Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

PRIMARY OBJECTIVES:

I. To provide a risk classification scheme for all patients with newly diagnosed acute lymphoblastic leukemia (ALL), which will be used to assign treatment on Children?s Oncology Group (COG) frontline ALL treatment studies.

II. To capture classification data for correlative studies accompanying current COG ALL treatment protocols.

III. To provide a central reference guide for all required and research studies that will be conducted in local and reference laboratories for all newly diagnosed ALL patients.

IV. To provide a mechanism for optional banking of leukemia and germline specimens for current and future research.

OUTLINE:

Patients undergo blood sample collection and bone marrow biopsies at baseline and during and after induction therapy for immunophenotyping for ALL confirmation and classification, deoxyribonucleic acid (DNA) ploidy, genomic variation, and cytogenetic (BCR-ABL, trisomies 4+10, and molecular testing for translocations) analysis by flow cytometry and fluorescent in situ hybridization (FISH). Immunophenotype results obtained on this study are used to determine patient's assignment to specific clinical-trial treatments. Some samples (leukemic and germline) may be banked for current and/or future analyses.

Inclusion criteria

• Patient has newly diagnosed acute leukemia:

• > 25% blasts on a bone marrow (BM) aspirate or
• If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM biopsy or
• A complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic blasts
• Adequate samples must be provided to the reference and/or COG-approved cytogenetics laboratories to allow completion of the studies needed for risk-stratification

• If a BM aspirate is not performed, or adequate material cannot be obtained, peripheral blood (PB) can be substituted for BM if there are at least 1,000 circulating blasts/uL (i.e., a white blood cell [WBC] count of 10,000/uL with 10% blasts or a WBC count of 5,000/uL with 20% blasts); if only PB is submitted, please obtain and send twice the volume of PB as the recommended BM volume specified; the patient will remain on AALL08B1 as long as all required central laboratory tests can be successfully performed; as long as there are at least 1,000/uL PB blasts, institutions are encouraged to submit PB in addition to BM samples to make sure that adequate material is available to perform the required studies
• If an adequate BM aspirate cannot be obtained and there are fewer than 1,000/uL PB blasts, the patient is not eligible for AALL08B1 or a frontline COG ALL clinical trial (there are NO exceptions to this rule)
• Patient has suspected ALL:

• Patients whose blast morphology is obviously myeloid, or whose blasts are myeloperoxidase positive, should not be enrolled on AALL08B1; however, patients with true biphenotypic or bilineage leukemia (i.e., patient presents with blasts with significant expression of multiple lymphoid and myeloid markers such that assignment to a single lineage is not possible) are eligible to enroll in AALL08B1 for cell banking
• Samples must be sent to a COG-approved cytogenetics laboratory, and COG Reference Laboratory studies; if informative results needed for treatment stratification are not available at specified time-points during induction, patients will not be eligible to receive post-induction therapy on a COG ALL trial
• 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

Exclusion criteria

• Patient must not have received prior cytotoxic therapy except for steroids or intrathecal chemotherapy
• Patient must not have secondary ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy