[Transplantation of highly purified CD34+ hematologic peripheral stem cells from haploidentical related donors in the treatment of children with non-malignant diseases]. / Transplantace vysoce cistených CD34+ kmenových bunek periferní krve od haploidentických rodinných dárcu v lécbe detí s nemaligními onemocneními.

BACKGROUND: Children suffering from rare inherited disorders can be cured using stem cell transplantation (SCT). For patients where HLA-identical donor could not be found, there is an excellent chance of identifying a family member who shares an identical haplotype with the patient but whose second haplotype is different. This situation is called an HLA-full haplotype mismatch. Risks of haploidentical transplantation are graft rejection and severe graft-versus-host disease (GVHD). Histocompatibility barriers can be overcome by infusing high doses of T-cell depleted peripheral CD34+ stem cells. METHODS AND RESULTS: Between December 1995 and March 2000, 5 children with rare inherited disorders were transplanted using highly purified CD34+ stem cells from haploidentical parents at the 2nd Department of Pediatrics, University Hospital Motol, Prague. Two children suffered from severe combined immunodeficiency (SCID), one child from malignant osteopetrosis, Wiskott-Aldrich syndrome and hemophagocytic lymphohistiocytosis, respectively. Positive selection of peripheral CD34+ stem cells from G-CSF stimulated donors was performed using the method of immunoabsorbtion (CellPro) (n = 2) or immunomagnetic separation (CliniMACS) (n = 3). Donor type engraftment was achieved in 4 children. In one of them early graft failure has developed successfully managed by second SCT from the same donor. One child with SCID had primary graft failure. Mild acute GVHD with good response to steroid therapy developed in 2 children. Three children are alive and 2 of them are cured. Two children died due to post-transplant complications--CMV pneumonia and encephalitis. CONCLUSIONS: Transplantation of highly purified CD34+ stem cells from haploidentical parents is a reasonable therapeutic option for children with some specific nonmalignant disorders lacking HLA identical donor. Risks of this type of SCT are the graft failure and severe infectious complications due to slow immunological reconstitution in comparison with SCT from HLA identical donors.

[Hematopoietic stem cell transplantation in autoimmune diseases in rheumatology practice]. / Transplantace krvetvorných bunek autoimunitních chorob v revmatologii.

Autoimmune diseases (AID) result from the impairment of the effector and/or recognition phase of the immune response. The autoimmune process plays a crucial role in the pathogenesis of the systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), and their treatment is therefore largely based on immunosuppression. However, some patients do not respond to its standard doses. The disease becomes intractable with the survival rate comparable to that of some haematological malignancies, or patients become soon handicapped with very poor quality of life, depending on continual administration of high doses of steroids. The new hope for those patients becomes therapy with high dose myelo- and immuno-ablative chemotherapy with autologous hematopoietic progenitor cell support (PBPC). Tens of patients with intractable forms of AID were transplanted in the pilot clinical studies with promising results. The most frequent indications included: SLE, SSc, and RA. Final conclusion of the therapeutic effects will be drawn from the analysis of larger trails.

[Immunoablation and hematopoietic stem cell transplantation in the treatment of multiple sclerosis]. / Imunoablace s transplantací krvetvorných bunek v lécbe roztrousené sklerózy.

High dose chemotherapy with autologous hematopoietic cell support is a standard approach in the management of selected hematological malignancies. Autoimmune diseases which do not respond to conventional immunosuppression might benefit from high dose immunoablative chemotherapy. The transplantation of hematopoietic cells is necessary after the high dose chemotherapy to restore bone marrow function. The immune system undergoes a new ontogeny which can result in the development of tolerance. Multiple sclerosis (MS) has so far been the most common indication for this kind of treatment. Experience with preclinical studies on murine experimental allergic encephalomyelitis (EAE), as well as the course of MS following bone marrow transplantation for coincidental malignancy in humans formed the basis of the first clinical studies involving high dose chemotherapy and autologous hematopoietic support. Results of the first studies confirm that the method is feasible in patients with MS, and that the effect is very promising. Nonetheless, more consistent results vis a vis the therapeutic effect should emanate from upcoming studies.

High-dose immunosuppressive therapy with PBPC support in the treatment of poor risk multiple sclerosis.

High-dose immunoablative chemotherapy with autologous haematopoietic cell support might be beneficial in the treatment of intractable forms of MS. We mobilised PBPC in 11 patients with secondary progressive MS and finally eight patients were grafted after high-dose BEAM chemotherapy with either in vitro or in vivo T cell depletion. Median EDSS and SNRS scores at the time of inclusion were 6.5 (6.5-7.5) and 56 (44-65), respectively. PBPC mobilisation was safe with no serious adverse effects, and without significant aggravation of disability. One patient improved significantly (by 1.0 point on EDSS) after the mobilisation. Two mobilisation failures were observed. No life-threatening events occurred during the transplantation. All grafted patients, except one, at least stabilised their disability status. One patient improved significantly (by 1.5 points on EDSS), two patients improved slightly (by 0.5 points on EDSS), one patient worsened by 1.0 point on the EDSS in 10 months. Improvement occurred with a delay of 2-4 months. Median EDSS and SNRS of grafted patients at the last follow up were 6.5 (5.5-8.5) and 64 (39-73), respectively with median follow-up of 8.5 months. Further follow-up is needed to determine the disease course after complete immune reconstitution. Bone Marrow Transplantation (2000) 25, 525-531.

[Purging of hemopoietic progenitor cells in autologous transplantation]. / Cistení hemopoetických progenitorových bunek pro autologní transplantace.

The authors describe the results of purification of bone marrow and peripheral progenitor cells (PBPC) for clinical transplantations. Vepeside was used to purify in 1990-1995 a total of 41 bone marrows of adults and children. Of these 23 were transplanted. Maphosphamide was used bone marrow purging in two patients; transplantation was performed in one case. By a combination of Vepeside with methylprednisolone haematopoietic cells of 24 patients were purged, transplantations were performed in 10. Three-day cultivation of haematopoietic cells in the presence of Desferal was used for purging cells of 22 patients with neuroblastoma; transplantations were performed in 10 patients. The authors give the values of nucleated cells, haematopoietic colonies of CFU-GM and CD34 positive cells obtained after purification calculated per kg body weight of the patient and the percentage yields.