What is the best approach to manage aplastic anemia in an adolescent who developed it after chemotherapy?

Management of Chemotherapy-Induced Aplastic Anemia in Adolescents

For an adolescent who developed aplastic anemia after chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the preferred first-line treatment if an HLA-matched sibling donor is available; if no matched sibling exists, immunosuppressive therapy with antithymocyte globulin (ATG) plus cyclosporine A should be initiated immediately. 1

Initial Assessment and Risk Stratification

The severity of aplastic anemia must be determined immediately, as this is therapy-related (secondary) aplastic anemia following chemotherapy exposure. 2 Key parameters to assess include:

• Absolute neutrophil count, platelet count, and reticulocyte count to classify severity 3
• Bone marrow cellularity via aspiration and biopsy 3
• HLA typing of the patient and all potential sibling donors should be performed urgently 1
• Transfusion requirements and bleeding risk 4

Treatment Algorithm Based on Donor Availability

If HLA-Matched Sibling Donor Available (Age <40 years)

Proceed directly to allo-HSCT without delay. 1 This is the definitive treatment with superior long-term outcomes in adolescents:

• Conditioning regimen: Cyclophosphamide plus antithymocyte globulin 1
• Stem cell source: Bone marrow is preferred over peripheral blood 1
• GVHD prophylaxis: Cyclosporine A plus methotrexate 1
• Expected outcomes: Children and adolescents in the HSCT cohort demonstrate 100% overall survival and 100% failure-free survival, significantly superior to immunosuppressive therapy 5

If No Matched Sibling Donor Available

Initiate immunosuppressive therapy immediately with ATG plus cyclosporine A. 1 This represents standard first-line treatment:

• Expected response rate: 57.6% at 6 months and 60.6% at 12 months 5
• Consider matched unrelated donor (MUD) or haploidentical transplant as second-line therapy if IST fails, particularly in younger patients 5, 6
• Adolescents who fail initial IST have significantly better outcomes with salvage HSCT (79.8% failure-free survival) compared to repeat IST (56.6% failure-free survival) 5

Critical Supportive Care Measures

While definitive treatment is being arranged, aggressive supportive care is mandatory:

Transfusion Strategy

• Maintain platelet count >10,000/μL (higher if bleeding or fever present) 4
• Use leukoreduced, irradiated blood products to prevent alloimmunization and transfusion-associated GVHD 2, 4
• Transfuse packed red blood cells to maintain hemoglobin >7-8 g/dL or higher if symptomatic 2

Infection Prevention and Management

• Antifungal prophylaxis is essential given the 20% incidence of invasive fungal infections in severely cytopenic patients 2, 4
• Antibacterial prophylaxis with fluoroquinolones should be considered 4
• Neutropenic fever requires immediate broad-spectrum antibiotics without waiting for culture results 4
• Avoid invasive procedures (central lines, lumbar punctures) until counts recover when possible 2

Iron Chelation

• Monitor ferritin levels and initiate chelation therapy if ferritin >1000 ng/mL with ongoing transfusion dependence 4
• This is particularly important in adolescents who may require prolonged transfusion support 4

Key Clinical Pitfalls to Avoid

Do not delay HLA typing and donor search. Time is critical, and early identification of transplant options directly impacts survival. 1

Do not use androgens or corticosteroids as primary therapy. These have been largely unsuccessful in treating aplastic anemia and should not delay definitive treatment. 3

Do not withhold transfusions based solely on arbitrary hemoglobin thresholds. Adolescents may be symptomatic at higher hemoglobin levels than adults, particularly if anemia developed acutely. 2

Do not attempt repeat chemotherapy for the underlying malignancy until hematologic recovery is achieved, as this will worsen the aplastic anemia. 2

Second-Line Treatment Options

If initial IST fails (no response by 6 months) or relapse occurs:

• Salvage allo-HSCT is strongly preferred in adolescents over repeat IST, with 100% survival in pediatric patients versus 50% with repeat IST 5
• Haploidentical transplant achieves 86.1% hematologic recovery at 12 months with acceptable GVHD rates (36.1% grades II-IV acute GVHD) 5
• Repeat ATG-based IST achieves only 60.6% response rate and inferior failure-free survival 5
• Thrombopoietin receptor agonists (eltrombopag) may be considered in combination with IST, though evidence in adolescents is limited 6

Long-Term Monitoring

Adolescent survivors require lifelong surveillance for:

• Clonal evolution to myelodysplastic syndrome or acute myeloid leukemia (occurs in 10-15% of IST-treated patients) 6
• Late transplant complications including chronic GVHD, endocrine dysfunction, and secondary malignancies 5
• Iron overload from chronic transfusions 4