The remarkable response to ponatinib therapy in a child with blastic phase of chronic myeloid leukemia

Background. Chronic myeloid leukemia (CML) rarely occurs in children and adolescents, which shows more aggressive features like high risk of more advanced disease at the time of diagnosis. Suboptimal response to tyrosine kinase inhibitors (TKIs), adverse events, or advanced disease may impede the treatment. Case. Herein we present a nine-year-old chronic phase CML case. He had no major molecular response (MMR) to imatinib, which was switched to dasatinib. MMR was ensured for 24 months, yet he developed a lymphoid blastic phase under dasatinib. He obtained a remarkable response to ponatinib when administered in parallel to multiagent induction chemotherapy.Conclusion. Ponatinib therapy is effective and promising as a bridge to hematopoietic stem cell transplantation in children. Although more studies are necessary to determine indications, dose, efficacy, and safety data.

PDF

___

1. Hijiya N, Schultz KR, Metzler M, Millot F, Suttorp M. Pediatric chronic myeloid leukemia is a unique disease that requires a different approach. Blood 2016; 127: 392-399.

2. Hijiya N, Suttorp M. How I treat chronic myeloid leukemia in children and adolescents. Blood 2019; 133: 2374-2384.

3. Shima H, Tokuyama M, Tanizawa A, et al. Distinct impact of imatinib on growth at prepubertal and pubertal ages of children with chronic myeloid leukemia. J Pediatr 2011; 159: 676-681.

4. Gore L, Kearns PR, de Martino ML, et al. Dasatinib in pediatric patients with chronic myeloid leukemia in chronic phase: results from a phase II trial. J Clin Oncol 2018; 36: 1330-1338.

5. Millot F, Maledon N, Guilhot J, Güneş AM, Kalwak K, Suttorp M. Favourable outcome of de novo advanced phases of childhood chronic myeloid leukaemia. Eur J Cancer 2019; 115: 17-23.

6. Nickel RS, Daves M, Keller F. Treatment of an adolescent with chronic myeloid leukemia and the T315I mutation with ponatinib. Pediatr Blood Cancer 2015; 62: 2050-2051.

7. Yamamoto M, Hori T, Igarashi K, Shimada H, Tsutsumi H. Response to ponatinib before hematopoietic stem cell transplantation in a child with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia. Pediatr Int 2018; 60: 85-87.

8. Millot F, Suttorp M, de Bont E, et al. PF417 Ponatinib in childhood Philadelphia positive leukemias: the experience of the International Registry of childhood chronic myleloid leukemia (I-CML-Ped-Study). HemaSphere 2019; 3: 161-162.

9. Rossoff J, Huynh V, Rau RE, et al. Experience with ponatinib in paediatric patients with leukaemia. Br J Haematol 2020; 189: 363-368.