.61, p=0.02) but not mortality risk (HR 0.93, p=0.74). Cytogenetic risk features were not associated with relapse or survival. There were no differences in hematopoietic recovery, acute and chronic GVHD. The results of BMT CTN 0501 appear generalizable to the population of trial eligible patients. The survival differences between the trial specified and other conditioning regimens support use of the TCF regimen to improve survival. It also indicates the importance of conditioning regimen for outcome and may serve as a stimulus to design trials to identify the optimal regimen for children with acute leukemia undergoing UCB transplantation. Disclosures No relevant conflicts of interest to declare.

scholarly journals Do Hematopoietic Cell Transplant Patients Treated on a Clinical Trial Do Better? Comparison of Characteristics and Outcomes of Patients Enrolled Versus Not Enrolled on Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) 0201 Trial

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 209-209
Author(s):  
Nandita Khera ◽  
Navneet S. Majhail ◽  
Ruta Brazauskas ◽  
Zhiwei Wang ◽  
Mahmoud Aljurf ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Clinical Trials ◽  
Disease Risk ◽  
Marrow Transplant ◽  
Trial Participation ◽  
Blood And Marrow Transplant ◽  
Gvhd Prophylaxis ◽  
Study Participants ◽  
Trial Participants

Abstract Background: The association of clinical trial participation with outcomes in cancer patients is controversial, with some studies reporting better outcomes for trial participants while others do not. It is possible that the difference in outcomes is due to differences in baseline characteristics of participants and non-participants. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 trial was a large randomized, multi-center study comparing peripheral blood (PB) with bone marrow (BM) for hematopoietic cell transplantation (HCT) from HLA-matched or 1 allele mismatched unrelated donors (URD) in patients with acute leukemia, chronic myeloid leukemia and myelodysplastic syndromes. The trial reported no significant survival differences between PB and BM; there was decreased risk of graft failure but increased risk of chronic graft-versus-host disease (GVHD) with PB grafts (Anasetti et al NEJM 2012). Methods: We compared characteristics of BMT CTN 0201 study participants (n=494) with HCT recipients who did not participate on the trial (n=1384) but were potentially eligible by virtue of known characteristics. These patients received similar conditioning and GVHD prophylaxis as trial participants at 38 United States trial centers during the study time-period. Centers that had no eligible non-trial participants were excluded. Outcomes between patients on and off trial were compared using Cox proportional hazards regression models. Data were obtained from the Center for International Blood and Marrow Transplant Research (CIBMTR) that collects patient data on all trial and non-trial allogeneic HCT recipients through its registry function. Results: Approximately 29% [494/1878] of apparently eligible patients were randomized and analyzed as part of the trial. There were no significant differences between study participants and non-participants in age or sex distribution, disease types, HLA or sex matching, comorbidities, or interval from diagnosis to HCT. Higher proportions of non-participants were Hispanic, had a lower performance status and lower disease risk, and received myeloablative conditioning and antithymocyte globulin (ATG) or Campath than the study participants. PB was used more commonly as the graft source in the non-participants as compared to the study participants (65% vs. 50%, p<0.001). In multivariate models, overall mortality (HR 1.09, 95% CI 0.95-1.25, p=0.22), transplant-related mortality (HR 1.08, 95% CI 0.89-1.32, p=0.42) and risks of acute grade II-IV (HR 0.96, 95% CI 0.82-1.12, p=0.57) and chronic GVHD (HR 1.06, 95% CI 0.92-1.23, p=0.41) were comparable between study non-participants and participants. Non-participants were at higher risk for relapse than participants (HR 1.24, 95%CI 1.04-1.49, p=0.02) in the multivariate analysis adjusted for disease risk and other clinical variables. Center effect was examined and was not found to be significant (p=0.10). There was no significant interaction between graft source and trial participation (P=0.22) and the risk of mortality was comparable for BM (HR 0.99, 95% CI 0.80-1.22, p=0.90) and PB recipients (HR 1.17, 95% CI 0.97-1.41, p=0.09) whether on trial or off trial. (Figure) Conclusion: Approximately 29% of patients who appeared eligible and were treated with conditioning and GVHD prophylaxis regimens allowed on the trial were enrolled. Despite some differences in clinical characteristics, most of the outcomes of non-trial participants were comparable to trial participants, suggesting that there is no definitive evidence that the outcomes of patients in a clinical trial are superior to those of the non-participants treated in a similar fashion. The comparable outcomes also indicate that the results of this trial were not seriously affected by selection bias and are therefore representative of the larger population. Figure 1: Adjusted overall survival in BMT CTN 0201 trial participants and non-participants Figure 1:. Adjusted overall survival in BMT CTN 0201 trial participants and non-participants Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Long-Term Follow-Up Of Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation For High Risk Follicular Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5519-5519
Author(s):  
Silvana Novelli ◽  
Albert Esquirol ◽  
Javier Briones ◽  
Pilar Leoz ◽  
Rodrigo Martino ◽  
...  
Keyword(s):  
High Risk ◽  
Median Time ◽  
Risk Score ◽  
Chronic Gvhd ◽  
Disease Status ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Related Donor

Abstract Introduction Follicular lymphoma (FL) is the most frequent indolent lymphoma. Autologous hematopoietic stem cell transplantation (ASCT) allows durable progression-free survival in selected relapsed patients. Recently, the EBMT lymphoma working party has published the recommendations for ASCT and allogeneic hematopoietic transplantation (alloTPH) in FL. For those high-risk young patients relapsing after ASCT, alloTPH is a valid therapeutic option; the majority being done with reduced intensity conditioning (alloRIC). Aims Our aim is to describe the outcome of patients with FL who underwent an alloTPH in our cente. Factors potentially influencing outcome such us age, sex, FLIPI at diagnosis, disease status prior alloTPH, EBMT risk score, type of donor, graft vs host disease (GVHD) prophylaxis and development of GVHD were also analized. Methods Actuarial estimates of OS and PFS rates were calculated using the Kaplan-Meier method. OS was estimated from the date of transplantation to the date of death or last follow-up. PFS was defined as the time from transplantation until progression or death from any cause. Patients We retrospectively found 26 alloTPH in the period 1999 - 2013. Two alloTPH were conditioned with a myeloablative regimen. Patients who underwent an alloRIC (n=24) were all conditioned with Fludarabine 30 mg/m2/5 days and Melphalan 70 mg/m2/1 day. Results AlloTPH was from a matched related donor in 70.8% of cases, from a mismatched related donor in 4.2%, matched unrelated donor in 8.3% and from a mismatched unrelated donor in 16.7%. The median age was 49.5 years (range 35-61). The median time from diagnosis to alloTPH was 48 months (range 9 – 190), male: female ratio was 2:1. FLIPI at diagnosis was 0 in 16.7%, FLIPI 1 in 25%, FLIPI 2 in 33.3%, FLIPI 3 in 8.3% and FLIPI 4 in 16.7. Mean number of treatment pre alloTPH was 4.5 (range 2-6). Ten patients (41.7%) had previously received an ASTC. Response before alloTPH was complete response in 54.2%, partial response in 37.5% and stable disease in 8.4%. The majority of patients (95.8%) had an EBMT risk score higher than 3. Graft vs host disease prophylaxis consisted on cyclosporine + short course of methotrexate in 54.2%, cyclosporine + micophenolate in 41.7% and sirolimus + tacrolimus in 4.2%. In vivo T-cell depletion was done in 4 patients receiving grafts from a mismatched unrelated donor (ATG or alemtuzumab, 2 patients each). Mean CD34 cells/Kg infused was 6.45 x106/kg (range 1.92 – 15.6). The median time to granulocyte recovery (>0.5x109/L) was 15 days (range 11-19) and the median time to platelets recovery (>50x109/L) was 14 days (range 6-56). Acute GVHD was developed in 45.8% of patients; it was global grade 1-2 in 36.4% ,and grade 3-4 in 63.6%. Chronic GVHD was present in 58.3% of patients. The median time of chronic GVHD presentation was 196 days after alloTPH (range 101 – 569 days). Regarding opportunistic infections, 20.8% of patients reactivated CMV with no disease, 16.7% had intestinal disease due to CMV. Thirteen per cent of patients developed pulmonary fungal infection (i.e Aspergillus sp). With a median follow up of 48.50 months (range 0-161), the 5 years OS was 66.1% (CI 95% 43.76 - 88.44) and the 5 years PFS was 63.8% (CI 95% 43.22 - 84.4). Overall morbidity at 3, 6 and 12 months after alloTPH was 5%, 5% and 10.3% respectively. Only 1 patient relapsed at 38 months after alloTPH but is still alive. Causes of death were refractory GVHD (n=5), sepsis (n=3) and acute renal failure due to microangiopathy (n=1). Survival was influenced by GVHD prophylaxis. At the median time of follow up (48.50 months) patients receiving cyclosporine-methotrexate had an OS of 82.5% vs 30% for patients receiving cyclosporine-MMF (p<0.01). Other variables (FLIPI at diagnosis, sex, age older than 60 years, the EBMT risk score pre alloTPH and disease status) had no influence on survival. Conclusions AlloTPH for high risk FL patients seems to overcome the negative effect of FL prognostic factors at diagnosis. This strategy shows an excellent disease control with a low transplant-related mortality. Disclosures: No relevant conflicts of interest to declare.

The Outcome of the Combination of Tacrolimus, Sirolimus, and ATG for GvHD Prophylaxis on Allogeneic Stem Cell Transplantation From Matched Unrelated Donors

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2345-2345
Author(s):  
Yaser Homsi ◽  
Dareen Alwan ◽  
Patrick Kiel ◽  
Lindsay Rosenbeck ◽  
Srivastava Shivani ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Fungal Infections ◽  
Chronic Gvhd ◽  
Corticosteroid Treatment ◽  
Marrow Transplant ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors

Abstract Abstract 2345 Background: Graft-vs-Host Disease (GvHD) remains a significant complication of allogeneic stem cell transplantation from matched unrelated donors (MUD). Compared to MTX-based regimen, Tacrolimus/Sirolimus was found to decrease the incidence of acute GvHD (Keil et al, Biol Blood Marrow Transplant. 2009;16(2):S319, and Cutler et al, Blood. 2007;109:3108–14), whereas, the incorporation of Antithymocyte globulin (ATG) into MTX-based regimen decreases the incidence of chronic GvHD (Bacigalupo et al, Biol Blood Marrow Transplant. 2002;8(12):656–61). There are no reports of the outcome of the combination of Tacrolimus/Sirolimus and ATG. We compared the results of MUD using tacrolimus and sirolimus (day-3 to day +180) combined with ATG (2.5 mg/kg day −3,−2, and −1) (TSA) prophylaxis in consecutive patients treated at our institution from September 2006 to March 2009, with those using MTX-based prophylaxis without ATG in consecutive patients treated from January 2000 to August 2006. The primary endpoints were incidence of acute and chronic GvHD, lethal infectious complications, relapse, and survival. Result: Between 1/2000 and 3/2009, 71 MUD stem cell transplants were performed. 27 patients received TSA regimen as GvHD prophylaxis and 44 patients received traditional MTX-based prophylaxis without ATG. More patients in the TSA group received PBSC compared to the MTX group (63% vs. 36%; P=0.029), otherwise both groups were matched for age, sex, underline malignancies, disease risk per ASBMT criteria, degree of HLA-match, CMV serology, and conditioning regimens. The cumulative incidence of Grade II-IV classic acute GvHD at day +100 was significantly lower in the TSA group compared to control group (11.7% vs. 41.6%; Gray's test P =0.008). However, the cumulative incidence of aGvHD at day +365 was not statistically significant between both groups (33.1% vs. 44.4%; Gray's test P=0.154); this was due to an increase rate of delayed-onset aGvHD in TSA group (18.5%) compared to MTX group (2.3%). The rate of limited cGvHD was 7.1% vs. 30% in the TSA group and MTX group, respectively (Fisher's P= 0.12). 23% of patients surviving beyond day +100 in MTX group developed extensive/overlap cGvHD, whereas, there were no cases in the TSA group. The rate of CMV infection in patients not receiving corticosteroid treatment for GVHD was higher in the TSA group, although not statistically significant (36.8% vs. 16%, P=0.27). The rate of invasive fungal infections was similar (10.7% vs. 11.8%). The cumulative incidence of relapse at 2 years was 38.5% vs. 22.8% in the TSA and MTX groups, respectively (Gray's test P=0.18). Non-relapse mortality at 2 years was similar in both groups (42% vs. 48%; Grays's test P=0.8). Day +100 mortality was 14.4% and 27.3% in TSA and MTX group respectively. The median survivals were 251 days (95% CI, 170–332) vs. 349 days (95% CI, 236–462) for TSA and MTX groups, respectively. The 1- and 2-year overall survival were 42.3% and 31.7% for TSA group vs. 47.7% and 34.1% for MTX group, respectively (P=0.704). While the mortality rate from bacterial sepsis were equivalent, more patients in the TSA group who were not receiving corticosteroid treatment for aGvHD died from viral and fungal infection (14.3% vs. 0% at 12 months, Fisher's P=0.014). Summary: This is the first report of the combination of TSA for GvHD prophylaxis in MUD transplants. This regimen resulted in a significant decrease in classic aGvHD as previously reported for combination of Tacrolimus/Sirolimus, and decrease in incidence of cGvHD as reported previously in the studies incorporated ATG in MTX-based regimens. Hence, this did not translate into benefit in overall survival due to an increased rate of relapse and lethal viral and fungal infections with TSA regimen. Our study does not demonstrate an appreciable benefit for the addition of ATG, at the dose used, to sirolimus and tacrolimus for GvHD prophylaxis. Further studies directed at optimizing the dose of ATG to lower the rate of lethal infections may result in an overall benefit. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A prognostic model based on seven immune-related genes predicts the overall survival of patients with hepatocellular carcinoma

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qian Yan ◽  
Wenjiang Zheng ◽  
Boqing Wang ◽  
Baoqian Ye ◽  
Huiyan Luo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
High Risk ◽  
Risk Score ◽  
Immune Cells ◽  
Prognostic Model ◽  
Risk Groups ◽  
Low Risk ◽  
Prognostic Performance ◽  
Immune Related Genes

Abstract Background Hepatocellular carcinoma (HCC) is a disease with a high incidence and a poor prognosis. Growing amounts of evidence have shown that the immune system plays a critical role in the biological processes of HCC such as progression, recurrence, and metastasis, and some have discussed using it as a weapon against a variety of cancers. However, the impact of immune-related genes (IRGs) on the prognosis of HCC remains unclear. Methods Based on The Cancer Gene Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort) datasets, we integrated the ribonucleic acid (RNA) sequencing profiles of 424 HCC patients with IRGs to calculate immune-related differentially expressed genes (DEGs). Survival analysis was used to establish a prognostic model of survival- and immune-related DEGs. Based on genomic and clinicopathological data, we constructed a nomogram to predict the prognosis of HCC patients. Gene set enrichment analysis further clarified the signalling pathways of the high-risk and low-risk groups constructed based on the IRGs in HCC. Next, we evaluated the correlation between the risk score and the infiltration of immune cells, and finally, we validated the prognostic performance of this model in the GSE14520 dataset. Results A total of 100 immune-related DEGs were significantly associated with the clinical outcomes of patients with HCC. We performed univariate and multivariate least absolute shrinkage and selection operator (Lasso) regression analyses on these genes to construct a prognostic model of seven IRGs (Fatty Acid Binding Protein 6 (FABP6), Microtubule-Associated Protein Tau (MAPT), Baculoviral IAP Repeat Containing 5 (BIRC5), Plexin-A1 (PLXNA1), Secreted Phosphoprotein 1 (SPP1), Stanniocalcin 2 (STC2) and Chondroitin Sulfate Proteoglycan 5 (CSPG5)), which showed better prognostic performance than the tumour/node/metastasis (TNM) staging system. Moreover, we constructed a regulatory network related to transcription factors (TFs) that further unravelled the regulatory mechanisms of these genes. According to the median value of the risk score, the entire TCGA cohort was divided into high-risk and low-risk groups, and the low-risk group had a better overall survival (OS) rate. To predict the OS rate of HCC, we established a gene- and clinical factor-related nomogram. The receiver operating characteristic (ROC) curve, concordance index (C-index) and calibration curve showed that this model had moderate accuracy. The correlation analysis between the risk score and the infiltration of six common types of immune cells showed that the model could reflect the state of the immune microenvironment in HCC tumours. Conclusion Our IRG prognostic model was shown to have value in the monitoring, treatment, and prognostic assessment of HCC patients and could be used as a survival prediction tool in the near future.

scholarly journals Non-Myeloablative Conditioning Regimen before T-Cell Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide for Advanced Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4614-4614
Author(s):  
Catalina Montes De Oca ◽  
Thomas Pagliardini ◽  
Stefania Bramanti ◽  
Sabine Furst ◽  
Jean Marc Schiano de Collela ◽  
...  
Keyword(s):  
Research Funding ◽  
Chronic Gvhd ◽  
Disease Status ◽  
Research Support ◽  
Myeloablative Conditioning ◽  
Term Survival ◽  
Gvhd Prophylaxis ◽  
Increased Risk ◽  
Low Incidence

Introduction: allogeneic transplantation (allo-HSCT) is a curative treatment for patients with advanced lymphoma. Haploidentical (haplo-SCT) transplantation extended the accessibility to allo-HSCT, overcoming the issue of donor availability. However, alternative donor allo-HSCT is still considered at higher risk of non-relapse mortality due to the HLA disparity and thus an anticipated higher incidence of GVHD. In this context, the use of a non myeloablative conditioning (NMAC) regimen combined with post transplantation cyclophosphamide (PT-Cy) based GVHD prophylaxis may reduce procedure related toxicity. The aim was to evaluate the toxicity and efficacy of haplo-SCT using NMAC with PT-Cy in advanced lymphoma patients. Methods: We here report the retrospective experience of a bicentric transplantation program. We analyzed a cohort of lymphoma patients undergoing Haplo-SCT and homogeneously receiving NMAC and PT-Cy. Inclusion criteria were: 1) first allo-HSCT for advanced lymphoma between 2009 and 2018; 2) haploidentical donor; 3) NMAC (fludarabine cyclophosphamide and 2 gray TBI GVHD prophylaxis consisted of PT-Cy day+3 and +4 , cyclosporine A and MMF starting from day +5. Multivariate analyses included age, disease type (NHL vs HL), HCT-CI (< vs ≥ 3), graft source (PBSC vs BM), disease status at haplo-SCT (CR vs other). Results: One hundred forty seven patients (73 NHL; 74 HL) with a median age of 46 years (range: 19-71) were included. PBSC (peripheral blood stem cell) was used as graft source in 96 patients (65%). Patients received a median number of 3 conventional chemotherapy lines before haplo-SCT (1-8). Sixty-five (44%) had relapse after Auto-HCT. At the time of haplo-SCT, 96 patients (66%) were in complete remission. The cumulative incidences of day+100 grade 2-4 and 3-4 acute GVHD were 30% and 3%, respectively. The cumulative incidences of 2-year chronic and moderate or severe chronic GVHD were 13% and 8%, respectively. With a median follow up of 39 months (6-114), 2-year NRM was 14%, with a trend for higher risk in patients with HCT-CI ≥ 3 (HR 0.39, 95CI [0.15-1.04] p = 0.061) while age was not associated with an increased risk of NRM (HR 1.01, 95CI [0.98-1.05], p = 0.450). Two-year cumulative incidence of relapse (CIR) was 21% and 18% in HL and NHL patients, respectively. Disease status at the time of haplo-SCT was strongly associated with relapse (HR 2.99, 95CI [1.41-6.35], p = 0.004) In HL patients, 2-year PFS, OS and GRFS were 65%, 77% and 57%, respectively, while corresponding values in NHL patients were 65%, 69% and 55%, respectively. Two-year PFS and GRFS were significantly higher in patients who underwent haplo-SCT in CR (PFS: CR vs. no CR: 72% vs. 55%, p=0.045; GRFS: CR vs. no CR: 63% vs. 42%, p=0.010). There was a trend for better 2-year OS in CR (OS: CR vs. no CR: 78% vs. 63%, p=0.063. Conclusion: We confirm the feasibility of haplo-SCT using NMAC and PT-Cy with low incidence of GVHD (notably severe forms) and NRM. In addition, we observed a relatively low incidence of relapse (19%) in this cohort of heavily pretreated patients, underlining a potent graft-versus-lymphoma effect after haplo-SCT, leading to promising survivals, including high rate of GRFS (>50%), suggesting a preserved long term quality of life in survivors. We conclude that NMAC haplo-SCT with PT-Cy should be considered as a valuable curative option for advanced lymphoma patients, with a favorable toxicity profile and promising long term survival. Figure Disclosures Stoppa: celgene: Other: travel fees, lecture fees; takeda: Other: travel fees. Carlo-Stella:MSD: Honoraria; BMS: Honoraria; Janssen: Other: Travel, accommodations; Boehringer Ingelheim: Consultancy; Genenta Science sr: Consultancy; Sanofi: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Other: Travel, accommodations, Research Funding; Novartis: Consultancy, Research Funding; Servier: Consultancy, Honoraria, Other: Travel, accommodations; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel, accommodations, Research Funding; Rhizen Pharmaceuticals: Research Funding; Celgene: Research Funding; Amgen: Honoraria; Takeda: Other: Travel, accommodations; Janssen Oncology: Honoraria; AstraZeneca: Honoraria. Chabannon:EBMT: Other: Working Party Chair, Board member; Fresenius Kabi: Other: research support; Miltenyi Biotech: Other: research support; Terumo BCT: Other: speaker's fees; Celgene: Other: speaker's fees; Novartis: Other: speaker's fees; Gilead: Other: speaker's fees, hospitalities; Sanofi SA: Other: research support, speaker's fees, hospitalities. Santoro:Takeda: Speakers Bureau; BMS: Speakers Bureau; Roche: Speakers Bureau; Abb-Vie: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Servier: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Lilly: Speakers Bureau; Sandoz: Speakers Bureau; Eisai: Consultancy, Speakers Bureau; Novartis: Speakers Bureau; Bayer: Consultancy, Speakers Bureau; MSD: Speakers Bureau; BMS: Consultancy. Blaise:Sanofi: Honoraria; Jazz Pharmaceuticals: Honoraria; Molmed: Consultancy, Honoraria; Pierre Fabre medicaments: Honoraria.

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