Evaluating measurable residual disease at myeloablative allogenic transplantation in patients with acute lymphoblastic leukemia

This study aimed to investigate if measurable residual disease (MRD) before transplant in patients with acute lymphoblastic leukemia (ALL) is associated with different outcomes in patients undergoing myeloablative total body irradiation (TBI)-based and chemotherapy (CT)-based conditioning. 

This study concluded that patients who have no MRD before transplant achieve better outcomes. It was also concluded that all patients with ALL benefit from myeloablative TBI-based conditioning. 

Myeloablative stem cell transplant uses high doses of chemotherapy and/or radiation to destroy cancer cells. During treatment stem cells are also destroyed. The patient then receives new stem cells to rebuild the blood cells and the immune system. MRD is when cancer cells remain after attempts to remove the cancer have been made. Assessing MRD is useful in the treatment and prognosis of ALL. MRD measured at the end of induction treatment (the first therapy used to treat a disease) can be used to select further treatment.  

MRD detected before transplant is known to be associated with poor outcomes. It is unclear if this differs with different types of conditioning. Conditioning treatment destroys cancer cells and bone marrow before the transplant. Myeloablative total body irradiation (TBI) and chemotherapy (CT) based conditioning were used in this study.  

It was not known if MRD before transplant is associated with different outcomes in patients who received TBI and CB conditioning.  

This study involved 2780 patients. Al patients underwent a first transplant during complete remission using sibling or unrelated donors. 65% of patients had no detectable MRD and 35% of patients had positive MRD. 76% of the patients received TBI conditioning. 24% received Ct-based conditioning.  

MRD positivity was a significant factor that predicted a 19% lower overall survival (OS) and a 26% lower leukemia-free survival (LFS). It also predicted a 51% higher relapse risk. TBI was associated with a 25% higher OS, a 30% higher LFS and a 40% lower relapse risk.  

No significant interaction was found between MRD status and conditioning. MRD positivity was associated with lower OS and LFS in the TBI group. MRD positivity was associated with higher relapse risk in both the TBI and CT groups.  

TBI conditioning was associated with improved outcomes in both MRD-negative and MRD-positive patients. 

This study concluded that patients who are MRD-negative before transplant have better outcomes and even more so in those who receive TBI conditioning. The authors also concluded that all patients with ALL benefit from TBI conditioning.  

This study did not account for how MRD was measured.