Is a bone marrow transplant an option for Chronic Myeloid Leukemia (CML)?

Is Bone Marrow Transplant an Option for CML?

Yes, allogeneic stem cell transplantation (alloSCT) remains an important therapeutic option for CML, but it is now reserved for specific clinical scenarios rather than being first-line therapy. 1

Current Role of Transplant in the TKI Era

The treatment landscape has fundamentally shifted since tyrosine kinase inhibitors became available. AlloSCT is now recommended as third-line or later therapy after failure of at least two TKIs in chronic phase CML. 1 The number of patients undergoing transplant for CML has decreased significantly, but it remains the only potentially curative option. 1, 2

Specific Indications for Transplant

Chronic Phase CML

Transplant should be considered for patients who:

• Fail to respond to at least two second-generation TKIs (dasatinib, nilotinib, bosutinib, or ponatinib) 1
• Harbor the T315I mutation after trial of ponatinib therapy 1
• Are at high risk for transformation to advanced phase, since outcomes after transformation are significantly worse 1
• Are resistant or intolerant to at least one second-generation TKI 1

Advanced Phase CML

For accelerated phase (AP): Transplant should be considered early in patients who develop AP during TKI treatment or high-risk patients with insufficient treatment response. 1

For blast phase (BP): AlloSCT is the only curative option and should be pursued if a second chronic phase can be established with intensive chemotherapy with or without TKI. 1 However, transplant should not be advocated for advanced disease with high transplant risk; ongoing drug treatment or best supportive care may be better options. 1

Pediatric CML

For children with CML-CP: Transplant is recommended for those who fail to achieve major molecular response or show failure to 3-4 lines of treatment, with the goal of achieving minimal residual disease before transplant. 1

Conditioning Regimen Selection

For chronic phase CML: There is no evidence that myeloablative conditioning offers advantages over reduced-intensity preparative regimens. 1 Reduced-intensity conditioning has improved non-relapse mortality, overall survival, and relapse-free survival without increasing relapse rates. 1

For blast phase CML: Myeloablative conditioning should be used where possible. 1

Donor Selection

Preferred donor sources in order:

• Well-matched (9 or 10/10 HLA loci) sibling donor (MSD) 1
• Matched unrelated donor (MUD) 1
• Haploidentical donor (HID) for patients without MSD or MUD 1

Bone marrow is the preferred stem cell source over peripheral blood to lower the risk of graft-versus-host disease. 1

Pre-Transplant Optimization

Patients should enter transplant with the best possible response (lower CML burden). 1 For chronic phase, this means aiming for at least cytogenetic response or better. 1 For advanced phase, chemotherapy is frequently required before transplant to control disease and make patients eligible. 1

Post-Transplant Management

Monitor patients after transplant by quantitative PCR and treat with:

• Donor lymphocyte infusion and/or TKI as clinically appropriate 1
• Pre-emptive TKI therapy (same TKI used pre-transplant or asciminib if resistant to all previous TKIs) in all patients who lose major molecular response (BCR::ABL1 > 0.1%) post-transplant, confirmed by two consecutive measurements 2-4 weeks apart 1
• Consider reduction of immunosuppression in patients with detectable minimal residual disease 1

Expected Outcomes

For chronic phase CML: 5-year overall survival rates range from 58% to 97% depending on donor match and conditioning regimen. 1 Cure rates range from 20% to 60% based on disease stage at transplant. 2

For advanced phase CML: Outcomes are significantly worse, with 2-10 year overall survival ranging from 18% to 75%. 1

Common Pitfalls to Avoid

Do not delay donor search: Assessment of donor availability should begin early for patients at high risk for transformation or those showing suboptimal responses to TKIs. 1

Do not transplant patients with uncontrolled blast crisis: In cases of uncontrolled, resistant blast phase, alloSCT is not recommended. 1

Do not overlook age and comorbidities: While reduced-intensity conditioning extends transplant eligibility to older patients, careful patient selection remains critical. 1

Do not forget that transplant timing has changed: Over the last 14 years, timing has shifted from first-line to third or fourth line after failure of second-line TKIs. 1