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MONITORING MINIMAL RESIDUAL DISEASE IN AUTOLOGOUS CELLULAR THERAPY PRODUCTS COLLECTED BY APHERESIS ? EXPERIENCE OF A THERAPY CELLULAR CENTER
Author(s): ,
Sara Ferreira
Affiliations:
Cellular Therapy,IPO PORTO,Porto,Portugal
,
Fatima Amado
Affiliations:
Cellular Therapy,IPO PORTO,Porto,Portugal
,
Sergio Lopes
Affiliations:
Cellular Therapy,IPO PORTO,Porto,Portugal
,
Filipa Bordalo
Affiliations:
Cellular Therapy,IPO PORTO,Porto,Portugal
,
Catarina Pinho
Affiliations:
Cellular Therapy,IPO PORTO,Porto,Portugal
Susana Roncon
Affiliations:
Cellular Therapy,IPO PORTO,Porto,Portugal
(Abstract release date: 05/19/16) EHA Library. Ferreira S. 06/09/16; 135076; PB2176
Mr. Sara Ferreira
Mr. Sara Ferreira
Contributions
Abstract
Abstract: PB2176

Type: Publication Only

Background
The autologous transplant of peripheral blood stem cells (PBSC), harvested by apheresis on oncologic patients after high-dose chemotherapy and/or radiotherapy, is a therapeutic strategy used in hematologic diseases and solid tumors.  Some studies suggest that incomplete disease eradication before collection could lead to the reinfusion of tumor cells and be associated with patient relapse and a lower survival. The search for minimal residual disease (MRD) has been performed in some centers through highly sensitive genetic techniques, contributing to improve the clinical decision and the patient outcome.

Aims
This study aims to evaluate the percentage of MRD-contaminated grafts in patients proposed to hematopoietic transplant with initial genetic alterations in our hospital. 

Methods
A retrospective study was performed from May 2006 to February 2016. The inclusion criteria was patients with genetic alterations at diagnosis or relapse. The research was performed using fluorescent in situ hybridization (FISH) or/and real time polymerase chain reaction (RT-PCR) techniques.   The data was analysed using an excel program.

Results
MRD was researched in samples of PBSC collected from 39 male and 28 female patients (n=67), with a median age of 51 years old (7 months – 70 years). Their diagnosis were: non Hodgkin’s lymphoma (NHL) n=24, multiple myeloma (MM) n=16, neuroblastoma n=17, acute myeloid leukemia (AML) n=5, acute lymphoblastic leukemia (ALL) n=2, Hodgkin's disease (HD) n=2 and Ewing’s sarcoma (Ewing S.) n=1. Only 6 grafts were MRD positive, but with a very low tumour cell contamination (1-2%): 1 AML with PML-RARA fusion RNA; 1 ALL with BCR-ABL mRNA; 2 MM with deletion of 13q14; 1 Ewing S. with translocation of 22q12; 1 neuroblastoma with deletion of 11q23. Three contaminated grafts were eliminated: 2 patients (1 AML and 1 neuroblastoma) were proposed to different chemotherapy lines, undergone new mobilization and collection program and received a negative cellular therapy product; the ALL patient died before the second mobilization. Two MM patients were infused with the autologous grafts. In the remaining patient (Ewing S.), we performed a positive selection of CD34+ cells after thawing and before graft infusion. At present, 2 patients are alive and in complete remission, 9 and 10 years after treatment (Ewing S. and AML); 3 patients deceased 1, 7 and 4 years after transplant (2 MM and 1 neuroblastoma, respectively).

Conclusion
As it was a very small and heterogeneous sample, conclusive remarks of the role of MRD significance in stem cells grafts are not possible. In the same way, we only performed one ex vivo tumoral purging with identical results to those found on literature. Future prospective trials should address physicians to choose which is the best option to eradicate tumor cells (chemotherapy pretransplantation or immunotherapy postransplantation).

Session topic: E-poster

Keyword(s): Minimal residual disease (MRD)
Abstract: PB2176

Type: Publication Only

Background
The autologous transplant of peripheral blood stem cells (PBSC), harvested by apheresis on oncologic patients after high-dose chemotherapy and/or radiotherapy, is a therapeutic strategy used in hematologic diseases and solid tumors.  Some studies suggest that incomplete disease eradication before collection could lead to the reinfusion of tumor cells and be associated with patient relapse and a lower survival. The search for minimal residual disease (MRD) has been performed in some centers through highly sensitive genetic techniques, contributing to improve the clinical decision and the patient outcome.

Aims
This study aims to evaluate the percentage of MRD-contaminated grafts in patients proposed to hematopoietic transplant with initial genetic alterations in our hospital. 

Methods
A retrospective study was performed from May 2006 to February 2016. The inclusion criteria was patients with genetic alterations at diagnosis or relapse. The research was performed using fluorescent in situ hybridization (FISH) or/and real time polymerase chain reaction (RT-PCR) techniques.   The data was analysed using an excel program.

Results
MRD was researched in samples of PBSC collected from 39 male and 28 female patients (n=67), with a median age of 51 years old (7 months – 70 years). Their diagnosis were: non Hodgkin’s lymphoma (NHL) n=24, multiple myeloma (MM) n=16, neuroblastoma n=17, acute myeloid leukemia (AML) n=5, acute lymphoblastic leukemia (ALL) n=2, Hodgkin's disease (HD) n=2 and Ewing’s sarcoma (Ewing S.) n=1. Only 6 grafts were MRD positive, but with a very low tumour cell contamination (1-2%): 1 AML with PML-RARA fusion RNA; 1 ALL with BCR-ABL mRNA; 2 MM with deletion of 13q14; 1 Ewing S. with translocation of 22q12; 1 neuroblastoma with deletion of 11q23. Three contaminated grafts were eliminated: 2 patients (1 AML and 1 neuroblastoma) were proposed to different chemotherapy lines, undergone new mobilization and collection program and received a negative cellular therapy product; the ALL patient died before the second mobilization. Two MM patients were infused with the autologous grafts. In the remaining patient (Ewing S.), we performed a positive selection of CD34+ cells after thawing and before graft infusion. At present, 2 patients are alive and in complete remission, 9 and 10 years after treatment (Ewing S. and AML); 3 patients deceased 1, 7 and 4 years after transplant (2 MM and 1 neuroblastoma, respectively).

Conclusion
As it was a very small and heterogeneous sample, conclusive remarks of the role of MRD significance in stem cells grafts are not possible. In the same way, we only performed one ex vivo tumoral purging with identical results to those found on literature. Future prospective trials should address physicians to choose which is the best option to eradicate tumor cells (chemotherapy pretransplantation or immunotherapy postransplantation).

Session topic: E-poster

Keyword(s): Minimal residual disease (MRD)

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