A 46 year woman with severe long-lasting SLE received an autologous bone marrow transplantation utilising CD34+ haematopoietic progenitors following a 3log T-lymphocyte depletion. The immunosuppressive regimen (conditioning) consisted of 15mg/kg Thiotepa followed by 100 mg/kg of cyclophosphamide over 2d. Granulocytic recovery was aided by G-CSF. The post-transplant course was uneventful, and a good clinical and immunologic remission (ANA negativisation) was achieved. This is the first case of SLE having received an autologous progenitor cell transplant for the autoimmune disease by itself, unaccompanied by a haematologic condition requiring transplantation. The potential, advantages and limits of this procedure, which are currently being explored worldwide, are briefly discussed.
Summary:and discontinuation of infusions before life-threatening GVHD has developed. Donor lymphocyte infusions (DLI) were given between Keywords: chronic myeloid leukemia; graft-versusJune 1990 and March 1996 to 18 patients with chronic leukemia; donor lymphocyte infusions myeloid leukemia (CML) for the treatment of cytogenetic (n ؍ 6) or hematologic relapse (n ؍ 12) following an allogeneic bone marrow transplant (BMT). Patients were divided in two groups: patients in group A (n ؍ 8)Graft-versus-leukemia (GVL) is thought to play an received a large dose of donor lymphocytes important role in preventing relapse in patients undergoing (у1 ؋ 10 8 /kg), whereas patients in group B (n ؍ 10) allogeneic bone marrow transplants (BMT). 1,2 Although received escalating numbers of cells (2 ؋ 10 5 up to GVL was described in animals almost 20 years ago 3,4 little 2 ؋ 10 8 /kg). The median number of DLI in group A was is known about the magnitude of this effect on effector cells 2 (range 1-3); the median number of infusions in group and target antigens, at least in humans. 5 In the experimental B was 7 (range 3-9). Acute GVHD occurred in 12 animal, cells separately mediating GVL or graft-versus-host patients (grades I-III) and was a major cause of death disease (GVHD) have been described and can be identified in two. The risk of developing GVHD correlated with by surface markers. 3,6 In humans we have indirect evidence the number of cells infused: 37%, 14%, 5% and 0%for GVL: programs involving T cell depletion expose the for DLI with cells у1 ؋ 10 8 , 2 ؋ 10 7 /kg, 2 ؋ 10 6 /kg, and patients to a high risk of leukemic relapse, 2 and this has 2 ؋ 10 5 /kg, respectively (P ؍ 0.01). Median transaminnow been shown in very large numbers of patients.1,2 ase levels were found to be significantly increased in If mature donor T cells infused on the day of marrow patients with, as compared to patients without, acute transplant (an average of 6 × 10 7 /kg) have such an GVHD (GPT 412 vs 28 IU/l; P ؍ 0.03). Severe aplasia important role in preventing relapse, the use of large numoccurred in four and was a contributing cause of death bers of donor T cells which have undergone maturation in in two patients. Overall, four patients died as a consethe donor thymus, would possibly be helpful in treating quence of DLI and all received Ͼ1 ؋ 10 8 /kg cells: the relapse. Indeed this has been shown to be the case, actuarial risk was 38% in group A and 14% in group especially in patients with chronic myeloid leukemia B (P ؍ 0.1). There were 10 complete and three partial (CML), both for unfractionated 7-17 and CD8-depleted cytogenetic responses: the actuarial probability at 5 cells.18 years of being Ph negative was 69%: it was 46% for The exact mechanism by which the leukemic clone can group A and 85% for group B (P ؍ 0.1). The longest be reduced is unknown. GVHD has a deleterious effect on patient is now 6 years post-DLI, Ph negative, BCR-ABL hematopoietic cells 19,20 and it is quite possible that the sonegative. The actuarial 3 y...
Eighty-one patients with acute myeloid leukemia (ANLL, n = 44) or acute lymphoblastic leukemia (ALL, n = 37), aged 10 to 50 years were randomized to receive 1 mg/kg per day (n = 41, group A) or 5 mg/kg per day (n = 40, group B) of cyclosporine A (CyA) from day -1 to day +20 after bone marrow transplant (BMT). All patients received CyA orally thereafter. All patients were prepared with cyclophosphamide (CY) 120 mg/kg and fractionated total body irradiation (TBI), and received unfractionated BM from an HLA-identical sibling. The two groups were comparable for diagnosis, disease status, French-American-British (FAB) classification, WBC count at diagnosis, cytogenetic abnormalities, extramedullary disease before BMT, donor/recipient age and sex, number of cells infused, and number of days with intravenous (IV) CyA. Median follow-up for surviving patients in group A was 983 v 632 days in group B. Patients in group A had lower serum levels of CyA (295 v 686 ng/mL, P = .004), lower bilirubin levels (1.9 v 2.6 mg/dL, P = .07), lower creatinine levels (0.9 v 1.4 mg/dL, P = .06), and a lower proportion of CD8+ cells in the peripheral blood (PB) within day +21 (19% v 28%, P = .07). First day to 0.5 x 10(9)/L neutrophils was comparable in the two groups (13 v 14 days; P = .1). In a Cox model, the actuarial risk of acute graft-v-host disease (GVHD) grade II+, after stratification for age (less than 20 years greater than) was significantly lower in group B patients (0.54, P = .04). The actuarial risk of developing chronic GVHD was comparable (P = .9). Actuarial transplant-related mortality (TRM) at 240 days was 28% and 26% (P = .8) in group A and B: the major cause of death was GVHD in group A (P = .02) and multiorgan toxicity in group B (P = .07). The actuarial risk of relapse at 2 years overall was 20% in group A and 52% in group B (P = .001); it was 9% v 43%, respectively, for patients in first remission (P = .0001) and 48% v 63% for patients in non-first complete remission (CR) (P = .1). Actuarial 2- year disease-free survival (DFS) in group A and B was 58% v 32% (P = .02) for all patients, 71% v 35% (P = .01), in first remissions, and 30% v 23% (P = .2) in advanced disease.(ABSTRACT TRUNCATED AT 400 WORDS)
Thirty-eight second allogeneic bone marrow transplants (BMT)of 25-70%. The positive prognostic factors reported were not for acute leukemia relapsed after first BMT were performed in homogeneous and their identification was precluded in most Twenty-four patients were male and 14 female, median age
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