Extracorporeal photopheresis (ECP) was given to 23 patients with steroid-refractory acute GVHD (aGVHD, grade II (n ¼ 10), III (n ¼ 7) or IV (n ¼ 6)). The median duration of ECP was 7 months (1-33) and the median number of ECP cycles in each patient was 10. Twelve patients (52%) had complete responses. Eleven patients (48%) survived and 12 died, 10 of GVHD with or without infections and two of leukaemia relapse. The average grade of GVHD was reduced from 2.8 (on the first day of ECP) to 1.4 (on day þ 90 from ECP) (P ¼ 0.08), and the average dose of i.v. methylprednisolone from 2.17 to 0.2 mg/kg/d (P ¼ 0.004). Complete responses were obtained in 70, 42 and 0% of patients, respectively, with grades II, III and IV aGVHD; complete responses in the skin, liver and gut were 66, 27 and 40%. Patients treated within 35 days from onset of aGVHD had higher responses (83 vs 47%; P ¼ 0.1). A trend for improved survival was seen in grade III-IV aGVHD treated with ECP as compared to matched controls (38 vs 16%; P 0.08). ECP is a treatment option for patients with steroid refractory aGVHD and should be considered early in the course of the disease.
In conclusion, SIdEM and GITMO have made a scientific effort to provide a useful tool to physicians involved in the field, thus supporting daily clinical practice, as well as strategic decisions in the setting of ECP treatment of GVHD.
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...
Summary. This trial was designed to test the use of CD34þ selected haemopoietic stem cells (HSC) in HLA-mismatched donor-recipient pairs, following intensive conditioning with thiotepa, antilymphocyte globulin (ALG), cyclophosphamide and single-dose total-body irradiation (sTBI). 10 patients aged 16-50 with advanced malignancies and a two-or three-antigen mismatched family donor entered this study. Donor marrow and G-CSF primed peripheral blood cells were processed separately on CD34 columns (Ceprate). The median number of infused CD34 þ cells were 5 . 66 × 10 6 / kg, with 0 . 55 × 10 6 /kg CD3 þ cells. Nine patients received cyclosporin for graft-versus-host disease (GvHD) prophylaxis. Median neutrophil counts on day 21 were 2 × 10 9 /l with a median platelet count of 60 × 10 9 /l, but CD4 counts remained extremely depressed throughout the study. Acute This study suggests that large numbers of positively selected mismatched HSC can rapidly engraft after intensive conditioning regimen: however, profound post-transplant immunodeficiency leads to a high risk of lethal infectious complications.
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