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Allogeneic haematopoietic stem cell transplantation is an effective treatment option for chemotherapy-refractory or relapsed haematological malignancies such as leukaemias and lymphomas. After conditioning with chemotherapy with or without total body irradiation, donor cells are infused to reconstitute haematopoiesis. Donor-derived immune cells induce immune reactions to control or eradicate the underlying disease, thereby going beyond the effect of chemotherapy. This graft-versus-tumour effect (GvT) is often accompanied by detrimental graft-versus-host reactions (graft-versus-host disease, GvHD), which substantially influence the mortality and morbidity after transplantation. The balance between GvHD and GvT, implementing various parameters such as donor selection, stem cell source, conditioning, immune reconstitution and immunosuppressive regimens, represents the challenge in the field of allogeneic stem cell transplantation., (Georg Thieme Verlag KG Stuttgart · New York.)

Unlabelled: PATIENT HISTORY AND CLINICAL FINDINGS: A 49-year old patient with chronic kidney disease was referred for evaluation of living donor kidney transplantation from his spouse in a blood group incompatible setting., Clinical Investigations: Patient blood group was 0, donor blood group was A, subtype A. recipient isoagglutinin titer against donor erythrocytes was 1:64. Crossmatch (CDC) and antibody screening were negative. There were no contraindications for living donor kidney transplantation from donor and recipient side., Diagnosis, Treatment and Clinical Course: For AB0-incompatible living donor kidney transplantation, recipient preconditioning using rituximab and selective immunoadsorption was initiated to obtain reduction of isoagglutinin titers < or = 1:4. Transplantation was performed without complications. With only moderate increases in titer, no immunoadsorption was required postoperatively. Monitoring of isoagglutinin titers was discontinued after day 14, since increasing titers do not result in organ loss any more (accomodation). 18 months after transplantation, renal function is excellent under corticosteroid-free maintenance immunosuppression., Conclusion: Recipient preconditioning nowadays allows successful blood group incompatible kidney transplantation in most cases, increasing the number of patients eligible for living donor kidney transplantation by up to 20%. No intensified maintenance immunosuppression is required and renal allograft function after AB0-incompatible transplantation is comparable to blood group compatible living donor kidney transplantation.

Background and Objective: Allogeneic transplantation can not be offered to many patients due to potential side-effects of conventional conditioning. Dose-reduced conditioning approaches improve tolerability, however, treatment efficacy may be reduced as well. We have, therefore, developed a dose intense but toxicity reduced conditioning regimen based on treosulfan and fludarabine and report first results., Patients and Methods: 65 patients with a median age of 50 years were transplanted from related (n = 21) or unrelated donors (n = 44) after conditioning with treosulfan (3 x 10, 3 x 12 or 3 x 14 g/m(2) i. v.) and fludarabine (5 x 30 mg/m(2) i. v.). 21 patients were in complete remission (CR) and 44 patients had not reached a CR at the time of transplantation. 59 of 65 patients were considered unfit for a conventional conditioning regimen., Results: The actuarial overall survival after 3 years is 59.2 %, the event-free survival 40.1 %. Patients with a related donor or transplantation in CR had a better overall (85.4 resp. 74.2 %) and event-free survival (52.2 % resp. 61.9 %). The cumulative incidence of relapse at 3 years was 26.2 %. Non-relapse mortality at day 100 is 17.4 % (cumulative incidence). In stepwise Cox regression analyses for overall survival, event-free survival and non-relapse mortality the covariables transplantation in CR vs. not in CR and the donor status were shown to be influential., Conclusions: These results with a conditioning therapy of treosulfan and fludarabine indicate that patients despite higher age, concomitant disease or after intensive pretreatment can be successfully transplanted without increased treatment-related mortality.

Allogeneic stem cell transplantation is an established treatment modality for a variety of hematologic malignancies. However this allogeneic stem cell transplantation carries the risk of severe complications which are partly due to the intensity of the conditioning regimen. Therefore, allogeneic stem cell transplantation has been so far only performed in younger patients with good performance status. Dose-reduced or non-myeloablative conditioning regimen has been proposed as an alternative that would allow exploiting the graft versus leukemia effect of allogeneic stem cell transplantation without severe toxicity. Clinical studies have shown that dose-reduced conditioning followed by allogeneic stem cell transplantation allows stable engraftment with lower toxicities which can be associated with long-term disease control. Therefore, dose-reduced conditioning followed by allogeneic stem cell transplantation can be offered to older and more debilitated patients who were no candidates for standard allogeneic stem cell transplantation.

Background and Objective: In the treatment of leukemia by stem cell transplantation, the immunological effects of allogeneic T-lymphocytes presumably play a greater part than high-dosage total-body irradiation (TBI) and chemotherapy. Using this immunological effect, attempts are currently being made to reduce the dosage of pre-treatment that is toxic to stem cell, such as TBI, thereby making transplantation available for a larger group of patients at high risk for transplantation. This study presents preliminary results of three current studies of this approach., Patients and Methods: Elderly patients with chronic myeloid leukemia (CML) have an increased transplantation risk. They were conditioned with TBI that was reduced stepwise (n = 27). Patients with advanced and refractory myeloid leukemia were treated with chemotherapy and dose-reduced TBI (FLAMSA protocol; n = 54). In patients with multiple myeloma, autologous transplantation with high-dose chemotherapy preceded allogeneic transplantation possible after dose-reduced conditioning (Tandem protocol; n = 6)., Results: All three protocols of TBI gave results that were not worse than those of previous studies. Relapse ocurred not more frequently in patients with CML. In patients with high-risk AML the FLAMSA protocol gave better results. Autologous-allogeneic tandem transplantation was well tolerated and led to a good response in all patients., Conclusion: Allogeneic transplantation after dose-reduced conditioning opens up new possibilities with respect to widening indications for transplantation and improving results in hematological diseases with previously unsatisfactory treatment.