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IMPACT OF FLT3 INTERNAL TANDEM DUPLICATION ON THE OUTCOME OF ALLOGENEIC STEM CELL TRANSPLANTATION FOR ACUTE MYELOID LEUKEMIA
Author(s): ,
Carolina Afonso
Affiliations:
Department of Clinical Hematology,Centro Hospitalar e Universitário de Coimbra,Coimbra,Portugal
,
Catarina Rodrigues
Affiliations:
Department of Clinical Hematology,Centro Hospitalar Tondela-Viseu,Viseu,Portugal
,
Joana Pimenta
Affiliations:
Department of Oncology,Centro Hospitalar de Trás-os-Montes e Alto Douro,Vila Real,Portugal
,
Rosa Branca Ferreira
Affiliations:
Department of Bone Marrow Transplantation,Instituto Português de Oncologia do Porto Francisco Gentil,Porto,Portugal
,
Luís Leite
Affiliations:
Department of Bone Marrow Transplantation,Instituto Português de Oncologia do Porto Francisco Gentil,Porto,Portugal
,
Gil Brás
Affiliations:
Department of Bone Marrow Transplantation,Instituto Português de Oncologia do Porto Francisco Gentil,Porto,Portugal
,
Pedro Coelho
Affiliations:
Department of Bone Marrow Transplantation,Instituto Português de Oncologia do Porto Francisco Gentil,Porto,Portugal
,
Carlos Pinho Vaz
Affiliations:
Department of Bone Marrow Transplantation,Instituto Português de Oncologia do Porto Francisco Gentil,Porto,Portugal
António Campos Jr
Affiliations:
Department of Bone Marrow Transplantation,Instituto Português de Oncologia do Porto Francisco Gentil,Porto,Portugal
EHA Library. Afonso C. 06/09/21; 325010; EP1290
Dra Carolina Afonso
Dra Carolina Afonso
Contributions
Abstract
Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP1290

Type: E-Poster Presentation

Session title: Stem cell transplantation - Clinical

Background

FMS-like tyrosine kinase 3 (FLT3) gene internal tandem duplication (ITD) occur in 20%‐30% of adult acute myeloid leukemia (AML) patients. FLT3‐ITD is widely accepted as an independent adverse prognostic factor associated with high relapse and poor survival rates. Therefore, allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is generally accepted as the standard of care for AML patients with FLT3‐ITD. Whether this mutation also affects outcome after allo‐HSCT is controversial.

Aims
To determine the impact of FLT3-ITD on the outcome of allo‐HSCT for adult AML.

Methods

Retrospective analysis of 95 adult AML patients (pts) who underwent allo-HSCT between January 2015 and December 2019 in a transplant center from north of Portugal. Clinical characteristics and outcomes were evaluated. The Kaplan-Meier method was used to describe time-to-event end points. The log rank test was used to compare the survival distribution of different groups.

Results

FLT3-ITD was detected in 17 pts (29%). Among these, 53% were female; median age at diagnosis was 43 years (22-60). Fifteen pts (88%) were transplanted in first remission, 1 in second remission and 1 in a more advanced stage of the disease. Donors were a matched sibling in eight pts (47%), a fully matched unrelated donor in six pts (35%), and a partial matched unrelated donor in 3 pts (18%). The stem cell source was peripheral blood in the majority of pts (n=16; 94%). Eight pts (47%) were treated with myeloablative conditioning (MAC) regimens while the remaining pts received reduced intensity conditioning (RIC). MAC regimens consisted of busulphan plus cyclophosphamide (BuCy), whereas RIC consisted of fludarabine with reduced doses of busulfan (FluBu); antithymocyte globulin (ATG) was added to the conditioning regimen for unrelated transplantations. Grade ≥ 2 acute graft versus host disease (GvHD) occurred in 5 pts (31%), at a median time of 32 days (12-81) after allo‐HSCT. Five pts experienced chronic GVHD; in 3 pts chronic GVHD evolved from acute GVHD. There were no statistically significant differences between FLT3-ITD-positive and -negative patients with respect to clinical characteristics (age, gender, disease status, donor type, stem cell source and conditioning), and GvHD (incidence and overall grade). The 1-year relapse-free survival (RFS) rates for FLT3-ITD-positive and -negative patients were 58% vs 79%, respectively (HR 1.19; p=0.276); the 1-year overall survival (OS) rates were 71% vs 69%, respectively (HR 0.64; p=0.423).

Conclusion

In our cohort, there was no difference in the outcomes of allo-HSCT between AML patients with FLT3‐ITD and those without the mutation. Although in the absence of allo-HSCT the FLT3-ITD mutation is predictive of a short OS, our results suggest that in patients who undergo allo-HSCT, the FLT3-ITD mutation status loses its predictive value.

Keyword(s): Acute myeloid leukemia, Allogeneic hematopoietic stem cell transplant

Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP1290

Type: E-Poster Presentation

Session title: Stem cell transplantation - Clinical

Background

FMS-like tyrosine kinase 3 (FLT3) gene internal tandem duplication (ITD) occur in 20%‐30% of adult acute myeloid leukemia (AML) patients. FLT3‐ITD is widely accepted as an independent adverse prognostic factor associated with high relapse and poor survival rates. Therefore, allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is generally accepted as the standard of care for AML patients with FLT3‐ITD. Whether this mutation also affects outcome after allo‐HSCT is controversial.

Aims
To determine the impact of FLT3-ITD on the outcome of allo‐HSCT for adult AML.

Methods

Retrospective analysis of 95 adult AML patients (pts) who underwent allo-HSCT between January 2015 and December 2019 in a transplant center from north of Portugal. Clinical characteristics and outcomes were evaluated. The Kaplan-Meier method was used to describe time-to-event end points. The log rank test was used to compare the survival distribution of different groups.

Results

FLT3-ITD was detected in 17 pts (29%). Among these, 53% were female; median age at diagnosis was 43 years (22-60). Fifteen pts (88%) were transplanted in first remission, 1 in second remission and 1 in a more advanced stage of the disease. Donors were a matched sibling in eight pts (47%), a fully matched unrelated donor in six pts (35%), and a partial matched unrelated donor in 3 pts (18%). The stem cell source was peripheral blood in the majority of pts (n=16; 94%). Eight pts (47%) were treated with myeloablative conditioning (MAC) regimens while the remaining pts received reduced intensity conditioning (RIC). MAC regimens consisted of busulphan plus cyclophosphamide (BuCy), whereas RIC consisted of fludarabine with reduced doses of busulfan (FluBu); antithymocyte globulin (ATG) was added to the conditioning regimen for unrelated transplantations. Grade ≥ 2 acute graft versus host disease (GvHD) occurred in 5 pts (31%), at a median time of 32 days (12-81) after allo‐HSCT. Five pts experienced chronic GVHD; in 3 pts chronic GVHD evolved from acute GVHD. There were no statistically significant differences between FLT3-ITD-positive and -negative patients with respect to clinical characteristics (age, gender, disease status, donor type, stem cell source and conditioning), and GvHD (incidence and overall grade). The 1-year relapse-free survival (RFS) rates for FLT3-ITD-positive and -negative patients were 58% vs 79%, respectively (HR 1.19; p=0.276); the 1-year overall survival (OS) rates were 71% vs 69%, respectively (HR 0.64; p=0.423).

Conclusion

In our cohort, there was no difference in the outcomes of allo-HSCT between AML patients with FLT3‐ITD and those without the mutation. Although in the absence of allo-HSCT the FLT3-ITD mutation is predictive of a short OS, our results suggest that in patients who undergo allo-HSCT, the FLT3-ITD mutation status loses its predictive value.

Keyword(s): Acute myeloid leukemia, Allogeneic hematopoietic stem cell transplant

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