Long Term Sorafenib Response for Extramedullary FLT3+AML Relapse after Allogeneic Stem Cell Transplantation

Case Report

Ann Hematol Oncol. 2020; 7(1): 1281.

Long Term Sorafenib Response for Extramedullary FLT3+AML Relapse after Allogeneic Stem Cell Transplantation

López-Pereira P1, Figuera A1, Sola E1, Cornago J1, Alegre A1, Aguado Bueno B1*

Hematology Department, Hospital Universitario La Princesa, Madrid, Spain

*Corresponding author: Beatriz Aguado, Hematology Department, Hospital Universitario La Princesa, Madrid, Spain

Received: December 06, 2019; Accepted: January 24, 2020; Published: January 31, 2020


We present a case of Acute Myeloid Leukemia (AML) with FLT3-ITD mutation, relapsing as extramedullary cardiac disease after allogeneic hematopoietic stem cell transplantation. This 50-year-old woman with FLT3-mutated AML, was treated with standard chemotherapy followed by allotransplant. Despite presenting chronic graft versus host disease, she experienced one first medullary relapse treated with chemotherapy and DLI, and a second extramedullary relapse treated with chemo and radiotherapy. As third relapse, she developed cardiac extramedullary sarcoma, without marrow involvement, and because of comorbidities she was treated with sorafenib monotherapy, reaching rapid and complete sustained response.

This case demonstrate a long-term control of refractory AML disease with Sorafenib as salvage therapy in a heavily pretreated allotransplant receptor.

Keywords: Acute myeloid leukemia; FLT-3-ITD; Extramedullary relapse; Transplantation; Sorafenib


Acute Myeloid Leukemia (AML) relapse after allogeneic Hematopoietic Stem Cell (HSCT) Transplantation has a dismal prognosis. Extramedullary relapse has been considered as a rare event, although it could be misdiagnosed [1].

Internal Tandem Duplications (ITDs) of the FMS-Like Tyrosine Kinase 3 gene (FLT-3) occur in approximately 20%-30% of newly diagnosed patients, mostly cases with normal karyotype, and confers a worse prognosis when treated with chemotherapy alone [2,3]. However, recently this receptor is being used as a target expanding the therapeutic scenario [3,4].

Treatment with FLT3 tyrosine kinase inhibitors is changing the standard of care for FLT-3 mutated AML [3]. Sorafenib, a multikinase inhibitor, have been used in monotherapy or combined with chemotherapy, either in induction and relapsed AML [5].

Case Report

A 50 year-old woman was diagnosed with AML secondary to Myelodysplastic Syndrome (MDS) with NPM1 mutation and internal tandem duplications of the FLT3 gene (FLT3-ITD) in October 2013. After achieving Complete Remission (CR) with conventional chemotherapy (idarubicine+cytarabine), she received a myeloablative allogeneic HSCT from a HLA sibling donor in February 2014 (conditioning regimen BuCy).

Four months later, AML relapsed only at medullary level (FLT3 ratio: 0,67%), treated with chemotherapy (IDICE) and Donor Lymphocytes Infusions (DLI). She achieved 2nd CR and developed limited chronic Graft-Versus-Host Disease (cGVHD).

Nine months later (April 2015), she suffered the first extramedullary relapse, with breast and skin involvement, with full donor chimerism. Disappearance of the lesions at all levels was achieved with chemo (cytarabine) and radiotherapy.

In December 2015, she referred atypical precordial pain irradiated to the back, without symptoms or echocardiographic signs of cardiac failure. A cardiac MRI and chest CT scan was performed finding moderate pericardial effusion and several masses in the pericardial sac, up to 5 cm in diameter. BM remained in CR with full donor chimerism.

Pericardial fluid showed massive infiltration by myeloid blasts with phenotype CD34+, CD117+, CD33+, CD16-, CD11b weak, CD14-, HLA-DR heterogeneous with FLT3 positive cells (ratio: 0,7%).

She was not considered candidate for further systemic chemotherapy nor radiotherapy, so treatment with FLT3 inhibitor (Sorafenib) was started.

Sorafenib was started (in December 2015) at dose of 400 mgr/12 h. After first month of treatment, pericardial lesions decreased from 5 to 1.7 cm in diameter. Subsequent CT scans showed progressive decrease of lesions until resolution in July 2016. In last CTs pericardial thickening is almost non-existent, without new lesions (see figure) (Figure 1).

Citation: López-Pereira P, Figuera A, Sola E, Cornago J, Alegre A, Aguado Bueno B. Long Term Sorafenib Response for Extramedullary FLT3+AML Relapse after Allogeneic Stem Cell Transplantation. Ann Hematol Oncol. 2020; 7(1): 1281.