Survival outcomes in patients treated with unrelated cord blood transplantation (UCBT) with fludarabine and melphalan (FM)-based reduced-intensity conditioning (RIC) regimens for lymphoma improved between the 2000s and 2010s, according to research published in the Annals of Hematology.

Researchers conducted a retrospective study using a nationwide registry database of adult patients with lymphoma who underwent UCBT with FM-based RIC between 2002 and 2017. They evaluated longitudinal changes in survival outcomes and the relationship between melphalan dose and graft vs host disease (GVHD) prophylaxis.

The team compared outcomes of patients treated with FM80/100 (melphalan dose, 80 or 100 mg/m2) and FM140 (melphalan dose, 140 mg/m2) and calcineurin inhibitor (CNI) plus methotrexate (MTX), CNI plus mycophenolate mofetil (MMF), and CNI alone.


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A total of 413 patients were included in the study and grouped based on treatment period (2000s vs 2010s). Compared with the 2000s cohort, the 2010s cohort had a greater median age (52 vs 57 years; P <.001) and a lower ECOG performance status (ECOG PS 0, 39.7% vs 20.2%; P <.001).

The researchers found that the proportion of patients with indolent B-cell lymphoma decreased (28.2% in 2000s vs 19.5% in 2010s) and the proportion of patients with T/NK-cell lymphoma increased (26.0% in 2000s vs 40.8% in 2010s; P =.022) over time.

The investigators found that the 3-year overall survival (OS) and non-relapse mortality (NRM) rates improved in both cohorts over time (OS, 27% in 2000s vs 42% in 2010s; P <.001; NRM, 43% in 2000s vs 26% in 2010s; P <.001).

Using multivariable analysis, they demonstrated that the melphalan dose and GVHD prophylaxis regimen did not affect any survival outcomes in the 2000s. They found that FM80/100 (vs FM140) was associated with better OS (hazard ratio [HR], 0.62; P =.01) and NRM (HR, 0.52; P =.016) in the 2010s.

They also found that MTX+CNI and CNI alone (vs CNI+MMF) were associated with worse OS (CNI+MTX: HR, 2.01; P <.001; CNI alone: HR, 2.65; P <.001) and relapse/progression (CNI+MTX: HR, 2.40; P <.001; CNI alone: HR, 2.13; P =.023).

The team also demonstrated that the use of FM80/100 (vs FM140) significantly reduced the risk of NRM (HR, 0.52; 95% CI, 0.31-0.89) and that the CNI+MTX and CNI alone groups had a significantly higher relapse/progression rate than the CNI + MMF group (HR, 2.40; 95% CI, 1.47-3.93; HR, 2.13; 95% CI, 1.11-4.09, respectively).

“This nationwide registry database study demonstrated that outcomes in FM-based RIC UCBT for lymphoma improved from the 2000s to the 2010s. In addition, lower melphalan doses of 80 or 100 mg/m2 in FM-based RIC regimens prior to UCBT for lymphoma showed higher rates of engraftment than melphalan 140 mg/m2, and subsequently demonstrated lower NRM and improved OS. Recurrence risk should be reduced by the enhanced graft-versus-lymphoma effect associated with moderate GVHD prophylaxis using MMF,” the researchers concluded.

Limitations of the study included the retrospective design, physician-dependent or institutional standard-based treatment choices, inability to evaluate differences between institutions due to insufficient registry data, limited number of patients who underwent UCBT for lymphoma, and lack of information on follicular lymphoma cases.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Sakatoku K, Kim SW, Okamura H, et al. Improved survival after single-unit cord blood transplantation using fludarabine and melphalan-based reduced-intensity conditioning for malignant lymphoma: impact of melphalan dose and graft-versus-host disease prophylaxis with mycophenolate mofetil. Ann Hematol. Published online October 5, 2022. doi:10.1007/s00277-022-04990-w

This article originally appeared on Hematology Advisor