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COMPARISON OF THE PROGNOSTIC SIGNIFICANCE OF MINIMAL RESIDUAL DISEASE AND THE CONVENTIONAL PROGNOSTIC FACTORS IN THE TREATMENT OF ADULT ACUTE LYMPHOBLASTIC LEUKAEMIA PATIENTS
Author(s): ,
Stefan Lozenov
Affiliations:
Clinical hematology department,NSHATHD,Sofia,Bulgaria
,
Branimir Spassov
Affiliations:
Clinical hematology department,NSHATHD,Sofia,Bulgaria
,
Yavor Petrov
Affiliations:
Clinical hematology department,NSHATHD,Sofia,Bulgaria
,
Vera Stoeva
Affiliations:
Clinical hematology department,NSHATHD,Sofia,Bulgaria
,
Tanya Yankova
Affiliations:
Clinical hematology department,NSHATHD,Sofia,Bulgaria
,
Kalina Ignatova
Affiliations:
Clinical hematology department,NSHATHD,Sofia,Bulgaria
,
Yuri Zhechev
Affiliations:
Clinical hematology department,NSHATHD,Sofia,Bulgaria
,
Mimoza Staneva
Affiliations:
Clinical hematology department,NSHATHD,Sofia,Bulgaria
,
Tanya Mihailova
Affiliations:
Clinical hematology department,NSHATHD,Sofia,Bulgaria
,
Doncho Peichev
Affiliations:
Clinical hematology department,NSHATHD,Sofia,Bulgaria
,
Stanislav Simeonov
Affiliations:
Clinical hematology department,NSHATHD,Sofia,Bulgaria
,
Desislava Nihtyanova
Affiliations:
Clinical hematology department,NSHATHD,Sofia,Bulgaria
,
Margarita Guenova
Affiliations:
Hematopathology department,NSHATHD,Sofia,Bulgaria
,
Georgi Balatzenko
Affiliations:
Molecular biology and cytogenetics laboratory,NSHATHD,Sofia,Bulgaria
,
Martin Donchev
Affiliations:
Clinical hematology department,NSHATHD,Sofia,Bulgaria
,
Georgi Arnaudov
Affiliations:
Clinical hematology department,NSHATHD,Sofia,Bulgaria
Georgi Mihaylov
Affiliations:
Clinical hematology department,NSHATHD,Sofia,Bulgaria
(Abstract release date: 05/19/16) EHA Library. Lozenov S. 06/09/16; 134508; PB1608
Dr. Stefan Lozenov
Dr. Stefan Lozenov
Contributions
Abstract
Abstract: PB1608

Type: Publication Only

Background
During the past couple of decades the response rates, the leukemia free survival and the 5 year overall survival (OS) in adult patients with acute lymphoblastic leukaemia (ALL) have improved significantly. There is an ongoing trend to improve further OS through better risk assessment. The risk stratification in different treatment protocols is usually based on groups of conventional prognostic risk factors, such as – white blood cells count (WBC) at diagnosis, immunophenotype, cytogenetic and molecular abnormalities, achievement of CR and time to achievement of CR,  age with some variations among the different study groups. To improve the results of risk stratification through the conventional risk factors, the evaluation of the level of minimal residual disease (MRD) and its use for treatment decision making have been introduced. Several studies have already established the contributory role of MRD levels for the prediction of relapse and continuous complete remission (CCR) in the ALL patients. Despite the growing involvement of MRD evaluation in the risk stratification of adult ALL patients, there is a continuing need to better address the specific role MRD examination should play among other ALL prognostic factors and to better establish the best time point for ALL MRD evaluation.

Aims
With the present retrospective assessment we aimed to compare the impact of minimal residual disease and a group of conventional prognostic factors on the overall survival of adult ALL patients. 

Methods
We analyzed retrospectively 81 patients with adult ALL, that were treated in the National Specialized Hospital for Active Treatment of Hematology Diseases (NSHATHD) between 1.1.2009 and 1.1.2016, of them 53 were CR achievers. The minimal residual disease (MRD) levels of the patients were measured through 8-color flow cytometry and through semiquantitative RT-PCR, following the BIOMED 1 program protocol for the patients with a MLL-AF4 and BCR-ABL fusion transcripts chromosome. MRD negativity or molecular complete remission (molCR) was defined as a level of less than 10-4 ALL cells or lack of expression of fusion transcripts.

Results
MRD negativity had a statistically significant impact on OS 70.3% vs. 10.7% for the MRD negativity non-achievers. The conventional risk factors did not seem to convey greater prognostic significance with differences between conventional risk groups in terms of OS not reaching statistical signifcance and the multivariate analysis demonstrating significance only of MRD status, WBC and PSECOG with hazard ratios of 5.241, 3.070, 2.061, respectively. Allogeneic hematopoietic stem cells transplantation significantly improved OS in the patients who did not achieve MRD negativity with 3-year overall survival of 38.9% vs 11.7%.

Conclusion
The impact of molCR status on survival will probably lead to new risk stratification strategies based to a greater extent or even exclusively on the MRD status. The optimal time for MRD risk stratification remains to be established.

Session topic: E-poster

Keyword(s): Acute lymphoblastic leukemia, Minimal residual disease (MRD), Prognostic factor
Abstract: PB1608

Type: Publication Only

Background
During the past couple of decades the response rates, the leukemia free survival and the 5 year overall survival (OS) in adult patients with acute lymphoblastic leukaemia (ALL) have improved significantly. There is an ongoing trend to improve further OS through better risk assessment. The risk stratification in different treatment protocols is usually based on groups of conventional prognostic risk factors, such as – white blood cells count (WBC) at diagnosis, immunophenotype, cytogenetic and molecular abnormalities, achievement of CR and time to achievement of CR,  age with some variations among the different study groups. To improve the results of risk stratification through the conventional risk factors, the evaluation of the level of minimal residual disease (MRD) and its use for treatment decision making have been introduced. Several studies have already established the contributory role of MRD levels for the prediction of relapse and continuous complete remission (CCR) in the ALL patients. Despite the growing involvement of MRD evaluation in the risk stratification of adult ALL patients, there is a continuing need to better address the specific role MRD examination should play among other ALL prognostic factors and to better establish the best time point for ALL MRD evaluation.

Aims
With the present retrospective assessment we aimed to compare the impact of minimal residual disease and a group of conventional prognostic factors on the overall survival of adult ALL patients. 

Methods
We analyzed retrospectively 81 patients with adult ALL, that were treated in the National Specialized Hospital for Active Treatment of Hematology Diseases (NSHATHD) between 1.1.2009 and 1.1.2016, of them 53 were CR achievers. The minimal residual disease (MRD) levels of the patients were measured through 8-color flow cytometry and through semiquantitative RT-PCR, following the BIOMED 1 program protocol for the patients with a MLL-AF4 and BCR-ABL fusion transcripts chromosome. MRD negativity or molecular complete remission (molCR) was defined as a level of less than 10-4 ALL cells or lack of expression of fusion transcripts.

Results
MRD negativity had a statistically significant impact on OS 70.3% vs. 10.7% for the MRD negativity non-achievers. The conventional risk factors did not seem to convey greater prognostic significance with differences between conventional risk groups in terms of OS not reaching statistical signifcance and the multivariate analysis demonstrating significance only of MRD status, WBC and PSECOG with hazard ratios of 5.241, 3.070, 2.061, respectively. Allogeneic hematopoietic stem cells transplantation significantly improved OS in the patients who did not achieve MRD negativity with 3-year overall survival of 38.9% vs 11.7%.

Conclusion
The impact of molCR status on survival will probably lead to new risk stratification strategies based to a greater extent or even exclusively on the MRD status. The optimal time for MRD risk stratification remains to be established.

Session topic: E-poster

Keyword(s): Acute lymphoblastic leukemia, Minimal residual disease (MRD), Prognostic factor

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