Konference: 2013 18th Congress of the European Hematology Association - účast ČR

Kategorie: Maligní lymfomy a leukémie

Téma: Acute myeloid leukemia - Clinical

Číslo abstraktu: B1273

Autoři: Ing. Jana Marková; Mgr. Jaroslav Polák; RNDr. Cedrik Haškovec, CSc.; MUDr. Jacqueline Soukupová (Maaloufová); MUDr. Markéta Marková-Šťastná, CSc.; MUDr. Petr Soukup; MUDr. Mgr. Cyril Šálek, Ph.D.; Ing. Milena Vraná; RNDr. Marie Dobrovolná; MUDr. Antonín Vítek; prof. MUDr. Petr Cetkovský, Ph.D.; MUDr. Jiří Schwarz, CSc.


CBF-AMLs carrying fusion genes AML1/ETO or CBFβ/MYH11 predict a relatively favourable outcome and are classified as a low risk AML group. Hardly ever these two aberrations appear simultaneously in a single patient.


To report a male patient with AML carrying both the AML1/ETO and CBFβ/MYH11 fusion genes at diagnosis, who developed a donor-derived AML with AML1/ETO translocation following hematopoietic stem cell transplant (HSCT).

Methods: At diagnosis, bone marrow expression of AML1/ETO and CBFβ/MYH11 fusion genes was screened by qualitative RT-PCR. Quantitative real-time RT-PCR was performed to monitor MRD (the two given fusions in bone marrow and WT1 gene expression in peripheral blood). To determine the origin of the AML1/ETO+ clone after the HSCT, real-time allelic discrimination assay for an HLA polymorphism was employed.

Results: Case Report:

In a 30-year-old male with WBC 256.1 G/l, AML FAB M1 type of AML was diagnosed on10.09.04, CNS infiltration was also suspected. CBFβ/MYH11 fusion associated with an exon 8 C-KIT frameshift mutation was detected. Screening for FLT3/ITD, FLT3/TKD, K-RASN-RAS and JAK2 mutations was negative.

After the classical “3+7” idarubicin + cytarabine induction therapy (+ intrathecal methotrexate), the patient reached complete remission (CR) with a nearly 3 log decrease of CBFβ/MYH11 transcript and WT1 on the borderline of normal expression on 13.10.04 (Fig. 1). Consecutively, he received 4 consolidation cycles of high-dose cytarabine, which was followed by another slight decrease (but not negativity) of CBFβ/MYH11 expression. WT1 expression was within normal levels (01.06.05). However, both CBFβ/MYH11 and WT1 positivity grew again considerably and on 15.08.05 another “3+7” therapy was given. Despite it, the patient faced overt clinical relapse (with CNS infiltration on top of it) on 02.01.06. He was rescued by the “HAM” protocol (mitoxanthrone + high dose cytarabine, with additional intrathecal methotrexate). He achieved second CR and underwent myeloablative HSCT from a 7 out of 10 HLA-matched unrelated donor on 16.02.06. Only on 18.10.07 he reached stable molecular remission as judged by CBFβ/MYH11 expression. Nevertheless, during the next two months, the WT1 expression grew above normal and the patient relapsed again on 17.01.08, while CBFβ/MYH11 expression remained negative.

A new molecular screening was performed and the AML1/ETO transcript was detected (Fig. 1). Therefore, all previously taken samples were tested for the presence of AML1/ETO and a very low expression was found in the diagnostic sample using real-time RT-PCR. The following samples oscillated around the sensitivity threshold of the RQ-PCR method (10-6). Although AML1/ETO was present already at diagnosis, donor-derived AML1/ETO clone was confirmed by allelic discrimination of the donor/recipient HLA polymorphisms, as well as by the chimerism analysis. The patient received induction treatment by “3+7” and underwent second HSCT from another donor with 3 mismatches on 13.01.09 after a non-myeloablative conditioning. On 08.07.09 he reached molecular remission ofAML1/ETO as well as WT1. However, this time he suffered grade II acute GvHD and succumbed due to CMV pneumonia and acute respiratory distress syndrome on 18.07.09.

Image / Pictures:


Summary / Conclusion:

We deem this is the first report of multiple CBF-AMLs in a single patient. The patient may have had some unrecognized predisposition in his environment or in his hematopoietic milieu. Developing of the donor cell leukemia is a quite rare but serious complication of the HSCT.

Keywords: AML1-ETO, HSCT, Inv(16)

Datum přednesení příspěvku: 13. 6. 2013