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UCBT, umbilical cord blood transplantation; ICBTR, International Cord Blood Transplant Registry; TNC, total nucleated cells; GVHD, graft-versus-host disease; TRM, transplant-related mortality; EFS, event-free survival; OS, overall survival; NA, not available.

aObserved at 60 days.

bObserved at 42 days cObserved in good risk malignancies.

dObserved in advanced malignancies.

eObserved at 1 year.

fObserved at 2 years.

gObserved in patients with leukemia.

hObserved at 100 days.

UCBT, umbilical cord blood transplantation; ICBTR, International Cord Blood Transplant Registry; TNC, total nucleated cells; GVHD, graft-versus-host disease; TRM, transplant-related mortality; EFS, event-free survival; OS, overall survival; NA, not available.

aObserved at 60 days.

bObserved at 42 days cObserved in good risk malignancies.

dObserved in advanced malignancies.

eObserved at 1 year.

fObserved at 2 years.

gObserved in patients with leukemia.

hObserved at 100 days.

Center (NYBC) (IBMTR)54 EuroCord Registry,49'50'55 and Minnesota56 (Table 97.4). The Minnesota/Duke group reported on 85 children with a median age of 5.6 years. The conditioning regimen varied, as did GVHD prophylaxis. Eleven percent were HLA identical, 35% were disparate at one locus, and the remaining grafts were mismatched at >2 loci. The NYBC registry (IBMTR) reported on 562 patients (460 of which were pediatric). Seven percent of the grafts were HLA identical, 39% were disparate at one locus, and 54% were mismatched at >2 loci. The EuroCord Registry reported on 291 patients with a median age of 5 years. The conditioning regimen varied according to disease. Seventeen percent were HLA identical with the remaining disparate at >1 loci. The Minnesota group reported on 102 patients (80 of which were pediatric). The median age was 7.4 years and the median weight was 25.9 kg. The conditioning regimen was mainly TBI/Cyclophosphamide(Cy). All patients received antithymocyte globulin (ATG). GVHD prophylaxis was largely cyclosporine and methylprednisolone. Fourteen percent were HLA identical, 43% were disparate at one locus, and the remaining grafts were mismatched at >2 loci.

The Minnesota/Duke group reported engraftment in 94% of the patients at a median of 24 days. Engraftment correlated with a cell dose >3 X 107/kg. The early use of granulocyte colony-stimulating factor and a conditioning regimen other than TBI also improved hematopoietic recovery. The IBMTR noted a median time to neutrophil recovery of 28 days. Ninety-one percent of the patients recovered their neutrophil counts by day 60. More rapid engraftment was associated with a greater number of UCB unit precryopreser-vation leukocytes and greater HLA identity. Platelet engraftment occurred in 58% of the patients by day 100 and 85% by day 180, with more rapid recovery in younger patients and those without infection or GVHD. The EuroCord Registry observed neutrophil recovery in 82% of the patients by day 60. The median time to recovery was 29 days. In a subgroup analysis, 79% of the patients with acute leukemia recovered neutrophil counts by 60 days. This correlated with a cell dose >3.7 X 107/kg. The Minnesota group recorded an engraftment rate of 88% by day 42. The median time to neutrophil recovery was 23 days and correlated with a CD34+ cell dose >1.7 X 105/kg. Platelet recovery occurred in 65% of the patients by six months, with a median time to recovery of 86 days. Platelet recovery was associated with younger age, higher CD34+ cell dose, and the lack of acute grade III-IV GVHD.

The Minnesota/Duke group noted acute grade II-IV GVHD in 40% of the patients and grade III-IV GVHD in 10%. No association between HLA disparity and acute GVHD was observed. The IBMTR, EuroCord Registry, and Minnesota group reported similar rates of acute grade II-IV GVHD. The IBMTR reported a trend (p = 0.06) toward significance of an association between acute GVHD and HLA disparity. The observed rates of chronic GVHD from these sources ranged from 9 to 25%.

The EuroCord Registry's subgroup analysis of patients with acute leukemia noted a 1-year TRM of 34% in those with good risk disease as compared to 65% in those with advanced disease. The Minnesota group reported 1- and 2-year TRM rates of 30 and 35%. By univariate analysis, a reduction in 1-year TRM to 20% was demonstrated if the CD34+ cell dose was >1.7 X 105/kg. Reduced TRM was also predicted by younger age, higher cell dose, and the absence of severe GVHD. By Cox regression analysis, CD34+ cell dose, development of severe GVHD, and age were the only factors predictive of TRM. The IBMTR noted relapse in 14% of the patients with leukemia. Higher rates were seen in patients with advanced disease and acute myeloid leukemia (AML). The EuroCord Registry reported relapse in 31% of the patients with good risk leukemia as compared to 77% in patients with poor risk disease. The Minnesota group observed a 37% cumulative incidence of relapse at 2 years. By Cox regression analysis, this was associated with age and malignancy risk group, but not cell dose, HLA match, or prior acute/chronic GVHD.

The IBMTR reported a 54% EFS at 100 days. By multivariate analysis, correlation was noted between EFS and cell dose, HLA identity, diagnosis (CML > Fanconi anemia > severe aplastic anemia), younger age, and the location of the transplantation center. The EuroCord Registry reported a 2-year EFS of 21% in patients with aplastic anemia, 36% with malignant diseases, and 51% with inborn errors of metabolism. Of the patients with acute leukemia, the 2-year EFS was 49% in good risk patients as compared to 8% in those with advanced disease. The Minnesota/Duke group reported a 40% OS at 2 years. The Minnesota group observed an OS of 58% at 1 year and 47% at 2 years. The OS increased to 70% at 1 year in patients receiving >1.7 X 105 CD34+ cells/kg. By univariate analysis, OS was associated with younger age, nonma-lignant disease, higher cell dose, and the absence of severe GVHD. By Cox regression analysis, HLA match, CD34+ cell dose, and absence of severe GVHD predicted OS.

The EuroCord Registry completed a comparative analysis of pediatric unrelated UCBTs and unmanipu-lated or T-cell depleted SCTs in patients with acute leukemia.57 The majority of UCBTs were HLA mismatched. The median cell dose for those undergoing

UCBT was 3.8 X 107/kg. Disease characteristics, conditioning regimens, and GVHD prophylaxis varied. A delay in neutrophil engraftment was noted in those undergoing UCBT (32 days as compared to 18 and 16 days in unmanipulated and T-cell depleted SCT, respectively). The rate of acute grade II-IV GVHD was reduced in UCBTs (35% as compared to 58 and 20%). A greater early TRM was observed in UCBTs (39%). Two-year EFS was improved in unmanipulated SCTs (43%), but was similar in T-cell depleted SCTs and UCBTs (37%, and 31%, respectively).

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