NEGATIVE PRE TRANSPLANT MINIMAL RESIDUAL DISEASE, ASSESSED BY FLOW CYTOMETRY, IMPROVES OUTCOME IN ADULT ACUTE LYMPHOBLASTIC LEUKEMIA, ESPECIALLY IF CLEARENCE IS ACHIEVED EARLY DURING INDUCTION
(Abstract release date: 05/19/16)
EHA Library. Gambella M. 06/09/16; 132402; E853
Dr. Massimiliano Gambella
Contributions
Contributions
Abstract
Abstract: E853
Type: Eposter Presentation
Background
With the introduction of pediatric-inspired induction regimen, prognosis of adult acute lymphoblastic leukemia (ALL) has substantially improved, leading to an increased assessment of minimal residual disease (MRD) during all induction course and a progressive use of MRD-driven therapeutic approach. In most modern pediatric protocols, persistence of MRD during the first courses of induction therapy is an adverse prognostic factor and constitutes a strong indication for early allogeneic bone marrow transplantation (BMT). However, it remains unclear if an effort towards MRD eradication should be attempted before BMT, as relatively few data are available on outcome of MRD positive adult ALL patients.
Aims
The aim of this study was to analyze the role of pre-BMT MRD assessment as predictor for the post-transplant relapse risk and to evaluate the impact of day 33 MRD status in pre-BMT MRD negative patients.
Methods
We retrospectively analyzed the outcome of 53 consecutive ALL patients receiving allo-BMT, with available pre-BMT multicolour flow cytometry (MFC) MRD assessment. Median age at transplant was 30 years. Disease phase was CR1 in 20 (38%), CR2 in 17 (32%), and CR3 in 14 patients (30%). Thirty-five patients (66%) had B lineage ALL, whereas 18 (34%) had T-ALL. Relapse-free survival (RFS) was calculated from the time of transplantation until last follow-up or documented leukemic relapse. Overall Survival (OS) was calculated from the time of transplantation until death by any cause or last follow-up. Median follow up was 62 months.A positive MFC MRD was defined by the presence of no less than 25 clustered leukemic cells/105 total events (threshold of2.5x10-4 residual leukemic cells) at four-color flow-cytometry.
Results
Relapse occurred in 30 patients (57%). Three-year RFS was 42.2% (median 10 months). The probability of relapse was significantly affected by disease status at BMT (CR1 vs CR2 or p<0.001), karyotype ( p <0.03) and MFC MRD (both day 33 and pre-BMT, p<0.03) . Pre-BMT MFC-MRD was a strong predictor of longer relapse free survival: 5 relapses occurred in the 17 MFC-MRD negative patients and 3-years RFS was 69.4% (median not reached), compared to 25 relapses observed in 36 MFC MRD positive patients, with a 3-year RFS of 29.4% (median 5 months). Multivariate analysis revealed that MFC MRD and disease status at transplantation were significant predictors of RFS duration (p <0.001 and p<0.05, respectively). Eleven patients with pre-BMT MRD negative had available day +33 assessment. Two relapses were observed among the 3 day 33 MRD positive patients (66%), compared to three relapses among 8 day 33 MFC MRD negative patients (37%). MRD evaluation was a strong predictor of long term survival, as 3- years OS was 65% for MFC MRD negative compared to 49.8% for MFC MRD positive patients (p<0.05).
Conclusion
Pre transplant MFC MRD evaluation is a feasible and reliable predictor of relapse risk in adults ALL patients. Patients with positive MFC MRD have a very high relapse risk and a poor outcome after BMT. Although small numbers prevented us to drive conclusion, persistence of MRD at day 33 seems to confer a worse prognosis in pre-BMT MRD patients. In the era of targeted therapy, at least for B-ALL, persistence of MRD after induction could be an indication for innovative approach, such as attempts of MRD eradication using recently developed immunoconjugated monoclonal anti-CD-22 antibodies or anti-CD3/anti-CD-19 bispecific antibodies.
Session topic: E-poster
Keyword(s): ALL, BMT, Induction chemotherapy, Minimal residual disease (MRD)
Type: Eposter Presentation
Background
With the introduction of pediatric-inspired induction regimen, prognosis of adult acute lymphoblastic leukemia (ALL) has substantially improved, leading to an increased assessment of minimal residual disease (MRD) during all induction course and a progressive use of MRD-driven therapeutic approach. In most modern pediatric protocols, persistence of MRD during the first courses of induction therapy is an adverse prognostic factor and constitutes a strong indication for early allogeneic bone marrow transplantation (BMT). However, it remains unclear if an effort towards MRD eradication should be attempted before BMT, as relatively few data are available on outcome of MRD positive adult ALL patients.
Aims
The aim of this study was to analyze the role of pre-BMT MRD assessment as predictor for the post-transplant relapse risk and to evaluate the impact of day 33 MRD status in pre-BMT MRD negative patients.
Methods
We retrospectively analyzed the outcome of 53 consecutive ALL patients receiving allo-BMT, with available pre-BMT multicolour flow cytometry (MFC) MRD assessment. Median age at transplant was 30 years. Disease phase was CR1 in 20 (38%), CR2 in 17 (32%), and CR3 in 14 patients (30%). Thirty-five patients (66%) had B lineage ALL, whereas 18 (34%) had T-ALL. Relapse-free survival (RFS) was calculated from the time of transplantation until last follow-up or documented leukemic relapse. Overall Survival (OS) was calculated from the time of transplantation until death by any cause or last follow-up. Median follow up was 62 months.A positive MFC MRD was defined by the presence of no less than 25 clustered leukemic cells/105 total events (threshold of2.5x10-4 residual leukemic cells) at four-color flow-cytometry.
Results
Relapse occurred in 30 patients (57%). Three-year RFS was 42.2% (median 10 months). The probability of relapse was significantly affected by disease status at BMT (CR1 vs CR2 or p<0.001), karyotype ( p <0.03) and MFC MRD (both day 33 and pre-BMT, p<0.03) . Pre-BMT MFC-MRD was a strong predictor of longer relapse free survival: 5 relapses occurred in the 17 MFC-MRD negative patients and 3-years RFS was 69.4% (median not reached), compared to 25 relapses observed in 36 MFC MRD positive patients, with a 3-year RFS of 29.4% (median 5 months). Multivariate analysis revealed that MFC MRD and disease status at transplantation were significant predictors of RFS duration (p <0.001 and p<0.05, respectively). Eleven patients with pre-BMT MRD negative had available day +33 assessment. Two relapses were observed among the 3 day 33 MRD positive patients (66%), compared to three relapses among 8 day 33 MFC MRD negative patients (37%). MRD evaluation was a strong predictor of long term survival, as 3- years OS was 65% for MFC MRD negative compared to 49.8% for MFC MRD positive patients (p<0.05).
Conclusion
Pre transplant MFC MRD evaluation is a feasible and reliable predictor of relapse risk in adults ALL patients. Patients with positive MFC MRD have a very high relapse risk and a poor outcome after BMT. Although small numbers prevented us to drive conclusion, persistence of MRD at day 33 seems to confer a worse prognosis in pre-BMT MRD patients. In the era of targeted therapy, at least for B-ALL, persistence of MRD after induction could be an indication for innovative approach, such as attempts of MRD eradication using recently developed immunoconjugated monoclonal anti-CD-22 antibodies or anti-CD3/anti-CD-19 bispecific antibodies.
Session topic: E-poster
Keyword(s): ALL, BMT, Induction chemotherapy, Minimal residual disease (MRD)
Abstract: E853
Type: Eposter Presentation
Background
With the introduction of pediatric-inspired induction regimen, prognosis of adult acute lymphoblastic leukemia (ALL) has substantially improved, leading to an increased assessment of minimal residual disease (MRD) during all induction course and a progressive use of MRD-driven therapeutic approach. In most modern pediatric protocols, persistence of MRD during the first courses of induction therapy is an adverse prognostic factor and constitutes a strong indication for early allogeneic bone marrow transplantation (BMT). However, it remains unclear if an effort towards MRD eradication should be attempted before BMT, as relatively few data are available on outcome of MRD positive adult ALL patients.
Aims
The aim of this study was to analyze the role of pre-BMT MRD assessment as predictor for the post-transplant relapse risk and to evaluate the impact of day 33 MRD status in pre-BMT MRD negative patients.
Methods
We retrospectively analyzed the outcome of 53 consecutive ALL patients receiving allo-BMT, with available pre-BMT multicolour flow cytometry (MFC) MRD assessment. Median age at transplant was 30 years. Disease phase was CR1 in 20 (38%), CR2 in 17 (32%), and CR3 in 14 patients (30%). Thirty-five patients (66%) had B lineage ALL, whereas 18 (34%) had T-ALL. Relapse-free survival (RFS) was calculated from the time of transplantation until last follow-up or documented leukemic relapse. Overall Survival (OS) was calculated from the time of transplantation until death by any cause or last follow-up. Median follow up was 62 months.A positive MFC MRD was defined by the presence of no less than 25 clustered leukemic cells/105 total events (threshold of2.5x10-4 residual leukemic cells) at four-color flow-cytometry.
Results
Relapse occurred in 30 patients (57%). Three-year RFS was 42.2% (median 10 months). The probability of relapse was significantly affected by disease status at BMT (CR1 vs CR2 or p<0.001), karyotype ( p <0.03) and MFC MRD (both day 33 and pre-BMT, p<0.03) . Pre-BMT MFC-MRD was a strong predictor of longer relapse free survival: 5 relapses occurred in the 17 MFC-MRD negative patients and 3-years RFS was 69.4% (median not reached), compared to 25 relapses observed in 36 MFC MRD positive patients, with a 3-year RFS of 29.4% (median 5 months). Multivariate analysis revealed that MFC MRD and disease status at transplantation were significant predictors of RFS duration (p <0.001 and p<0.05, respectively). Eleven patients with pre-BMT MRD negative had available day +33 assessment. Two relapses were observed among the 3 day 33 MRD positive patients (66%), compared to three relapses among 8 day 33 MFC MRD negative patients (37%). MRD evaluation was a strong predictor of long term survival, as 3- years OS was 65% for MFC MRD negative compared to 49.8% for MFC MRD positive patients (p<0.05).
Conclusion
Pre transplant MFC MRD evaluation is a feasible and reliable predictor of relapse risk in adults ALL patients. Patients with positive MFC MRD have a very high relapse risk and a poor outcome after BMT. Although small numbers prevented us to drive conclusion, persistence of MRD at day 33 seems to confer a worse prognosis in pre-BMT MRD patients. In the era of targeted therapy, at least for B-ALL, persistence of MRD after induction could be an indication for innovative approach, such as attempts of MRD eradication using recently developed immunoconjugated monoclonal anti-CD-22 antibodies or anti-CD3/anti-CD-19 bispecific antibodies.
Session topic: E-poster
Keyword(s): ALL, BMT, Induction chemotherapy, Minimal residual disease (MRD)
Type: Eposter Presentation
Background
With the introduction of pediatric-inspired induction regimen, prognosis of adult acute lymphoblastic leukemia (ALL) has substantially improved, leading to an increased assessment of minimal residual disease (MRD) during all induction course and a progressive use of MRD-driven therapeutic approach. In most modern pediatric protocols, persistence of MRD during the first courses of induction therapy is an adverse prognostic factor and constitutes a strong indication for early allogeneic bone marrow transplantation (BMT). However, it remains unclear if an effort towards MRD eradication should be attempted before BMT, as relatively few data are available on outcome of MRD positive adult ALL patients.
Aims
The aim of this study was to analyze the role of pre-BMT MRD assessment as predictor for the post-transplant relapse risk and to evaluate the impact of day 33 MRD status in pre-BMT MRD negative patients.
Methods
We retrospectively analyzed the outcome of 53 consecutive ALL patients receiving allo-BMT, with available pre-BMT multicolour flow cytometry (MFC) MRD assessment. Median age at transplant was 30 years. Disease phase was CR1 in 20 (38%), CR2 in 17 (32%), and CR3 in 14 patients (30%). Thirty-five patients (66%) had B lineage ALL, whereas 18 (34%) had T-ALL. Relapse-free survival (RFS) was calculated from the time of transplantation until last follow-up or documented leukemic relapse. Overall Survival (OS) was calculated from the time of transplantation until death by any cause or last follow-up. Median follow up was 62 months.A positive MFC MRD was defined by the presence of no less than 25 clustered leukemic cells/105 total events (threshold of2.5x10-4 residual leukemic cells) at four-color flow-cytometry.
Results
Relapse occurred in 30 patients (57%). Three-year RFS was 42.2% (median 10 months). The probability of relapse was significantly affected by disease status at BMT (CR1 vs CR2 or p<0.001), karyotype ( p <0.03) and MFC MRD (both day 33 and pre-BMT, p<0.03) . Pre-BMT MFC-MRD was a strong predictor of longer relapse free survival: 5 relapses occurred in the 17 MFC-MRD negative patients and 3-years RFS was 69.4% (median not reached), compared to 25 relapses observed in 36 MFC MRD positive patients, with a 3-year RFS of 29.4% (median 5 months). Multivariate analysis revealed that MFC MRD and disease status at transplantation were significant predictors of RFS duration (p <0.001 and p<0.05, respectively). Eleven patients with pre-BMT MRD negative had available day +33 assessment. Two relapses were observed among the 3 day 33 MRD positive patients (66%), compared to three relapses among 8 day 33 MFC MRD negative patients (37%). MRD evaluation was a strong predictor of long term survival, as 3- years OS was 65% for MFC MRD negative compared to 49.8% for MFC MRD positive patients (p<0.05).
Conclusion
Pre transplant MFC MRD evaluation is a feasible and reliable predictor of relapse risk in adults ALL patients. Patients with positive MFC MRD have a very high relapse risk and a poor outcome after BMT. Although small numbers prevented us to drive conclusion, persistence of MRD at day 33 seems to confer a worse prognosis in pre-BMT MRD patients. In the era of targeted therapy, at least for B-ALL, persistence of MRD after induction could be an indication for innovative approach, such as attempts of MRD eradication using recently developed immunoconjugated monoclonal anti-CD-22 antibodies or anti-CD3/anti-CD-19 bispecific antibodies.
Session topic: E-poster
Keyword(s): ALL, BMT, Induction chemotherapy, Minimal residual disease (MRD)
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