Author(s): ,
Shotaro Hagiwara
Division of Hematology, Internal Medicine,National Center for Global Health and Medicine,Shinjuku,Japan
Sohtaro Mine
Division of Hematology, Internal Medicine,National Center for Global Health and Medicine,Shinjuku,Japan
Ana-Iris Schiefer
Clinical Institute of Pathology,Medical University Vienna,Vienna,Austria
Lukas Kenner
Department of Experimental Pathology and Pathology of Laboratory Animals,Medical University Vienna,Vienna,Austria;Ludwig Boltzmann Institute for Cancer Research Vienna,University of Veterinary Medicine Vienna,Vienna,Austria
William Tse
James Graham Brown Cancer Center,University of Louisville School of Medicine,Louisville,United States
EHA Library. Hagiwara S. Jun 9, 2016; 132831; E1282 Disclosure(s): Celgene Corporation: Advisory board member
Dr. Shotaro Hagiwara
Dr. Shotaro Hagiwara
Abstract: E1282

Type: Eposter Presentation

Multiple myeloma is an intractable hematological malignancy with various clinical manifestations, especially extramedullary disease (EMD). The prognosis of patients with EMD is extremely poor due to limited treatment options and aggressive nature of EMD, however the mechanism of the progression of EMD is not well known.AF1q is an oncogene which expressed in leukemia cells, located in 1q21. The gene is well known as one of the fusion partners of MLL, and as a poor prognostic factor in acute myeloid leukemia and myelodysplastic syndrome .  Recently, we reported that high expression of AF1q results in an autonomous Wnt activity that promotes distant metastasis of breast cancer.

We hypothesized that high expression of AF1q is a poor prognostic factor of multiple myeloma and associated with EMD.To evaluate our hypothesis, we analyzed the expression of AF1q in patients with multiple myeloma and investigated the impact on the prognosis and the progression of EMD.

Newly diagnosed multiple myeloma patients in National Center for Global Health and Medicine hospital from January 2001 to March 2013 were studied. Patients were treated with vincristine-adriamycin-dexamethason or bortezomib-dexamethason induction therapy followed by autologous stem cell transplantation using high dose melphalan.The expression of AF1q was evaluated using the immunostaining of bone marrow clot samples at the diagnosis of multiple myeloma. The expression of AF1q was graded from “-“ to “+++”.  EMD was diagnosed by pathological examination and/or CT/MRI/PET. The clinical response, progression free survival (PFS), and overall survival (OS) were analyzed using Kaplan Meier method with Log-rank test. Correlation between EMD and AF1q expression was tested by Chi-square test.

Clinical data and bone marrow clot samples of 117 patients were analyzed. Mean age was 54.9 years old, and 51.9% was male. The grades of AF1q expression were 7 of “-”, 33 of “+”, 35 of “++”, and 42 of “+++”. We defined the cases with “-” and “+” as low expression, “++” and “+++” as high expression. Very good partial response or better was obtained after completion of autologous stem cell transplantation in 42.5% of patients with low AF1q expression and 37.7% of high expression. There was no statistically significant difference. Survival analysis using Log Rank method showed that high expression of AF1q was associated with significantly shorter progression free survival (3 year PFS was 56.2% in low AF1q expression vs. 30.5% in high AF1q expression, p=0.009), but not overall survival (3 year OS was 89.6% in low AF1q expression vs. 73.3% in high AF1q expression, ns. ).EMD was found in 25.0% of patients with low AF1q expression and 44.7% of high expression. Chi-square test showed that the incidence of EMD was significantly higher in patients with high AF1q expression than low expression (p=0.045).

To our knowledge, this is the first study that demonstrates a molecular marker associated with myeloma with EMD. We found that the high expression of AF1q was an adverse prognostic factor in multiple myeloma.

Session topic: E-poster

Keyword(s): Multiple myeloma, Prognostic factor, Stem cell transplant

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