1.
Impact on outcome of MRD prior hematopoietic stem cell transplantation after FLAMSA-busulfan conditioning regimen: a retrospective monocentric study
Meur, G. L., Plesa, A., Larcher, M. V., Fossard, G., Barraco, F., Loron, S., Balsat, M., Ducastelle-Lepretre, S., Gilis, L., Thomas, X., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) conditioned by sequential association of fludarabine, amsacrine, cytosine arabinoside (FLAMSA) followed by a reduced intensity conditioning regimen emerged for patients with high-risk acute myeloid leukemia (AML), especially in refractory or relapsing patients. OBJECTIVE We aimed to address retrospectively the impact of pre-transplant minimal residual disease (MRD) by flow cytometry (FCM) on outcome of high-risk AML patients who underwent allo-HSCT after sequential FLAMSA-Busulfan (FLAMSA-BU) based conditioning regimens. STUDY DESIGN We included 165 high-risk AML patients transplanted after FLAMSA-BU in this retrospective one-center "real life" study. All patients received in vivo T-cell depletion using anti-thymocyte globuline (5 mg/kg). MRD detection was based on leukemia associated immunophenotype (LAIP) using the ELN recommendations, with a threshold of 0.1%. Univariate and multivariate analysis were performed using R software version 4.1.1. RESULTS With a median follow-up of 4.0 years post-transplant, median overall survival (OS) was 54.9 months. Overall, 41 patients (24.8%) relapsed post-transplant with a resulting cumulative incidence of relapse (CIR) at 2 and 5 years of 26.7% and 34.0% respectively. Detectable MRD preceding allo-HSCT, as refractory status, were both associated with worse median OS and CIR rates compared to patients without detectable MRD. However, OS was not significantly different between pre-HSCT MRD+ and refractory patients (median 0.7 vs 2.0 years, p=0.3). Conversely, pre-HSCT MRD negativity was associated with a reduced 2-year cumulative incidence of relapse (CIR). Neither European LeukemiaNet (ELN) risk stratification nor age did significantly influence OS. In the multivariate analysis, only pre-HSCT MRD positivity and lower conditioning regimen intensity were significantly associated with a poorer OS. Cumulative incidence of extensive chronic graft versus host disease (cGVHD) at 2 years was 26.15%. Estimated non-relapse mortality (NRM) of the entire cohort at 2 years was 23.1%, with age and unrelated donor as risk factors of higher NRM. CONCLUSION FLAMSA-Busulfan did not reverse the pejorative effect of detectable pre-HSCT MRD, suggesting that such patients should be offered alternative strategies prior HSCT to reach deeper remission.
2.
Flow cytometry minimal residual disease after allogeneic transplant for chronic lymphocytic leukemia
Algrin, C., Golmard, J. L., Michallet, M., Reman, O., Huynh, A., Perrot, A., Sirvent, A., Plesa, A., Salaun, V., Bene, M. C., et al
European Journal of Haematology. 2017;98(4):363-370
Abstract
OBJECTIVES This study investigates whether achieving complete remission (CR) with undetectable minimal residual disease (MRD) after allogeneic stem cell transplantation (allo-SCT) for chronic lymphocytic leukemia (CLL) affects outcome. METHODS We retrospectively studied 46 patients transplanted for CLL and evaluated for post-transplant MRD by flow cytometry. RESULTS At transplant time, 43% of the patients were in CR, including one with undetectable MRD, 46% were in partial response, and 11% had refractory disease. After transplant, 61% of the patients achieved CR with undetectable MRD status. By multivariate analysis, reaching CR with undetectable MRD 12 months after transplant was the only factor associated with better progression-free survival (P = 0.02) and attaining undetectable MRD, independently of the time of negativity, was the only factor that correlated with better overall survival (P = 0.04). CONCLUSION Thus, achieving undetectable MRD status after allo-SCT for CLL is a major goal to improve post-transplant outcome. Copyright © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
3.
Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis
Bleyzac, N., Cuzzubbo, D., Renard, C., Garnier, N., Dubois, V., Domenech, C., Goutagny, M. P., Plesa, A., Grardel, N., Goutelle, S., et al
Bone Marrow Transplantation. 2016;51(5):698-704
Abstract
There is currently a major concern regarding the optimal immunosuppression therapy to be administered after hematopoietic stem cell transplantation (HSCT) to reduce both the toxicity of GvHD and the rate of relapse. We report the outcome of high-risk leukemia children transplanted with a new way of managing cyclosporine (CsA)-based GvHD prophylaxis. A total of 110 HSCT in 109 ALL or AML children who received CsA without mycophenolate or methotrexate in matched related as well as in matched or mismatched unrelated stem cell transplantation were included. CsA dosage regimens were individualized to obtain specific trough blood concentrations values. The incidences of grade I-II and III-IV acute GvHD were 69.1% and 1.8%, respectively, and 8.4% for chronic GvHD. GvHD was neither more frequent nor severe in unrelated than in related HSCT. GvHD occurred in 87% of patients with a mean CsA trough concentration 120ng/mL versus 43% with concentration >120ng/mL (P<0.0001). Five-year disease-free survival (DFS) and overall survival were 78% and 83.6%, respectively. DFS was 76.9% for ALL and 80.4% for AML patients. There was no difference in DFS between matched siblings and matched unrelated or mismatched unrelated HSCT. DFS in patients with minimal residual disease (MRD) 10(-3) and in those with MRD <10(-3) before SCT was comparable. Our results indicate that a GvHD prophylaxis regimen based on CsA without mycophenolate or methotrexate is safe and effective whatever the donor compatibility is. These results suggest that GvL effect may be enhanced by this strategy of GvHD prophylaxis.