Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Jul 2007
Allogeneic transplantation for adult acute leukemia in first and second remission with a novel regimen incorporating daily intravenous busulfan, fludarabine, 400 CGY total-body irradiation, and thymoglobulin.
A myeloablative conditioning regimen incorporating daily intravenous busulfan, fludarabine, and 400 cGy total-body irradiation was given before allogeneic stem cell transplantation (SCT) to 64 adults with acute leukemia in first and second remission. Graft-versus-host disease (GVHD) prophylaxis included methotrexate, cyclosporine A, and rabbit antithymocyte globulin (Thymoglobulin). For 31 matched related (MRD) and 33 alternate donor (AD) SCT the incidence of acute GVHD grade II-IV was 11% +/- 6% versus 35% +/- 9% (P = .047), acute GVHD grade III-IV was 0% versus 10% +/- 6% (P = .09), and chronic GVHD was 40% +/- 9% versus 66% +/- 9% (P = NS), respectively. ⋯ For MRD SCT DFS is 77% +/- 9%, OS 87% +/- 6%, for AD SCT the respective figures are 71% +/- 8% and 74% +/- 8%. OS and DFS in patients without and with high-risk features are 100% versus 71% +/- 7% (P = .007) and 88% +/- 8% versus 68% +/- 7% (P = .04), respectively. This combination appears relatively well tolerated, gives equivalent final outcomes from MRD and AD, and may be a reasonable alternative to conventional myeloablative regimens.
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Biol. Blood Marrow Transplant. · Jun 2007
Reconstitution of natural killer cell receptor repertoires after unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation: analyses of CD94:NKG2A and killer immunoglobulin-like receptor expression and their associations with clinical outcome.
The effect of natural killer (NK) cell alloreactivity on the outcome of haploidentical hematopoietic stem cell transplantation (HSCT), with or without in vitro T cell depletion, remains controversial. Killer immunoglobulin-like receptors (KIRs) recognize human leukocyte antigen C and B epitopes on target cells, thereby regulating NK cell activity. To examine the recovery of CD94:NKG2A and KIR (CD158a, CD158b, and CD158e) expression by NK cells, we used flow cytometry to evaluate samples from 24 patients and their donors before and in the year following unmanipulated HLA-haploidentical/mismatched blood and marrow transplantation. ⋯ Univariate analysis showed that patients with high CD94 expression by day 60 (>90%) or who received donors with high CD94 expression (>80%) were associated with higher transplantation-related mortality (P = .006 or .067, respectively) and poorer leukemia-free survival (P = .012 or .094, respectively). Thus, the occurrence of aGVHD or the receipt of high doses of T cells in the allograft altered KIR reconstitution. Furthermore, high levels of CD94 expression in donors or in recipients by day 60 might be a good predictor for poor prognosis.
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Biol. Blood Marrow Transplant. · Jun 2007
Clinical TrialLong-term outcome of unrelated donor transplantation for AML using myeloablative conditioning incorporating pretransplant Alemtuzumab.
The outcome of 55 patients who underwent matched unrelated donor (MUD) transplantation for acute myelogenous leukemia (AML) following a conditioning regimen of cyclophosphamide and total-body irradiation (TBI) with the addition of Alemtuzumab 10 mg/kg/day on days -5 to -1 is described. All patients received graft-versus-host disease (GVHD) prophylaxis with cyclosporine as well as 3 doses of posttransplant methotrexate. Forty-one patients were transplanted in complete remission (CR) (20 in CR1, 20 in CR2, and 1 in CR3), and 14 were not in remission at the time of transplantation as they were refractory to chemotherapy either at induction or at relapse. ⋯ Seven of the 12 patients transplanted in CR1 with adverse risk cytogenetics remain alive and in remission, and the predicted 5-year overall survival (OS) for this group is 50%. These results support the use of Alemtuzumab for unrelated donor hematopoietic stem cell transplant (HSCT) for poor risk AML in CR1 and for relapsed AML in CR2. The addition of Alemtuzumab is highly effective in preventing both rejection and severe acute and extensive chronic GVHD without an increased relapse risk.
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Biol. Blood Marrow Transplant. · Jun 2007
Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy.
Adrenoleukodystrophy (ALD) is an X-linked disorder caused by a defect in the metabolism of long chain fatty acids leading to demyelination, neurodegeneration, and death. The disease typically presents in young boys and adolescent boys. Allogeneic bone marrow transplantation has been used to halt progression of the disease. ⋯ Transplantation of boys with X-linked ALD using partial HLA-matched umbilical cord blood yields similar results to those previously reported after bone marrow transplantation. Superior outcomes were seen in neurologically asymptomatic boys less than 3.5 years of age at the time of transplantation. Baseline Loes scores were a strong predictor of cognitive and motor outcome.
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Biol. Blood Marrow Transplant. · May 2007
Comparative StudyEquivalent survival for sibling and unrelated donor allogeneic stem cell transplantation for acute myelogenous leukemia.
Recent studies have shown comparable survival outcomes for unrelated donor (URD) stem cell transplantation in chronic myelogenous leukemia compared to sibling donors. We compared outcomes for 105 patients aged 16 to 59 years undergoing URD transplants for acute myelogenous leukemia (AML) who were reported to the Australasian Bone Marrow Transplant Recipient Registry between 1992 and 2002, and a strictly selected matching set of 105 HLA-matched sibling donor (MSD) transplants. There was no significant difference between URD and MSD controls in the distributions of time from diagnosis to transplant, donor-recipient sex match, prior therapies, donor age, or performance status. ⋯ Relapse occurred in 28% of good risk URD subjects and 16% of siblings (P = .3), and in poor risk subjects 39% and 29%, respectively (P = .2). Based on this data, URD allografts should be considered in AML patients without a matched sibling donor. This study provides a rationale for a larger prospective study of risk factors in allogeneic transplantation for AML and a guide on the subset of patients who may most benefit from an unrelated donor allograft in AML.