scholarly journals Predictive value of disease risk comorbidity index for overall survival after allogeneic hematopoietic transplantation

2019 ◽  
Vol 3 (3) ◽  
pp. 230-236 ◽  
Author(s):  
Nelli Bejanyan ◽  
Claudio G. Brunstein ◽  
Qing Cao ◽  
Aleksandr Lazaryan ◽  
Celalettin Ustun ◽  
...  
Keyword(s):  
Overall Survival ◽  
Scoring System ◽  
Hematological Malignancies ◽  
Clinical Decision Making ◽  
Disease Risk ◽  
Risk Index ◽  
Assessment Tools ◽  
Free Survival ◽  
Comorbidity Index ◽  
Disease Free

Abstract Allogeneic hematologic cell transplantation (alloHCT) is the only curative therapy for many adults with hematological malignancies. However, it can be associated with substantial risks of morbidity and mortality that are dependent on patient comorbidity– or disease risk–related factors. Several pretransplantation prognostic scoring systems have been developed to estimate survival of patients undergoing alloHCT; however, there is significant interstudy variability in the predictive capacity of these assessment tools. We tested the prognostic capability of a composite scoring system including the disease risk index and HCT comorbidity index (DRCI). The DRCI scoring system was applied pretransplantation to determine whether it predicted clinical outcomes of 959 adult patients with hematological malignancies undergoing alloHCT from 2000 to 2013 at the University of Minnesota. The DRCI score categorized patients into 6 risk groups, with 2-year overall survival ranging between 74% for the very low-risk DRCI group and 34% for the very high-risk DRCI group. In multiple regression analyses adjusted for patient age and donor type, the risk of overall mortality independently increased as the DRCI score increased. Additionally, the DRCI score independently predicted risk of relapse, disease-free survival, and graft-versus-host disease–free/relapse–free survival. Our data demonstrate that the pretransplantation DRCI scoring system predicts outcomes after alloHCT and can be used to guide clinical decision making for patients considering alloHCT.

Reduced Intensity Conditioning Based On Fludarabine, Intravenous Busulfan (2 Days) and Antithymocyte Globulins (2 Days) Results In High Disease Free Survival Without Persisting Gvhd In Patients Transplanted For Hematological Malignancies: Large Single Center Cohort With Long Follow-Up

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3364-3364
Author(s):  
Raynier Devillier ◽  
Sabine Furst ◽  
Roberto Crocchiolo ◽  
Samia Harbi ◽  
Luca Castagna ◽  
...  
Keyword(s):  
Hematological Malignancies ◽  
Disease Risk ◽  
Risk Index ◽  
Chronic Gvhd ◽  
Free Survival ◽  
Grade Ii ◽  
Disease Free

Abstract Introduction Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative option for most of advanced hematological malignancies. In the last fifteen years, the development of reduced intensity conditioning (RIC) regimens allowed the use of Allo-HSCT in patients unfit for standard myeloablative regimens, with low procedure-related mortality and long term anti-tumor effect. Thus, RIC regimens were modified over years to improve survival as well as to decrease long term toxicity after Allo-HSCT but the optimal balance between safety and efficacy is still undefined. We report here our recent experience of RIC regimen based on fludarabine, intravenous busulfan and rabbit antithymocyte globulin (r-ATG). Patients and Methods Selection criteria were 1) patients undergoing first Allo-HSCT for hematological malignancies in our center from 2005 to 2012; 2) RIC regimen based on fludarabine (30 mg/m² daily, from day-6 to day-2), intravenous busulfan (3.2 mg/kg daily, at day-4 and day-3) and r-ATG (2.5 mg/kg daily, at day-2 and day-1 or at day-3 and day-2); 3) peripheral blood stem cell as graft source; 4) matched sibling donor (MSD) or 10/10 matched unrelated donor (MUD) as donor; 5) cyclosporine A as GVHD prophylaxis (started at day-1 at 3 mg/kg). Disease risk index (DRI) and HCT-CI score were applied to each patient to stratify the risk of relapse and non-relapse mortality (NRM) respectively. Results Patient characteristics are illustrated in the Table 1. Two hundred and seven patients with a median age of 59 years (range (19-71) were analyzed. Only 25 patients (12%) had low risk disease according to the disease risk index (DRI, Armand et al., Blood, 2012) and 90 patients (46%) had HCT-CI => 3. Grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) at day 100 were 23% and 9% percent respectively. Overall cumulative incidences of total and extensive chronic GVHD were 37% and 22% respectively. Early NRM (day-100) and overall NRM (5-year) were 5% and 22% respectively. The 5-year cumulative incidence of relapse was 36%. Five-year progression-free survival (PFS) and overall survival (OS) were 41% and 52% respectively. At last follow up, 101 patients were disease free. Among them, 85 (84%) were free of GVHD treatment suggesting an unaltered quality of life for long term cured patients. Outcome according to age (< 60 and => 60) did not express different patterns. The use of MUD results in higher grade II-IV acute GVHD than with MRD transplant (MRD: 13% vs. MUD: 39%, p<0.001). This lead to higher NRM (MRD: 17% vs. MUD: 30%, p=0.013). Inversely, MUD recipients had lower 5-year incidence of relapse (MRD: 42% vs. MUD: 28%, p=0.044) than MRD recipients. This results in similar 5-year PFS (MRD: 41% vs. MUD: 41%, p=0.791) and 5-year OS (OS: MRD: 55% vs. MUD: 48%, p=0.128). Two-year OS was 84%, 68%, 48% and 17% in patients with low, intermediate, high and very high risk disease according to the DRI (p=0.005). Patients with HCT-CI => 3 had shorter OS than those with HCT-CI < 3 (5-year OS: 60% vs. 43%, p=0.013). In multivariate analyses, disease risk (intermediate, HR=2.0 (95CI: 0.8-5.1), p=0.140; high, HR=3.4 (95CI: 1.3-9.0), p=0.015; very high, HR=5.8 (95CI: 1.7-20.4), p=0.006), HCT-CI (=> 3, HR=1.9 (95CI:1.2-2.9), p=0.009) but not age or donor type significantly influenced OS. Discussion and Conclusion RIC Allo-HSCT prepared by fludarabine, 2 days of intravenous busulfan and 2 days of r-ATG results in low incidence of NRM and prolonged survivals. Few patients were concerned with recurrent extensive chronic GVHD, and most of survivors were actually free of both disease and immunosuppressive treatment, suggesting a preserved quality of life. This allows safely extending the use of Allo-HSCT, even over 60 years. However, disease recurrence remains the major issue in this setting notably in advanced stage diseases. New pre- and post-transplantation strategies are needed to improve the overall outcome this relatively safe allogeneic procedure. Disclosures: Prebet: CELGENE: Honoraria.

Induction Therapy with Dasatinib and Prednisone for Patients with Philadelphia Positive ALL

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4907-4907
Author(s):  
Abhishek Chilkulwar ◽  
Salman Fazal ◽  
Jocelyn T. De Yao ◽  
Parik Padhi ◽  
Cyrus Khan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Induction Therapy ◽  
Disease Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Comorbidity Index ◽  
High Comorbidity ◽  
Disease Free ◽  
Matched Donor

Abstract Background: The addition of a Tyrosine Kinase Inhibitor (TKI) to induction chemotherapy has improved the outcome of patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). However, the treatment related mortality and morbidity of intensive treatment increases with age. The use of a TKI alone for induction is less toxic and yields CR rates comparable to combined therapy. Eligibility for post remission hematopoietic stem cell transplantation is less likely to be compromised with TKI induction. We present a retrospective review of patients with Ph+ ALL treated at our institution with dasatinib and prednisone induction who subsequently underwent allogeneic hematopoietic stem cell transplant (allo-HSCT) as post remission therapy. Methods: We retrospectively identified 15 patients with Ph+ ALL treated at our institution between February 2012 and June 2015. Patients received induction therapy with dasatinib at 100 mg or 140mg daily till complete hematological response. Prednisone 60 mg/m2/day (capped at 120 mg daily) was administered until day 24 and then tapered and stopped at day 32. Intrathecal chemotherapy with MTX and Ara-C were administered twice during the induction period. Dasatinib dose reduction/discontinuation was permitted for non-hematological toxicity. Patients who achieved remission proceeded to allo-HSCT if a suitable HLA-matched donor was available. Patients who did not have a suitable HLA matched donor received TKI + POMP maintenance. We calculated CHR, CCyR, disease-free survival (DFS) and overall survival (OS). Results: The median age of patients treated with dasatinib plus prednisone was 62 years (range: 19-73). Baseline patient and disease characteristics are summarized in Table 1. Median WBC count was 22.5 x 109/L. Fourteen of 15 patients treated with dasatinib achieved a CHR (93.3%), 1 patient did not undergo a bone marrow biopsy but had normal blood counts. Median time to CHR was 42 days (range: 22-69). CCYR was obtained in 11 patients (73%) and MMR was achieved in 5 patients (33%). No patient died during induction therapy. The 14 patients who were in CHR after induction, underwent allo-HSCT (n=7), are being evaluated for allo-HSCT (n=3), were unable to undergo allo-HSCT due to a high comorbidity index and/or lack of a suitable donor (n=3) or were lost to follow-up (n=1). Of the 3 patients who were unable to undergo allo-HSCT, 2 patients continue on dasatinib maintenance and 1 patient takes ponatinib. Of 8 patients not yet transplanted 3 relapsed, while only 1 relapse was seen in 7 patients who underwent allo-HSCT. Median DFS was 315 days (range: 57-1061) and median OS was 354 days (range: 107-1082) corresponding Kaplan Meier curves for OS and DFS are shown below. Conclusions: In our adult Ph+ ALL patients induction therapy with dasatinib and prednisone was effective and well tolerated. Patients achieving CHR were able to undergo allo-HSCT with curative intent. This strategy retrospectively appears equal or better than results with induction chemotherapy of conventional variety. Table 1. Patient characteristics Male sex, n (%) 5 (33.3) Age <20, n (%) 1 (6.7) 20-49, n (%) 1 (6.7) ³50, n (%) 13 (86.6) Median (range) 62 (19-73) Median follow-up in months (range) 11.7 (4.1-40) Presenting WBC x 10 9/L < 30, n (%) 8 (53.3) ³ 30, n (%) 7 (46.7) Median (range) 22 (2.8-358.4) Bcr-Abl type p190, n (%) 12 (80) p210, n (%) 2 (13.3) P190 and p210, n (%) 1 (6.7) Bcr-Abl level (1 unknown)* Mean (range) 35.1 (1.8-194.4) Median time to CHR in days (1 unknown), (range) 41.5 (22-69) Induction dose of dasatinib 70mg BID, n (%) 1 (6.7) 100mg daily, n (%) 8 (53.3) 140mg daily, n (%) 6 (40) CCyR after induction achieved, n (%) 11 (73.3) MMR achieved after induction, n (%) 5 (33.3) Dasatinib Dosing after Induction None, n(%) 1 (6.7) 70mg BID, n(%) 1 (6.7) 100mg/day, n(%) 12 (80) 140mg/day, n(%) 1 (6.7) POMP + TKI post induction, n(%) 4 (26.7) Post remission therapy (3 being evaluated for transplant, 1 never achieved CHR, 1 lost to ff-up)+ Transplant, n (%) 7 (46.7) Ponatinib, n (%) 1 (6.7) Dasatinib, n (%) 1 (6.7) HyperCVAD±, n (%) 1 (6.7) TKI maintenance after transplant, n (% of transplanted) 3 (42.9) M351T mutation, n (%) 1 (6.7) F317L mutation, n (%) 1 (6.7) Bcr-Abl detection by PCR with unit in ratio (international scale), +poor performance status or high comorbidity index is the reason for no transplant, ±hyperCVAD initiated but not tolerated. Figure 1. Overall Survival. Figure 1. Overall Survival. Figure 2. Disease Free Survival Figure 2. Disease Free Survival Disclosures Fazal: Novartis: Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau. Off Label Use: Dasatinib use for newly diagnosed Ph+ ALL.

scholarly journals A disease risk index for patients undergoing allogeneic stem cell transplantation

Blood ◽  
2012 ◽  
Vol 120 (4) ◽  
pp. 905-913 ◽  
Author(s):  
Philippe Armand ◽  
Christopher J. Gibson ◽  
Corey Cutler ◽  
Vincent T. Ho ◽  
John Koreth ◽  
...  
Keyword(s):  
Overall Survival ◽  
Disease Risk ◽  
Risk Index ◽  
Progression Free Survival ◽  
Disease Status ◽  
Risk Groups ◽  
Disease States ◽  
Comorbidity Index ◽  
Available Information ◽  
Conditioning Intensity

Abstract The outcome of allogeneic HSCT varies considerably by the disease and remission status at the time of transplantation. Any retrospective or prospective HSCT study that enrolls patients across disease types must account for this heterogeneity; yet, current methods are neither standardized nor validated. We conducted a retrospective study of 1539 patients who underwent transplantation at Dana-Farber Cancer Institute/Brigham and Women's Hospital from 2000 to 2009. Using multivariable models for overall survival, we created a disease risk index. This tool uses readily available information about disease and disease status to categorize patients into 4 risk groups with significantly different overall survival and progression-free survival on the basis of primarily differences in the relapse risk. This scheme applies regardless of conditioning intensity, is independent of comorbidity index, and was validated in an independent cohort of 672 patients from the Fred Hutchinson Cancer Research Center. This simple and validated scheme could be used to risk-stratify patients in both retrospective and prospective HSCT studies, to calibrate HSCT outcomes across studies and centers, and to promote the design of HSCT clinical trials that enroll patients across diseases and disease states, increasing our ability to study nondisease-specific outcomes in HSCT.

Reduced Intensity Allogeneic Tranplants Are Well Tolerated In Patients Over the Age of 60: Identification of Factors Predicting Overall Survival

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2361-2361
Author(s):  
Emmanouil Nikolousis ◽  
Sandeep Nagra ◽  
Janice Ward ◽  
Fiona L Dignan ◽  
Bronwen E. Shaw ◽  
...  
Keyword(s):  
Overall Survival ◽  
Older Patients ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Free Survival ◽  
Post Transplant ◽  
Comorbidity Index ◽  
Bed Days ◽  
Disease Free ◽  
Reduced Intensity

Abstract Abstract 2361 Introduction: Reduced intensity allogeneic transplants represent a potentially curative therapy in older patients with haematological malignancies. However the upper age limit for transplantation using a sibling or unrelated donor is unclear and few studies have addressed this important issue. In the UK in vivo T cell depletion utilising alemtuzumab is commonly used as a strategy to reduce the risk of acute and chronic graft-versus-host disease (GVHD) but this manoeuvre impairs immune reconstitution and may pose a particular problem in older patients. Aim: We analysed the outcome of patients over the age of 60 after an alemtuzumab based reduced intensity allograft from five UK Transplant Centres with the aim of identifying factors determining long term outcome and also factors affecting the duration of inpatient admission during the first 100 days post transplant. A modified Charlson's comorbidity index score (Sorror modified HCT comorbidity index) was applied to analyse the transplant outcomes of these patients according to the presence of transplant co-morbidities. Patients and Methods: We have studied the outcome of 161 patients (89 male, 72 female) after an alemtuzumab conditioned reduced allograft allograft for a haematological malignancy. The median age of the patients was 62 years(range 60–72). 115 patients had a transplant for myeloid malignancies (87 acute myeloid leukaemia, 21 myelodysplastic syndrome, 2 chronic myeloid leukaemia, 5 myelofibrosis) and 46 for lymphoid malignancies (18 Non_Hodgkin's lymphoma, 14 chronic lymphocytic leukaemia, 4 T-prolymphocytic leukaemia, 7 multiple myeloma and 3 acute lymphoblastic leukaemia). 93 patients received an unrelated donor transplant and 68 had a sibling transplant. The great majority of patients were transplanted using a Fludarabine/Melphalan conditioning regimen(n=118) whilst 13 received a combination of fludarabine and busulphan, 21 BEAM (BCNU, cytarabine, etoposide, melphalan) and 9 a combination of BEAM and fludarabine. The median follow up was 19.1 months (range 2–94 months). Results: The one year overall survival for the whole group was 52% and the predicted two year OS 46%. The transplant related mortality (TRM) was 19% in the first 100 days post transplant and 23% in the first year post transplant. 40 patients (25%) relapsed. 25 patients (21%) developed Grade III-IV acute GvHD and 16 (10%) patients developed chronic extensive GvHD. There was a weakly negative correlation between Age and Bed Days(p:0.05843) but the correlation between high comorbidity index (3 or greater than 3) and increased bed days is significant(P:0.0013). Transplant outcomes were affected by Sorror modified comorbidity index for HCT.A score of 3 and above was significantly associated with decreased overall survival (P:0.001) and interestingly with decreased disease free survival (P:0.02). CMV status and stem cell dose did not have any impact on overall survival and disease free survival and CR1 at transplantation was showed a trend towards increased overall survival(P:0.05). Conclusions: Reduced intensity alemtuzumab based stem cell transplant can be delivered safely in patients above the age of 60. It appears that a Sorror comorbidity score of 3 and above has a negative impact on overall survival and disease free survival of these patients and significantly increases inpatient days.These observations require confirmation in a larger cohort of patients but suggest that the selection of patients above the age of 60 for a reduced intensity transplants will be facilitated by incorporation of the Sorror HCI comorbidity index into a transplant algorithm. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Hematopoietic Cell Transplantation for Elderly Patients: Prognosis Determined By Disease Risk Index

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2305-2305
Author(s):  
Fiona C. He ◽  
Aleksandr Lazaryan ◽  
Qing Cao ◽  
Claudio G Brunstein ◽  
Shernan G. Holtan ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Treatment Failure ◽  
Hematological Malignancies ◽  
Hematopoietic Cell Transplantation ◽  
Disease Risk ◽  
Risk Index ◽  
Chronic Gvhd ◽  
Free Survival ◽  
Entire Cohort ◽  
Neutrophil Engraftment

Abstract Survival of elderly patients with hematological malignancies remains suboptimal despite many older adults receiving reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT). We studied the impact of disease risk index (DRI) on clinical outcomes of 196 elderly patients (≥60 years old) with hematological malignancies receiving RIC alloHCT between 2000-2013. Median age at transplant was 64.8 years (range, 60-75; 53% age 60-64 and 47% age ≥65). More comorbidities (HCT-CI ≥3) were present in 70 patients (35.7%) and Karnofsky performance score (KPS) was < 80% in 34 patients (17.3%) prior to transplant. Peripheral blood or bone marrow allografting was performed in 100 patients (51.1%) and umbilical cord blood allografting in 96 patients (48.9%). DRI classified 12 patients (6.1%) as low risk (LR), 146 patients (74.5%) as intermediate risk (IR), and 38 patients (19.4%) as high or very high-risk (HR/VHR). Neutrophil engraftment at day 42 did not differ between LR/IR and HR/VHR (95% vs. 100%, p=.40), whereas platelet engraftment at 6 months was significantly lower for HR/VHR (76% vs. 58%, p=.08). Treatment related mortality (TRM) at 2 years was similar in LR/IR and HR/VHR (28% vs. 34%, p=.12). Overall relapse incidence was 30% in the entire cohort and increased in HR/VHR (26% for LR/IR vs. 44% for HR/VHR; p<.01). Notably, 2-year disease free survival (DFS) and overall survival (OS) were both significantly lower in HR/VHR groups. DFS was 39% in entire cohort (44% for LR/IR vs. 21% for HR/VHR; p<.01), and OS in entire cohort was 47% (52% for LR/IR vs. 29% for HR/VHR; p<.01; Figure). For LR/IR and HR/VHR DRI groups, the incidence of grade II-IV acute GVHD was similar (41% and 47% at 6 months, p=.32) and the incidence of chronic GVHD was similar (35% and 31% at 2-years, p=.07). GVHD and relapse free survival (GFRS) at 2-years was significantly worse for HR/VHR DRI group (25% for LR/IR vs. 0% for HR/VHR; p<.01). All clinical outcomes were similar between those 60-64 and ≥65 years of age. In multiple regression analysis, after adjusting for a graft source, platelet recovery was worse for HR/VHR DRI group (HR=0.56; 95% CI 0.35-0.91; p=.02), while neutrophil engraftment was not influenced by DRI. HR/VHR DRI was a risk factor for increased risk of relapse after alloHCT (HR=2.05; 95% CI 1.14-3.69; p=.02). After adjusting for graft source, KPS and year of HCT, treatment failure (inverse of DFS; HR=1.83; 95% CI 1.16-2.87; p=.02) and overall mortality (HR=1.87; 95% CI 1.16-3.02; p=.01) were significantly increased for HR/VHR DRI group. Although DRI did not affect the risk of acute or chronic GVHD, GRFS was significantly worse for patients with HR/VHR DRI (HR=2.13; 95% CI 1.46-3.11; p<.01). We conclude that in this cohort of elderly patients, worse DRI remains a significant prognostic factor for post-transplant relapse, treatment failure, mortality and GRFS. While eligible elderly patients up to age 75 with hematologic malignancies should be considered for RIC alloHCT, alternative or novel therapies should be considered for those with HR/VHR DRI. Figure Figure. Disclosures No relevant conflicts of interest to declare.

The Disease Risk Index Is a Robust Tool for Allogeneic Hematopoietic Stem Cell Transplantation Risk Stratification: An Independent Validation Study on a Large Cohort of the European Society for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 988-988 ◽  
Author(s):  
Roni Shouval ◽  
Joshua Fein ◽  
Myriam Labopin ◽  
Nicolaus Kroger ◽  
Rafael F. Duarte ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Hematological Malignancies ◽  
Disease Risk ◽  
Risk Index ◽  
Risk Groups ◽  
Advisory Committees ◽  
Very High

Abstract Background: Allogeneic stem cell transplantation is a potentially curative procedure to a long list of hematological malignancies, but involves substantial risk of morbidity and mortality. Means for accurately predicting outcome and assessing risk are thus greatly needed. The Disease Risk Index (DRI) is a prognostic tool developed and validated by Armand et al. across a wide range of hematological malignancies (Blood 2012, Blood 2014) on cohorts of American patients. The Index stratifies patients into 4 distinct risk groups (low, intermediate, high, very high) and has yet to be validated in an international cohort. We sought to evaluate the validity of the DRI in a large cohort of European patients. Methods: This was a retrospective validation study on an independent cohort of patients undergoing allogeneic HSCT and reported the European Society for Blood and Marrow Transplantation (EBMT). Patients included had a hematological malignancy and underwent allogeneic transplantation between the years of 2000 and 2015. Risk groups were coded in accordance with the refined DRI (Blood, 2014). Outcomes were evaluated 4 years after the allogeneic HSCT. Overall survival (OS) was calculated with the Kaplan-Meier method. The log-rank test was used for comparisons of Kaplan-Meier curves. Cumulative incidence curves for nonrelapse mortality (NRM) and relapse with or without death were constructed reflecting time to relapse and time to NRM, respectively, as competing risks. The difference between cumulative incidence curves in the presence of a competing risk was tested with the Gray method. The prognostic effect of the DRI strata was estimated using a Cox proportional hazard model for OS and a Fine and Gray model for NRM and relapse. Results: A total of 89,061 patients from 423 transplantation centers were included in the analysis. Median age was 48.3 (IQR 36.2-57.5). The most frequent indication for transplantation was AML (39,530 patients) followed by ALL (16,206) and MDS (9,750); other indications spanned the spectrum of hematological malignancies. The majority of patients were in 1st or 2nd complete remission (54%). The median follow-up period was 3.6 years. Approximately 63% of patients were classified as intermediate risk by DRI, suggesting that this group could be further partitioned. The 4 year overall survival (95% CI) of the low, intermediate, high, and very high risk groups was 60.8% (59.9-61.8), 51.3% (50.8‐51.8), 27.0% (26.1‐27.8), 18.4% (17.1-19.8) (Figure 1). The same groups corresponded with increasing cumulative incidence of relapse; 8.9% (8.3-9.4), 19.3% (18.9-19.7), 39.0% (37.8-39.6), 45.1% (43.4-46.7), respectively. The DRI groups also showed increasing hazard between strata in the overall survival setting; intermediate risk was associated with a hazard ratio of 1.32, high risk 2.67 and very high risk 3.71 relative to low risk. Relapse showed a similar pattern. NRM was less strongly stratified by DRI (Table 1). The DRI groups maintained a similar risk, regardless of whether the transplantation was performed prior or after 2008. DRI was the strongest determinant of overall survival and relapse when introduced to a multivariable model with additional covariates. AUC for the index at 4 years was 62.5 for OS, 58.5 for NRM and 68.2 for relapse. Conclusions: We have validated the Disease Risk Index in a massive European data set. The groupings suggested by the DRI corresponded with distinct risk groups for overall mortality and relapse. Overall, our results indicate the international applicability of this robust prognostic tool. Figure 1. Kaplan-Meyer survival curves for overall survival, stratified by DRI Figure 1. Kaplan-Meyer survival curves for overall survival, stratified by DRI Table 1 Table 1. Disclosures Bader: Medac: Consultancy, Research Funding; Riemser: Research Funding; Neovii Biotech: Research Funding; Servier: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Bonini:Molmed SpA: Consultancy; TxCell: Membership on an entity's Board of Directors or advisory committees. Dreger:Gilead: Consultancy; Janssen: Consultancy; Novartis: Speakers Bureau; Gilead: Speakers Bureau; Novartis: Consultancy; Roche: Consultancy. Kuball:Gadeta B.V,: Membership on an entity's Board of Directors or advisory committees. Montoto:Roche: Honoraria; Gilead: Research Funding.

scholarly journals Haploidentical Transplant with Peripheral Blood Hematopoietic Cell Grafts in Older Adults with AML or MDS

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4658-4658
Author(s):  
Michael Slade ◽  
John F DiPersio ◽  
Peter Westervelt ◽  
Ravi Vij ◽  
Geoffrey L. Uy ◽  
...  
Keyword(s):  
Older Adults ◽  
Overall Survival ◽  
Cumulative Incidence ◽  
Older Patients ◽  
Research Funding ◽  
Disease Risk ◽  
Risk Index ◽  
Hematopoietic Cell ◽  
Comorbidity Index

Background: Modern post-transplant cyclophosphamide (PTCy) protocols with haploidentical (haplo) donors have dramatically expanded the donor pool for patients requiring hematopoietic cell transplantation (HCT). Initial studies were performed with bone marrow grafts, which require the donor to undergo anesthesia during harvest. Consequently, the use of mobilized peripheral blood hematopoietic cells (PBHC) may be desirable, especially with older donors. However, data on PBHC haplo-HCT in older adults is lacking. Objectives: To report the impact of age on transplant-related outcomes in a large cohort of patients undergoing haplo-HCT with PTCy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Methods: We retrospectively identified all adult patients undergoing T cell replete haplo-HCT with PTCy for AML or MDS at our institution from January 2009 to June 2016. Patients were grouped into three cohorts: Age1 (<55), Age2 (55-65) and Age3 (>65). Patients were scored for disease risk and underlying comorbidities using the Disease Risk Index (DRI) and HCT Comorbidity Index (HCT-CI). Overall survival (OS) was analyzed using a Cox Proportional Hazards (CPH) model, with all variables pre-specified. Results: We identified 107 patients, 92 with AML and 15 with MDS. Median follow up was 8.0 months in all patients and 18.3 months in patients surviving at last follow-up. Median donor age was 39, 34 and 49 in Age1, Age2 and Age3, respectively (p = 0.02). Donor relationship was also significantly different among Age1 (child: 25%, sibling: 53%, parent, 22%), Age2 (62%, 38%, 0%) and Age3 (64%, 36%, 0%) (p < 0.001). Younger patients were significantly more likely to receive myeloablative conditioning (55% vs. 35% vs. 27%, p = 0.04). Median OS was 448, 417 and 147 days in Age1, Age2 and Age3 patients. Actuarial 2-year OS was 40%, 34% and 11%, respectively. The 2-year cumulative incidence of relapse was 34%, 30% and 56%. The 2-year cumulative incidence of treatment-related mortality was 30%, 45% and 35%. There was a trend towards a lower 100-day cumulative incidence grade II-IV acute graft-versus host-disease (aGVHD) in older patients (44% vs. 35% vs. 15%, p = 0.07) but not in grade III-IV aGVHD (16% vs. 7% vs. 5%, p = 0.42). Similarly, there was a trend towards a lower 1-year cumulative incidence of cGVHD in older patients (37% vs. 36% vs. 10%, p = 0.07), but not severe cGVHD (5% vs. 0% vs. 0%, p = 0.16). No significant difference was seen in median time to neutrophil engraftment (17 vs. 18 vs. 17 days, p = 0.14) or platelet engraftment (28 vs. 30.5 vs. 32 days, p = 0.93). Univariate and multivariate CPH model of OS is summarized in table 1. Age > 65 and prior allogeneic HCT were associated with significantly worse survival. Conclusions: The use of PBHC haplo-HCT in older adults with AML or MDS is a feasible treatment option. However, a careful pre-transplant evaluation and analysis of risks and benefits is warranted when offering this transplant modality to older adults. Even after adjusting for pre-transplant comorbidity and disease risk, older age is associated with inferior survival in this cohort. Cox Proportional Hazard Analysis of Overall Survival. Abbreviations: Hematopoietic Cell Transplant Comorbidity Index (HCT-CI), Disease Risk Index (DRI) Figure 1 Overall survival by age Figure 1. Overall survival by age Disclosures DiPersio: Incyte Corporation: Research Funding. Vij:Takeda: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Novartis: Honoraria; Celgene: Consultancy; Bristol-Myers Squibb: Honoraria; Janssen: Honoraria; Karyopharm: Honoraria. Schroeder:Incyte Corporation: Honoraria, Research Funding.

Comparison of clinical outcomes between enucleation and regular pancreatectomy in patients with non-functional pancreatic neuroendocrine tumors: a retrospective multicenter and propensity score-matched study

2021 ◽  
Author(s):  
Zhen Yang ◽  
Hengjun Gao ◽  
Jun Lu ◽  
Zheyu Niu ◽  
Huaqiang Zhu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Postoperative Complications ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Neuroendocrine Tumors ◽  
Disease Free Survival ◽  
Pancreatic Neuroendocrine Tumors ◽  
Free Survival ◽  
Estimated Blood Loss ◽  
Disease Free

Abstract Objective There are limited data from retrospective studies on whether therapeutic outcomes after regular pancreatectomy are superior to those after enucleation in patients with small, peripheral and well-differentiated non-functional pancreatic neuroendocrine tumors. This study aimed to compare the short- and long-term outcomes of regular pancreatectomy and enucleation in patients with non-functional pancreatic neuroendocrine tumors. Methods Between January 2007 and July 2020, 227 patients with non-functional pancreatic neuroendocrine tumors who underwent either enucleation (n = 89) or regular pancreatectomy (n = 138) were included. Perioperative complications, disease-free survival, and overall survival probabilities were compared. Propensity score matching was performed to balance the baseline differences between the two groups. Results The median follow-up period was 60.76 months in the enucleation group and 43.29 months in the regular pancreatectomy group. In total, 34 paired patients were identified after propensity score matching. The average operative duration in the enucleation group was significantly shorter than that in the regular pancreatectomy group (147.94 ± 42.39 min versus 217.94 ± 74.60 min, P &lt; 0.001), and the estimated blood loss was also significantly lesser (P &lt; 0.001). The matched patients who underwent enucleation displayed a similar overall incidence of postoperative complications (P = 0.765), and a comparable length of hospital stay (11.12 ± 3.90 days versus 9.94 ± 2.62 days, P = 0.084) compared with those who underwent regular pancreatectomy. There were no statistically significant differences between the two groups in disease-free survival and overall survival after propensity score matching. Conclusion Enucleation in patients with non-functional pancreatic neuroendocrine tumors was associated with shorter operative time, lesser intraoperative bleeding, similar overall morbidity of postoperative complications, and comparable 5-year disease-free survival and overall survival when compared with regular pancreatectomy.

scholarly journals The role of functional polymorphisms in oxidative stress-related genes on early-stage breast cancer survival

2021 ◽  
pp. 172460082110111
Author(s):  
Erika Korobeinikova ◽  
Rasa Ugenskiene ◽  
Ruta Insodaite ◽  
Viktoras Rudzianskas ◽  
Jurgita Gudaitiene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Single Nucleotide Polymorphisms ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Free Survival ◽  
Disease Free

Background: Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer. Methods: The current study investigated the associations of functional single nucleotide polymorphisms in the NFE2L2, HMOX1, P21, TXNRD2, and ATF3 genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I–II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays. Results: The CA+AA genotypes of P21 rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size ( P=0.041 and P=0.022, respectively). The TT genotype in ATF3 rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status ( P=0.023, P=0.046, and P=0.040, respectively). In both, univariate and multivariate Cox analysis, TXNRD2 rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; P=0.025) and overall survival (multivariate HR 2.248; P=0.029). The ATF3 rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; P=0.006), metastasis-free survival (multivariate HR 4.759; P=0.018), and overall survival (multivariate HR 3.280; P=0.048). Conclusion: Our findings suggest that P21 rs1801270 is associated with lymph node metastasis and larger tumor size, and ATF3 rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, TXNRD2 rs1139793 and ATF3 rs11119982, were detected. Further investigations are needed to confirm the results of the current study.

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