Mesenchymal Stem Cells as a Salvage Treatment for Severe Refractory Graft-vs-Host Disease in Children After Bone Marrow Transplantation.

Application of mesenchymal stem cells (MSC) enables a novel approach to the therapy of graft- vs-host disease (GVHD) after hematopoietic stem cell transplantation. Herein we present our preliminary experience with the use of allogeneic bone marrow‒derived MSC in 9 pediatric patients after hematopoietic transplantation complicated by severe acute or chronic GVHD (aGVHD, cGVHD) resistant to steroids and second-line immunosuppressants. The MSC therapy was applied concurrently with immunosuppressive treatment in 5 patients as a single infusion, in four patients as 2-6 infusions. The median dose of cells per infusion was 1.9 × 106/kg of recipient body weight (range, 0.1-6.5 × 106/kg). The median quantity of cells applied to patients was 1.2 × 106/kg (range, 0.2-30.9 × 106/kg). We did not observe any adverse symptoms of MSC therapy. Overall, partial, or complete remission (PR and CR, respectively) was obtained in 56% of patients after the first MSC infusions, and 44% after completing therapy. In those with skin involvement 50% achieved permanent CR, 38% in those with gastrointestinal manifestations, and 33% in those with liver GVHD. Three patients with overlap syndrome had amelioration, but none had permanent remission. Long-term improvement after consecutive MSC doses was observed in 3 patients. In the 4- to 8-year follow-up, 3 patients are alive and 2 have attained permanent remission. Six patients died during follow-up: 4 with aGVHD and 2 with infectous complications. Co-treatment of streoid-resistant GVHD with MSC and conventional immunosuppression can improve the outcome, although therapy regimens remain to be established.

Adoptive therapy with donor lymphocyte infusion after allogenic hematopoietic SCT in pediatric patients.

The aim of this study was to analyse the experience of Polish Pediatric Group for Hematopoietic Stem Cell Transplantation in respect to donor lymphocyte infusion procedure. The study included 51 pediatric patients with malignant (45) and non-malignant (6) diseases treated with DLI in the period 1993-2012. The indications for DLI were as follows: (1) increasing recipient chimerism after non-ablative hematopoietic SCT (18 patients); (2) immunomodulation after a reduced intensity conditioning regimen (2 patients); (3) increase in minimal residual disease detection (3 patients); and (4) relapse (28 patients). DLI was carried out at a median of 6 (0.5-79) months after SCT. DLI was administered as either a single-dose (in 19 cases) or in escalating-dose regimens (in 32 cases). The median total dose of CD3-positive T cells was 28.0 (0.1-730.0) × 10(6)/kg body weight. The time for assessment of DLI efficacy ranged from 0 to 70 (median 3) months. At evaluation, 18 patients experienced CR, 3 achieved PR, 19 showed relapse and 11 rejected the graft. DLI was found to be effective in 39% of cases. Complications of the procedure occurred in 18 patients; of these, 2 died. To sum up DLI shows efficacy in a significant percentage of children. Mortality related to the therapy adverse effects is low. However, this method requires standardization.

[Class II human leukocyte antigens in minimal change nephrotic syndrome and focal segmental glomerulosclerosis--preliminary study]. / Antygen zgodnosci tkankowej klasy II w submikroskopowym klebuszkowym zapaleniu nerek oraz w ogniskowym segmentalnym szkliwieniu klebuszków--doniesienie wstepne.

The aim of research was to compare the frequencies of HLA class-II antigens between children with minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS). The two morphological courses of glomerulosclerosis were considered: FSGS as a progressive state of minimal lesions (shown by renal rebiopsy results in a given patient), and primary (idiopathic) FSGS. The study group consisted of 38 children observed at least for four years. 15 patients were diagnosed as MCNS, 17 children had minimal lesions shown in the initial biopsy findings, but later progressed to glomerulosclerosis and 6 children had idiopathic FSGS. The control group consisted of 51 healthy unrelated individuals. HLA class II antigens were typed with the microlymphocytotoxicity test and with the method of sequence specific oligonucleotide DNA probes hybridisation (PCR-SSO). In minimal change nephrotic syndrome and glomerulosclerosis which followed the formerly found minimal lesions, the significant associations with HLA-DR3, DR7, and HLA-DQ2 were found. HLA-DQ1 was significantly rare in these groups. Differently idiopathic focal segmental glomerulosclerosis associates with the presence of HLA-DR4.