Acute Lymphoblastic Leukemia Occurring in Patient with Acute Myeloid Leukaemia: An Unrelated Leukemia Rather Than a Therapy-Related Malignancy. About 2 Cases.
Authors: El-Nawakil Chadi , Garand Richard , Vigouroux Stephane , Harousseau Jean-Luc , Chevallier Patrice 
Published: April 2020

Abstract
Introduction: Therapy-related acute myeloid leukaemia (AML) is a well known event which can occur few years after a chemotherapy with alkylating agents or topoisomerase II inhibitors received for primary malignancies such as Hodgkin and non-Hodgkin lymphomas, Acute lymphoblastic leukaemia (ALL) or solid tumors. More exceptional are acute B or T-ALL following AML (11 cases in literature so far, Liso et al, Haematologica, 1998; Leung et al, Leukemia, 2001; Tsuboi et al, Int J Hematol, 2003) raising the question of the origin of this second event. Among 1486 AML cases diagnosed between 1985 and 2006 in our institution, we report only 2 cases of B-cell ALL occurring 1 and 19 years after AML.
Case1: A 36-year-old man was admitted in our institution in 1985. The peripheral blood examination showed: Hemoglobin level 6.2 g/dL, leukocyte count 27.8 *109/L with 32% of monocytes and platelet count 52 *109/L. Blast cell infiltrate was 40% on blood and 55% on bone marrow smears, with 80% exhibiting myeloperoxydase (MPO) activity. Morphology was typical of FAB-M4 AML with eosinophil subtype. Unfortunately, phenotype and caryotype evaluations were not performed. Patient was treated according to POF trial. Complete Remission (CR) was achieved after induction therapy and persisted 19 years after 3 consolidations. In 2004, blast cells reappeared in the blood (7%) and bone marrow (96%) aspirates Interestingly, MPO activity was negative and flow cytometer analysis revealed a CD19+ CD10+ TdT+ CD79a+ (EGIL-BII) B-Cell Precursor (BCP) ALL immunophenotype with only the sole CD13+ myeloid marker expression. Cytogenetic studies showed a hypodiploidy (33–35 chromosomes) without Bcr-Abl and MLL rearrangements. Patient achieved CR after induction chemotherapy according to GRAALL2003 trial. He then received consolidation by high-dose methotrexate but develop a polyneuropathy and died rapidly.
Case2: A AML, FAB-M5B subtype, was first diagnosed in 2005 in a 48-year-old woman. Hemoglobin level was 10.4 g/dL, leukocyte count 73.2 *109/L with 79.5% of abnormal monocytic cells and platelet count 100 *109/L. Typically, monoblastic bone marrow cells (71%) showed a low (5%) MPO and a strong (80%) butyrate activities, together with a CD13+ CD14+ CD15+ CD33+ CD34+ CD36+ CD65+ CD117− immunophenotype without B-cell marker expression. Cytogenetic analysis showed no caryotypic abnormalities. The patient was treated according to LAM2001 trial and CR was achieved after 2 courses of induction chemotherapy. The patient was autografted in October 2005. She presented with a pancytopenia in April 2006 and the diagnosis of BCP-ALL was made. The bone marrow was infiltrated with 76.5% of MPO negative, butyrate negative blasts exhibiting a CD19+ CD10−CD79a+TdT+ (EGIL-BI/Pro-B subtype without any myeloid marker expression. Cytogenetic analysis showed a t (4;11) (q21;q23) with MLL rearrangement on 44% of the blasts. The patient achieved CR after induction therapy according to GRAALL2003 trial but developed a disseminated fusariosis. She is still alive in CR but due to the persistence of the infectious complication, she has not yet received consolidation.
Conclusion: Our study shows that ALL occurring after AML is a very occasional event. Prognosis seems poor related to treatment toxicity. We found no argument supporting a link between both leukaemia subtypes or a relationship with therapy. Additional cases are warranted to determine if this association is unrelated or not.