Adult Unrelateddonor Ucbt

Adult unrelated-donor UCBT has been performed predominantly in relapsed hematological malignancies, with the exception of a small series of patients with de novo AML.65 The adult UCBT data are less mature than those of the pediatric population, yet reasonable rates of engraftment have been observed. Unfortunately, high TRM rates and marginal survival limit this treatment option to a select group of adult patients. The data have been reported in abstract form66-68 and from the following sources: EuroCord,50'69 Laughlin et al.,70 Sanz et al.,71 and Duke7273(Table 97.5). The EuroCord Registry reported on 108 patients with a median age of 26 years and a median weight of 60 kg. GVHD prophylaxis was predominantly cyclosporine and corticosteroids. 6% of the grafts were HLA identical, 35% were disparate at one locus, and 59% were mismatched at >2 loci. Laughlin et al. reported on 68 patients with a median age of 31.4 years and a median weight of 69.2 kg. The conditioning regimen was largely TBI

based/ATG. GVHD prophylaxis was cyclosporine alone or cyclosporine and methylprednisolone. Two grafts were HLA identical, 26% were disparate at one locus, and 71% were mismatched at >2 loci. Sanz et al. reported on 22 patients with a median age of 29 years and a median weight of 69.5 kg. The conditioning regimen consisted of Bu/Cy/ATG/thiotepa. GVHD prophylaxis was cyclosporine and prednisone. One graft was HLA identical, 13 were disparate at one locus, and 8 were mismatched at >2 loci. The Duke group reported on 57 patients with a median age of 31 years and a median weight of 70 kg. The conditioning regimen was TBI or Bu based plus ATG. GVHD prophylaxis was cyclosporine and methylprednisolone. Two grafts were HLA identical, eight were disparate at one locus, and the remaining grafts were mismatched at >2 loci.

The EuroCord Registry reported engraftment in 81% of the patients at 60 days. The median time to neutrophil recovery was 32 days and was associated with a cell dose >1.7 X 107/kg. Laughlin et al. reported a 90% engraftment rate at 42 days. The median time to neutrophil recovery was 27 days, while the median times to platelet and RBC recovery were 58 and 60 days, respectively. The neutrophil recovery rate was more rapid if the TNC count before freezing was >1.87 X 107/kg. Sanz et al. observed engraftment in all 20 patients who survived longer than 30 days. The median time to neutrophil recovery was 22 days. The Duke group recorded a median time to neutrophil recovery of 26 days. No association was noted with cell dose. The median time to platelet recovery was 84 days and was predicted by a CD34+ cell dose >1.37 X 105/kg.

The EuroCord Registry documented acute GVHD in 38% of the patients and chronic GVHD in 26%. Laughlin et al. noted acute grade II-IV GVHD in 60% of the patients and grade III-IV GVHD in 20%. Sanz et al. reported similar rates. Long et al. noted grade II-IV GVHD in 30% of the patients and grade III-IV GVHD in 16%. Eight of 25 evaluable patients developed chronic GVHD.

The EuroCord Registry experienced a TRM of 56% at 180 days. This was improved with a cell dose >2.0 X 107/kg, greater HLA identity, inactive disease, and transplantation after 1998. Laughlin et al. noted a 100-day TRM of 50%, similar to that reported by Sanz et al. and Long et al. The EuroCord Registry noted a "low" rate of relapse, as did Laughlin et al. (4 of 54 patients with a malignancy). Sanz et al. did not report any relapses. The Duke group observed relapse in 7 of 25 patients who engrafted and survived longer than 100 days.

The EFS reported by the EuroCord Registry was 21% at 1 year. Laughlin et al. noted a 26% EFS at 22 months. This correlated with a CD34+ dose >1.2 X 105/kg. Long et al. recorded a 3-year EFS of 15%, improved with age <32 years. The EuroCord Registry reported an OS of 27% at 1 year. This was improved in patients with CML in chronic phase or acute leukemia in CR1/CR2. The cell dose was also important since those patients who received <1 X 107/kg had a 75% probability of death as compared to 30% if the dose was >3 X 107/kg. Laughlin et al. noted an OS of 28% at 22 months. Sanz et al. observed an 8-month OS of 55% (five patients had CML). Long et al. reported a 3-year OS of 19%.

0 0

Post a comment