Complete Hematological Remission after Decitabine Treatment in a Patient with Congenital Agammaglobulinemia, FLT3- and TP53-Mutated Acute Myeloid Leukemia

Case Report

Austin Oncol Case Rep. 2021; 4(1): 1014.

Complete Hematological Remission after Decitabine Treatment in a Patient with Congenital Agammaglobulinemia, FLT3- and TP53-Mutated Acute Myeloid Leukemia

Vigna E¹, Caracciolo D¹, Tenuta R², Martino E¹, Mendicino F¹, Caruso N¹, Greco F², Botta C¹, Morelli R³, Gentile M¹*

¹Hematology Unit AO of Cosenza, Cosenza, Italy

²Microbiology and Virology Unit, AO of Cosenza, Cosenza, Italy

³Internal Medicine Department, AO of Cosenza, Cosenza, Italy

*Corresponding author: Massimo Gentile, MD, Hematology Unit, AO of Cosenza, 87100 Cosenza, Italy

Received: April 12, 2021; Accepted: April 30, 2021; Published: May 06, 2021


Older and unfit patients with Acute Myeloid Leukemia (AML), which are uneligible for standard induction therapy, have limited treatment options. The therapeutic approach in these cases is based on the use of hypomethylating agents, either decitabine or azacitidine, or Low-Dose Cytarabine (LDAC). However, despite the extensive use of these agents, there is no consensus regarding the extent of their efficacy, and clinical benefit deriving from their use is very modest. We present a case of FLT3- and TP53-mutated AML in an unfit patient with congenital agammaglobulinemia, responsive to single agent decitabine, with a response duration of over 20 months.

Keywords: AML; Decitabine; TP53-mutated; FLT-3 mutated


Acute Myeloid Leukemia (AML) is a hematological malignancy characterized by abnormal proliferation of immature hematopoietic progenitor cells of the myeloid lineage. Importantly, no standard of care therapy is present for older or unfit patients and therefore outcomes are generally worse than in younger and fit patients [1].

In this context, therapy with hypomethylating agents (decitabine or azacytidine) as single agents or in combination with targeted therapies, has also been increasingly used in older or unfit AML patients. However, these therapeutic strategies in the older and unfit population, offer a modest survival advantage with a median OS ranging from 7.5 to 11 months [2]. Immunodeficiency increases the risk of malignancies, which occur earlier in life of these patients in respect to the general population. Congenital agammaglobulinemia is a Primary Immunodeficiency Disorder (PID) characterized by a severe reduction of all classes of serum immunoglobulins and by the absence of mature CD19+ B-cells. Although different malignancies have been observed in patients with congenital agammaglobulinemia [3], in this work we have presented the first reported case of FMSLike Tyrosine Kinase 3- (FLT3) and TP53-mutated AML in a young patient with congenital agammaglobulinemia. Furthermore, despite the poor prognosis of our clinical case, we here show the complete remission of AML after single agent decitabine treatment with duration of over 20 months.

Case Presentation

A 29-year-old woman, with a history of recurrent pulmonary infections and mental retardation due to agenesis of the corpus callosum, was followed for about 10 years by our Hematologic clinic for a congenital agammaglobulinemia, managed with intravenous immunoglobulin replacement therapy.

In June 2019 she went to the emergency room with fever without an apparent focus of infection. Laboratory tests revealed hyperleukocytosis [White Blood Cells count (WBC) of 64.2x103/ μl], anemia [hemoglobin (Hb) 8 gr/dL] and normal platelet count (PLT 153x103/μl). Morphologic analysis of peripheral blood smear revealed the presence of 70% myeloid blasts and the subsequent bone marrow (BM) aspiration confirmed the diagnosis of AML with 80% myeloid blasts. Flow-cytometry identified the presence of aberrant cells with the follow immunophenotype: MPO-, cyCD3-, cyCD79a-, TdT-, CD34+, CD117+/, CD33+, CD13+/-, HLADr+, CD38+, CD15+/-, CD11b-, CD16-, CD14-, CD64/+, CD4+/-, CD7+, CD56+. Cytogenetic analysis revealed a complex karyotype (45, XX,-5, der (6),-8,-12,-13,-14,+5der(?)[14]/46, XX[6]) (Figure 1) and bio-molecular analysis reported FLT3-ITD mutation with high allelic burden (>0,5) and TP53 mutation, while no mutations were found on NPM1 gene. Bone marrow aspiration confirmed also B-cell hypoplasia with significant reduction of CD19+ B-cells.

Citation: Vigna E, Caracciolo D, Tenuta R, Martino E, Mendicino F, Caruso N, et al. Complete Hematological Remission after Decitabine Treatment in a Patient with Congenital Agammaglobulinemia, FLT3- and TP53- Mutated Acute Myeloid Leukemia. Austin Oncol Case Rep. 2021; 4(1): 1014.