Lessened severe graft-versus-host after “minitransplantations”

We greatly appreciate Dr Brian Abbott's commentary¹  on the publication by Diaconescu et al,²  which compared toxicities and non-relapse mortality in patients undergoing HLA-matched related hematopoietic cell transplantation (HCT) following either nonablative or ablative conditioning, and we would like to make 3 points in response to his cautionary notes. First, we recently published very similar observations in patients given unrelated HCT.³  All nonablative patients in that study received 2 Gy total body irradiation preceded by 3 doses of fludarabine, 30 mg/m²/d for 3 days. Even though nonablative patients had significantly higher pretransplantation comorbidity scores, were older, and had more often failed preceding ablative HCT and cytotoxic chemotherapies, they experienced fewer grades III-IV toxicities than ablative patients. The 1-year nonrelapse mortality was 20% in nonablative compared with 32% in ablative patients, a difference that was significant after adjusting for pretransplantation differences between the 2 groups of patients (P = .04).

Second, while we agree that no long-term follow-up data on disease control are available as yet, early results in patients with multiple myeloma, non-Hodgkin lymphoma, chronic lymphocytic leukemia, and acute myelocytic leukemia look encouraging.^4-7 

Third, the graft-versus-host disease (GVHD) incidence among nonablative recipients was lower than that among their ablative counterparts,^3,8  and this was most pronounced for grades III-IV acute GVHD among unrelated recipients (Figure 1).

Finally, we share Dr Abbott's enthusiasm for the use of the Charlson Comorbidity Index (CCI) to evaluate patients before HCT. Patients with CCI scores of 1 or higher might benefit from undergoing nonablative HCT, regardless of their age.