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R Formánková

Publications and source records attributed to R Formánková.

9 recordsLinked to original sources
PubMed2006

Low mortality of children undergoing hematopoietic stem cell transplantation from 7 to 8/10 human leukocyte antigen allele-matched unrelated donors with the use of antithymocyte globulin.

Human leukocyte antigen (HLA)-matched sibling donor hematopoietic stem cell transplantation (HSCT) is available for only approximately 30% patients needing HSCT. Use of alternative donors is associated with a high incidence and severity of graft-versus-host disease (GVHD). Here we report our experience with GVHD prophylaxis using pre-transplant rabbit antithymocyte globulin (rATG), in addition to post transplant cyclosporin A and methotrexate. Seventy-five children received unmanipulated grafts from 7 to 10/10 HLA allele-matched unrelated donors. Median follow-up was 25 months (range, 6-65 months). Only 2/75 patients (2.5%) developed acute GVHD grades III-IV, and 17/75 (25%) developed extensive chronic GVHD. Overall survival was 79%. It was similar in patients receiving grafts from 7 or 8/10 to 9 or 10/10 allele-matched donors, and similar in patients receiving peripheral blood stem cells and marrow. Six (11%) patients died owing to relapse, and 10 (13%) due to transplant-related complications. The addition of rATG appears to result in a low incidence of severe GVHD and overall mortality.

Adolescent↗
PubMed2006

[Familial haemophagocytic lymphohistiocytosis caused by perforin deficit can be successfully treated by haematopoietic stem cell transplantation--the first diagnosed case in the Czech Republic].

Familial haemophagocytic lymphohistiocytosis (FHL) is an inherited disorder characterized by an impaired cytotoxicity of T lymphocytes and NK cells typically manifesting within first few months after birth. If not treated adequately, it is inevitably fatal within several months. The incidence in Caucasians has been estimated to 1: 50 000 births. Haematopoietic stem cell transplantation represents the only curative treatment for FHL. Recently, several genetic defects underlying molecular defects in FHL have been identified. In approximately 30% of patients FHL is caused by mutations in PRF1 gene coding for perforin. Further 30% of patients were found to have mutations in UNC13D coding for hMunc13-4 protein. Very recent report has identified another cause of FHL, mutations in STX11 gene on chromosome 6, coding for syntaxin 11. Absence of any of those proteins severely impairs the process of exocytosis of cytotoxic granules. We describe patient with clinical symptoms of FHL. Immunological and molecular biology methods led to the identification of perforin mutation as a cause of the disease. Patient received an allogeneic SCT from HLA-matched unrelated donor. SCT was followed by rapid normalization of clinical symptoms and laboratory findings. In patient described in this study, FHL manifested with typical clinical and laboratory symptoms. Adequate immunosuppressive treatment and subsequent SCT led to the sustained remission of FHL and correction of molecular defect. This is the first case of FHL in Czech Republic where perforin mutation was identified as a molecular cause both at cellular and molecular level.

Female↗
PubMed2006

[EBV quantification in children after allogeneic hematopoietic stem cell transplantation].

BACKGROUND: Patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT) are endangered by developing Epstein-Barr virus-related post-transplant lymfoprolipherative disease (EBV-LPD). The aims of the study were to retrospectively characterise the viral loads in four patients who died of this complication, and to test possible risk factors for EBV reactivation in a prospectively observed cohort of children after AHSCT. METHODS AND RESULTS: Serial DNA samples extracted from whole blood from four patients who died of post-transplant EBV-LPD in year 2000 were retrospectively analysed for EBV load using quantitative real-time PCR. First detection of EBV activation preceded death by 24-91 days. All four patients exceeded a viral load of one million EBV copies per 100,000 human genome equivalents. A cohort of 72 children undergoing AHSCT between 2001-2004 was prospectively followed-on using the same quantification method from regularly obtained samples of whole blood, and clinical and laboratory data were recorded on a weekly basis, totalling at 3,896 person-weeks of observation. Approximately one half of the cohort experienced at least one episode of EBV reactivation during the first 100 days after AHSCT, four of the episodes being accompanied with viral loads higher than our provisional threshold of 10,000 copies per 100,000 human genome equivalents. Three of the four patients developed EBV-LPD and were successfully treated by intravenous administration of anti-CD20 antibody. Testing of possible clinical and laboratory predictors of EBV reactivation did not reveal any clinically useful association. CONCLUSIONS: The cornerstone of predicting EBV-LPD in AHSCT is a regular monitoring of EBV viral load using quantitative methods. Using this strategy with a threshold of 10,000 EBV copies per 100,000 human genome equivalents was proved to be effective, as shown by no death of EBV for the study period, compared to four cases in the year before the quantitative monitoring.

Child↗
PubMed2003

Long-term follow-up of chimerical state of the patients transplanted for different haematologic diseases.

Long-term follow-up of peripheral cellular chimerism in patients treated with BMT or PBSCT revealed the usefulness of their continuous monitoring at molecular level. Our results are based on monitoring of 120 patients, who were followed for at least 24 months. Comparison of the patients treated for chronic myelogenous leukemia (CML), acute myelocytic leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndromes (MDS) and aplastic anaemia (AA) revealed that mixed chimerism was practically absent in MDS and relatively long-lasting in ALL and AA (regardless to substantially different post-transplantation treatment). The first disease relapses signalized by molecular checking of mixed peripheral chimerism were observed also after a period of remission lasting for several years. Molecular watching enables us to detect relapses at their very beginning that would remain hidden to less sensitive methods. We believe that all of the transplanted patients ought to be monitored for residual disease i.e. cellular chimerism using molecular methods without time limits. On the other hand low level of mixed cellular chimerism is not necessarily a sign of disease progression and can remain unchanged as "status quo" for a very long period.

Adult↗
PubMed2002

[Transplantation of highly purified CD34+ hematologic peripheral stem cells from haploidentical related donors in the treatment of children with non-malignant diseases].

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.

Antigens, CD34↗
PubMed2001

Hematopoietic stem cell transplantation in children with hematological malignancies across HLA barriers--reasonable alternative?

The aim of this study was to evaluate the efficiency and risks of T-cell depletion in prevention of graft versus host disease (GVHD) using HLA haploidentical family donors as an alternative source of hematopoietic stem cells (HSC) in children with hematological malignancies without suitable matched donor. Ten children, median age 12 years (range, 3-17), were transplanted from haploidentical family donors for acute lymphoblastic leukemia (n = 4), acute myelogenous leukemia (n=2), chronic myelogenous leukemia (n = 2), non-Hodgkin lymphoma (n = 1) and myelodysplastic syndrome (n = 1). Parents were donors for nine, sibling for one patient. T-cell depletion of HSC was performed using CellPro followed by antiCD2/CD3 depletion in 7, and CliniMacs magnetic sorting in 3 grafts. Primary engraftment was achieved in nine patients. Patient with graft failure was successfully re-grafted. Primary acute GVHD was diagnosed in one patient who got higher amount of T-cells in the graft. Secondary GVHD was induced by add-backs of lymphocytes in four patients. Three patients developed chronic GVHD. Four patients died due to transplant related mortality (40%), one from veno-occlusive disease, two due to CMV pneumonia and one of aspergillosis with extensive chronic GVHD. Four patients relapsed with leukemia within 35-98 days post transplant, three without previous signs of GVHD, and all died. Two patients are alive and well 26 and 42 months after transplant. Haploidentical family donors appear to be a reasonable alternative option for patients with urgent indications for allogeneic transplant and/or without a matched donor.

Adolescent↗
PubMed2000

Prediction and reversion of post-transplant relapse in patients with chronic myeloid leukemia using mixed chimerism and residual disease detection and adoptive immunotherapy.

In the prospective study, we examined hematopoietic mixed chimerism (using polymerase chain reaction (PCR) of variable number of tandem repeat-VNTR sequences) and minimal residual disease (MRD) status (using qualitative and in the case of positivity quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for the BCR/ABL fusion mRNA) in serial peripheral blood samples taken from 25 patients after bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). Increasing mixed chimerism in correlation with increasing signal of MRD was detected in 10 patients. In two patients mixed chimera status and BCR/ABL rearrangement led to hematologic relapse, in five patients molecular relapse was followed by reappearance of Ph chromosome and three patients developed molecular relapse only. Adoptive immunotherapy-donor lymphocyte infusion (DLI), interferon (INF) and discontinuation of post-transplant immunosupression-separately or in different combinations was used in nine patients with molecular, cytogenetic or hematologic relapse of CML. The results demonstrate that significant response at the molecular level can be achieved for a majority of CML patients and that using of all forms of adoptive immunotherapy controlled by MC and MRD is more efficient in patients treated in early molecular relapse-with minimal disease burdens.

Adolescent↗
PubMed2000

Detailed monitoring of hematopoietic chimerism in a child treated by adoptive immunotherapy for high risk of relapse after BMT for acute myeloid leukemia.

We report a case of a 13-year-old boy who was transplanted for relapse of acute myeloid leukemia (AML). A detailed study of hematopoietic chimerism was performed using polymerase chain reaction (PCR) of variable number of tandem repeats (VNTR) at very short time intervals. We used discontinuation of post-transplant immunosuppression and donor lymphocyte infusions (DLI) in order to prevent leukemia relapse that was indicated by a progressive increase in autologous hematopoiesis. Despite the fact that the boy relapsed 10 months after BMT, we could see a significant influence of adoptive immunotherapy on the mixed chimerism status during the post-transplant period.

Acute Disease↗