Remission induction in refractory, drug resistant pediatric PICALM::MLLT10+ B-cell acute lymphoblastic leukemia by venetoclax

Acute lymphoblastic leukemia (ALL), with over 80% arising from B-cell lineage precursors (BCP-ALL), is the most common hematologic malignancy in children and adolescents.Intensified treatment strategies have increased survival rates to around 90%. ALL induction therapy according to e.g. the AIEOP-BFM ALL 2017 protocol [1] combines high-dose steroids, vincristine, daunorubicin and asparaginase and remission is achieved in most patients after 33 days of treatment, monitored by measurable residual disease (MRD) using clonotypic markers.Subsequent treatment and risk stratification depend on the MRD response and genetic factors.Patients unresponsive to treatment have a very poor prognosis [2].Here, we report the case of a primary refractory pediatric patient suffering from a PICALM::MLLT10 + BCP-ALL, who could be salvaged by venetoclax identified by prospective ex vivo drug response profiling (DRP) as the only active drug.A 10-year-old boy presented with fever of up to 40 C, fatigue, sore throat and night sweats for about a week, resulting in a Lansky score of 50.Blood test showed mild tricytopenia with 76.5% peripheral lymphoid blasts.Bone marrow (BM) analysis revealed 95% pro-B-ALL blasts (CD19 + , CD22 + , HLA-DR + , CD10-, intermediate CD45), confirming the diagnosis of BCP-ALL without extramedullary disease.An aberrant expression of CD7, CD5, and CD33 indicated a rather immature immunophenotype.After informed consent by the parents, induction therapy was initiated according to the AIEOP-BFM-ALL 2017 protocol (prednisone, vincristine, asparaginase and daunorubicin).Despite initial reduction of peripheral blood (PB) leukemia cells on day 8 (Fig. 1A), assessment by flow MRD on day 15 revealed 70% residual leukemic cells in the BM resulting in stratification to the high-risk group (FCM-MRD on day 15 > 10%).After end of induction (day 33), 92% of blasts in the BM indicated refractory