Contributions
Abstract: EP1254
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
Measurable Residual Disease (MRD) in Ph negative (-) Acute Lymphoblastic Leukemia (ALL) patients before allogeneic hematopoietic cell transplantation (allo-HCT) has been proposed as a major risk factor for imminent relapse.
Aims
To study the prognostic value of pre-transplantation (pre-HCT) MRD in Ph(-) ALL adjusted to other disease characteristics.
Methods
Sixty-seven consecutive patients who underwent allo-HCT in our JACIE center between 2009-2020 for B- (39), T- (24) ALL or Mixed phenotype acute leukemia (MPAL,4) were evaluated. Eight color flow cytometry (FC) MRD analysis was performed pre-HCT and post-HCT in 3-month intervals. FC-MRD was considered positive if >=0.01%. In case of positive MRD pre-HCT, further treatment, mostly chemotherapy, was administered. In case of post-HCT MRD positivity, immunosuppression was reduced promptly.
Results
Thirty-one out of 67 transplants were matched unrelated, 27 sibling and 9 alternative ones. Most patients received 14,4 Gy total body irradiation (TBI) in conditioning regimen (53/67). Median age was 31 (14-57) years and patients were transplanted in first CR1,44/67 or >CR1, 23/67. Median follow-up was 26 (2-138) months.Overall, 8 presented hematological relapse out of 16 patients with positive MRD post-HCT,successfully reversed by immunotherapeutic intervention. On univariate analysis positive pre-HCT MRD was associated with shorter Time To Progression (TTP) (HR: 8.75 CI95%: 2.06-37.06, p=0.03), shorter Relapse Free Survival (RFS) (HR: 2.33 CI95%: 1.05-5.18, p<0.05) but not Overall Survival (OS). On multivariate analysis adjusted for transplant characteristics only the association with TTP persisted. We also studied the interaction between pre-HCT MRD and other transplant characteristics (age, type of transplant, cytogenetics, disease phase at transplant and conditioning regimen) on TTP, RFS and OS. We found that in the subgroup with disease phase >CR1, patients with positive pre-HCT MRD had shorter TTP (HR: 11.5, CI95%:1.78-74.21%, p=0.01) and shorter RFS (HR: 5.42, CI95%:1.61-18.18%, p=0.006) compared to patients with negative pre-HCT MRD. These associations did not occur in the subgroup transplanted in CR1. Comparing outcome of patients in CR1 vs >CR1, 4-year RFS and OS were: 61.4% [CI95%:44.5-74.5] and 61.4% [CI95%:44.5-74.5%] for CR1 and 44.2% [CI95%:20.6-65.6%] and 56.1% [CI95%:26.3-77.9%] for >CR1 respectively.
Conclusion
Detectable pre-HCT MRD in patients transplanted in >CR1 is associated to worse outcomes and remains a major failure barrier for transplant. In our small study population, it seems that allo-HCT may overcome the chemo-resistance of residual disease in CR1 performed transplants, as outcome is not related to pre-HCT MRD status. MRD post-HCT is an important tool and its monitoring with sensitive techniques could detect potentially high-risk patients who may benefit from abrupt cessation of immunosuppression. In the current era, the role of novel agents should be defined in large prospective studies in order to optimize the transplant outcome.
Keyword(s): ALL, Allo-SCT, MRD
Abstract: EP1254
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
Measurable Residual Disease (MRD) in Ph negative (-) Acute Lymphoblastic Leukemia (ALL) patients before allogeneic hematopoietic cell transplantation (allo-HCT) has been proposed as a major risk factor for imminent relapse.
Aims
To study the prognostic value of pre-transplantation (pre-HCT) MRD in Ph(-) ALL adjusted to other disease characteristics.
Methods
Sixty-seven consecutive patients who underwent allo-HCT in our JACIE center between 2009-2020 for B- (39), T- (24) ALL or Mixed phenotype acute leukemia (MPAL,4) were evaluated. Eight color flow cytometry (FC) MRD analysis was performed pre-HCT and post-HCT in 3-month intervals. FC-MRD was considered positive if >=0.01%. In case of positive MRD pre-HCT, further treatment, mostly chemotherapy, was administered. In case of post-HCT MRD positivity, immunosuppression was reduced promptly.
Results
Thirty-one out of 67 transplants were matched unrelated, 27 sibling and 9 alternative ones. Most patients received 14,4 Gy total body irradiation (TBI) in conditioning regimen (53/67). Median age was 31 (14-57) years and patients were transplanted in first CR1,44/67 or >CR1, 23/67. Median follow-up was 26 (2-138) months.Overall, 8 presented hematological relapse out of 16 patients with positive MRD post-HCT,successfully reversed by immunotherapeutic intervention. On univariate analysis positive pre-HCT MRD was associated with shorter Time To Progression (TTP) (HR: 8.75 CI95%: 2.06-37.06, p=0.03), shorter Relapse Free Survival (RFS) (HR: 2.33 CI95%: 1.05-5.18, p<0.05) but not Overall Survival (OS). On multivariate analysis adjusted for transplant characteristics only the association with TTP persisted. We also studied the interaction between pre-HCT MRD and other transplant characteristics (age, type of transplant, cytogenetics, disease phase at transplant and conditioning regimen) on TTP, RFS and OS. We found that in the subgroup with disease phase >CR1, patients with positive pre-HCT MRD had shorter TTP (HR: 11.5, CI95%:1.78-74.21%, p=0.01) and shorter RFS (HR: 5.42, CI95%:1.61-18.18%, p=0.006) compared to patients with negative pre-HCT MRD. These associations did not occur in the subgroup transplanted in CR1. Comparing outcome of patients in CR1 vs >CR1, 4-year RFS and OS were: 61.4% [CI95%:44.5-74.5] and 61.4% [CI95%:44.5-74.5%] for CR1 and 44.2% [CI95%:20.6-65.6%] and 56.1% [CI95%:26.3-77.9%] for >CR1 respectively.
Conclusion
Detectable pre-HCT MRD in patients transplanted in >CR1 is associated to worse outcomes and remains a major failure barrier for transplant. In our small study population, it seems that allo-HCT may overcome the chemo-resistance of residual disease in CR1 performed transplants, as outcome is not related to pre-HCT MRD status. MRD post-HCT is an important tool and its monitoring with sensitive techniques could detect potentially high-risk patients who may benefit from abrupt cessation of immunosuppression. In the current era, the role of novel agents should be defined in large prospective studies in order to optimize the transplant outcome.
Keyword(s): ALL, Allo-SCT, MRD