High Levels of Interleukin-12 Are Associated with Reduced Incidence of Relapse and Death without Increasing Acute Graft-Versus-Host Disease (AGVHD) after Allogeneic Stem Cell Transplantation (SCT).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 295-295
Author(s):  
Vijay Reddy ◽  
Andrew G. Winer ◽  
Erika Eksioglu ◽  
Jeffery Levine ◽  
Herwig-Ulf Meier-Kriesche ◽  
...  
Keyword(s):  
Stem Cell ◽  
Disease Risk ◽  
Significant Risk ◽  
Interleukin 12 ◽  
P Value ◽  
Group Level ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Post Transplant ◽  
Medium Group

Abstract We recently found that a low number of circulating dendritic cells (DC) is predictive of increased relapse, acute GVHD, and poor survival following allogeneic SCT (Reddy V et al, Blood2004;103(11):4330–5). Interleukin-12 (IL-12) is an immunostimulatory cytokine involved in the activation of naïve T cells by DC (Rissoan et al. Science1999;283(5405):1183–6). We hypothesized that patients with high levels of circulating IL-12 in the post transplant period have improved relapse free survival. We studied 134 patients, 120 of whom were evaluable and transplanted during the period of July 1999 to April 2004. Seventy-two patients had transplants from related and 48 from unrelated donors, for predominantly high risk (88%) hematologic malignancies. Median follow up was 1158 days (range 70–1792). Blood samples were collected as baseline prior to conditioning, on day 0 prior to stem cell infusion and during the first week (day 4 and/or 7) after transplant. Plasma IL-12 levels were measured by ELISA. To determine the independent effect of post-transplant IL-12 levels and clinical outcomes, a cluster analysis was performed on the logarithmically transformed mean IL-12 concentration at days 4 and 7 post-transplant. The analysis generated a low, medium and high IL-12 group. Forty-six patients had low levels of IL-12 (median=2 pg/ml, range 0–6.5), 49 patients had medium (median=20.5 pg/ml, range 7–75.5) and 25 patients had high levels (median=181 pg/ml, range 84–623). There was a significant association between IL-12 level and onset of relapse. Using a multivariate Cox model with the low group level as reference, the high IL-12 group level had an adjusted hazard ratio (HR) of 0.27 (95% C.I. 0.09–0.79) and the medium group level a HR of 0.65 (95% C.I. 0.31–1.36). Incidence of relapse at 500 days by Kaplan-Meier analysis by IL-12 group were 23.0% (high group), 40.3% (medium group), and 48.8% (low group). Covariates in the multivariate models were gender match, disease risk, graft source, patient age, donor relation. There was a significant relationship between IL-12 levels and composite death and relapse, the high IL-12 group had a HR of 0.37 (95%C.I.=0.17–0.80) and the medium group a HR of 0.85 (95%.C.I. 0.50–1.45). There was no association between IL-12 levels and risk of AGVHD (p-value=0.51). In addition to IL-12, disease risk was a significant risk factor for the composite endpoint of relapse or death (HR=5.4, p-value=0.0052). The model generated for the outcome of relapse only did not have any additional significant risk factors. In conclusion, high post-transplant levels of IL-12 are associated with less relapse and improved relapse free survival after transplantation. This data suggests that IL-12 administration should be considered as a possible component in studies addressing treatment of relapse after transplantation. Figure Figure

Prevention of Graft-Versus-Host Disease (GVHD) with Tacrolimus after Allogeneic Grafting for Hematological Malignancies Following Sub-Myeloablative Conditioning.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5321-5321
Author(s):  
Joseph Fay ◽  
Giovanna Saracino ◽  
Edward Agura ◽  
Brian Berryman ◽  
Luis Pineiro ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Hematological Malignancies ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
P Value ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Allogeneic Hsct ◽  
Post Transplant

Abstract Severe acute or chronic GVHD following allogeneic hematopoietic stem cell transplantation therapy (HSCT) has a deleterious effect on the successful treatment of hematological malignancies. We have retrospectively studied mycophenolate mofetil (MMF) and tacrolimus (FK) or cyclosporine (CSA) following allogeneic HCST in the prevention of GVDH and the induction of immune tolerance in 93 patients with hematological malignancies using non-myeolablative pre-transplant conditioning. In the current study, there were 35 patients with leukemia, 36 patients with lymphoma, 12 patients with myelodysplastic syndrome or a myeloproliferative disorder and 10 patients with multiple myeloma. There were 63 women and the median age was 42 (15–75) years. Twenty patients had relapsed after previous autologous or allogeneic HSCT and 45 patients were older than 59 years. The remaining patients had co-morbid medical conditions that precluded the use of chemotherapy/radiotherapy dose-intensive pre-conditioning. Conditioning prior to allogeneic HSCT (94 blood stem cell grafts and 1 marrow graft) was fludarabine (90 mg/m2 in three daily doses) and TBI (200cGy) in 86 patients, fludarabine (120 mg/m2 in 4 daily doses) and cyclophosphamide (50mg/kg) in 5 patients, and TBI (200 cGy) only in 4 patients. Forty-three patients received sibling and 50 unrelated grafts. Median follow-up post transplant is 3.0 (0.2–6.1) years. Five (5.3%) patients did not experience sustained hematological chimerism post-transplant. MMF and FK were administered to 33 recipients and MMF and CSA to 60 recipients. The dose and schedule of MMF, CSA and FK have been published (Laport et al. Blood, 2006 and Fay et al. Blood, 1996.) There was no difference in the degree of HLA mismatching between the two groups of patients. Cumulative incidences were used to estimate the incidence of acute and chronic GVHD, all deaths and disease progressions not related to GVHD being considered as the competing events. The Gray test was used to compare cumulative incidences between groups. The unadjusted cumulative incidence of grade III–IV acute GVHD that required oral or systemic corticosteroid therapy, was 54% (95% CI, 40%–68%) in evaluable patients who received CSA in contrast to 38% (95% CI, 18%–58%) in patients who received FK (p-value=0.25). Furthermore, the unadjusted cumulative incidence of extensive chronic GVHD at 1 year was 45% (95% CI, 32%–58%) for CSA versus 34% (95% CI, 14%–54%) for FK (p-value=0.48). Progression-free survival between patients who received FK or CSA at the time of the analysis of this study is similar (p-value=0.6191). The progression-free survival at 1 year was 43% (95% confidence interval [CI], 24%–62%) for CSA versus 43% (95% CI, 31%–55%) for FK. Analyses of the overall morbidity and the incidence of infectious complications between the 2 groups are ongoing. FK combined with MMF may be superior to CSA and MMF in the prevention of GVHD post sub-myeloablative allogeneic HSCT therapy for hematological malignancies and FK may result in improvement of treatment outcome. We believe further study is warranted.

scholarly journals Current Graft-Versus-Host Disease (GVHD), Relapse-Free Survival - a Novel, Dynamic Composite Endpoint to Better Define Effectiveness Following Allogenic Hematopoietic Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1170-1170 ◽  
Author(s):  
Scott R. Solomon ◽  
Connie Sizemore ◽  
Michelle Ridgeway ◽  
Xu Zhang ◽  
Melhem Solh ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Gvhd ◽  
Composite Endpoint ◽  
Cell Transplant ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Post Transplant ◽  
Dynamic Event ◽  
Grade 3 ◽  
Very High

Abstract Introduction GVHD-free, relapse-free survival (GRFS) has been previously developed as a novel composite endpoint designed as a measure of transplant effectiveness, which attempts to take into account the morbidity associated with GVHD (Holtan et al. Blood 2015). The conventional definition of GRFS however considers grade 3-4 acute GVHD and immunosuppression-requiring chronic GVHD (cGVHD) as static endpoints, whereas in reality these outcomes are often reversible. Patients with short-lived GVHD are considered treatment failures, which may not represent an accurate measure of transplant success. Therefore, we have developed a statistical method that provides an estimate of the probability, at any time post-transplant, of being alive, in remission, and without clinically significant cGVHD, defined as moderate-severe by the NIH consensus criteria. Methods In this new composite endpoint, which we call current GRFS (CGRFS), death and relapse are treated as terminal events, while cGVHD is considered a dynamic event, which can "resolve" once manifestations are quiescent and systemic immunosuppression discontinued. Grade 3-4 acute GVHD was intentionally not included in this endpoint, as this event almost universally will either resolve with time or convert to either death or cGVHD, which are both captured as part of CGRFS. Statistically, the CGRFS was defined as the sum of the survival without evidence of relapse and moderate-severe cGVHD and the probability that one recovered from moderate-severe cGVHD. The probability that one recovered from moderate-severe cGVHD was calculated by looking at the differences of relevant Kaplan-Meier estimates. Comparison of CGRFS between two independent samples was implemented by the simulation-based supremum test. Results We evaluated 437 consecutive patients receiving an allogeneic hematopoietic stem cell transplant at a single institution from a matched related (MRD, n=125), matched unrelated (MUD, n=165), or haploidentical (HID, n=132) donor between January 2010 and July 2015. Transplant recipients had a median age of 54 years (range 18-77), DRI high/very high in 30%, and HCT-CI ³3 in 46%. Myeloablative conditioning was used in 50% and PBSC was the stem cell source in 78%. GVHD was prospectively documented by a dedicated practitioner on an ongoing basis. With a median follow-up time of 36 months, estimated 3-yr overall and disease-free survival was 61% and 54%, respectively. Conventionally defined GRFS at 1, 2, 3 and 4 years was 33%, 26%, 23%, and 22% respectively. In contrast, when moderate-severe cGVHD was treated as a dynamic event, corresponding CGRFS was 45%, 46%, 47% and 49%, respectively (Figure 1). The corresponding gain in CGRFS survival, due to the treatment of cGVHD as a dynamic event, was 12%, 20%, 24% and 27% respectively (Figure 2). Patients living with active mod-severe cGVHD decreased over time, quantitated at 23%, 14%, 7% and 4% respectively at 1, 2, 3 and 4 years post-transplant (Figure 3). CGRFS was significantly correlated with DRI (low/intermediate vs. high/very high, p<0.01), but not transplant type, age, HCT-CI, graft source, regimen intensity or year of transplant. Conclusion Whereas only a third of patients achieve "transplant success" by conventional 1-yr GRFS, nearly half of patients by CGRFS are considered cured without the morbidity of ongoing GVHD. We propose that CGRFS may represent are more accurate estimate of transplant effectiveness. Disclosures No relevant conflicts of interest to declare.

High Prognostic Impact of Mixed Chimerism of Blood and Marrow In the First Year After Allogeneic Hematopoietic Stem Cell Transplantation: The Need to Rapidly Establish Complete Donor Chimerism.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3464-3464
Author(s):  
Ellen Meijer ◽  
Lucia Duinhouwer ◽  
Eric Braakman ◽  
Joke Boonstra ◽  
Inge de Greef ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Progression Free Survival ◽  
Disease Recurrence ◽  
Mixed Chimerism ◽  
P Value ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Post Transplant ◽  
Donor Chimerism

Abstract Abstract 3464 Introduction: Monitoring hematopoietic chimerism following allogeneic hematopoietic stem cell transplantation (alloSCT) after non-myeloablative (NMA) conditioning is commonly used to document engraftment. While mixed chimerism (MC) is frequently observed after NMA alloSCT, it occurs only rarely after myeloablative (MA) alloSCT. Persistent mixed chimerism is generally considered a risk factor for both relapse and rejection of the donor graft, irrespective of the type of conditioning regimen. However, it is still unknown to what extent mixed chimerism quantitatively predicts for relapse and whether patients at high risk for relapse can accurately be identified by assaying chimerism in either blood, marrow, and/or T cells. Therefore, we prospectively evaluated the establishment of complete and mixed chimerism in blood, marrow, and CD3+ selected T cells at 3, 6 and 12 months following alloSCT to investigate the predictive value of mixed chimerism in either subset for relapse. Methods: The study cohort included 152 recipients of an alloSCT, performed between October 2005 and December 2009 because of hematological malignancies (AML: n=61, ALL: n=25, NHL: n=18, Myeloma: n=15, CML: n=5, CLL: n=18, MDS: n=6, MPN: n=4). Median age was 50 years (range 17–67). Seventy-eight patients received a sibling donor transplant, 74 a transplant from a matched related donor. MA and NMA conditioning consisted of Cyclophosphamide/TBI 1200 cGy (n=45) and Fludarabine/TBI 200cGy (n=107), respectively. Chimerism tests were routinely performed in bone marrow (BM), peripheral blood (PB) and CD3 selected samples at 3, 6 and 12 months post transplant, using PCR and electrophoresis of variable number of tandem repeats or fluorescent in-situ hybridization by sex-chromosome specific probes. Complete (donor) chimerism (CC) was defined as >95% donor hematopoiesis, MC as ≤95% donor hematopoiesis. The cumulative incidence of disease recurrence/progression and progression free survival by chimerism status was evaluated as from 3, 6 and 12 months post transplant and adjusted for type of conditioning, donor type, patient/donor sexe and age. Results: MC appeared very rare after MA conditioning, but was more frequently observed after NMA alloSCT with incidences of BM-MC of 28, 22 and 9% at the 3, 6 and 12 month timepoints, respectively. MC in BM as well as PB samples at 6 and 12 months post transplant was highly predictive for disease recurrence/progression, both after univariate and multivariate analyses (BM: hazard ratio (HR) at 6 months: 3.52 (1.30-9.53 95% confidence interval (CI)), p-value 0.013; at 12 months: 5.42 (1.17-25.13 95%CI), p-value 0.031). The probability to develop a relapse increased to 40% in time if MC was detected at 6 months following transplantation, as compared to 15% in the CC group. MC detected at 12 months resulted in a relapse incidence of ≥50% (Figure 1). Moreover, MC at these timepoints also predicted for decreased progression free survival (BM: HR at 6 months: 2.35 (1.04-5.27 95%CI), p-value 0.039; at 12 months: 9.36 (2.94-29.92 95%CI), p-value 0.000). Chimerism results in CD3+ selected T cell fractions did not show a significant association with relapse/progression or progression free survival. Conclusion: These results show that patients with MC at 6 and 12 months post transplant in either BM or PB are at a 3 to 9 fold higher risk of disease recurrence/progression. T cell chimerism appeared not associated with relapse, which may be explained by a significant different and protracted pattern of kinetics after transplantation as compared to kinetics of PB and BM chimerism, thereby identifying different subgroups of patients. Collectively, this study highlights the need to rapidly establish complete donor chimerism both after MA and NMA alloSCT. The preferred medical intervention in patients with MC after NMA conditioning, however, remains to be established in a prospective study. Disclosures: No relevant conflicts of interest to declare.

Új lehetőségek a refrakter és relabált Hodgkin-lymphomás betegek kezelésében

2015 ◽  
Vol 156 (45) ◽  
pp. 1824-1833 ◽  
Author(s):  
Árpád Illés ◽  
Ádám Jóna ◽  
Zsófia Simon ◽  
Miklós Udvardy ◽  
Zsófia Miltényi
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Relapse Free Survival ◽  
Term Survival ◽  
Free Survival ◽  
Novel Treatment ◽  
Refractory Hodgkin Lymphoma

Introduction: Hodgkin lymphoma is a curable lymphoma with an 80–90% long-term survival, however, 30% of the patients develop relapse. Only half of relapsed patients can be cured with autologous stem cell transplantation. Aim: The aim of the authors was to analyze survival rates and incidence of relapses among Hodgkin lymphoma patients who were treated between January 1, 1980 and December 31, 2014. Novel therapeutic options are also summarized. Method: Retrospective analysis of data was performed. Results: A total of 715 patients were treated (382 men and 333 women; median age at the time of diagnosis was 38 years). During the studied period the frequency of relapsed patients was reduced from 24.87% to 8.04%. The numbers of autologous stem cell transplantations was increased among refracter/relapsed patients, and 75% of the patients underwent transplantation since 2000. The 5-year overall survival improved significantly (between 1980 and 1989 64.4%, between 1990 and 1999 82.4%, between 2000 and 2009 88.4%, and between 2010 and 2014 87.1%). Relapse-free survival did not change significantly. Conclusions: During the study period treatment outcomes improved. For relapsed/refractory Hodgkin lymphoma patients novel treatment options may offer better chance for cure. Orv. Hetil., 2015, 156(45), 1824–1833.

scholarly journals Investigating the Relationship between CD34+and CD3+ Cell Doses, One-Year Graft-Versus-Relapse-Free-Survival, Graft-Versus-Host Disease, and Overall Survival in Haploidentical Hematopoietic Stem Cell Transplantation: A Single Center Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2051-2051 ◽  
Author(s):  
Mindy Hsiao ◽  
Anastasia Martynova ◽  
George Yaghmour ◽  
Chris Foss
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Optimal Dose ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Improved Outcomes ◽  
The Mean ◽  
Related Mortality

Background: Haploidentical hematopoietic cell transplantation (haplo-HCT) has emerged as a popular alternative to traditional HLA-matched hematopoietic cell transplant. As the number of haplo-HCT's rises, investigating the factors that may affect outcomes is necessary in order to improve overall survival and reduce transplant-related mortality. The optimal dose of CD34+ cells used during haplo-HCT to ensure favorable outcomes using PTCy has not yet been reported though a range of 2 to 5.00x106 cells/kg is commonly used.Furthermore, the optimal dose of CD3+ cells is unknown however recent data has suggested less than 3.00x108 cells/kg may prevent the development of acute GVHD. The importance of studying the impact of CD34+/CD3+ cell dosing may help to improve outcomes in this setting. Methods: We retrospectively analyzed adult patients at USC Norris Cancer Hospital (age ≥ 21) who received haplo-HCT from 2014 to 2019. The primary end-point assessed was 1-year GVHD-free/relapse-free survival (GRFS) defined as grade 3-4 acute GVHD, systemic therapy-requiring chronic GVHD, relapse, or death in the first post-HCT year. Secondary end-points included 1-, 2-, and 3-year relapse-related mortality (RRM) and overall survival (OS) in addition to 1-year transplant related mortality (TRM) and incidence of both acute and chronic GVHD. Results: A total of 67 adult haplo-HCT recipients were reviewed. Of the patients evaluated, approximately 50% (n = 33) were male and 49% (n = 32) were female. The age range was 21-71 years old (median = 44), and the most common underlying hematologic disorders included AML (40%), ALL (38%), aplastic anemia (7.7%), and others (MDS, lymphoma, myelofibrosis, and HLH) (13.8%). 67% of patients received myeloablative conditioning regimens while 33% received reduced intensity regimens. 70% (n = 47) of patients received peripheral blood as a stem cell source with 30% (n = 20) receiving bone marrow. The mean CD34+ dose infused was 6.07x106 cells/kg and the mean CD3+ dose was 2.94x108 cells/kg. The mean time to recovery of platelets, neutrophils, and lymphocytes was 25, 18, and 37 days respectively. CD34+ stem cells ≥5.00x106 cells/kg was significantly associated with shorter time to lymphocyte recovery (p = 0.0265) though recovery less than 30 days was not significantly associated with OS (p = 0.5268). Incidence of 1-year GRFS was 71% (n= 46) and 1-, 2-, and 3-year RRM were 4.6%, 6%, and 7.7% respectively. 1-year TRM was 15.3% with 50% of deaths from acute GVHD. 1-, 2-, and 3-year OS were 80%, 78%, and 77% respectively. Factors significantly associated with increased mortality included use of RIC regimen (p = 0.004) and disease status at time of transplant (p = 0.04). Cumulative incidence of GVHD was 63% (n = 42) with 33% (n = 22) and 30% of patients (n = 20) with acute and chronic GVHD respectively. Lack of mild chronic GVHD was associated with increased mortality (p = 0.0029) and use of a myeloablative regimen (p = 0.0029) was significantly associated with GVHD. Subgroup analysis of those who received CD34+ dose ≥7.00x106 cells/kg (n = 24) and ≥10x106 cells/kg (n = 7) were found to have 1-year OS of 87.5% and 85.7% compared with 77% and 80% in those that received lower doses (p= 0.2229 and p = 1.00) respectively however this was not found to be significantly associated with increased incidence of GVHD, relapse, or mortality. Discussion: Our results demonstrate improved outcomes specifically 71% survived 1 year without experiencing at least 1 GRFS event compared with 24-35% reported by CIBMTR, Holtan et al 2015, and Solh et al 2016 with 3-year OS of 77% when compared with a previously reported 48%. The mean CD34+ cell dose of our population is higher than the standard range which may account for the improved outcomes however the dosing of CD34+/CD3+ cells were not significantly associated with our primary and secondary end-points. It was significantly associated, however, with shorter time to lymphocyte recovery, a factor that has been reported to be associated with decreased RRM and therefore improved OS. Furthermore, subgroup analysis of higher CD34+ dose did show a better 1-year OS though this was not statistically significant. Limitations of this study include small sample size and short follow-up period. Further research with a prospective study identifying the optimal CD34+/CD3+ cell dose in addition to comprehensive evaluation of immune recovery is warranted in order to improve haplo-HCT outcomes. Figure Disclosures Yaghmour: Jazz Pharmaceutical company: Consultancy, Speakers Bureau; Astella company: Speakers Bureau; Takeda: Speakers Bureau.

scholarly journals Autologous Stem Cell Transplant Outcome in Classic Hodgkin Lymphoma Patients in the Era of Post-Transplant Brentuximab Vedotin Consolidation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3935-3935
Author(s):  
Shanee Chung ◽  
Jennifer White ◽  
Cynthia L. Toze ◽  
Heather J. Sutherland ◽  
David Sanford ◽  
...  
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Median Number ◽  
Salvage Chemotherapy ◽  
Brentuximab Vedotin ◽  
Relapse Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Classic Hodgkin Lymphoma

Abstract Introduction: Patients newly diagnosed with classic Hodgkin lymphoma (CHL) have over 80% chance of remission with first-line chemotherapy, such as ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) regime. However, 10-40% of patients relapse eventually and require salvage therapy. High-dose therapy with autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed or refractory CHL, offering a cure rate of around 50%. This may be further improved to around 60% with post-transplant consolidation with brentuximab vedotin (BV). Post-SCT BV consolidation has been offered to all patients, regardless of the risk group, in British Columbia since late 2015. We set out to review the ASCT outcome in CHL patients in the recent decade at our institution. Methods: All adult patients who received ASCT for relapsed or refractory CHL between July 2011 and June 2020 were included in this retrospective analysis. Information pertaining to their demographics, disease characteristics, treatment history, transplant details, clinical outcomes and post-relapse therapy was obtained by review of electronic data. The data cut-off date was June 28, 2021. Survival outcomes were censored at the last known clinic visit for patients without relapse or death during follow up. Survival analysis was performed using Kaplan-Meier survival function and log-rank test. Pearson's chi-square test and ANOVA were used for comparison between cohorts. The statistical program used was Stata® version 16.1 (Texas, USA). Results: 114 patients underwent ASCT for relapsed/refractory CHL. Bulky disease and extranodal involvement were seen in 11% and 40% respectively at relapse. Looking at the 'high risk criteria' as defined in the AETHERA trial: 45/114 (40%) patients had primary refractory CHL, 21/114 (18%) had relapsed within 12 months of completing the front-line chemotherapy and 15/114 (13%) had relapsed beyond one year of completing initial treatment but with an extranodal disease. The most commonly used salvage chemotherapy regime was GDP (gemcitabine, dexamethasone, cisplatin; 111/114; 97%). 10/114 (9%) patients received BV after failing salvage chemotherapy pre-SCT. The median number of lines of therapy pre-SCT was two (range 2-5). 94/108 (98%) had a chemosensitive disease with 35/108 (32%) achieving complete remission. 6/108 (6%) patients had a progressive disease at the time of SCT. For the transplant, all patients had a peripheral blood stem cell source and the conditioning regime was either Carmustine/Etoposide/Cytarabine/Melphalan (76%) or Etoposide/Melphalan (24%). After median follow up of 62.2 months, 50/114 (44%) patients relapsed with median relapse-free survival of 20.2 months (range 0.9 - 113.5) and 16/114 (14%) died. The direct cause of death was lymphoma progression in all but three patients (PJP pneumonia, pulmonary fibrosis, traumatic subdural hematoma). Whereas only 4/51 (8%) patients (2 without relapse) received post-SCT BV consolidation via a compassionate access program between July 2011 and October 2015 (cohort 1), 45/63 (71%) patients (33 in remission) received routine BV consolidation between November 2015 and June 2020 (cohort 2). In cohort 2, 44% had primary refractory CHL compared to 33% in cohort 1 but the number of 'low risk' patients was similar at 29% (Table 1). The most common reason for no post-SCT BV consolidation in cohort 2 was patient refusal (7/18; 40%). Other causes included BV pre-SCT, early disease progression and patient comorbidities. Only 9/42 (21%) patients with available data in cohort 2 completed the planned 16 cycles of BV consolidation. The median number of cycles was 10.5 (range 1-16). The most common reasons for early termination of BV consolidation were peripheral neuropathy (22/33; 67%) and disease progression (9/33; 27%). There was no statistically significant difference in PFS or OS demonstrated between the two cohorts (Graphs 1, 2). Conclusion: After median follow up of 5 years, 86% of patients remain alive and 56% are alive in remission. In British Columbia, post-SCT BV consolidation has been widely adopted with over 70% of patients receiving at least one cycle since late 2015. Successful completion of post-SCT BV consolidation is, however, limited by a high rate of treatment-limiting peripheral neuropathy. Relapse-free survival benefit of routine post-SCT BV consolidation is not demonstrated in this single-centre cohort. Figure 1 Figure 1. Disclosures White: Novartis: Honoraria. Sutherland: Janssen: Consultancy, Research Funding; GSK: Research Funding; Karyopharm: Research Funding; Celgene: Consultancy; Amgen: Consultancy. Sanford: Abbvie: Membership on an entity's Board of Directors or advisory committees; Stellar: Membership on an entity's Board of Directors or advisory committees. Abou Mourad: Amgen: Consultancy; Paladin: Consultancy; Pfizer: Consultancy. Song: Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Consultancy, Honoraria; GlaxoSmithKline: Honoraria; Kite, a Gilead Company: Honoraria; Bristol Myers Squibb: Honoraria; Sanofi: Honoraria.

scholarly journals Prognostic Factors on the Graft-versus-Host Disease-Free and Relapse-Free Survival after Adult Allogeneic Hematopoietic Stem Cell Transplantation

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Yao-Chung Liu ◽  
Sheng-Hsuan Chien ◽  
Nai-Wen Fan ◽  
Ming-Hung Hu ◽  
Jyh-Pyng Gau ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prognostic Factors ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Hematologic Malignancy ◽  
Relapse Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Graft Versus Host ◽  
Disease Free

The cure of hematologic disorders by allogeneic hematopoietic stem cell transplantation (HSCT) is often associated with major complications resulting in poor outcome, including graft-versus-host disease (GVHD), relapse, and death. A novel composite endpoint of GVHD-free/relapse-free survival (GRFS) in which events include grades 3-4 acute GVHD, chronic GVHD requiring systemic therapy, relapse, or death is censored to completely characterize the survival without mortality or ongoing morbidity. In this regard, studies attempting to identify the prognostic factors of GRFS are quite scarce. Thus, we reviewed 377 adult patients undergoing allogeneic HSCT between 2003 and 2013. The 1- and 2-year GRFS were 40.8% and 36.5%, respectively, significantly worse than overall survival and disease-free survival (log-rankp<0.001). European Group for Blood and Marrow Transplantation (EBMT) risk score > 2 (p<0.001) and hematologic malignancy (p=0.033) were poor prognostic factors for 1-year GRFS. For 2-year GRFS, EBMT risk score > 2 (p<0.001), being male (p=0.028), and hematologic malignancy (p=0.010) were significant for poor outcome. The events between 1-year GRFS and 2-year GRFS predominantly increased in relapsed patients. With prognostic factors of GRFS, we could evaluate the probability of real recovery following HSCT without ongoing morbidity.

Evaluating Gvhd Outcomes Using Post-Transplant Cyclophosphamide/Tacrolimus/Mycophenolate Mofetil As Gvhd Prophylaxis Compared with Methotrexate/Tacrolimus in Matched-Related and Matched-Unrelated Hematopoietic Stem Cell Transplant in Relation to the Haplo-Identical Setting: A Single Center Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-6
Author(s):  
Mindy Hsiao ◽  
Preet M. Chaudhary ◽  
George Yaghmour
Keyword(s):  
Stem Cell ◽  
Mycophenolate Mofetil ◽  
Board Of Directors ◽  
Relapse Free Survival ◽  
Advisory Committees ◽  
End Points ◽  
Free Survival ◽  
Gvhd Prophylaxis ◽  
Grade 3 ◽  
Haplo Group

Background: The use of post-transplant cyclophosphamide (PTCy)/tacrolimus/mycophenolate mofetil (MMF) for GVHD prophylaxis has improved outcomes in haploidentical hematopoietic cell transplantation (haplo-HCT). PTCy is now being evaluated in matched-related (MRD) and matched-unrelated (MUD) allo-HCT. Previous studies demonstrated improved GVHD-free/relapse-free survival (GRFS) when PTCy was combined with two immunosuppressive agents and PTCy has also been associated with better relapse-free survival (RFS) as demonstrated in De Jong et al 2019, though only one immunosuppressive agent was used. Currently, there is limited published data comparing outcomes using PTCy/tacrolimus/MMF to standard MRD/MUD GVHD prophylaxis of methotrexate (MTX)/tacrolimus. The importance of studying this comparison may help to improve GVHD outcomes in MRD and MUD allo-HCT. Methods: We retrospectively analyzed adult patients at USC Norris Cancer Hospital (age ≥ 19) who received allo-HCT from 2018 to 2020. The primary end-points assessed were incidence and severity of 1-year aGVHD and cGVHD. Secondary end-points included day+100 mortality, 1-year overall survival (OS), 1-year RFS, 1-year transplant-related mortality (TRM), and 1-year GRFS, defined as grade 3-4 acute GVHD, systemic therapy-requiring chronic GVHD, relapse, or death in the 1-year post-HCT period. Results: A total of 65 adult MRD and MUD allo-HCT recipients and 53 haplo-HCT patients were reviewed. Of the MRD/MUD patients evaluated, approximately 51% (n = 33) were female and 49% (n = 32) were male. The age range was 20-69 years old (median = 46), and the most common diseases included ALL (46%), AML (31%), MDS (11%), and others (i.e. lymphoma, aplastic anemia (AA), myelofibrosis) (12%). 34% (n = 22) of patients received PTCy on D+3 and D+4 with tacrolimus/MMF/ on D+5 as GVHD prophylaxis and 66% (n = 43) of patients received MTX/tacrolimus on D+1, +3, +6, and +11 as GVHD prophylaxis. All haplo-HCT patients received standard PTCy/tacrolimus/MMF. Stem cell source was primarily PBSC except in HLH and AA patients. The PTCy group had more MUD allo-HCT (64%), degree of antigen mismatch (56%), and median age of 50.5 years compared with the MTX group at 44%, 47%, and 44 years respectively. 70% in the MTX group received MAC compared with 45% in the PTCy group. The haplo group had similar demographics to the MTX group. The mean CD34 cell doses in the PTCy, MTX, and haplo groups were 4.87, 5.36, and 7.24x106 cells/kg respectively. Incidences of total GVHD, aGVHD, and aGVHD grade 3 or 4 in the PTCy group were 55%, 50%, and 4.5% respectively compared with 65%, 35%, and 7% in the MTX group, though not significant. The haplo group had 68%, 55%, and 1.9% respectively. Incidence of total cGVHD and cGVHD requiring systemic therapy in the PTCy group was 4.5% and 0% respectively compared with 30% (p = .02) and 23% (p =.01). The haplo group had 13% and 1.9% respectively. Day+100 mortality, 1-year OS, 1-year RFS, 1-year TRM, and 1-year GRFS in the PTCy group were 0%, 80%, 60%, 0%, and 64% respectively compared with 7%, 88%, 90%, 7.3%, and 59%. The haplo group had 3.8%, 86%, 89%, 14%, and 66%. In a univariate analysis, factors significantly associated with GVHD were disease status (p = .0.12) and CD34 dose (p = 0.015) and antigen mismatch (p = 0.04) was associated with increased mortality. Discussion: Our results demonstrate improved overall and extensive cGVHD outcomes in the PTCy group and thus an improvement in 1-year GRFS. Furthermore, incidence and severity of 1-year cGVHD in this group are improved when compared with previously reported outcomes. 1-year GRFS reported in De Jong et al 2019 was 45% and 1-year GRFS reported for all groups in our study is higher at 66%, 64%, and 59% for the haplo, PTCy, and MTX groups respectively. Although this was not significant, it may be clinically meaningful given the significant improvement in extensive GVHD and improvement in all other secondary end-points except 1-year OS and RFS. Furthermore, the PTCy group had a higher percentage of mismatched antigens yet demonstrated superior outcomes. 1-year OS and RFS were superior in the MTX group however this is likely due to sample size differences. The improved extensive cGVHD and GRFS outcomes observed using PTCy/tacrolimus/MMF in the MRD/MUD setting should continue to be evaluated and currently there is an ongoing prospective, randomized study to further investigate. Disclosures Yaghmour: Jazz: Consultancy, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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