scholarly journals Assessment Of The Utility Of Subset Donor Chimerism For Predicting Event-Free Survival After Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation Using TLI And ATG

2010 ◽  
Vol 16 (2) ◽  
pp. S272
Author(s):  
A.C. Logan ◽  
B.B. Turnbull ◽  
P.W. Lavori ◽  
D.B. Miklos ◽  
R.S. Negrin ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Event Free Survival ◽  
Free Survival ◽  
Donor Chimerism

Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation in Relapsed, Refractory, and Transformed Indolent Non-Hodgkin's Lymphoma

2008 ◽  
Vol 26 (2) ◽  
pp. 211-217 ◽  
Author(s):  
Andrew R. Rezvani ◽  
Barry Storer ◽  
Michael Maris ◽  
Mohamed L. Sorror ◽  
Edward Agura ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Hodgkin's Lymphoma ◽  
Free Survival ◽  
Allogeneic Hct ◽  
Non Hodgkin's Lymphoma ◽  
Indolent Disease

Purpose Few effective treatment options exist for chemotherapy-refractory indolent or transformed non-Hodgkin's lymphoma (NHL). We examined the outcome of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) in this setting. Patients and Methods Sixty-two patients with indolent or transformed NHL were treated with allogeneic HCT from related (n = 34) or unrelated (n = 28) donors after conditioning with 2 Gy of total-body irradiation with or without fludarabine. Nine unrelated donors were mismatched for ≥ one HLA antigen. Sixteen patients had histologic transformation before HCT. Twenty patients (32%) had progressive disease after previous high-dose therapy with autologous HCT. Median age was 54 years, and patients had received a median of six lines of treatment before HCT. Median follow-up time after HCT was 36.6 months. Results At 3 years, the estimated overall survival (OS) and progression-free survival (PFS) rates were 52% and 43%, respectively, for patients with indolent disease, and 18% and 21%, respectively, for patients with transformed disease. Patients with indolent disease and related donors (n = 26) had 3-year estimated OS and PFS rates of 67% and 54%, respectively. The incidences of grade 2 to 4 acute graft-versus-host disease (GVHD), grade 3 and 4 acute GVHD, and extensive chronic GVHD were 63%, 18%, and 47%, respectively. Among survivors, the median Karnofsky performance status at last follow-up was 85%. Conclusion Nonmyeloablative allogeneic HCT can produce durable disease-free survival in patients with relapsed or refractory indolent NHL, even in this relatively elderly and heavily pretreated cohort. Outcomes were particularly good in patients with untransformed disease and related donors, whereas patients with transformed disease did poorly. Long-term survivors reported good overall functional status.

scholarly journals Factors Predicting Gvhd Free, Relapse Free Survival (GRFS) after Allogeneic Hematopoietic Cell Transplantation; A Multivariable Analysis of 531 Allografts from a Single Center

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2028-2028
Author(s):  
Melhem Solh ◽  
Xu Zhang ◽  
Katelin Connor ◽  
Stacey Brown ◽  
H. Kent Holland ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Disease Risk ◽  
Multivariable Analysis ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Relapse Free Survival ◽  
Free Survival ◽  
One Year ◽  
Very High

Abstract The ideal outcome of allogeneic hematopoietic cell transplantation (allo-HCT) is based on survival that is free of morbidity. The most common causes of treatment failure and morbidity after HCT are relapse, GVHD and non-relapse death. A composite endpoint that measures survival free of clinically significant negative events may be a useful way to determine the success of allo-HCT (1). We assessed GVHD and relapse-free survival (GRFS) where the events were acute GVHD grade 3-4, moderate to severe chronic GVHD, relapse or death in 531 consecutive adult patients who received an allo- HCT between 2006 and 2014 at our center. Median follow up of living patients was 46 months (12-123). Patients were treated using standardized supportive care algorithms at our center. Although this was a retrospective analysis, patient characteristics and outcomes including GVHD grading were obtained from our institutional database where they had been prospectively documented. The median age was 52 (18-77) years. 266 (50%) received myeloablative conditioning, and 428 (81%) received PBSC as stem cell source. Donor type was HLA matched related (MRD, n=198, 37%), matched unrelated (MUD, n=205, 39%) and haploidentical using T-replete grafts and post-transplant cyclophosphamide (HIDT, n=128, 24%). 36% of patients had a high/very high Dana farber disease risk index (DRI). The most common indications for transplant were AML (n=197, 37%), MDS/MPS (n=114, 21%), NHL (n=132, 25%) and ALL (n=68, 13%).1 year OS, disease free survival DFS and GRFS were 78%, 64% and 33% respectively. GRFS after MRD, MUD and HIDT was 39%, 27% and 35% respectively, with MRD recipients having a better GRFS than MUD (p=0.004). Regression analysis showed that GRFS at the one year was lower for, patients transplanted before 2011 than those transplanted between 2011 and 2014(27% vs 39%, p=0.0031), high CIBMTR disease risk than low CIBMTR risk (24% vs 39%, p=0.009) and high/very high DRI than low DRI (23% vs 48%, p<0.001). On multivariable analysis, year of transplant before 2011 (HR =1.2, p=0.03), age >= 50 years (HR 1.22, p=0.05), MUD donor (HR 1.3, p=0.004) and high/very high DRI risk (HR 2.05, p<0.001) were all associated with a worse GFRS at one year post HCT. GFRS is an endpoint that is worth investigating in further trials as a marker of successful HCT. These data suggest that GRFS can be predicted by patient age and DRI but not by HCT-CMI. Importantly the GRFS appears to have improved in more recently transplanted patients and MUD donors produce inferior GRFS to MRD whereas haploidentical donors do not. Table 1. Predictors of GRFS at one year N=531 1 year GRFS HR 95% CI P value Year of BMT2005-2010 2011-2014 270 (51%) 261 (49%) 30% 37% 1.00 0.80 25%-35% 32%-43% - 0.03 AgeAge <50 years Age >= 50 years 228 (43%) 303(57%) 37% 31% 1.00 1.22 31%-43% 26%-36% - 0.05 Donor TypeMRD MUD Haplo Haplo vs MUD 198(37%) 205 (39%) 128 (24%) 39% 27% 35% 1.00 1.30 1.13 0.81 33%-45% 22%-33% 27%-42% - 0.004 0.379 0.112 DRILow Intermediate High/very high 78(15%) 258 (49%) 189 (36%) 48% 36% 23% 1.00 1.42 2.05 38%-58% 31%-42% 18%-29% - 0.025 <0.001 1. Holtan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125(8):1333-8. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Does Early T Cell Chimerism Predict Outcomes after Allogeneic Hematopoietic Cell Transplantation ?

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3360-3360
Author(s):  
Tania Jain ◽  
Luke Mountjoy ◽  
Katie L. Kunze ◽  
Pierre Noel ◽  
Nandita Khera ◽  
...  
Keyword(s):  
T Cell ◽  
Clinical Outcomes ◽  
Cell Transplantation ◽  
Hematological Malignancies ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Time Points ◽  
Donor Chimerism ◽  
Time To Relapse

Abstract Introduction: Donor T cell chimerism is tested frequently early after allogeneic hematopoietic cell transplantation (HCT). However, the predictive ability of testing this early after HCT, i.e. at day +30 or day +60, has not been well described, outside of smaller single center studies. Herein, we evaluate the correlation of early donor T cell chimerism with clinical outcomes of overall survival (OS) and relapse in patients undergoing HCT for various hematological malignancies. Methods: We identified patients who received HCT with 8/8 matched unrelated donors at our center between 2007 and 2016 and obtained the clinical data retrospectively. Chimerism studies were included for patients who had testing done at day+30 and/ or day +60. Chimerism is tested using PCR based technique. Due to limited variability in chimerism levels <100% donor chimerism, a cut-off of 100% was used for analysis. Hence, patients were divided into those who achieved full donor chimerism in CD3 fraction (100%) and those in whom CD3 donor chimerism was < 100% at the respective time points. Clinical outcomes evaluate for this abstract were OS and time to relapse. Univariate and multivariate Cox proportional hazard regression models were used using variables of interest, the later adjusted for age at HCT, use of ATG, conditioning regimen and disease risk index (DRI). Results: Baseline patient and HCT data: There were 209 patients who met the selection criteria of which 4 died within 30 days from HCT and hence, were not included in the analysis. Among the 205, 87 (42%) were women and median age at HCT was 55 (range, 18 - 74) years. The hematological malignancy diagnosis was acute myeloid leukemia (AML)/ myelodysplastic syndrome (MDS) in 112 (55%), acute lymphoblastic leukemia (ALL) in 35 (17%), chronic leukemias in 13 (6%), lymphomas in 13 (6%) and myeloproliferative neoplasm in 20 (10%); with DRI being very high in 9 (5%), high in 53 (27%), intermediate in 120 (60%) and low in 17 (9%) patients. Myeloablative conditioning was used in 81 (40%) and reduced intensity conditioning in 124 (60%). Graft versus host disease prophylaxis used was calcineurin inhibitor with methotrexate of mycophenolate in all patients while anti-thymocyte globulin was used in 125 (61%) patients. All patients received a peripheral blood graft. Outcomes: Median follow-up for all included patients was 615 (range, 30 - 3147) days. At day +30, 138 patients had achieved 100% donor CD3 chimerism of 189 patients in whom this data was available (73%) while at day +60, 131 (76%) out of 173 had 100% donor CD3 chimerism. In the univariate model, CD3 donor chimerism level at day +30 as well as day +60, was not predictive of OS (HR 1.5, 95% CI 0.82 - 2.9; p = 0.18 for day +30, HR 1.8, 95% CI 0.81 - 4.0, p = 0.15 for day +60). As for time to relapse, CD3 chimerism did not significantly affect the risk of relapse at these time points (HR 0.43, 95% CI 0.17 - 1.1, p = 0.08 for day +30; HR 0.55, 95% CI 0.18 - 1.6, p = 0.28 for day +60). In the multivariate model also, after adjustment as described above, CD3 at day +30 or at day +60 was not significantly associated with the risk of OS or time to relapse (Figure 1). Kaplan Meier curves for OS for CD3 chimerism at day +30 and day +60 are shown in Figure 2. Conclusions: In this study, T cell chimerism as early as day +30 or day +60 does not seem to predict OS or relapse in patients undergoing HCT for various hematological malignancies. Given the limitations of a smaller retrospective design, this must be validated in a larger study, possibly using registry data. If these findings are indeed confirmed, then the practice of testing chimerism early and frequently, that adds additional expense to the overall cost of HCT, must be reconsidered. Disclosures Palmer: Novartis: Research Funding.

scholarly journals Superior Outcomes with Fludarabine-Busulfan (Flu/Bu) Based Conditioning for Allogeneic Hematopoietic Cell Transplantation in Myelofibrosis - a Comparative Analysis By CIBMTR

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 912-912
Author(s):  
Guru Subramanian Guru Murthy ◽  
Soyoung Kim ◽  
Noel Estrada-Merly ◽  
Ronald M. Sobecks ◽  
Betul Oran ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Multivariable Analysis ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Unrelated Donor ◽  
Free Survival ◽  
Grade 3

Abstract Background: Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative therapeutic modality for patients with myelofibrosis (MF). However, the optimal conditioning regimen for allo-HCT either in the myeloablative conditioning (MAC) or in the reduced intensity conditioning (RIC) setting is not well known. Methods: Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified adults aged ≥18 years with MF who underwent allo-HCT between the years 2008-2018. Donor types included matched sibling donor (MSD), 8/8 matched unrelated donor (MUD), and 7/8 MUD. Outcomes were compared separately in the MAC and RIC cohorts based on the most common conditioning regimens used in each setting - MAC [(Fludarabine/Busulfan (Flu/Bu) vs. Busulfan/cyclophosphamide (Bu/Cy)] or RIC [(Flu/Bu vs. Fludarabine/melphalan (Flu/Mel)]. Overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM), relapse, acute and chronic graft versus host disease (GVHD) and GVHD-free relapse-free survival (GRFS) were evaluated. Survival analysis was done using Kaplan-Meier method and significant predictors were evaluated using Cox-proportional hazard regression method. Multivariable regression model included main effect (conditioning regimen) and covariates (patient age, gender, race, CMV match, disease subtype, DIPSS at HCT, comorbidities score (HCT-CI), Karnofsky performance status, prior therapy (ruxolitinib use/splenic radiation therapy/splenectomy), interval between diagnosis and transplant, conditioning intensity, stem cell source, donor-recipient HLA-match, GVHD prophylaxis, ATG/alemtuzumab use, transplant year, and center affect). All analyses were performed at a two-sided significance level of 0.05. Results: Of 872 patients who met the study criteria, 379 patients underwent allo-HCT using MAC (Flu/Bu=247, Bu/Cy=132) and 493 patients using RIC (Flu/Bu=166, Flu/Mel=327). Key baseline characteristics of the patients are summarized in Table 1. In multivariable analysis, significant differences in outcomes were observed in the MAC and RIC setting based on the choice of conditioning regimen (Table 2). In the MAC setting, Bu/Cy was associated with a higher risk of acute GVHD (grade 2-4 HR 2.33, 95% CI 1.67-3.25, p&lt;0.01; grade 3-4 HR 2.31, 95% CI 1.52-3.52, p&lt;0.01) and inferior GRFS (HR 1.94, 95% CI 1.49-2.53, p&lt;0.01) as compared to Flu/Bu. In the RIC setting, Flu/Mel was associated with inferior OS (HR 1.80, 95% CI 1.15-2.81, p&lt;0.01), higher risk of NRM (HR 1.81, 95% CI 1.12-2.91, p=0.01) and acute GVHD (grade 2-4- HR 1.45, 95% CI 1.03-2.03, p=0.03; grade 3-4 HR 2.21, 95%CI 1.28-3.83, p&lt;0.01) as compared to Flu/Bu. These higher risks associated with Flu/Mel were primarily observed early post-transplant. The results were consistent when the outcomes were evaluated based on the two common melphalan doses employed in the RIC setting (100mg/m 2 vs 140mg/m 2). Conclusions: Our study demonstrates that the choice of conditioning regimen significantly influences the outcomes of allo-HCT in MF. The results favor Flu/Bu based conditioning in the MAC (lesser acute GVHD and better GRFS) and RIC (better OS, lower NRM, lower acute GVHD) setting. Hence, this aspect should be explored in future studies as the modification of conditioning strategies could lead to improved outcomes. Figure 1 Figure 1. Disclosures Guru Murthy: TG therapeutics: Other: Advisory board; Cardinal Health Inc.: Honoraria; Qessential: Consultancy; Guidepoint: Consultancy; Techspert: Consultancy; Cancerexpertnow: Honoraria. Sobecks: CareDX: Membership on an entity's Board of Directors or advisory committees. Scott: Bristol Myers Squibb: Consultancy, Honoraria, Research Funding. Saber: Govt. COI: Other.

Results of Second or Third Allogeneic Hematopoietic Cell Transplantation As Salvage Therapy for Patients Failing Primary Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4516-4516
Author(s):  
Birgit Federmann ◽  
Christoph Faul ◽  
Wichard Vogel ◽  
Lothar Kanz ◽  
Wolfgang A. Bethge
Keyword(s):  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Free Survival ◽  
Off Label ◽  
Allogeneic Hct ◽  
Pre Treatment

Abstract Abstract 4516 Introduction: Patients with relapse after allogeneic hematopoietic cell transplantation (HCT) have generally a very poor prognosis. Besides donor lymphocyte infusions, chemotherapy or supportive care, second or even third allogeneic HCT have been performed in selected patients. This is often associated with a high incidence of non-relapse-mortality (NRM) because of heavy pre-treatment or reduced performance status due to comorbidities or pre-treatment related complications. Method: We report a retrospective analysis of our single center experience with second or third allogeneic HCT between 2000–2011. We searched our database for patients receiving >1 allogeneic HCT in the past 10 years. Details on characteristics and clinical course of the patients were confirmed by retrospective chart review. Result: 47 patients received more than one allogeneic HCT (second HCT, n=44, second and third HCT, n=3). Median age of the patients was 40 (range, 18–65) years. 27 patients were male, 20 female. Diagnoses were acute myeloid leukemia (n=28), acute lymphoblastic leukemia (n=11), multiple myeloma (n=1), chronic myeloid leukemia (n=2), myelodysplastic syndrome (n=2), osteomyelofibrosis (n=2) and non-Hodgkin lymphoma (n=1). Reasons for second or third HCT were relapse (n=49) or primary graft failure (n=1). Median time between first and second HCT was 17 (range, 3–137) months, 12 months between second and third HCT (range, 10–16). For the first HCT 35 patients received myeloablative (MAC) and 12 reduced intensity conditioning (RIC). For the second HCT 16 patients received MAC and 31 RIC, for the third HCT RIC was used in all patients. 6/47 patients (13%) received salvage chemotherapy followed by RIC out of aplasia. Before salvage HCT disease status of the patients was CR=14, PR=33. Time to neutrophil engraftment after second and third HCT was 16 (range, 6–77) and 10 (range, 9–13) days, respectively; to platelet engraftment 16 (range, 9–71) and 23 (range, 14–73) days, respectively. 12 of 47 patients (26%) after second HCT are alive (CR=11, PR=1) and 1 of 3 patients is alive and in remission after receiving a third HCT. Kaplan-Meier estimated 3-year overall and event-free survival is 30% and 25%, respectively, with a median follow-up of 62 (range 6–111) months of patients alive. Outcome was better for patients in CR at HCT (3-year OS with 43% vs. 24%, p=0.13). In the subgroup of patients with acute leukemia 3-year OS and EFS was superior in patients with AML (32% and 31%) while all patients with ALL died. Older age had no negative impact on survival as 3-year OS in patients ≥40 years (n=25) was 43% compared to 15% in patients <40 years (n=22) (p=0.04). Cumulative incidence of NRM at 3 years with death due to relapse as competing risk after second HCT was 43%. 2 of 3 patients after third HCT died due to NRM. The use of RIC was associated with an inferior 3-year OS compared to MAC with 18% vs. 53%, p=0.08. Causes of death were relapse=18, infection=12, multiorgan failure=3, GVHD=1, EBV-LPD=1 and PML=2. Outcome was inferior if the second HCT was performed within 6 months after first HCT with a 3-year OS of 0% vs. 31%, p=0.02. In 8 patients the same donor as for primary HCT was used while in 39 patients an alternative donor (MRD=7, MUD=10, MMUD=7, MMRD=2, haplo=21) was chosen. Using the same donor seems to result in a better outcome with 3-year OS of 63% vs. 23%, p=0.08. Incidence of grade II-IV GVHD was 17%, of chronic GVHD 30%. Presence of cGVHD after second allogeneic HCT was associated with better survival (3-year OS 42% vs. 26%, p=0.31) especially after using RIC (33% vs. 11%, p=0.09) Conclusion: In view of the otherwise dismal prognosis of patients with relapse after allogeneic HCT, second or third allogeneic HCT is feasible and can achieve long term disease free survival in up to a third of patients, even in patients of more than 40 years of age. Thus, retreatment with allogeneic HCT appears to be the most promising salvage strategy besides DLI for relapse >6 months after allogeneic HCT. Disclosures: Off Label Use: The use of some agents in the conditioning is off-label.

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