Umbilical cord blood transplantation (CBT), combined with ultra-low-dose methotrexate (uldMTX) as a graft-versus-host disease (GVHD) prophylaxis, provides superior survival for patients with high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), according to a study published in Leukemia & Lymphoma.
Patients who received CBT with uldMTX (CBT-uldMTX) achieved a significantly higher 2-year overall survival (OS) rate compared to patients who received more traditional bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT; 58.8% vs 31.9%; P =.008). Significantly higher rates of 2-year disease-free survival (DFS) were also observed in the CBT-uldMTX group (47.9% vs 28.5%; P =.019).
“These findings indicate that CBT provides a safe and effective donor platform with competitive outcomes across diverse alternative donor settings in high-risk AML/MDS,” the authors said.
Multivariate Cox regression analysis of subgroups showed that CBT still had superior 2-year OS rates compared to matched related donors (MRD; hazard ratio [HR]3.64; 95% CI, 1.07-12.4; P =.039)), matched unrelated donors (MUD; HR 2.63; 95% CI, 1.03–6.74; P =.044), and mismatched related donors (MMRD; HR, 4.00; 95% CI 1.69–9.47; P =.002). These results establish CBT-uldMTX as a highly effective alternative donor strategy for this patient population.
No significant differences were found between CBT-uldMTX and mismatched unrelated donors (MMUD; P =.33), but this is potentially due to the small number of MMUD recipients (n=3).
Importantly, the superior survival with CBT-uldMTX was achieved without the delayed hematopoietic recovery that has historically limited the use of cord blood. Neutrophil and platelet engraftment times were comparable to those of bone marrow and peripheral blood stem cell grafts. This suggests the uldMTX regimen may strike an optimal balance, preserving a potent graft-versus-leukemia (GVL) effect while mitigating the treatment-related toxicities that can delay engraftment or increase non-relapse mortality (NRM).
The overall incidences of NRM, acute GVHD, and chronic GVHD did not significantly differ between the CBT-uldMTX group and the cohort receiving other graft types. However, donor-specific analyses revealed that MRD grafts were independently associated with a higher risk of moderate-to-severe chronic GVHD (P =.039). In contrast, MMUD grafts were associated with an increased incidence of severe acute GVHD (P =.024). These specific comparisons highlight a more favorable GVHD profile for the CBT-uldMTX approach.
The study included a total of 76 patients with high-risk AML/MDS, including 47 who received CBT-uldMTX, 6 who received MRD grafts, 10 who received MUD grafts, 10 who received MMRD grafts, and 3 who received MMUD grafts.
This article originally appeared on Rare Disease Advisor
