What are the management strategies for conditions characterized by target cells, such as sickle cell disease and thalassemia major?

Management Strategies for Conditions with Target Cells: Sickle Cell Disease and Thalassemia Major

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for sickle cell disease and thalassemia major, with current worldwide experience showing more than 90% patient survival and approximately 80% disease-free survival. 1

Overview of Target Cell Disorders

Target cells (codocytes) are characteristic findings in several hemoglobinopathies, most notably:

• Thalassemia major (TM) - originating from Mediterranean, Middle Eastern, and Asian regions 1
• Sickle cell disease (SCD) - originating from central Africa 1

Both conditions now occur globally due to migration patterns and represent growing health problems worldwide 1.

Management of Thalassemia Major

Standard Supportive Care

• Chronic red blood cell transfusions to maintain hemoglobin levels and suppress ineffective erythropoiesis 2
• Iron chelation therapy to prevent progressive iron overload and subsequent endocrine, cardiac, and hepatic dysfunction 2
• Management of complications related to iron overload 1

Curative Approach

• Allogeneic HSCT is the only proven curative treatment 1
• Recent transplantation results show improved outcomes with modern approaches and careful patient selection 1
• 20-year probability of thalassemia-free survival of 73% in patients transplanted from HLA-identical sibling donors 1
• Current experience shows >90% patient survival and approximately 80% disease-free survival 1

Novel Therapies

• Gene therapy with betibeglogene autotemcel (LentiGlobin BB305) approved for TDT patients ≥12 years old who are non-β0/β0 without matched sibling donors 3
• Luspatercept (erythroid maturation agent) approved for adult beta-thalassemia patients 3

Management of Sickle Cell Disease

Standard Supportive Care

• Hydroxyurea - FDA-approved for patients ≥2 years old 3
  • Increases fetal hemoglobin production
  • Reduces frequency of painful crises, acute chest syndrome, and need for blood transfusions 4
  • Dose should be reduced by 50% in patients with creatinine clearance less than 60 mL/min 4
• Blood transfusions (simple or exchange) for acute complications and stroke prevention 3
• Pain management during vaso-occlusive crises 5

Novel Therapies

• L-glutamine (FDA approved) 3
• Crizanlizumab (FDA and EMA approved for patients ≥16 years) - targets vaso-occlusion 3
• Voxelotor (FDA and EMA approved for patients ≥12 years) - targets hemoglobin S polymerization 3

Curative Approach

• HSCT is the only proven curative treatment 1
• Fewer transplants have been performed for SCD compared to thalassemia due to:
  • Lack of consensus about indications and timing 1
  • Lower chance of identifying unrelated donors 1

Complications Management

Infection Prevention and Management

• Increased susceptibility to infections due to:
  • Underlying disease pathophysiology 6
  • Iron overload 6
  • Transfusion therapy 6
  • Functional asplenia or post-splenectomy state 6
• Preventive strategies:
  • Appropriate vaccination schedules, particularly in asplenic patients 6
  • Prophylactic antibiotics in selected cases 6
  • Careful surveillance for transfusion-transmitted infections 6

Hypercoagulability Management

• Both conditions manifest biochemical and clinical evidence of hypercoagulability 7
• Decreased levels of natural anticoagulant proteins and increased markers of thrombin generation and platelet activation 7
• Anticoagulation therapy may be required in selected cases 7

Transplantation Considerations

Patient Selection

• Decisions on patient selection for HSCT remain primarily dependent on:
  • Retrospective analyses 1
  • Clinical experience of transplant centers 1
• For thalassemia, HSCT is accepted as standard clinical practice with extensive experience 1
• For SCD, fewer transplants have been performed, with ongoing debate about optimal timing and indications 1

Donor Selection

• HLA-identical sibling donors provide the best outcomes 1
• Limited availability of matched unrelated donors, particularly for SCD patients 1

Future Perspectives

• Gene therapy approaches are emerging as potential alternatives to HSCT 1
• However, availability of optimal conventional medical therapy and gene therapy remains limited to industrialized countries 1
• HSCT remains the only widely available curative approach, particularly in a global setting 1

Common Pitfalls and Caveats

• Delayed recognition of iron overload complications in transfusion-dependent patients 2
• Underestimation of infection risk in asplenic patients 6
• Inadequate monitoring for transfusion-related complications 6
• Limited access to curative therapies in resource-constrained settings 1
• Myelosuppression with hydroxyurea therapy requires careful monitoring of blood counts 4
• Live vaccinations should be avoided in patients taking hydroxyurea 4