scholarly journals Predictive Factors for Adverse Outcomes After Use of Donor Cell Infusion (DCI) in Patients with Relapsed Hematological Malignancies Treated with Allogeneic Hematopoietic Cell Transplantation (alloHCT)

2012 ◽  
Vol 18 (2) ◽  
pp. S351
Author(s):  
N. Bejanyan ◽  
B. Bolwell ◽  
L. Rybicki ◽  
D. Abounader ◽  
H. Duong ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Predictive Factors ◽  
Hematological Malignancies ◽  
Hematopoietic Cell Transplantation ◽  
Donor Cell ◽  
Adverse Outcomes ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation

Validation of Favourable Impact of Large Granular Lymphocytosis after Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3936-3936
Author(s):  
Marc Poch Martell ◽  
Jieun Uhm ◽  
Naheed Alam ◽  
Vikas Gupta ◽  
Jeffrey H. Lipton ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Predictive Factors ◽  
Lymphocyte Count ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Gvhd Prophylaxis ◽  
Significant Difference ◽  
Persistent Elevation

Abstract Introduction: We previously reported on the incidence of large granular lymphocytosis (LGL) following allogeneic hematopoietic cell transplantation (allo-HCT), its favorable impact on outcome and the predictive factors associated with its development (D Kim, BMT, 2013). In the current study we aimed to validate our previous findings in an independent set of patients. Methods:All 408 patients undergoing allo-HCT at Princess Margaret Cancer Centre, Toronto, from 2007 to 2012 (replication set) were included retrospectively. Data from the previously reported set of patients undergoing allo-HCT from 2000 to 2007 (n = 418) (original set) were updated. Results:There were significant differences between original and replication sets in baseline characteristics (age, underlying disease, conditioning, GvHD prophylaxis, graft source, donor type, and incidences of GvHD and CMV viremia) in accordance to the changes over a decade in allo-HCT procedures. The cumulative incidence of LGL lymphocytosis at 3 years was 21.8% in the original set and 11.7% in the replication set (P<0.001). The median onset of LGL lymphocytosis was 362 days after HCT in the original set and 223 days in the replication set. Patients with LGL lymphocytosis showed a persistent elevation of lymphocyte count compared to patients without LGL lymphocytosis (P<0.001). Patients with LGL lymphocytosis showed a higher overall survival (OS) (86.4% vs 46.1%, P<0.001, Fig. A) and lower non-relapse mortality (NRM) (10.5% vs 36.3%, P<0.001, Fig. B) at 3 years. No significant difference was found in relapse incidence according to the development of LGL lymphocytosis (13.9% vs 19.6%, P=0.25). Multivariable analysis confirmed the favorable impact of LGL lymphocytosis on OS (HR 0.30, P=0.02) and a trend towards lower NRM (HR 0.27, P<0.001, original set; HR 0.50, P=0.22, replication set). No effect of LGL lymphocytosis on relapse incidence was demonstrated (HR 1.24, P=0.37, original set; HR 0.53, P=0.29, replication set). Patients with LGL lymphocytosis showed a trend towards a higher incidence of IST cessation after cGvHD: 63.6% at 7 years vs 53.4% in patients without LGL lymphocytosis, P=0.07. The previously identified predictive factors for the development of LGL lymphocytosis were replicated: higher incidence of LGL lymphocytosis with 1) CMV seropositive recipients (29.6% vs 5.1%, P < 0.001); 2) CMV viremia (31.0% vs 8.9%, P<0.001) and 3) chronic GvHD (28.2%, vs 5.0%, P<0.001). Conclusions: The favorable impact of LGL lymphocytosis following allo-HCT in OS and NRM, as well as the predictive factors for the development of LGL lymphocytosis were successfully validated in an independent cohort of patients. No impact of LGL lymphocytosis on relapse incidence was noted. The difference in transplantation procedures between the two cohorts, such as GvHD prophylaxis/T-cell depletion, may explain the lower incidence of LGL lymphocytosis in the replication cohort. Patients with LGL lymphocytosis showed a trend towards a higher incidence of IST cessation after cGvHD, which may explain the lower NRM. Patients with LGL lymphocytosis showed a persistent elevation of lymphocyte count and had an indolent course. OS and NRM according to the development of LGL lymphocytosis 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.

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