Cord blood from an unrelated donor is an alternative source of hematopoietic stem cells for adults with acute leukemia who lack an HLA-matched bone marrow donor.
Although transplants from alternative donors are effective in some patients with leukemia, treatment failure is higher than after HLA-identical sibling transplants. Outcome depends on leukemia state, donor-recipient relationship, and degree of HLA matching. In early leukemia, alternative donor transplants have a more than twofold increased risk of treatment failure compared with HLA-identical sibling transplants. This difference is less in advanced leukemia.
Summary. Allogeneic stem cell transplantation from an HLA-identical sibling donor is a curative treatment option for a young patient with myelodysplastic syndrome, limited by age and lack of sibling donors. Alternative stem cell sources have been used more recently, such as unrelated donors, non-identical family members or autologous transplants. This analysis of 1378 transplants reported to the European Group for Blood and Marrow Transplantation (EBMT) addresses the outcome of the varying procedures according to the known risk factors. The estimated diseasefree survival (DFS) and estimated relapse risk at 3 years were both 36% for 885 patients transplanted with stem cells from matched siblings. In the multivariate analysis, age and stage of disease had independent prognostic significance for DFS, survival and treatment-related mortality. Patients transplanted at an early stage of disease had a significantly lower risk of relapse than patients transplanted at more advanced stages. The estimated DFS at 3 years was 25% for the 198 patients with voluntary unrelated donors, 28% for the 91 patients with alternative family donors and 33% for the 126 patients autografted in first complete remission. The nonrelapse mortality was 58% for patients with unrelated donors, 66% for patients with non-identical family donors and 25% for autografted patients. The relapse rate of 18% was relatively low for patients with non-identical family donors, 41% for patients with unrelated donors and 55% for patients treated with autologous stem cell transplantation. Both allogeneic and autologous stem cell transplantation have emerged as treatment options for patients with myelodysplastic syndromes. Transplantation with an HLA-identical sibling donor is the preferred treatment option. Patients without an HLA-identical sibling donor may be treated with either autologous stem cell transplantation or an alternative donor transplantation. Patients younger than 20 years may be treated with an unrelated donor transplantation. Patients older than 40 years, and probably also patients between 20 and 40 years, may benefit most from an autologous stem cell transplantation.
The immune reactivity of allogeneic lymphocytes plays a major role in the control of leukemia after bone marrow transplantation. In patients with recurrent leukemia after marrow transplantation, chimerism and tolerance provide ideal conditions for adoptive immunotherapy with donor lymphocytes. We studied the effect of donor lymphocyte transfusions on acute and chronic leukemia in relapse after bone marrow transplantation. One hundred thirty-five patients with chronic myeloid leukemia (CML) (N = 84), acute myeloid leukemia (AML) (N = 23), acute lymphoblastic leukemia (ALL) (N = 22), myelodysplastic syndrome (MDS) (N = 5), and polycythemia vera with osteomyelofibrosis (PCV) (N = 1) were treated with transfusions of donor lymphocytes. Patients were monitored for response of leukemia, including in CML, the use of the polymerase chain reaction for bcr/abl mRNA transcripts and for the occurrence of graft-versus-host disease (GVHD) and myelosuppression. Complete remissions were induced by donor lymphocyte transfusions in 54 patients with CML (73%) and in the patient with PCV; complete remissions were also induced in five patients (29%) with AML and a patient with MDS. In contrast, ALL did not respond to adoptive immunotherapy with donor lymphocyte transfusions. Remissions were durable in patients treated for CML in chronic phase (probability of remission: 87% at 3 years). Lymphocyte transfusions were also given to 18 patients with ALL, AML, MDS, and transformed phase CML who were in remission after chemotherapy. These remissions were not durable. Fifty- two patients (41%) developed GVHD of grade 2 or more, and 41 patients (34%) showed signs of myelosuppression. Seventeen patients died without leukemia, 14 patients with GVHD and/or myelosuppression. Donor lymphocyte transfusions exert strong effects against myeloid forms of leukemia and induce durable remissions in CML.
Summary:the diagnosis of MDS may improve prognosis due to a lower treatment-related mortality and a lower relapse risk. Allogeneic bone marrow transplantation (BMT) offers a potential cure for younger patients with myelodysplasticKeywords: allogeneic bone marrow transplantation; HLA-identical sibling; first-line treatment; myelodysplastic syndromes (MDS) or secondary acute myeloid leukemia (sAML). More than 600 patients from 50 European censyndrome; secondary acute myelogenous leukemia ters have now been reported to the European Group for Blood and Marrow Transplantation (EBMT). We retrospectively analyzed 131 patients reported to the Myelodysplastic syndromes (MDS) comprise a heteroChronic Leukemia Working Party of the EBMT who geneous group of hematopoietic stem cell disorders with underwent BMT from HLA-identical siblings without varying clinical, laboratory and morphological features. prior remission induction chemotherapy. At the time ofAccording to the proposals of the French-American-British BMT 46 patients had refractory anemia (RA) or RA Cooperative Group (FAB) five morphological entities can with ringed sideroblasts, 67 patients had more advanced be distinguished, including refractory anaemia (RA), refrac-MDS subtypes and 18 patients had progressed to sAML.tory anaemia with ring sideroblasts (RARS), refractory aneThe 5-year disease-free (DFS) and overall survival (OS) mia with excess of blasts (RAEB), refractory anemia with for the entire group of patients was 34 and 41%, excess of blasts in transformation (RAEB/T), and chronic respectively. Fifty patients died from transplant-related myelomonocytic leukemia (CMML). 1 Treatment of MDS complications, most commonly graft-versus-host disease and secondary acute myelogenous leukemia (sAML) has and/or infections. Relapse occurred in 28 patients generally been unsatisfactory. Because of their advanced between 1 and 33 months after BMT, resulting in an age most patients have been treated solely with supportive actuarial probability of relapse of 39% at 5 years. DFS measures. Limited success has been reported with low-dose and OS were dependent on pretransplant bone marrow cytosine arabinoside, 2 retinoic acid, 3 corticosteroids, 4 and blast counts. Patients with RA/RARS, RAEB, RAEB/T hematopoietic growth factors. 5 Young patients with and sAML had a 5-year DFS of 52, 34, 19 and 26%, advanced MDS may achieve prolonged, disease-free surrespectively. The 5-year OS for the respective patient vival when treated with intensive antileukemic chemogroups was 57, 42, 24 and 28%. In a multivariate analytherapy. 6 However, remission duration has generally been sis, younger age, shorter disease duration, and absence short. 7 Nowadays, allogeneic BMT is considered the treatof excess of blasts were associated with improved outment of choice for younger patients with histocompatible come. From these data we conclude that patients with siblings. The timing of transplant in the management of myelodysplasia who have appropriate marrow donors, the disease remains controversial....
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