The Pediatric Acute Leukemia (PedAL) Screening Trial - A Study to Test Bone Marrow and Blood in Children With Leukemia That Has Come Back After Treatment or Is Difficult to Treat - A Leukemia & Lymphoma Society and Children's Oncology Group Study

Inclusion Criteria:

• Patients must be less than 22 years of age at the time of study enrollment

• Patient must have one of the following at the time of study enrollment:

• Patient has known or suspected relapsed/refractory (including primary refractory) AML as defined in protocol

• This includes isolated myeloid sarcoma

• Patient has known or suspected relapsed/refractory (including primary refractory) myeloid leukemia of Down syndrome (ML-DS)

• Patient has known or suspected relapsed ALL as defined in protocol that meets one of the following criteria:

• Second or greater B-ALL medullary relapse, excluding KMT2Ar

• Any first or greater B-ALL medullary relapse involving KMT2Ar

• Any first or greater T-ALL medullary relapse with or without KMT2Ar

• Patient has known or suspected relapsed/refractory (including primary refractory) mixed phenotype acute leukemia (MPAL) as defined in protocol

• Patient has known or suspected de novo or relapsed/refractory (including primary refractory) treatment-related AML (t-AML)

• Patient has known or suspected de novo or relapsed/refractory (including primary refractory) myelodysplastic syndrome (MDS) or treatment-related myelodysplastic syndrome (t-MDS)

• Note: Relapsed/refractory disease includes stable disease, progressive disease, and disease relapse.

• Patient has known or suspected de novo or relapsed/refractory (including primary refractory) juvenile myelomonocytic leukemia (JMML)

• Note: Relapsed/refractory disease includes stable disease, progressive disease, and disease relapse.

• All patients and/or their parents or legal guardians must sign a written informed consent

• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met