| Disease |
Acute myeloid leukemias 1238 (AML) and myelodysplastic syndromes (MDS) |
| Phenotype / cell stem origin |
t(6;9)(p22;q34) is a rare subtype of pediatric AML earlier only described in small series and case reports (Gupta, et al 2010, Ishiyama, et al 2012, Slovak, et al 2006). Two large studies both published in 2014 described the clinical, morphologic, and genetic characteristics: the I-BFM-study including 62 children of which 54 was diagnosed as AML and 8 as MDS, and the COG study investigating 48 children all diagnosed as AML (Sandahl, et al 2014, Tarlock, et al 2014). This review is based upon the 110 children from these two series.
There are no pediatric studies of stem cell origin. AML in children with t(6;9) is associated with French-American-British (FAB) type M2 (44%) and FAB type M4 (25%) (Sandahl, et al 2014, Tarlock, et al 2014). |
| Epidemiology | The t(6;9)(p22;q34) was first described in a pediatric patient in 1982 (Kaneko, et al 1982). It is rare, found in only about 1% of all pediatric AML (Sandahl, et al 2014, Slovak, et al 2006, Tarlock, et al 2014) and associated with late onset with a median age 11 years and no patients below 2 years of age (Sandahl, et al 2014, Tarlock, et al 2014). There is an equal sex distribution with 53% males. |
| Cytology | Basophilia is common in adults with t(6;9). In the I-BFM study, peripheral blood smears from 11 children and bone marrow smears from 15 children with t(6;9)(p22;q34) were evaluable for central review (Sandahl, et al 2014). All had mild to moderate bilinear dysplasia. Basophils were present in five patients (33%), four of which had 2% basophils, one patient (6%) had 1% basophils, none had > 2%. From the remaining 47 AML patients, reports on basophils were available in 16 cases; four patients had 1-2% basophils in BM smears, one had 0.4%, and no basophils were reported in the remaining 11. No Auer rods were seen in this reviewed pediatric series. Pseudo-Pelger cells were found in all reviewed material. Furthermore, almost all had tadpole blasts and many have bilobar blasts, both characteristic of AML-M3. However no patients were classified as FAB M3. |
| |  |
|
| BM biopsies from pediatric t(6;9) AML illustrating morphologic characteristics A Pseudo-Pelger-Hüet anomaly tadpole blasts. Illustration from central review by Gitte Kerndrup (2013) |
|
| Treatment | It has been suggested that Hematopoietic stem cell transplantation (HSCT) in first complete remission may improve outcome. In the I-BFM-study, the 5-year event-free survival was improved among patients treated the HSCT in CR1 compared with chemotherapy alone (68% vs. 18%; P<0.01) but it did not effect the OS (68% vs. 54%; P=0.48). In the COG study those who received HSCT in CR1 or CR2 had a survival of 60% vs. 21% in those treated with chemotherapy alone (Tarlock, et al 2014). |
| Prognosis | Complete remission rate is significantly lower compared with pediatric AML patients without t(6;9)(Tarlock, et al 2014), but reported CR rates varied between 67 and 93%. (Sandahl, et al 2014, Tarlock, et al 2014) Furthermore, t(6;9) was associated with high risk of relapse 57%-64%, low 5-year EFS of 32% and 5-year OS around 45%(Sandahl, et al 2014, Tarlock, et al 2014).
The outcome seems better among pediatric t(6,9) patients compared with adults (Slovak, et al 2006).(Ishiyama, et al 2012, Slovak, et al 2006).
Among t(6;9) patients FLT3-ITD had a non-significant negative influence on survival with a 5-year overall survival compared with non-FLT3-ITD (22% versus 62%; p=0.13) in the I-BFM study (Sandahl, et al 2014). The OS in the COG study was in contrast higher with FLT3-ITD than without (40% vs. 27%; p>0.9) which may be explained by FLT3-ITD being allocated to hematopoietic stem cell transplantation (HSCT) (Sandahl, et al 2014, Tarlock, et al 2014) |
| The t(6;9)(p22;q34) in myeloid neoplasms: a retrospective study of 16 cases |
| Gupta M, Ashok Kumar J, Sitaram U, Neeraj S, Nancy A, Balasubramanian P, Abraham A, Mathews V, Viswabandya A, George B, Chandy M, Srivastava A, Srivastava VM |
| Cancer Genet Cytogenet 2010 Dec;203(2):297-302 |
| PMID 21156248 |
| |
| NUP98/NSD1 characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOX gene expression pattern |
| Hollink IH, van den Heuvel-Eibrink MM, Arentsen-Peters ST, Pratcorona M, Abbas S, Kuipers JE, van Galen JF, Beverloo HB, Sonneveld E, Kaspers GJ, Trka J, Baruchel A, Zimmermann M, Creutzig U, Reinhardt D, Pieters R, Valk PJ, Zwaan CM |
| REFERENCE Blood 2011 Sep 29;118(13):3645-56 |
| PMID 21813447 |
| |
| Prognostic factors for acute myeloid leukemia patients with t(6;9)(p23;q34) who underwent an allogeneic hem atopoietic stem cell transplant |
| Ishiyama K, Takami A, Kanda Y, Nakao S, Hidaka M, Maeda T, Naoe T, Taniguchi S, Kawa K, Nagamura T, Tabuchi K, Atsuta Y, Sakamaki H |
| Leukemia 2012 Jun;26(6):1416-9 |
| PMID 22157737 |
| |
| Chromosome pattern in childhood acute nonlymphocytic leukemia (ANLL) |
| Kaneko Y, Rowley JD, Maurer HS, Variakojis D, Moohr JW |
| Blood 1982 Aug;60(2):389-99 |
| PMID 6953984 |
| |
| t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients |
| Sandahl JD, Coenen EA, Forestier E, Harbott J, Johansson B, Kerndrup G, Adachi S, Auvrignon A, Beverloo HB, Cayuela JM, Chilton L, Fornerod M, de Haas V, Harrison CJ, Inaba H, Kaspers GJ, Liang DC, Locatelli F, Masetti R, Perot C, Raimondi SC, Reinhardt K, Tomizawa D, von Neuhoff N, Zecca M, Zwaan CM, van den Heuvel-Eibrink MM, Hasle H |
| Haematologica 2014 May;99(5):865-72 |
| PMID 24441146 |
| |
| A retrospective study of 69 patients with t(6;9)(p23;q34) AML emphasizes the need for a prospective, multice nter initiative for rare 'poor prognosis' myeloid malignancies |
| Slovak ML, Gundacker H, Bloomfield CD, Dewald G, Appelbaum FR, Larson RA, Tallman MS, Bennett JM, Stirewalt DL, Meshinchi S, Willman CL, Ravindranath Y, Alonzo TA, Carroll AJ, Raimondi SC, Heerema NA |
| Leukemia 2006 Jul;20(7):1295-7 |
| PMID 16628187 |
| |
| Acute myeloid leukaemia (AML) with t(6;9)(p23;q34) is associated with poor outcome in childhood AML regardless of FLT3-ITD status: a report from the Children's Oncology Group |
| Tarlock K, Alonzo TA, Moraleda PP, Gerbing RB, Raimondi SC, Hirsch BA, Ravindranath Y, Lange B, Woods WG, Gamis AS, Meshinchi S |
| Br J Haematol 2014 Jul;166(2):254-9 |
| PMID 24661089 |
| |
