Graft-Versus-Leukemia (GVL) Effect After Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) as Treatment for Acute Myeloid Leukemia (AML): a Survey From the Acute Leukemia Working Party of the EBMT.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3313-3313
Author(s):  
Frederic Baron ◽  
Myriam Labopin ◽  
Mohamad Mohty ◽  
Nadezda Basara ◽  
Dietger Niederwieser ◽  
...  
Keyword(s):  
High Risk ◽  
Lower Risk ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Working Party ◽  
Cox Models ◽  
Landmark Analysis ◽  
Factors Associated ◽  
The Impact ◽  
Risk Of Relapse

Abstract Abstract 3313 Poster Board III-201 RIC allo-SCT has been increasingly used as treatment for AML patients (pts) ineligible for myeloablative allo-SCT. Previous studies have observed a lower risk of relapse in pts who experienced chronic GVHD after RIC allo-SCT versus in those who did not. The objective of the current study was to further investigate the association between chronic GVHD and relapse in a large cohort of pts given RIC allo-SCT as treatment for AML. Data from 1188 AML pts in first or second CR transplanted between 2000 and 2008 following a RIC regimen at EBMT affiliated centers were analyzed. Patients were given PBSC from HLA-identical sibling (MRD, n=879), or from HLA-matched unrelated donors (MUD, n=309). RIC was defined as Busulfan conditioning regimens containing ≤ 8mg/kg total dose, or TBI <6 Gy. Median pt age at transplantation was 55 (range, 18-76) yrs in pts given grafts from MRD, versus 57 (range, 19-72) yrs in those given grafts from MUD. 54 pts had good risk (4.5%), 564 standard-risk (47.5%), and 116 high-risk (9.8%) cytogenetics, while cytogenetic was unknown in 454 pts (38.2%). The impact of chronic GVHD on relapse risk, non-relapse mortality (NRM) and leukemia-free survival (LFS) was assessed by time-dependent multivariate Cox models and in a landmark analysis. Three-yr incidences of relapse, NRM and LFS were 35 ± 2%, 14 ± 2%, and 50 ± 2%, respectively, while 2-yr incidence of chronic GVHD was 49 ± 2%. In a landmark analysis at 18 months after allo-SCT, 5-year relapse rates were 10 ± 2% versus 19 ± 3% for patients with or without chronic GVHD (P=0.04), respectively. In multivariate Cox models, CR2 versus CR1 (P=.003), pt age > 55 yrs (P=.008), alemtuzumab use in the RIC (P=.048), TBI-based RIC (P=.006), high-risk cytogenetics (P=.001), and absence of chronic GVHD (P=.015) were each associated with higher risk of relapse. Factors associated with high NRM were MUD versus MRD (P=.003), grade II-IV acute GVHD (P<.001), and chronic GVHD (P=.002). Factors associated with lower LFS were CR2 versus CR1 (P=.003), pt age > 55 yrs (P=.007), alemtuzumab use in the RIC (P=.012), and high-risk cytogenetics (P=.003). In conclusion, in this cohort of AML patients transplanted in remission, chronic GVHD was associated with a lower risk of relapse while profound in-vivo T cell depletion with alemtuzumab was associated with higher relapse rate suggesting that GVL effects play a role in preventing AML relapse in patients given RIC allo-SCT. Therefore, closed surveillance of patients in this setting not presenting chronic GVHD such as decreasing of immunosuppression should be further investigated. Disclosures No relevant conflicts of interest to declare.

scholarly journals The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia

2019 ◽  
Vol 3 (4) ◽  
pp. 670-680 ◽  
Author(s):  
Moshe Yeshurun ◽  
Daniel Weisdorf ◽  
Jacob M. Rowe ◽  
Martin S. Tallman ◽  
Mei-Jie Zhang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lower Risk ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Low Grade ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Graft Versus Leukemia ◽  
The Impact ◽  
Risk Of Relapse

Abstract Allogeneic hematopoietic cell transplant is a potential curative therapy for acute lymphoblastic leukemia (ALL). Delineating the graft-versus-leukemia (GVL) effect as a function of graft-versus-host disease (GVHD) offers the potential to improve survival. We examined 5215 transplant recipients with ALL reported to the Center for International Blood and Marrow Transplant Research registry. Overall survival (OS) was compared according to the presence and severity of GVHD and evaluated in 3 cohorts: 2593 adults in first or second complete remission (CR1/CR2), 1619 pediatric patients in CR1/CR2, and 1003 patients with advanced (CR ≥3 or active disease) ALL. For patients in CR1/CR2, development of acute GVHD (aGVHD) or chronic GVHD (cGVHD) was associated with lower risk of relapse than no GVHD (hazard ratio [HR], 0.49-0.69). Patients with advanced ALL developing grades III and IV aGVHD or cGVHD were also at lower risk of relapse (HRs varied from 0.52 to 0.67). Importantly, adult and children in CR1/CR2 with grades I and II aGVHD without cGVHD experienced the best OS compared with no GVHD (reduction of mortality with HR, 0.83-0.76). Increased nonrelapse mortality accompanied grades III and IV aGVHD (HRs varied from 2.69 to 3.91) in all 3 cohorts and abrogated any protection from relapse, resulting in inferior OS. Patients with advanced ALL had better OS (reduction in mortality; HR, 0.69-0.73) when they developed cGVHD with or without grades I and II aGVHD. In conclusion, GVHD was associated with an increased GVL effect in ALL. GVL exerted a net beneficial effect on OS only if associated with low-grade aGVHD in CR1/CR2 or with cGVHD in advanced ALL.

Impact of Targeted Immunotherapies and Novel Cytogenetic and Clinical Risk Groups on Outcome after Allogeneic Hematopoietic Stem Cell Transplant (AlloHCT) for Acute Lymphoblastic Leukemia (ALL): The Mayo Clinic Cohort

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2588-2588
Author(s):  
Zaid Abdel Rahman ◽  
Michael G. Heckman ◽  
Kevin C. Miller ◽  
Patricia Greipp ◽  
Matthew R Spiegel ◽  
...  
Keyword(s):  
High Risk ◽  
Tyrosine Kinase ◽  
Targeted Therapies ◽  
Mayo Clinic ◽  
Lower Risk ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Risk Groups ◽  
Increased Risk ◽  
The Impact

Introduction Novel high-risk groups have been identified in adult ALL, including secondary (sALL) and Philadelphia-like ALL (Ph-like, based on CRLF2, IgH, ABL2, JAK2 and other tyrosine kinase translocations), and those with minimal residual disease >0.1% (MRD+) after induction therapy. Novel targeted therapies are now routinely incorporated into 1st line regimens, including tyrosine kinase inhibitors (BCR-ABL1-pos), rituximab (CD20+) and blinatumomab (Blina) for MRD+. The impact of these novel high risk groups and therapies after alloHCT is unknown; therefore, we evaluated their impact on overall survival (OS), relapse rate (REL), non-relapse mortality (NRM) and acute and chronic GVHD. Methods We evaluated pts receiving 1st Allo-HCT for ALL at Mayo Clinic (Rochester, Phoenix, and Jacksonville) from 2008-2018 for outcomes of interest, specifically the impact of novel therapies and risk groups. Associations of patient factors with outcomes were examined using univariable (UVA) and multivariable (MVA) Cox proportional hazards regression models, where the cause-specific hazard of the given outcome was modeled to account for the competing risk of death. Results We identified 261 consecutive AlloHCT recipients during the study period. Median age at transplant was 48 years (18-72) and 147 (56.3%) were male. The median comorbidity (HCT-CI) score was 2 (0-8). 213 pts (81.6%) had B-lineage ALL, of which 85 (32.6%) were BCR-ABL-pos, 17 (6.5%) Ph-like (identified by FISH), 16 (6.1%) hypoploidy/near triploidy (Hy/Tri), and 67 (25.7%) pre-B ALL NOS. The remaining 48 (18.4%) had T-ALL. 30 pts (11.5%) had sALL (i.e. prior chemo/radiotherapy for another malignancy). HyperCVAD was the most common 1st line regimen (68.2%). 243 (93.1%) pts achieved Complete Remission (CR1) after induction therapy, and 203 (77.8%) were in CR1 at the time of alloHCT. Blina was administered for MRD+ in 14 pts (5.4%), and for relapsed/refractory ALL (R/R) in 13 (27% of R/R pts), 7 of whom received Blina as initial therapy for R/R. Donors were matched unrelated in 149 (57.1%), matched related in 98 (37.5%), and haploidentical in 14 (5.4%). Peripheral blood (PB) grafts were used in 233 (89.3%). 103 (54.5%) were donor:recipient (D:R) sex-matched, and 86 D:R mismatched [47 (24.9%) M:F; and 39 (20.6%) F:M]. Myeloablative conditioning was used for the majority (78.5%) mostly with Cy/TBI (60.5%). Standard GVHD prophylaxis regimens were used. Outcomes Median follow-up after transplant was 22.4 months (0.5-135), and 51 (19.5%) had REL. The 1, 2 and 5-year survival rates were 71.9%, 64.9%, and 54.1%, respectively (Figure 1). Acute GVHD developed in 144 (55.2%) and chronic GVHD in 100 (38.3%). Ph-like ALL, Blina for MRD+, Blina for R/R, sALL and CD20-pos had no independent impact on OS. In contrast, age>60, Hy/Tri, and >CR1 at alloHCT were associated with worse OS in UVA, however, in MVA only pre-B ALL NOS was associated with better OS. Female:male D:R status was associated with inferior OS. Blina for R/R disease was associated with increased risk of REL in UVA [HR 5.26 95% CI (1.33, 20.00), p=0.017], whereas other novel high risk groups had no impact on REL. In contrast, T-ALL, Hy/Tri and >CR1 at AlloHCT were associated with increased REL in UVA, but only T-ALL and Hy/Tri continued to predict for increased REL in MVA. Secondary ALL was associated with increased NRM in UVA [HR 1.96 95% CI (1.07, 3.57), p=0.028], whereas other novel high risk groups had no impact on NRM. In contrast, age>60, >CR1 at AlloHCT and D:R sex mismatch were associated with higher NRM in UVA, but only sex mismatch and >CR1 at AlloHCT were associated with higher NRM in MVA. TBI use was associated with higher risk of acute GvHD (p=0.008) and ATG use with lower risk chronic GVHD (p<0.001). Similarly non-PB grafts were associated with a lower risk of chronic GVHD (p=0.005). Results for OS, REL, NRM, acute and chronic GVHD analysis are shown in Table 1. Conclusion Novel high risk groups (CD20+, Ph-like and sALL) do not appear to adversely impact OS after alloHCT, although sALL was associated with increased risk of NRM. Interestingly, pre-B-ALL NOS appear to be associated with favorable OS. Novel targeted therapies also do not independently predict outcome, with the exception of Blina for R/R ALL which may be associated with REL after subsequent alloHCT (a subgroup for whom novel maintenance strategies should be explored). Our analysis highlights the importance of allo-HCT for novel high risk ALL subgroups. Disclosures Patnaik: Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy. Foran:Agios: Honoraria, Research Funding.

scholarly journals Impact of Chronic Graft-Versus-Host disease (GVHD) After Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) As Treatment for Acute Myeloid Leukemia (AML): A Survey From the Acute Leukemia Working Party of the EBMT

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 321-321
Author(s):  
Frederic Baron ◽  
Myriam Labopin ◽  
Dietger Niederwieser ◽  
noel-Jean Milpied ◽  
Jan J Cornelissen ◽  
...  
Keyword(s):  
Lower Risk ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Time Dependent ◽  
Graft Versus Leukemia ◽  
Grade Ii ◽  
The Impact ◽  
Risk Of Relapse ◽  
Time Point

Abstract Abstract 321 The goal of RIC allo-SCT is to harness the graft-versus-leukemia (GVL) effect, while minimizing toxicities and the risk of GVHD. However, prior studies have shown a lower risk of relapse in AML patients (pts) who experienced chronic GVHD after RIC allo-SCT versus in those who did not. Here, we investigated the impact of occurrence of GVHD on transplantation outcomes in a large cohort of AML pts given allogeneic PBSC after RIC conditioning. Data from 1859 AML pts in first (n=1439) or second (n=420) CR transplanted between 2000 and 2009 following a RIC regimen at EBMT affiliated centres were analyzed. Pts were given PBSC from HLA-identical sibling (MRD, n=1208), or from HLA-matched unrelated donors (MUD, n=651). Median pt age at transplantation was 56 y (range, 18–77). 338 male pts were given grafts from female donors. RIC was based on low-dose TBI in 520 (28%) pts, while the remaining pts received chemotherapy-based RIC. ATG was given in 269 (22%) MRD and in 267 (41%) MUD recipients, respectively, while 151 (13%) MRD and 165 (25%) MUD recipients received in-vivo T cell depletion with alemtuzumab. The impact of chronic GVHD on relapse risk, non-relapse mortality (NRM), leukemia-free survival (LFS), and overall survival (OS) was assessed using time-dependent multivariate Cox models and in a landmark analysis at 18 months after transplant. Three-year incidences of relapse, NRM, LFS and OS were 34±1%, 15±1%, 51±2% and 60±2% in MRD recipients, respectively, and 34±2% (p=NS), 24±2% (P<0.001), 42±2% (P=0.001) and 47±2% (P=0.001) in MUD recipients, respectively. Grade II, III and IV acute GVHD were observed in 133 (11%), 61 (5%) and 30 (2%) MRD recipients and in 119 (18%), 41 (6%) and 24 (4%) MUD recipients, respectively. The 3-y cumulative incidence of chronic GVHD was 47%. Fifty-three percent of patients with chronic GVHD had extensive chronic GVHD, while the remaining 47% had limited chronic GVHD. In multivariate analyses, occurrence of grade II-IV acute GVHD was associated with a lower risk of relapse (HR=0.8; P=0.04), a higher risk of chronic (HR=2.2; P<0.001) and extensive chronic GVHD (HR=2.8; P<0.001), a higher risk of NRM (HR=2.4 P<0.001), a worsened LFS (HR=1.3; P=0.01), and a worsened OS (HR=1.5; P<0.001). In multivariate time-dependent analyses, occurrence of limited chronic GVHD was associated with a lower risk of relapse (HR=0.7; P=0.05), comparable NRM (HR=1.4; P=0.16), comparable LFS (HR=0.9; P=0.29) and better OS (HR=0.5; P<0.001), while occurrence of extensive chronic GVHD was associated with a lower risk of relapse (HR=0.6; P=0.01), higher NRM (HR=3.2; P<0.001), a trend for worsened LFS (HR=1.3; P=0.06) and comparable OS (HR=0.9; P=0.34). The median interval from transplantation to occurrence of chronic GVHD was 163 (range, 100–1545) days. To further assess the graft-versus-leukemia effect of chronic GVHD, we performed a landmark analysis in patients who were leukemia-free at 18 months after transplantation (n=776). Median follow-up from this landmark time-point was 24 (range, 0.1–112) months. Two-year relapse, NRM, LFS and OS were 16±2%, 2.5±1%, 82±2%, and 89±2%, respectively, in patients without chronic GVHD before the landmark time-point, versus 9±1% (P=0.001), 8±1% (P<0.001), 83±2% (P=0.65), and 86±2% (P=0.38), respectively, in patients with chronic GVHD before the landmark time-point.In conclusion, in this cohort of AML patients transplanted in remission, occurrence of chronic GVHD was associated with a lower risk of relapse that translated to better OS in patients with limited chronic GVHD but not in those with extensive chronic GVHD who experienced higher long term NRM, highlighting the need for long term prospective assessment of long term effects and quality of life in patients receiving RIC allo-SCT. Disclosures: No relevant conflicts of interest to declare.

Clofarabine Containing Conditioning Regimen for Allo-SCT in AML/ALL Patients: A Survey From the Acute Leukemia Working Party of EBMT

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3004-3004
Author(s):  
Patrice Chevallier ◽  
Myriam Labopin ◽  
Stefanie Buchholz ◽  
Arnold Ganser ◽  
Fabio Ciceri ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Working Party ◽  
Acute Leukemias ◽  
Conditioning Regimens ◽  
Reduced Toxicity ◽  
Active Disease

Abstract Abstract 3004FN2 Clofarabine (CLO), a second generation purine analogue, has demonstrated an efficient anti-leukemia activity while showing a favorable toxicity profile. The aim of our study was to analyse the results of CLO as part of the conditioning regimen prior to allo-SCT for the treatment of patients with AML or ALL. This retrospective multicenter report assessed the outcome of 90 patients who received a clofarabine-containing conditioning regimen allogeneic stem cell transplantation (allo-SCT) for AML (n=69) or ALL (n=21) between November 2006 and September 2010 and reported on the EBMT registry. The median age was 42 years (range: 18–69) at transplant. The majority of patients presented with an active disease at transplant (CR1 n=8; CR2 n=16, active disease n=66). All patients had received a CLO-containing conditioning regimen (RIC n=88; MAC n=2) with the following combinations: CLO/TBI n=27; CLO/Busulfan n=10; CLO/Busulfan/ATG n=32; CLO/others drugs n=21. With a median follow-up of 14 months (range: 1–45), 2-years OS, LFS, relapse incidence, non-relapse mortality (NRM) and chronic GVHD were 28+-5%, 23+-5%, 41+-6%, 35+-5% and 38+-7%, respectively. When comparing AML and ALL patients, OS and LFS were significantly higher for AML patients (OS: 35+-6% vs 0%, p<0.0001); LFS: 30+-6% vs 0%, p<0.0001). Overall, engraftment was achieved in 84% of patients with no difference between AML and ALL patients. Patients achieving CR from an active disease were 66.5% in AML vs 40% in ALL (p=0.06). Also, 2-year chronic GVHD was 35% in AML vs 17% in ALL, p=0.32. In a Cox multivariate analysis, AML was the only factor associated with a better LFS (HR=0.37; 95%CI: 0.21–0.66, P=0.001). We conclude that the use of CLO-containing conditioning regimen for allo-SCT is an effective treatment for high-risk AML patients as CLO seems to provide higher anti-tumor and alloreactivity effects. In high-risk ALL patients, disappointing results are observed. Prospective studies are needed to evaluate the potential role of CLO as part of reduced toxicity conditioning regimens in acute leukemias. Disclosures: No relevant conflicts of interest to declare.

Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplant (HSCT) for Myeloma (MM) - Chronic Graft Versus Host Disease (GVHD) is Associated with Lower Risk of Relapse and Superior Progression Free Survival (PFS) - A CIBMTR Analysis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 53-53
Author(s):  
Parameswaran N Hari ◽  
A. John Barrett ◽  
Smriti Shrestha ◽  
Gisela Tunes da Silva ◽  
Mei-Jie Zhang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Lower Risk ◽  
Research Funding ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Allogeneic Hsct ◽  
Matched Sibling ◽  
The Impact ◽  
Reduced Intensity ◽  
Risk Of Relapse

Abstract Abstract 53 Prior studies have demonstrated a graft-versus-malignancy effect following allogeneic HSCT that is variably linked to acute or chronic GVHD. Although a graft vs. Myeloma (MM) effect has been shown after myeloablative allogeneic HSCT, a higher treatment related mortality (TRM) risk leads to inferior survival compared with autologous HSCT. Non-myeloablative (NMA) and reduced intensity conditioning (RIC) approaches are used to reduce the risk of TRM while preserving the graft vs. MM effect. The clinical benefit of lower intensity conditioning regimens is thus especially dependent on the impact of acute or chronic GVHD on graft vs. MM effect and TRM. We analyzed the outcomes of 177 matched sibling allogeneic HSCT recipients reported to the CIBMTR between 1997 and 2005 following NMA (n=120) or RIC (n=57) performed within 18 months of diagnosis. Median age was 50 (range 24-69) years and 62% were Durie-Salmon Stage III. Tandem autologous followed by allogeneic HSCT (autologous+ allogeneic) recipients (n=105) were more likely to receive NMA conditioning vs. recipients of an upfront allogeneic HSCT (n=72). Majority (98%) received peripheral blood stem cell grafts. Outcomes at a median follow-up of 36 (3 - 98) months are summarized in table 1. In order to assess the impact of GVHD on outcomes, Cox proportional hazards regression models were built with GVHD as the main effect treating it as a time dependent covariate (Table 2). Other covariates in the multivariate models included age, sex, performance status, IgG vs. non IgG myeloma, disease status and chemosensitivity, prior lines of chemotherapy, donor-recipient sex match, NMA vs. RIC and year of transplant. AGVHD was associated with an increased risk of TRM. Tandem autologous + allogeneic HSCT was associated with reduced relapse risk (RR= 0.49, p=0.008). AGVHD had no impact on relapse/progression of MM while cGVHD was associated with a reduced risk of relapse (Figure. 1). The protective effect of cGVHD on relapse was significant in the non IgG MM subgroup. AGVHD had no impact on PFS whereas cGVHD was associated with superior PFS and lower risk of treatment failure. Later year of HSCT was also associated with superior PFS. Overall survival was not affected by cGVHD while recipients of tandem autologous + allogeneic HSCT had a higher mortality in the presence of aGVHD (RR=3.60, p= 0.01). After matched sibling allogeneic HSCT for MM, aGVHD is associated with a higher risk of TRM whereas cGVHD decreases the risk of relapse and improves PFS. The effect of cGVHD may vary with the type of MM with greater impact in non IgG MM. Further study to identify subtypes of MM susceptible to an immune mediated graft vs. MM effect is suggested. Disclosures: Lonial: Celgene: Consultancy; Millennium: Consultancy, Research Funding; BMS: Consultancy; Novartis: Consultancy; Gloucester: Research Funding.

scholarly journals Evaluation of a mandatory phishing training program for high-risk employees at a US healthcare system

2019 ◽  
Vol 26 (6) ◽  
pp. 547-552 ◽  
Author(s):  
William J Gordon ◽  
Adam Wright ◽  
Robert J Glynn ◽  
Jigar Kadakia ◽  
Christina Mazzone ◽  
...  
Keyword(s):  
High Risk ◽  
Training Program ◽  
Lower Risk ◽  
Healthcare Systems ◽  
Intervention Period ◽  
Substantial Impact ◽  
Hospital Employees ◽  
Mandatory Training ◽  
Before And After ◽  
The Impact

Abstract Objective The study sought to understand the impact of a phishing training program on phishing click rates for employees at a single, anonymous US healthcare institution. Materials and Methods We stratified our population into 2 groups: offenders and nonoffenders. Offenders were defined as those that had clicked on at least 5 simulated phishing emails and nonoffenders were those that had not. We calculated click rates for offenders and nonoffenders, before and after a mandatory training program for offenders was implemented. Results A total of 5416 unique employees received all 20 campaigns during the intervention period; 772 clicked on at least 5 emails and were labeled offenders. Only 975 (17.9%) of our set clicked on 0 phishing emails over the course of the 20 campaigns; 3565 (65.3%) clicked on at least 2 emails. There was a decrease in click rates for each group over the 20 campaigns. The mandatory training program, initiated after campaign 15, did not have a substantial impact on click rates, and the offenders remained more likely to click on a phishing simulation. Discussion Phishing is a common threat vector against hospital employees and an important cybersecurity risk to healthcare systems. Our work suggests that, under simulation, employee click rates decrease with repeated simulation, but a mandatory training program targeted at high-risk employees did not meaningfully decrease the click rates of this population. Conclusions Employee phishing click rates decrease over time, but a mandatory training program for the highest-risk employees did not decrease click rates when compared with lower-risk employees.

scholarly journals Impact of donor age and kinship on clinical outcomes after T-cell–replete haploidentical transplantation with PT-Cy

2020 ◽  
Vol 4 (16) ◽  
pp. 3900-3912 ◽  
Author(s):  
Jacopo Mariotti ◽  
Anna Maria Raiola ◽  
Andrea Evangelista ◽  
Angelo Michele Carella ◽  
Massimo Martino ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Clinical Outcomes ◽  
Chronic Gvhd ◽  
Multivariable Analysis ◽  
Cell Transplant ◽  
Donor Age ◽  
Hematopoietic Cell Transplant ◽  
The Impact ◽  
Risk Of Relapse

Abstract Donor selection contributes to improve clinical outcomes of T-cell–replete haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-Cy). The impact of donor age and other non-HLA donor characteristics remains a matter of debate. We performed a multicenter retrospective analysis on 990 haplo-SCTs with PT-Cy. By multivariable analysis, after adjusting for donor/recipient kinship, increasing donor age and peripheral blood stem cell graft were associated with a higher risk of grade 2 to 4 acute graft-versus-host-disease (aGVHD), whereas 2-year cumulative incidence of moderate-to-severe chronic GVHD was higher for transplants from female donors into male recipients and after myeloablative conditioning. Increasing donor age was associated with a trend for higher nonrelapse mortality (NRM) (hazard ratio [HR], 1.05; P = .057) but with a significant reduced risk of disease relapse (HR, 0.92; P = .001) and improved progression-free survival (PFS) (HR, 0.97; P = .036). Increasing recipient age was a predictor of worse overall survival (OS). Risk of relapse was higher (HR, 1.39; P &lt; .001) in patients aged ≤40 years receiving a transplant from a parent as compared with a sibling. Moreover, OS and PFS were lower when the donor was the mother rather than the father. Pretransplant active disease status was an invariably independent predictor of worse clinical outcomes, while recipient positive cytomegalovirus serostatus and hematopoietic cell transplant comorbidity index &gt;3 were associated with worse OS and PFS. Our results suggest that younger donors may reduce the incidence of aGVHD and NRM, though at higher risk of relapse. A parent donor, particularly the mother, is not recommended in recipients ≤40 years.

No Improvement of Overall-Survival in Children with High-Risk Acute Myeloid Leukemia by Stem Cell Transplantation in 1st Complete Remission.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 320-320 ◽  
Author(s):  
Dirk Reinhardt ◽  
Bernhard Kremens ◽  
Martin Zimmermann ◽  
Josef Vormoor ◽  
Michael Dworzak ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Complete Remission ◽  
Children And Adolescents ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Hla Typing ◽  
Unrelated Donor ◽  
The Impact

Abstract One aim of the AML-BFM 98 study was to evaluate prospectively the impact of matched sibling donor (MSD)-SCT in 1st complete remission (CR) in children with high-risk (HR)-AML. Patients: Between 7/1998 and 3/2004 494 children and adolescents were enrolled in the studies AML-BFM 98 and the AML-BFM 98 Interim 2003. Patients with favorable cytogenetics [t(8;21), inv(16), t(15;17)], corresponding morphology (AML FAB M1/2 with Auer rods, M4eo, M3) and < 5% blasts on day 15 were defined as standard risk (SR)-group (n=177). All others were stratified to HR-group (n=317) and eligible for SCT in 1st CR. Out of 275 patients achieving 1st CR (87%) 63 patients had a MSD and 188 had no MSD (intent-to-treat group, ITT) while 24 patients had to be excluded due to missing HLA typing or initial refusal to SCT. Thirty-six patients received MSD-SCT (=as-treated group), another two children were transplanted from a matched unrelated donor (MUD) although an MSD was available. The reasons not performing SCT in 1st CR in the remaining 25 children with a donor available were early relapse (n=7), death in CR (n=2), clinical reasons (n=8), or refusal of SCT (n=8). Chemotherapy (CHT) only was given in 192 patients (n=167 without MSD, n=25 with a MSD). Another 21 children were transplanted from an unrelated donor (n=18), family donor (n=1), haploidentical donor (n=2). The reasons were slow response, very poor cytogenetics or other clinical reasons. Treatment: All patients received double induction and consolidation. MSD-SCT in 1st was scheduled after 4 blocs of treatment. Children who were not transplanted in 1st CR received intensification and a 1-year maintenance therapy. The recommended conditioning regimen consisted in busulfan and cyclophosphamide. Results ITT analysis revealed no significant differences in of 5 year disease-free survival (DFS) and overall survival (OS) between children with or without a donor (no donor vs. donor: DFS 43±4% vs. 47±7% plog rank 0.52; OS 56±4% vs. 58±9%, plog rank 0.16). The as-treated analysis gave similar results: CHT only vs. MSD-SCT: DFS 35±11% vs. 59±9% p Mantel-byar 0.13; OS 59±13% vs. 62±12%, p Mantel-byar 0.51). The major reasons of treatment failures were relapses in all groups [CHT only n=100 (52%), MSD-SCT n=13 (34%), MUD-SCT n=9 (50%)]. A 2nd CR was achieved in 71% of the CHT only group (n=74). After SCT in 2nd CR, OS was 40±6%. By contrast, only two children (9%) of 22 children after relapse following SCT in 1st CR could be salvaged. Severe late adverse events (e.g. severe chronic GvHD CTC grade IV, destruction of big joints, intracerebral bleedings) were more frequent in children transplanted in 1st CR (15%) than in those with CHT only (including SCT in 2nd CR; 5%, p×2< 0.05). Conclusion: In the population-based, prospective multi-center study AML-BFM 98 allogeneic MSD-SCT in 1st CR showed no advantage in children and adolescents with HR-AML. Considering the higher toxicity of allogeneic SCT, in the ongoing trial AML-BFM 2004, this SCT (MSD or MUD) is restricted to patients in 2nd CR and refractory AML.

Fludarabine, Cyclophosphamide, Anti-Thymocyte Globulin, with or without “ 2Gy TBI, for Alternative Donor Transplants in Acquired Aplastic Anemia (SAA): A Report From the EBMT-SAA Working Party.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1207-1207
Author(s):  
Andrea Bacigalupo ◽  
Gerard Socie' ◽  
Edoardo Lanino ◽  
Arcangelo Prete ◽  
Franco Locatelli ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Graft Failure ◽  
Causes Of Death ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Working Party ◽  
Lymphoproliferative Disease ◽  
Actuarial Survival ◽  
Alternative Donor ◽  
Family Donor

Abstract Abstract 1207 Poster Board I-229 Patients. Data from 100 patients with acquired severe aplastic anemia (SAA) undergoing an alternative donor transplant, were analyzed. Patients were prepared with a combination of fludarabine (30 mg/m 2×4), cyclophosphamide (300 mg/m 2×4), antithymocyte globulin (3.75 mg/lgx4) (FCA) (n=52, median age 13 years), or FCA supplemented with low dose (2 Gy) total body irradiation (FCA-TBI), but with a lower dose of ATG (total 7.5 mg/kg) (n=48, median age 27 years). The donor was unrelated (n?87) or a one antigen mismatched family donor (n=13). GvHD. Acute graft versus host disease (GvHD) grade III-IV was seen in 13% and 7% ; extensive chronic GvHD was recorded in 1 FCA patient and in 4 patients receiving FCA-TBI. Graft failure. Rejection/graft failure was seen in 17 patients, equally distributed in the two groups: 9/17 patients survive long term, 3 with autologous recovery, and 6 after a second transplant.. As to predictors of graft failure, patients with a longer interval from diagnosis to transplant (> 2 years) had a trend for a higher risk of GF (22%) as compared to patients grafted <1 year (12%) or between 1-2 years (14%) (p=0.3). Chimerism data: within 100 days from BMT the average donor chimerism was 93% and 84% in the FCA and FCA-TBI regimens. Beyond day +100 the average was 89% and 80%. Survival. With a median follow up of 1204 days, the overall actuarial 5 year survival is 75%, respectively 73% for the FCA and 79% for the FCA-TBI. The interval diagnosis-transplant (<1 year, 1-2 years and >2 years) was a significant predictor of survival in univariate and multivariate analysis : actuarial survival was 87%, 86%, 58% respectively (p=0.004). Older age and HLA mismatch was a significant predictor of survival in the FCA group, but not in the FCA-TBI patients. Causes of death. Twentythree patients died, 13/52 in the FCA group and 10/48 in the FCA-TBI group (p=ns): major causes of death were rejection (n=7), post-transplant-lymphoproliferative-disease (n=4) and GvHD (n=4). Conclusions. This study confirms a significantly improved outcome of alternative donor transplants in SAA patients, and suggests that best results are achieved if the transplant is performed within 2 years from diagnosis. FCA seems appropriate only for children with well matched donors, whereas FCA-TBI is preferable in adults, especially when the donor is HLA mismatched. Complications such as rejection and EBV reactivation need to be addressed with modifications of the transplant regimens. Disclosures: No relevant conflicts of interest to declare.

Long-Term Survival and Late Relapse in 5-Year Survivors of Allogeneic Hematopoietic-Cell Transplantation (HCT) for Chronic Myeloid Leukemia (CML) in First Chronic Phase.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3321-3321
Author(s):  
John M. Goldman ◽  
Navneet S. Majhail ◽  
John P. Klein ◽  
Zhiwei Wang ◽  
Kathleen A. Sobocinski ◽  
...  
Keyword(s):  
General Population ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Chronic Phase ◽  
Term Survival ◽  
Long Term Survival ◽  
Late Mortality ◽  
Allogeneic Hct ◽  
Risk Of Relapse

Abstract Abstract 3321 Poster Board III-209 Prior to the advent of tyrosine kinase inhibitors, allogeneic HCT was standard therapy for CML. However, very long-term outcomes of allogeneic HCT for CML are not well described. To evaluate the probability and risk factors for late mortality and relapse in this patient population, we conducted a retrospective cohort study that included 2444 patients who received a myeloablative allogeneic HCT for CML in first chronic phase between 1978 and 1998 and had survived in continuous complete remission for at least 5 years. Relapse was considered the earliest reported date of the following: hematologic recurrence, cytogenetic recurrence or initiation of therapy for recurrence. The median followup of our cohort was 11 years (range, 5-25) from HCT; 377 patients had followup >15 years. Donor sources were HLA-matched siblings (MSD) in 1692, unrelated donors (URD) in 639 and other related donors in 113 patients. The median age at HCT was 35 years and patients primarily received bone marrow grafts (96%) and conditioning using either total-body irradiation (TBI, 61%) or BuCy (38%) regimens. Acute and chronic graft-versus-host disease (GVHD) occurred in 43% and 62% of patients, respectively. The probabilities of overall survival at 15 years were 88% (95% CI, 86-90%) for MSD and 87% (83-90%) for URD recipients. Corresponding cumulative incidences of relapse at 15 years were 8% (7-10%) and 2% (1-4%), respectively. The latest reported relapse occurred 18 years post-HCT. In multivariable analyses addressing the importance of patient, disease and transplant related factors for long-term survival, older age at HCT, use of female donor for a male recipient, use of TBI based conditioning, acute GVHD and chronic GVHD all independently increased the risk of late mortality. Chronic GVHD reduced the risk of relapse, but increased the risk of non-relapse mortality. Recipients of MSD and URD had similar risks of long-term mortality, relapse and non-relapse mortality. Compared to an age, gender and race adjusted general population, 5 year survivors of HCT for CML were 2.9 times (95% CI, 1.9-3.9) more likely to die at 6 years and 2.5 times (1.3-3.7) more likely to die at 10 years after HCT. However, by 15 years after HCT, their relatively mortality (2.3 [0-4.9]) was not significantly different than the general population. In summary, recipients of allogeneic HCT for CML in first chronic phase who remain in remission for at least 5 years after HCT have very favorable subsequent long-term survival with mortality rates eventually approaching those of the general population. There is a small but continuing risk of relapse even in these long-term survivors. Chronic GVHD protects against relapse but increases the risks of non-relapse mortality. Disclosures No relevant conflicts of interest to declare.

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