Cytogenetic/Molecular Findings and Treatment Outcome of Childhood Acute Megakaryoblastic Leukemia. Possible Favorable Effect of High Dose Cytarabine and Stem Cell Transplantation.
Authors: Kato Keisuke , Tagusagawa Ayako , Kobayashi Chie , Koike Kazutoshi , Tsuchida Masahiro 
Published: October 2019

Abstract
Acute megakaryoblastic leukemia (AMKL) is a rare hematological malignancy. Childhood AMKL is classified into three categories including AMKL associated with Down syndrome (AMKL-DS), AMKL with t(1;22)(p13;q13)/RBM15-MKL1, and others. Previous studies have revealed AMKL with t(1;22)(p13;q13) occurs mainly in infant with poor prognosis, and patients with AMKL-DS generally show favorable course, mostly associated with GATA-1 mutation. Appropriate treatment strategy and the role of hematopoietic stem cell transplantation (SCT) remained controversial in childhood AMKL.
Cases and Methods: Eleven cases with AMKL were analyzed and reviewed. Cytogenetic analysis was performed with G banding. Expression of RBM15-MKL1 was analyzed with RT-PCR method on seven cases with the material available.
Results. The age at onset ranged from 6 months to 2 years and 6 months. Three were males and eight females. Five of 11 cases were AMKL-DS. Three were AMKL with t(1;22)(p13;q13), of which both two cases analyzed express RBM15-MKL1. Translocation at 11q23 was confirmed in two. Preceding MDS had been confirmed in one AMKL-DS and one AMKL with t(1;22)(p13;q13). The treatment differed among the cases; however, the regimens including high dose cytarabine (HD-CA) were utilized as first-line therapy in eight cases out of 11, resulting in long term remission in five. In particular, three AMKL with t(1;22)(p13;q13) attained long term remission with HD-CA containg regimen. Three cases underwent SCT on disease and two of three remain in remission for 7 years and 4 months, respectively. Two poor prognostic AMKL-DS cases had breakpoint at 22q13 where MKL1 resides and at 17p13 where TP53 is localized.
Discussion. Childhood AMKL is heterogenous on cytogenetic/molecular aspects. HD-CA containing regimens might have favorable effect even on AMKL with t(1;22)(p13;q13) and the other poor prognostic AMKL. SCT might be effective even for refractory disease.
patient characteristics case sex age at onset clinical feature karyotype RBM15-MKL1 treatment outcome abbreviations: M, male; F, female; y, year; mo, month; MDS, myelodysplastic syndrome; TMD, transient myeloproliferative disorder; NA, not available; CA, chemotherapeutic regimen containing normal dose of cytarabine; HD-CA, chemotherapeutic regimen containing high dose cytarabine; CR, complete remission; Rel, relapse; and DOD, died of disease 1 M 1y DS 53, XY, +6, +8, +10, +13, +14, +19, 21 NA CA 18y11mo CR 2 F 1y7mo 50, XX, +8, +19, +21, +22 − HD-CA 11y10mo CR 3 F 6mo preceding MDS 46, XX, t(1;22), t(11;14)(q23;q22) NA HD-CA 13y10mo CR 4 F 1y5mo 48, XX, t(1;22)(p13;q13), +2, +mar + HD-CA 12y10mo CR 5 F 2y6mo 46, XX, t(9;11;17)(p22;q23;q21) NA HD-CA, SCT 10y3mo CR 6 F 1y7mo DS 47, XX, +21 NA HD-CA 4y5mo CR 7 M 1y9mo 51, XY, t(1;22)(p13;q13), +6, +8, −17, +20, +21, +21, +mar + HD-CA 9y8mo CR 8 M 1y11mo DS 47, XY, der(5)t(1;5)(q21;q33), del(5)(q?), add(9)(q34), +21, add(22)(q13) − HD-CA, SCT induction failure, 7y8mo CR after SCT on disease 9 F 1y3mo DS, preceding TMD and MDS 48, XX, +8, +21 − CA 7y8mo CR 10 F 11mo DS 45, XX, add(3)(p25), −7, +11, add(11)(p11)X2, −13, der(17)t(13;17)(q12;p13) − CA, HD-CA, SCT 7mo Rel after CA, re-induction failure after HD-CA, SCT on disease, 1mo Rel, DOD 11 F 1y11mo 46, XX, inv(2)(p23;q37), der(5)t(5;15)(p15;q11)t(6;15)(p11;q26), der(6)t(6;15), del(15)(q11) − HD-CA, SCT 6mo Rel after HD-CA, SCT on disease, 4mo CR