Total Marrow and Lymphoid Irradiation Shows Promise Prior to alloHCT in Relapsed or Refractory Acute Leukemia

Clinical Summary:

• Design/Population: A single-center phase 2 trial evaluated total marrow and lymphoid irradiation plus high-dose etoposide and cyclophosphamide as myeloablative conditioning before allogeneic hematopoietic cell transplantation in patients with relapsed or refractory acute myeloid leukemia or acute lymphoblastic leukemia.
• Key Outcomes: The regimen was safely delivered without unacceptable toxicity in the safety lead-in cohort and was associated with encouraging 2-year progression-free survival. Toxicities were consistent with intensive conditioning and 1 treatment-related death from sinusoidal obstruction syndrome was reported.
• Clinical Relevance: Total marrow and lymphoid irradiation-based conditioning may provide a feasible intensification strategy before allogeneic transplantation, warranting further study to clarify its impact on long-term disease control and transplant-related toxicity.

Total marrow and lymphoid irradiation combined with high-dose etoposide and cyclophosphamide was feasible and associated with encouraging outcomes among patients with relapsed or refractory acute leukemia undergoing allogeneic hematopoietic cell transplantation (alloHCT), as demonstrated by results from a phase 2 trial. 

“Total marrow and lymphoid irradiation delivers augmented doses of radiation to the bone marrow and lymph nodes while maintaining low doses to vital organs,” stated Anthony Stein, MD, City of Hope, Duarte, California, and coauthors. “We aimed to assess the effectiveness of combining total marrow and lymphoid irradiation with high-dose cyclophosphamide and etoposide as a conditioning regimen before [alloHCT].”

In this open-label, single-center study, 106 adult patients with either relapsed or refractory acute myeloid leukemia or acute lymphoblastic leukemia received 2000 cGy of total marrow and lymphoid irradiation on days –9 to –5, followed by 60 mg/kg of etoposide on day –4 and 100 mg/kg of cyclophosphamide on day –2 prior to alloHCT. Patients received bone marrow or peripheral blood stem cells from sibling, matched unrelated, or one-allele mismatched unrelated donors. Graft versus host disease prophylaxis consisted of tacrolimus and sirolimus. Primary end points included initial safety lead-in and progression-free survival (PFS).

At a median follow-up of 1.8 years for the overall cohort and 3.1 years among surviving patients, no patients in the initial 6-patient safety lead-in cohort experienced unacceptable toxicity. The 2-year estimated PFS was 34% in all patients. The most frequently reported grade 3/4 adverse events included cytopenias (91%), metabolic disorders (78%), oral mucositis (42%), diarrhea (24%), nausea (20%), and palmar-plantar erythrodysesthesia syndrome (10%). Sinusoidal obstruction syndrome led to 1 treatment-related death. 

“Adverse events were few, probably due to organ sparing by total marrow and lymphoid irradiation,” concluded Dr Stein et al. “Total marrow and lymphoid irradiation 2000 cGy could be safely delivered in combination with high-dose etoposide and cyclophosphamide… [and] was associated with encouraging 2-year [PFS] rates.” 

Source:

Stein A, Wang Y, Malki MMA, et al. Total marrow and lymphoid irradiation in combination with cyclophosphamide and etoposide before haematopoietic cell transplantation for relapsed or refractory acute leukaemia: A single-centre, open-label, phase 2 trial. Lancet Haematol. Published online: May 18, 2026. doi:10.1016/s2352-3026(26)00014-1