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Graft-versus-host disease (GVHD) is a major obstacle in allogeneic hematopoietic stem cell transplantation (HSCT). Mature donor T-cells present in the graft play a pivotal role in the development of acute GVHD. On the other hand, mature donor T-cells in the graft are also crucial for the elimination of residual tumor cells still present in the patient after HSCT. Whether donor T cells act non-specifically against the patient, including an overlapping GVHD/GVL reactivity, or some donor T cells have GVHD reactivity while other donor T cells have GVL reactivity is still unclear. Some in-vitro data are suggestive that selective T cell depletion techniques are possible by which GVHD-reactive T cells can be eliminated while GVL-reactive T cells are preserved. Here we update some approaches of selective T cell depletion that have been developed in our laboratory.

Contains fulltext : 79862schattenberg.pdf (Publisher’s version ) (Closed access) Matched unrelated donor stem cell transplantation (MUD-SCT) provides the only curative option for patients with follicular lymphoma (FL) who fail conventional therapies and do not have a sibling donor. The purpose of this study was to analyse the outcome of patients with FL treated with MUD-SCT included in the European Group for Blood and Marrow Transplantation registry. 131 patients treated with reduced-intensity conditioning (RIC, n = 87) or conventional myeloablative (CONV, n = 44) MUD-SCT between 2000 and 2005 were included. Median time from diagnosis to MUD-SCT was 47 months and the median number of previous therapeutic regimens was 4 (previous autograft: 47%). RIC recipients were significantly older, with a longer interval from diagnosis to MUD-SCT and had failed a previous autograft more frequently than CONV recipients. Non-relapse mortality (NRM) was 24% and 30% at 100-d and 1-year, respectively. After a median follow-up of 36 months, 17% of the patients developed disease progression, the 3-year progression-free survival (PFS) being 47%. Three-year overall survival (OS) for the whole series was 51%. On multivariate analysis, RIC regimens were associated with at lower NRM and a significantly longer PFS and OS. This retrospective study demonstrated that MUD-SCT results, even in heavily pre-treated populations, in a meaningful PFS and OS.

The adverse impact of positive-recipient Cytomegalovirus (CMV) serostatus on the outcome of matched-unrelated donor (MUD) grafts has been stressed. We evaluated whether CMV-seropositive MUD recipients transplanted after 1999 still showed inferior outcome compared with CMV-seronegative recipients. Two important changes in transplantation procedure were introduced in 1999: (1) reduction of antithymocyte globulin dose, (2) introduction of sequence-based typing of HLA-DRB1. Thirty-six patients received partial T cell-depleted grafts before 1999, and 44 after 1999. CMV-seropositive patients transplanted before 1999 showed a highly significant inferior outcome compared with seronegative recipients. In contrast, no difference in outcome was observed between the two groups of patients transplanted after 1999.

In this study, we analysed the chimaeric status of peripheral blood leucocytes (PBLs) in recipients of allogeneic bone marrow transplantation (BMT) with the use of short tandem repeat (STR) microsatellite markers for monitoring the efficacy of BMT and donor leucocyte infusions (DLIs). A set of four STR markers was used with a highly discrimative capacity between individuals. STRs were detected by polymerase chain reaction (PCR) and were analysed by gene scanning (STR-GS). Between June 1990 and December 1998, 52 patients treated with BMT for chronic myeloid leukaemia (CML) were analysed. Seventeen patients relapsed after BMT and two patients never achieved remission after BMT. Fourteen of the 17 patients achieved a complete donor chimaerism after BMT, as detected by the presence of only donor STR-GS fragments, and in three cases a weak recipient STR-GS signal remained persistently detectable after BMT. A reappearance or increase of recipient STR-GS signals was indicative of relapse, which was mostly detected by STR-GS several months before relapse was diagnosed clinically. Nineteen patients were treated with DLI for reappearance of CML after BMT which resulted in complete remission in 17 patients, concordant with the disappearance of recipient STR-GS signals. More importantly, DLI treatment could be guided based upon the STR-GS data, which prevented unnecessary extra DLI courses that could cause toxicity. This study indicates that STR-GS is an effective and reliable method for monitoring BMT recipients.

Purpose: The hematopoietic growth factors (HGFs) introduced into induction chemotherapy (CT) of acute myeloid leukemia (AML) might be of benefit to treatment outcome by at least two mechanisms. HGFs given on days simultaneously with CT might sensitize the leukemic cells and enhance their susceptibility to CT. HGFs applied after CT might hasten hematopoietic recovery and reduce morbidity or mortality. Materials and Methods: We set out to evaluate the use of granulocyte-macrophage colony-stimulating factor (GM-CSF; 5 mu g/kg) in a prospective randomized study of factorial design (yes or no GM CSF during CT, and yes or no GM-CSF after CT) in patients aged 15 to 60 years (mean, 42) with newly diagnosed AML. GM-CSF was applied as follows: during CT only (+/-, n = 64 assessable patients), GM-CSF during and following CT (+/+, n = 66), no GM-CSF (-/-, n = 63), or GM-CSF after CT only (-/+, n = 60). Results: The complete response (CR) rate wets 77%. At a median follow-up time of 42 months, probabilities of overall survival (OS) and disease-free survival (DFS) at 3 years were 38% and 37% in all patients. CR rates, OS, and DFS did not differ between the treatment groups (intention-to-treat analysis). Neutrophil recovery (1.0 x 10(9)/L) and monocyte recovery were significantly faster in patients who received GM-CSF after CT (26 days v 30 days; neutrophils, P

In a retrospective study we calculated the costs of introducing autologous BMT in the treatment of patients with malignant lymphoma and acute leukaemia in The Netherlands. The cost analysis has been performed in five university hospitals and one cancer centre, in a series of patients with intermediate and high grade non-Hodgkin's lymphoma (NHL) and patients with AML, Conventional treatment consisted of chemotherapy. The average costs of the conventional NHL treatment varied from US$3120 to US$12 900. The costs of autologous BMT amounted to US$40 220, In the AML group the costs of conventional treatment amounted to about US$11 040, as only 50% of the patients were treated further. The costs of autologous BMT including a follow-up period of 2 years, amounted to US$55 440. In The Netherlands the total number of autologous BMTs per year in these patient groups was estimated at 230; 180 in the NHL group and 50 in the AML group. The costs of introducing autologous BMT to the NHL group will vary between 4.93 and 6.68 million dollars and for the AML group these costs were estimated at 2.22 million dollars. As a result, the total extra costs of introducing autologous BMTs are expected to be between 7.15 and 8.9 million dollars.

The objective of this phase-I study was to establish the maximum tolerable dose of recombinant human interleukin-3 (rhIL-3) after salvage chemotherapy in patients with malignant lymphoma. Twenty-one patients with relapsed Hodgkin's disease or intermediate/high-grade non-Hodgkin's lymphoma received rhIL-3 after the second cycle of DHAP chemotherapy (cisplatin, cytosine-arabinoside, dexamethasone). Cycles 1 and 3 were given without rhIL-3. The rhIL-3 was administered as a continuous intravenous infusion for 10 days starting 48 h after chemotherapy in cycle 2. Five different dose levels of rhIL-3 (0.25, 1.0, 2.5, 5.0, and 10.0 mug/kg/day) were sequentially tested. At the three lowest dose levels one double-blinded placebo was included for every four patients per dose level. Low-grade fever occurred in 15/21 patients, unrelated to the dose of rhIL-3. Nausea and vomiting (grade 1-2) occurred in seven patients. Headache was dose related, with 3/4 patients at a dose of 10 mug/kg/day experiencing troublesome grade-2 headache precluding further dose escalation. Facial flushing developed in 3/8 patients at the highest dose levels of rhIL-3. There was a significant increase in eosinophil count during rhIL-3 (p = 0.03 cycle 2 vs cycle 1 and p = 0.002 cycle 2 vs cycle 3) without accompanying clinical signs or symptoms. No increase in basophil count was observed. There were no increased plasma levels of interleukin-6 or macrophage colony-stimulating factor (M-CSF) during rhIL-3. We conclude that rhIL-3 can be safely administered as a continuous intravenous infusion for 10 days after DHAP chemotherapy. Dose-limiting side effects, especially headache, occur at a dose of 10 mug/kg/day.