The clinical results in 107 patients receiving a peripheral blood stem cell (PBSC) graft mobilized by granulocyte colonystimulating factor (G-CSF) from HLA-A, -B, and -DR-compatible unrelated donors were compared to 107 matched controls receiving unrelated bone marrow (BM) transplants. Engraftment was achieved in 94% of the patients in both groups. The PBSC graft contained significantly more nucleated cells, CD34 ؉ , CD3 ؉ , and CD56 ؉ cells (P < .001), and resulted in a significantly shorter time-to-neutrophil (15 versus 19 days) and platelet engraftment (20 versus 27 days), compared to the BM control group (P < .001). Probabilities of acute graft-versus-host disease (GVHD) grades II to IV were 35% and 32% (not significant [NS]) and of chronic GVHD 61% and 76% (NS) in the PBSC and BM groups, respectively. There was no difference between the 2 groups in bacteremia, cytomegalovirus reactivation or disease, and fungal infection. The 3-year transplant-related mortality (TRM) rates were 42% in the PBSC group and 31% in the BM controls (P ؍ .7) and the survival rates were 46% and 51%, respectively. The probability of relapse was 25% and 31% in both groups (NS), resulting in diseasefree survival rates of 43% in the PBSC group and 46% in the BM controls (NS). In the multivariate analysis, early disease, acute GVHD grade 0 to I, and presence of chronic GVHD were independent factors associated with a better disease-free survival in this study. PBSC from HLAcompatible unrelated donors can be used safely as an alternative to BM for stem cell transplantation. (Blood. 2001;98: 1739-1745)
Summary:We analysed data for 213 patients with ALL and AML who received either peripheral blood stem cells (PBSC) (n ¼ 74) or bone marrow (BM) (n ¼ 139) from an HLAmatched unrelated donor (EBMT acute leukaemia registry; January 1994 to January 1999). The two groups of patients (by cell source) were comparable with respect to age, sex, disease status, year at transplant and graft T cell depletion. Engraftment was achieved in about 90% regardless of stem cell source or leukaemia type. Kinetics of neutrophil and platelet recovery, similar for both sources in ALL patients, were faster for PBSC in AML patients. The incidence of acute graft-versus-host disease was similar for both sources in AML patients, but higher for PBSC in ALL patients (74 vs 54%, P ¼ 0.05). The 1-year probability of chronic graft-versus-host disease was 40 and 45% (P ¼ 0.66) in ALL patients compared to 49 and 35% (P ¼ 0.13) in AML patients (PBSC vs BM). In AML patients, none of the following differed significantly with cell source: transplant-related mortality, relapse incidence, leukaemia-free survival and overall survival. In ALL patients, the transplant-related mortality for PBSC vs BM was 61 vs 47% (P ¼ 0.13), the relapse incidence was 47 vs 39% (P ¼ 0.17), the leukaemia-free survival was 21 vs 32% (P ¼ 0.04) and the overall survival was 24 vs 34% (P ¼ 0.04). These data suggest that the short-term outcome of allogeneic PBSC is not significantly different from that of BM in AML patients who underwent a transplant from a matched unrelated donor but, conversely, that survival with PBSC may be decreased in ALL patients. In conclusion, the source of transplant cells needs to be evaluated by disease, especially when dealing with unrelated donors.
Four cases of cytomegalovirus (CMV) retinitis (CMVR) after allogeneic blood stem cell transplant (SCT) were documented in Huddinge University Hospital between 1994 and 1999. Prior to 1994, only one case was documented. All five patients were transplanted due to malignant disease, two with sibling donors and three with matched unrelated donors. Despite adequate antiviral treatment against CMV retinitis, the result has been almost total unilateral blindness in three patients. However rare, the complication seems to have become more common since we began doing more matched unrelated donor transplants, which leads to a more pronounced T-cell defect and to a delayed immune reconstitution compared to sibling transplants. We conclude that CMV retinitis is a rare but important complication to allogeneic blood stem cell transplantation.
We studied the importance of human leucocyte antigen (HLA)-A, -B and -DRB1 high-resolution matching on the outcome of haematopoietic stem cell transplantation (HSCT) with matched unrelated donors (MUDs) vs single allele-mismatched unrelated donors. Fifty consecutive HSCT patients receiving an HLA-A, -B or -DR allele-level-mismatched unrelated graft (mmUD) were compared with a matched cohort of 100 patients with an HLA-A, -B and -DR-MUD. Rejection occurred in seven patients (14%) in the mmUD group and in four patients (4%) in the MUD group (P = 0.04), but this was mainly an effect of HLA-C mismatch. The cumulative incidence of acute graft vs host disease (GVHD) grades II-IV were 61%, 26% and 33% in the class I mmUD, class II mmUD and MUD groups, respectively. In multivariate analysis, HLA class I mismatch was associated with an increased risk of acute GVHD grades II-IV (2.09, P = 0.007) and transplant-related mortality (TRM) (1.99, P = 0.06). The 5-year overall survival was 81% in patients with a class II allele-mismatched donor compared with 52% (P = 0.025) and 50% (P = 0.017) in patients with a class I mismatch and a MUD. In multivariate analysis, HLA class II allele mismatch was associated with improved survival (3.38, P = 0.019). Relapse-free survival were 53%, 37% and 42% in patients with a class II mmUD, class I mmUD and a MUD, respectively (not significant). An HLA-C or -DQ mismatch had no significant impact on survival, TRM and relapse. In conclusion, compared with MUD, HLA class I allele mmUD had an increased risk of acute GVHD and TRM.
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