Acute lymphoblastic leukemia (ALL) - pediatric

Transplant advances and outcomes

Note: Pediatric defined as <39 years.

Approximately 6,250 cases of acute lymphoblastic leukemia (ALL) are diagnosed annually in the United States, representing about 23% of new acute leukemias. Children and adolescents younger than 20 years comprise about 54% of these cases, making ALL the most common type of pediatric cancer. [1]

ALL is the most common indication for allogeneic hematopoietic cell transplantation (HCT) in patients <18 years with hematological malignancies. [2] Research suggests that allogeneic HCT is recommended for pediatric ALL patients who experience primary induction failure, but subsequently achieve a first complete remission (CR1). Human leukocyte antigen (HLA) matched related and matched unrelated HCT provide equivalent outcomes. [3]

Recommended timing for transplant consultation

  • Infant at diagnosis
    • unfavorable genetics
    • age <3 months with any WBC, or <6 months with WBC >300,000 at presentation or any infant with measurable (also known as minimal) residual disease (MRD)+ after consolidation
  • Primary induction failure (M3 marrow) after achieving MRD negative status
  • Presence of MRD after initial therapy; MRD ≥0.01% following consolidation (9–12 weeks from diagnosis)
  • High/very high-risk CR1, including:
    • Philadelphia chromosome positive slow-TKI responders or with IKZF1 deletions; Philadelphia-like if MRD+ at end of consolidation, or persistently detectable low level of molecular disease
    • iAMP21 if MRD+ at end of consolidation
    • 11q23 rearrangement if MRD+ at end of consolidation
  • First relapse with aim to transplant in CR2
  • CR2 and beyond, if not previously evaluated, including:
    • all young adults in CR2
    • early relapse (≤36 months from diagnosis for medullary disease, ≤18 months from diagnosis for EMD)
    • MRD+ (>0.1% for medullary disease or equivalent for EMD) after re-induction (4–8 weeks from relapse)
    • T cell ALL
    • CR3 and beyond
  • Chimeric antigen receptor therapy (CAR-T), including:
    • patients who receive CD19 4-1BB and achieve MRD negative CR if they have not already received HCT
    • patients who receive CD22 or other investigational therapie

References

  1. SEER Stat Fact Sheets: Acute Lymphocytic Leukemia. Accessed 1 November, 2017. Access
  2. D'Souza A, Fretham C. Current Uses and Outcomes of Hematopoietic Cell Transplantation (HCT): CIBMTR Summary Slides, 2017. Available at: http://www.cibmtr.org
  3. Oliansky DM, Camitta B, Gaynon P, et al. Role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of pediatric acute lymphoblastic leukemia: Update of the 2005 Evidence-Based Review. Biol Blood Marrow Transplant. 2012; 18(4): 505-522. Access
  4. NMDP/Be The Match and ASTCT Recommended Timing for Transplant Consultation. Download PDF
  5. National Comprehensive Cancer Network. Pediatric Acute Lymphoblastic Anemia. (Version 1.2023). Access
  6. Determine Efficacy and Safety of CTL019 in Pediatric Patients With Relapsed and Refractory B-cell ALL (ELIANA) (ClinicalTrials.gov identifier: NCT02435849). Access