What is the role of stem cell transplantation in treating leukemia?

Stem Cell Transplantation in Leukemia Treatment

Direct Recommendation

Allogeneic stem cell transplantation is the definitive consolidation therapy for acute myeloid leukemia (AML) patients in first complete remission who have intermediate- or poor-risk disease features and an HLA-identical sibling donor, while good-risk patients should receive chemotherapy alone. 1

Risk-Stratified Approach to Stem Cell Transplantation

Good-Risk AML Patients

• Do not perform allogeneic stem cell transplantation (allo-SCT) in first remission for good-risk patients (including those with favorable cytogenetics such as t(15;17), t(8;21), inv(16), NPM1-mutated without FLT3-ITD, or bi-allelic mutant CEBPα AML), as the transplant-related mortality exceeds the benefit since these patients have a relapse risk of 35% or less. 1
• These patients should receive at least one cycle of intensive consolidation chemotherapy with high-dose cytarabine instead. 1
• Allo-SCT can be reserved as salvage therapy if they relapse into second remission. 1

Intermediate- and Poor-Risk AML Patients

• All intermediate- and poor-risk patients with an HLA-identical sibling donor are candidates for allo-SCT in first remission, provided their age and performance status permit. 1
• Meta-analyses demonstrate significant improvement in disease-free survival and overall survival (hazard ratio 1.4) with allo-SCT from HLA-identical sibling donors, particularly in patients with high-risk cytogenetics and those under 40 years of age. 1
• The benefit is driven by significantly lower relapse rates compared to chemotherapy alone, though this comes at the cost of transplant-related mortality and graft-versus-host disease (GVHD). 1

Alternative Donor Sources When No Matched Sibling Available

• Patients with poor-risk features and no HLA-identical family donor should be offered allo-SCT from a matched unrelated donor (MUD). 1
• MUD transplantation now achieves survival rates comparable to matched sibling transplants due to improved HLA typing techniques. 1, 2
• Haploidentical transplants may be considered when a KIR mismatch is present. 1
• Cord blood transplantation represents a viable alternative for patients without matched donors who urgently need transplantation, with acceptable outcomes despite higher graft failure rates. 1, 2

Timing and Patient Selection

When to Identify Transplant Candidates

• HLA typing should be performed early during induction therapy on all patients who are potential transplant candidates, including their family members. 1
• Candidates for allo-SCT must be identified during induction to allow timely transplant planning. 1

Patients Who Should Proceed Directly to Transplant

• Patients failing to achieve complete remission after 1-2 cycles of induction chemotherapy (refractory disease) are at very high risk and should be considered immediate candidates for allo-SCT. 1
• Patients with late achievement of complete remission benefit from allo-SCT. 1

Conditioning Regimens

Standard Myeloablative Conditioning

• Myeloablative allo-SCT from a fully matched sibling donor is recommended for children with intermediate-high risk cytogenetics and adults under 50-60 years. 1
• Standard conditioning typically includes busulfan and cyclophosphamide. 3

Reduced Intensity Conditioning (RIC)

• RIC regimens may be used for patients over 50 years of age or those in the upper age range, enabling transplantation in elderly patients who cannot tolerate myeloablative conditioning. 1
• RIC results in lower acute GVHD and transplant-related mortality but higher relapse rates compared to myeloablative conditioning, with similar overall disease-free survival and overall survival. 1

Relapsed or Refractory Disease

• Patients in second or subsequent remission should be offered allo-SCT with an unrelated HLA-matched donor. 1
• Allo-SCT is the only curative option for patients who fail induction therapy. 2
• For acute promyelocytic leukemia (APL) that relapses, arsenic trioxide can induce remission before proceeding to transplant. 1

Critical Pitfalls to Avoid

• Do not delay transplant evaluation in intermediate- or poor-risk patients, as outcomes are superior when transplant occurs in first complete remission rather than after relapse. 1, 4
• Do not offer allo-SCT to good-risk patients in first remission, as this exposes them to unnecessary transplant-related mortality without survival benefit. 1
• Do not proceed with haploidentical or cord blood transplants outside of specialized centers with active programs, as these procedures require special expertise. 1
• Ensure infectious complications from induction are under control before proceeding to allo-SCT. 1

Role of Autologous Stem Cell Transplantation

• The role of high-dose consolidation chemotherapy with autologous peripheral stem cell support in AML remains controversial. 1
• Recent data suggest autologous transplant may be a reasonable option for intermediate-risk patients as an alternative to allo-SCT, potentially prolonging remission duration, though its impact on overall survival is uncertain. 1

Chronic Myeloid Leukemia (CML) Context

• In the era of tyrosine kinase inhibitors (TKIs) like imatinib, allo-SCT has shifted from first-line to second- or third-line therapy for CML. 1, 5
• Allo-SCT should be considered for CML patients who fail TKI therapy, progress to accelerated phase or blast crisis, or demonstrate TKI resistance. 1
• Prior imatinib use does not compromise subsequent transplant outcomes. 1