Myelodysplastic Syndromes and Acute Myeloid Leukemia with t(6;9)(p23;q34).
Authors: Delmonte John , Kantarjian Hagop M. , Ravandi Farhad , Borthakur Gautam , Giles Francis J. , Abruzzo Lynne , Pierce Sherry , Cortes Jorge 
Published: October 2019

Abstract
The t(6;9)(p23;q34) is found in <1% of acute myeloid leukemia (AML). This translocation generates a fusion between the dek gene at 6p23 and the can gene at 9q34, with unclear role in leukemogenesis. Few patients (pts) have been described, usually with multilineage dysplasia, bone marrow (BM) basophilia, frequent FLT3 mutations, younger age at diagnosis and poor outcome. We searched the M.D. Anderson leukemia database to identify all pts diagnosed with t(6;9)(p23;q34) from 1993–2007. Clinical, laboratory, hematopathologic, and molecular data were reviewed. We identified 21 pts (18 AML, 2 MDS, 1 CMML) with t(6;9)(p23;q34) among 2,389 pts with AML and 597 pts with MDS seen over this period, representing 1% of all pts. Median age was 51 years (range, 20–82), 12 were female, median WBC 15.1 x109/L (range, 0.5–60.1), peripheral blast 12% (range, 0–86), hemoglobin 9.5 (range, 5.3–12.3), and platelet count 43 (range, 6–203). BM characteristics included median blast 62% (range, 7–87) and 2/21 (10%) pts with basophilia. The t(6;9)(p23;q34) translocation was the only cytogenetic abnormality in 13 (62%) pts; 8 (38%) had other chromosomal aberrations, often trisomy 8 (n=3). 8/12 (67%) pts tested for FLT3 mutations had an internal tandem duplication (ITD). Induction therapy was cytarabine-based (n=16), nucleoside analog/anthracycline-based (n=1), hypomethylating agent (n=1), and supportive care (n=3). 13/18 (72%) treated pts achieved CR, 6 (33%) were refractory, and 1 (6%) died during induction. Median CR duration was 53 weeks (wk) (range, 11–160) and 9/13 (69%) pts relapsed. 3/4 (75%) pts underwent stem cell transplant in 1st CR; two pts were FLT3-ITD negative. 5 pts who relapsed received salvage chemotherapy followed by stem cell transplant, but all subsequently died [median overall survival 45 wk (range, 28–121)]. Median overall survival (OS) for the entire group was 62 wk (range, 1–180). We then compared the t(6;9) AML pts to others treated in the same time period, grouped as: diploid (excluding APL), favorable (defined as inv 16 or t(8;21)), poor-risk (defined as -5 or -7), and other cytogenetic abnormalities. The t(6;9) AML subset was significantly younger (median 51 yrs) than the diploid (63 yrs) (p=0.001), poor-risk (63 yrs) (p<0.001), and other (62 yrs) (p=0.003) groups, but similar to favorable (44 yrs)(p=0.57). With regard to CR rate (72%) the t(6;9) AML subset did worse than favorable (91%)(p=0.017), better than poor-risk (40%)(p=0.006), and similar to the diploid (62%)(p=0.373) and other (52%)(p=0.089) groups. The tables show CR duration and OS for each group. In conclusion, AML with t(6;9)(p23;q34) represents a rare entity characterized by younger age at diagnosis, high frequency of FLT3-ITD, and clinical outcome similar to AML with diploid/intermediate risk cytogenetics. In this population, stem cell transplantation in 1st CR should be considered. The addition of FLT3 inhibitors to therapy should also be investigated.
Complete Remission 1 year (%) 2 years (%) Median (weeks) p-value t(6;9) 54 35 53 Diploid 56 37 59 0.772 Favorable 79 54 187 0.017 Other 48 30 50 0.682 Poor-risk 22 11 24 0.021 Overall Survival 1 year (%) 2 years (%) Median (weeks) p-value t(6;9) 66 35 67 Diploid 53 34 60 0.741 Favorable 84 67 233 <0.001 Other 41 24 40 0.15 Poor-risk 19 7 19 <0.001