The results of 1904 allogeneic HLA identical sibling donor bone marrow transplants performed in 52 European centers between 1979 and 1986 and reported to the EBMT leukemia registry were analysed by geographical location of the transplant. Patients were grouped into six regions: United Kingdom, Nordic Group, Benelux, France, Central Europe and Southern Europe. There were significant differences between these regions with respect to patient population and outcome. The relative proportion of the three major disease categories, stage and subtype of the diseases, graft-versus-host disease prevention methods, donor recipient sex combinations, age of the patient, year of the transplant and the time intervals from diagnosis to transplant, from diagnosis to first complete remission for acute leukemia and the time from first complete remission to the transplant varied from region to region. The analysis of outcome parameters showed a significant difference in relapse incidence from region to region. This influence of region was confirmed in a multivariate analysis and was independent of the other factors known to affect outcome. Leukemia-free survival and transplant-related mortality were not different. The reasons for these differences could not be explained by the data in the registry. We conclude that regional factors must be considered when bone marrow transplant data are compared and we postulate that pretransplant factors probably affect outcome more than was previously realized.
Twenty-four patients with multiple myeloma received an allogeneic bone-marrow graft from HLA-compatible sibling donors (n = 23), or a twin donor (n = 1). Eighteen patients are alive, 1-36 months post bone-marrow transplantation (median 14 months). Ten of these patients had no signs of multiple myeloma as judged by immunoglobulins in serum, light chains in urine, or the percentage of plasma-cells in bone-marrow aspirate. Bone lesions on X-ray were mainly unchanged. Six patients died from transplant-related complications 3 weeks to 5 months post transplantation. One of these patients had severe acute graft-versus-host disease (aGVHD). In other patients aGVHD was a minor problem. Allogeneic bone-marrow transplantation appears to be a promising method for treatment of a selected group of patients with multiple myeloma.
50 patients with a median age of 41 years (range 29-54) underwent allogenic bone marrow transplantation for multiple myeloma. 35 patients were on second-line treatment, and 15 on first-line treatment. 24 patients were considered refractory to previous treatment. 45 patients received marrow from HLA-matched sibling donors (3 of these from twin donors), and 5 from unrelated or related non-sibling donors. 21 patients entered complete remission, while 15 had persistent disease following repopulation of the marrow. 14 patients were not evaluable for remission status because of early transplantation-related death. The overall median survival from bone marrow transplantation was 27 months, with a projected long-term survival of 34%. Patients who were 40 yr of age or older had a survival that was not different from that of patients between 29 and 40 yr of age. The median disease-free survival of patients who entered complete remissions was 41 months. These patients tended to have a longer survival than patients with persistent disease following repopulation of the marrow. Allogeneic bone marrow transplantation appears to be a promising method for treatment of certain patients with multiple myeloma.
At Huddinge Hospital 275 patients underwent allogeneic bone marrow transplantation. Among children in first remission of acute leukemia or chronic phase CML (early leukemia), with HLA-identical marrow the 8-year leukemia-free survival was 77%. This was better than 38% in children undergoing transplantation in second to fourth remission (p less than 0.0009). In adults with early leukemia, the 8-year leukemia-free survival was 47% compared to 21% for intermediate-risk adults (p = 0.007). Among 25 patients with severe aplastic anemia receiving marrow from HLA-identical siblings, the actuarial 10-year survival was 78%. In 14 patients with various metabolic disorders, of whom half received marrow from HLA-mismatched donors, the actuarial 7-year survival was 71%. Forty-three patients were given marrow from HLA-mismatched donors and had an increased incidence of acute graft-versus-host disease (GvHD) and death due to GvHD compared to recipients of HLA-identical bone marrow. The major causes of death among our patients were relapse of leukemia, death due to GvHD, cytomegalovirus (CMV) pneumonitis, bacterial infection and invasive fungal infections. By preventing GvHD with T-cell depletion or methotrexate (MTX) combined with cyclosporine (CsA) acute GvHD decreased, but the incidence of relapse increased compared to patients treated with MTX or CsA alone. This resulted in improved survival in patients older than 30 years, but a nonsignificant decrease in leukemia-free survival in younger patients. There was an association between herpes virus immunity in the recipient and GvHD. CMV pneumonitis increased following GvHD and decreased in patients treated with MTX combined with CsA. Invasive fungal infections may be treated or prevented using amphotericin B encapsulated in liposomes with few side effects.
86 previously untreated patients with multiple myeloma stage III entered a randomized trial comparing combination chemotherapy (VMCP/VBAP) (n = 42) with intermittent oral melphalan and prednisone (MP) treatment (n = 44). The treatment gropus were well comparable with regard to major prognostic factors. There was no statistically significant difference in the response rates, 52% (VMCP/VBAP) vs 61% (MP); in the response duration times, median 19 months vs 22 months, or in the survival times, median 24 months vs 28 months. However, survival of patients older than 65 years was significantly shorter in the VMCP/VBAP group (median 15 months) compared to the MP group (median 23 months) (p = 0.03). No significant difference in non-hematological or hematological toxicity was noted. The study further supports the notion that MP therapy should be used as primary standard treatment for patients with multiple myeloma.
Eight patients with aplastic anemia were transplanted with marrow from HLA-identical donors. Two patient rejected their grafts and died while 5 patients (71%) show no ill effects 3 months, 10 months, and more than 1, 2 and 4 years after the transplantation. Three of the patients who received unirradiated donor buffy coat after transplantation developed chronic graft-versus-host disease (GVHD) which, however, resolved following treatment with Prednisolone and Azathioprine. One patient with end-stage acute myeloid leukemia, who was transplanted with marrow from an identical twin, died 6 days after the transplantation of bleedings and sepsis. Eight patients with acute non-lymphoblastic leukemia (ANL) were transplanted, while in remission, with marrow from HLA-identical siblings. One patient died of interstitial pneumonia 3 months after transplantation, while another patient recovered from GVHD of the gut at 5 months after the transplantation. Seven out of 8 patients with ANL (88%) are home and well between 2 and 12 months after the transplantation.