Özet:

In the treatment of many diseases seen in childhood, such as benign and malign hematological diseases, immune disabilities and metabolic disorders, hematopoetic root cell transplant (HKHN) is used for curative treatment purposes. HLA-compatible donor is an alternative treatment option for patients with no HLA-compatible donor. In recent years, in-vivo or in-vitro T cell deplessions, for the prevention of graft versus host disease (GVHH), have made significant increases in transplant successes. In haploidentic transfers, different in-vitro graph manipulation techniques have been used, such as CD 34 selection, CD 3 deplession, CD 3/CD 19 deplession and TCR-αβ (+) /CD19 deplession. In this article, at the Erciyes Pediatric CIT Center, the results of the patients followed with the cause of immunodeficiency made by in vitro CD19 depletion with only TcR αβ (+) depletion and haploidentic HKHN. Materials and Methods: In our center in December 2012-October 2019 children made of haploidentic HKHN with TCR αβ (+) depletion were included in the study. 19 children (11 boys, 8 girls) received a total of 23 haploidentic HKHNs. The diagnoses of patients were: 3 RAGII deficiency, 2 Griscelli syndrome, 2 Wiskott Aldrich syndrome, 2 IL7R deficiency, one patient was leukocyte adhesion deficiency, ADA enzyme deficiency, XLF deficiency. Two patients who have not yet completed genetic analyses with Omenn syndrome, 4 patients transmitted with severe combined deficiency diagnoses while a patient transmitted with relapse lymphoma caused by a mutation in the RAGRP1 gene. Seven patients were not given a preparation regime, while the other patients were used ATG, fludarabin, tiotepa, melfalan or busulfan-based protocols. Thirteen transplanted mothers, ten transplanted fathers were used as donors. The number of TCR αβ (+) in the graft content is above 2.5x104/kg and mycophenolate mofetil or cyclosporine is given for GVHH profylaxis. Patients with pre-transplant EBV infection were added to the rituximab preparation regime in -1 day for the purpose of post-transplant lymphoproliferative disease (PTLH) profylaxis. The remaining part, except the transplanted part of the root cells of TCR αβ (+), was frozen as DLI in 1x106 doses to be used in the treatment of viral infections that cannot be controlled by medical treatment. The average age of patients involved in the study was 1.96 ± 1.8 years. In the product content given to patients, the median value of the CD34 cells was 23.6 x 106 (±8.6x106) /kg. In the TcR αβ (+) depletion, 99.7 % (95.8-99.9) of purity was provided and the product was given to patients with a median value of 0.17 (0.013- 1.3) x 105TcR αβ (+) cell. In patients given the preparation regime, the median incubation days are +10,5 (±0,55) and +13 (±3,8) days for myeloids and platelet, respectively. Four patients developed grade I-II GVH (21%) and other complications were only treated with steroids without developing. One patient was transmitted 3 times with the reason of rejection, 2 patients 2 times with the reason of rejection. Seven patients who had no preparation regime had mixed chemistry, while other patients had full chemistry. The most common viral infection was CMV (56%). 3 patients who did not receive rituximab developed post-transplant lymphoproliferative disease associated with EBV (%13). The patient’s monitoring period was 1.6 years (±1.1 years) and the transplant-related mortality rate was 26%. Discussions: In the treatment of immune disorders, in the event of the failure to find a fully compatible HLA donor, alternative donor use brings problems such as acute and chronic GVHH, graft failure, late immune formation related infections. However, haploidentic transplants performed with TcR αβ (+) depletion take into account early infection and immune formation, with acceptable acute GVHH rates. In the success of antiviral activity, anti-tumor effect, early infection and immune formation of these transplantations, the remaining TcR γδ (+) cells in the product may be responsible. This situation is especially beneficial for patients who are transmitted with infection (1). The acute GVHH accumulative incidence of grade II-IV in the haploidentic transplants they performed with TcR αβ / CD19 (+) depletion with the cause of immunodeficiency was at 33% (2). In the study they included patients with immune failure, Bertaina and her colleagues found the incidence of acute GVHH of grade I-II at 13.1%. In the same study there were no acute GVHH and chronic GVHH of grade III-IV (3). In our study, the rate of acute GVHH of grade I-II was 21%, in no of our patients there were acute GVHH of grade III-IV and chronic GVHH that threatened life. In transplants with TcR αβ / CD19 (+) deplessions, the graft failure rate was by 16-30% (1, 2, 3), and this rate was found in our patients in accordance with literature as 17.4%. PTLH is derived from 80% to 85% B cells, 10% to 15% T cells. Rarely natural killer cells are also PTLH (4, 5). Childhood is associated with CD20 (+) and most of the Epstein-Barr virus (EBV) infection (6, 7) in PTLH caused by cell B. If in allogenic HKHN the recipient has HLA incompatibility, if the product has T cell deplessed or if anti-citric globulin is used in the preparation regime, the frequency of PTLH increases. Compared to solid organs, HKHN is fewer, but its mortality is higher (8, 9). In patients transplanted with TcR αβ / CD19 (+) the incidence of PTLH varies between 0% and 16% (3, 10). In our study, 3 of our cells (13%) developed PTLH and EBV was related. Despite Rituximab treatment, one of our patients was lost. The infection that was widely seen in our patients in accordance with the literature was CMV (1, 2, 3). In transplants with TcR αβ / CD19 (+) depletion, the transplant-related mortality rate was 9.3%, (3), and in our patients it was 26%. Three of our patients were monitored by a mechanical ventilator when they were transmitted. The reason for our high mortality rate may be that the clinics of the patients we are transmitted are heavy. The result: the haploidentic HKHN made by TCR-αβ deplession, without donor and without curetaif treatment options, in patients with high immunodeficiency, mortality-mobidity preserves its hopeful character with early abortion, acceptable GVHH rates.