allogeneic stem cell transplantation Dotaz Zobrazit nápovědu
The deletion (5q) karyotype (del [5q]) in patients with myelodysplastic syndrome (MDS) is the most common karyotypic abnormality in de novo MDS. An increased number of blasts and additional karyotypic abnormalities (del [5q]+) are associated with a poor outcome. We analyzed the outcome of allogeneic hematopoietic cell transplants (HCT) in patients suffering from MDS with only del (5q) or del (5q)+ . A total of 162 patients, of median age 54 years (range, 9 to 73), having MDS and del (5q) abnormalities received HCT from identical siblings (n = 87) or unrelated donors (n = 75). The cumulative incidence of nonrelapse mortality and relapse incidence at 4 years was 29% (95% CI, 22 to 36) and 46% (95% CI, 38 to 54), whereas the estimated 4 year survival, relapse-free and overall, was 25% (95% CI, 18 to 33) and 30% (95% CI, 23 to 38), respectively. In a multivariate analysis patients with del (5q) and a blast excess displayed poorer survival (hazard ratio, 2.38; 95% CI, 1.44 to 3.93; P < .001), whereas female recipient sex resulted in improved survival (hazard ratio, .61; 95% CI, .41 to .90; P = .01). We conclude that allogeneic HCT can cure a subset of patients with MDS and a del (5q) abnormality.
- Klíčová slova
- Allogeneic stem cell transplantation, MDS, del (5q),
- MeSH
- alografty MeSH
- chromozomální delece * MeSH
- databáze faktografické * MeSH
- dospělí MeSH
- incidence MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 5 genetika MeSH
- míra přežití MeSH
- myelodysplastické syndromy * genetika mortalita terapie MeSH
- přežití bez známek nemoci MeSH
- recidiva MeSH
- sexuální faktory MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Allogeneic stem cell transplantation (AlloSCT) has been currently recommended in the treatment of patients with chronic myeloid leukemia (CML) as a second option after imatinib failure or in selected group of patients with high-risk CML and low risk for transplant-related mortality. The actual role of reduced-intensity conditioning (RIC) before AlloSCT in CML patients has not been yet conclusively established. The Czech National Hematopoietic Stem Cell Transplantation Registry has conducted a retrospective analysis of all patients (n=29) transplanted after RIC from the Registry database containing 295 patients with CML transplanted in the Czech Republic in years 1988-2005 and compared them with patients at comparable age (median age 48.3 and 50.6 years, respectively; p=0.587) transplanted during the same period of time using conventional myeloablative conditioning (n=26). Survival advantage of patients transplanted after RIC has been confirmed by log rank test (p=0.036) despite the fact that the relapse rate was significantly higher in RIC group (44.8% versus 0%). Both groups did not differ significantly in the use of voluntary unrelated donors, type of the grafts and in incidence of acute graft versus host disease (GVHD). However, there were trends for higher risk of CML and higher use of unrelated donors in the myeloablative group while peripheral stem cell grafts and chronic GVHD were observed more frequently in the RIC group. Transplant-related mortality was the leading cause of death in both groups of patients. Our results should be interpreted with caution because they may be influenced by small groups of subjects and also the impact of patients with high EBMT risk score on inferior survival in the myeloablative group cannot be fully eliminated. More retrospective and prospective studies are needed to elucidate the actual role of RIC before AlloSCT for CML.
- MeSH
- analýza přežití MeSH
- chronická myeloidní leukemie mortalita terapie MeSH
- chronická nemoc MeSH
- dárci tkání statistika a číselné údaje MeSH
- lidé MeSH
- myeloidní leukemie mortalita terapie MeSH
- přežití bez známek nemoci MeSH
- příprava pacienta k transplantaci škodlivé účinky MeSH
- registrace MeSH
- retrospektivní studie MeSH
- transplantace kmenových buněk metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Cytomegalovirus enterocolitis is a rare but potentially life threatening complication after allogeneic stem cell transplantation. Its early diagnosis and treatment are essential for a successful outcome. OBJECTIVE: To determine the potential benefit of fecal CMV DNA detection in the diagnosis of CMV colitis among stem cell transplant recipients. STUDY DESIGN: Biopsies from the lower gastrointestinal tract, taken during 69 episodes of diarrhea, were compared with fecal samples previously examined for CMV DNA in 45 patients after allogeneic stem cell transplantation. RESULTS: Six confirmed cases of CMV colitis were observed, with 16 out of 69 (23%) fecal samples proving positive for CMV DNA. Only one positive sample correlated with histologically confirmed CMV colitis, and 15 samples were evaluated as false positive. These results provide a 16.7% sensitivity and 76.2% specificity in the diagnosis of CMV enterocolitis. CONCLUSION: The examination of fecal samples for the presence of CMV DNA has very low potential in the diagnosis of CMV enterocolitis after allogeneic stem cell transplantation; therefore, a biopsy of the gastrointestinal mucosa is still warranted for correct diagnosis.
- Klíčová slova
- CMV enterocolitis, CMV infection, allogeneic stem cell transplantation,
- MeSH
- cytomegalovirové infekce diagnóza MeSH
- Cytomegalovirus genetika izolace a purifikace MeSH
- DNA virů izolace a purifikace MeSH
- enterokolitida diagnóza virologie MeSH
- feces virologie MeSH
- hematologické nádory terapie MeSH
- homologní transplantace MeSH
- lidé středního věku MeSH
- lidé MeSH
- retrospektivní studie MeSH
- senioři MeSH
- transplantace kmenových buněk škodlivé účinky MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- Názvy látek
- DNA virů MeSH
BACKGROUNDS: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a substantial therapeutic procedure for the treatment of a wide spectrum of severe diseases. Despite advancements in treatment and supportive care, alloHSCT still carries a considerable mortality risk, primarily caused by graft-versus-host disease (GvHD). Our retrospective analysis aimed to identify the factors influencing overall survival and GvHD development in HLA-identical sibling alloHSCT. We have analyzed patients' and donors' age, AB0 compatibility, recipient-donor gender match, stem cell source, time from the diagnosis to alloHSCT, conditioning regimen type, GvHD prophylaxis, and relapse. PATIENTS AND METHODS: Our study included 96 patients (54 male, 42 female) who underwent HLA-identical sibling alloHSCT. The median follow-up was 64.5 months (range 1-218 months), and the median age of both recipients and donors was 34 years. Malignant hematological diseases were the most common indications for alloHSCT. RESULTS: GvHD and its complications accounted for the highest number of deaths (N = 24; 46.2%), followed by relapse (N = 18; 34.6%). Acute GvHD developed in 30 patients (31.3%), while chronic GvHD occurred in 25 patients (26.0%), resulting in a total of 45 patients (46.9%) experiencing GvHD. Male recipients with female donors had significantly worse overall survival compared to other patients (P = 0.01; HR = 2.33). Overall survival was better in patients transplanted within 1 year from the diagnosis compared to those transplanted after 1 year (P = 0.03; HR = 1.93). No factor reached statistical significance regarding the impact on acute GvHD, chronic GvHD, or overall GvHD. CONCLUSION: We confirmed that sex mismatch, specifically in the case of a female donor and a male recipient, significantly negatively affects overall survival after alloHSCT. Additionally, overall survival is significantly shorter when the interval between the diagnosis and alloHSCT exceeds one year.
- Klíčová slova
- GVHD, haematopoietic stem cell transplantation, hematopoietic stem cell transplantation, overall survival,
- MeSH
- dospělí MeSH
- homologní transplantace * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nemoc štěpu proti hostiteli * etiologie mortalita MeSH
- příprava pacienta k transplantaci MeSH
- retrospektivní studie MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky mortalita MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The authors present a case study which describes the development of bilateral optic neuropathy as a complication of allogeneic hematopoietic stem cell transplantation (HSCT) in a patient who underwent a transplant for B-cell acute lymphoblastic leukemia (B-ALL). The patient, who was in remission with regard to the underlying hematological disease, developed edema of both optic discs and maculas three months after transplantation. The morphological finding regressed after treatment with corticoids and comprehensive systemic anti-infective therapy. However, the loss of function was not entirely restored. CASE REPORT: One year after the healing, the atrophy of the optic discs persisted, with corresponding findings in vessel density (VD), retinal nerve fibre layer (RNFL) and visual field changes. Electrophysiological examination by pattern electroretinogram (PERG) showed an alteration in retinal ganglion cells in the left eye, but with significant damage to nerve fibres on both sides. Visual evoked potential (VEP) verified bilateral non-inflammatory neurogenic lesions. This finding was also confirmed by functional magnetic resonance imaging (fMRI). Examination by structural magnetic resonance imaging (MRI) showed inflammatory changes in the optic nerve sheaths over time and a consequent marked narrowing of them. CONCLUSION: The authors believe that edema of the optic discs and maculas was caused by a combination of several factors. Firstly, MRI showed inflammatory changes in the optic nerve sheaths, which led to a blockade of axoplasmic transport. Another factor that may have played a part in the outcome was endothelial damage to blood vessels with impaired microcirculation supplying the optic nerve fibres, which contributed to the occurrence of macular edema.
- Klíčová slova
- MRI, allogeneic transplantation, edema, hematopoietic stem cell, lymphoblastic leukemia, macula, optic disc,
- MeSH
- lidé MeSH
- macula lutea * MeSH
- nemoci zrakového nervu * etiologie patologie MeSH
- nervus opticus MeSH
- optická koherentní tomografie MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky MeSH
- zrakové evokované potenciály MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) offers potentially curative therapy for numerous malignant and non-malignant diseases. The number of survivors and length of follow-up after successful HSCT is continually increasing. Hematopoietic stem cell transplantation can induce damage of various organs and tissues - from minimal potentially progressive subclinical changes to life-threatening conditions. The aim of this thesis was the evaluation of the prevalence of metabolic syndrome (MS) among survivors of allogeneic HSCT. PATIENTS AND METHODS: We analyzed 74 patients with a median age at transplant of 35 years, who had been followed for a median of 5 years (2-23 years) after allogeneic HSCT. MS was defined according to the National Cholesterol Education Programs Adult Treatment Panel III (NCEP ATP III) criteria and by the International Diabetes Federation (IDF) definition. RESULTS: The prevalence of MS among HSCT recipients was 40.5% applying the NCEP ATP III definition and 39.2% the IDF, a 2.02-fold increase compared to the general Slovak population. MS was more common in men. The most common MS features were abdominal obesity, hypertriglyceridemia and hypertension. The lowest prevalence of MS was in the age group of 20-29 years; and the highest prevalence in the age group of 60-69 years. The 10-year cumulative incidence of MS was 32.5%. The most significant risk factor for MS was total body irradiation, positive family history and age > 40 years at HSCT. Seven patients (9.45%) developed cardiovascular complications. The median 10-year general cardiovascular risk scores for males and females were found to be 13.3% and 6.68%, respectively. CONCLUSIONS: Detected increased prevalence of metabolic syndrome after allogeneic HSCT in patients surviving more than 2 years after this procedure may provide next stimulus to promote longer follow-up studies and to design of interventions to prevent late effects among survivors of serious hematologic diseases.
- Klíčová slova
- NAFLD, allogeneic hematopoietic stem cell transplantation, late effects, metabolic syndrome,
- MeSH
- adenosintrifosfát MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolický syndrom * komplikace etiologie MeSH
- mladý dospělý MeSH
- obezita MeSH
- přežívající MeSH
- senioři MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adenosintrifosfát MeSH
UNLABELLED: Although allogeneic haematopoietic stem cell transplantation (allo-HSCT) offers a unique curative potential, it may be connected with high treatment-related morbidity and mortality. Besides many organ complications, allo-HSCT may significantly affect quality of life (QOL). PATIENTS AND METHODS: Between January 2011 and December 2012, five hundred and ninety patients (pts) from 6 transplant centers in the Czech Republic filled in the questionnaire for the quantitative measurement of QOL using Functional Assessment of Cancer Therapy-General (FACT-G) version 4. Study cohort characteristics were as follows: 325 males, 340 pts received myeloablative conditioning, 383 pts received PBPC, representation of diagnoses; acute leukemia (n=270), bone marrow failure (n=36), chronic myeloid leukemia (n=74), myelodysplastic/myeloproliferative syndrom (n=110), lymphoproliferative disease (n=93). The median age at allo-HSCT was 43 years (range: 1.7 - 71.0), the median time from allo-HSCT to questionnaire completing was 3.8 years (range: - 0.2 - 21.6). The earliest allo-HSCT was performed in November 1989, the last in September 2012. In this retrospective study, we investigated the impact of various factors on the QOL after allo-HSCT: age, gender, diagnosis, type of conditioning, time from diagnosis to allo-HSCT, disease stage, graft type, donor type, time from allo-HSCT to questionnaire completing, GVHD, relapse. Only data from patients who were more than 3 months after allo-HSCT were used for the multivariate analysis. The overall results of the total FACT-G score (median=85.0; range: 29-108) as well as the results of each specific dimension - PWB (median=23.0; range: 5-28), SWB (median=24.0; range: 7-28), EWB (median= 19.0; range: 4-24), FWB (mean=21.0; range: 2-28) showed a value in the highest quartile of the possible evaluation. In multivariate analysis, an inferior QOL score was reported for patients with aGVHD (p=0.002), cGVHD (p<0.001), QOL decreased with increasing age (p=0.048) and increased with time elapsed since allo-HSCT (p<0.001).Allogeneic HSCT represents an important intervention into the overall integrity of the organism. In particular, the development of GVHD can cause very serious organ, but also mental problems which can significantly reduce the QOL. The QOL is steadily increasing with increasing interval from allo-HSCT but improvement and disappearance of these complications may take many years, and sometimes these effects may probably persist permanently.
- Klíčová slova
- FACT-G., QOL, allogeneic, transplantation,
- MeSH
- dospělí MeSH
- homologní transplantace MeSH
- kvalita života psychologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoc štěpu proti hostiteli patologie MeSH
- průzkumy a dotazníky MeSH
- retrospektivní studie MeSH
- senioři MeSH
- transplantace hematopoetických kmenových buněk škodlivé účinky psychologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Česká republika MeSH
Although complex approaches in haematopoietic stem cell transplantation (aHSCT) improved substantially in the last decades, considerable proportion of patients still suffer from life-threatening complications including graft versus host disease (GvHD). Great effort has therefore been dedicated to identification of biomarkers of the aHSCT outcome. Recently, prognostic scores for the prediction of GvHD and non-relapse mortality based on circulating molecules, such as tumour necrosis factor receptor-1, IL-33receptor (ST2) and regenerating islet-derived 3-alpha were proposed and evaluated in multicentre studies. Furthermore, several biomarkers, for example, ST2, represent promising targets for therapeutic intervention in severe GvHD. These results bring us closer to the clinical strategies to effectively control complications following aHSCT, and therefore to the tailored stem cell therapy with higher benefits for the patients.
- Klíčová slova
- allograft/allogeneic transplantation, biomarkers, graft versus host disease, immune response,
- MeSH
- biologické markery krev MeSH
- hematologické nádory krev diagnóza terapie MeSH
- homologní transplantace škodlivé účinky MeSH
- lidé MeSH
- nemoc štěpu proti hostiteli krev diagnóza MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- biologické markery MeSH
Outcome of 333 children with acute myeloid leukaemia relapsing after a first allogeneic haematopoietic stem cell transplantation was analyzed. Four-year probability of overall survival (4y-pOS) was 14%. 4y-pOS for 122 children receiving a second haematopoietic stem cell transplantation was 31% and 3% for those that did not (P = <0·0001). Achievement of a subsequent remission impacted survival (P = <0·0001). For patients receiving a second transplant survival with or without achieving a subsequent remission was comparable. Graft source (bone marrow vs. peripheral blood stem cells, P = 0·046) and donor choice (matched family vs. matched unrelated donor, P = 0·029) positively impacted survival after relapse. Disease recurrence and non-relapse mortality at four years reached 45% and 22%.
- Klíčová slova
- acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation, children, relapse, second hematopoietic stem cell transplantation,
- MeSH
- akutní myeloidní leukemie mortalita patologie terapie MeSH
- analýza přežití MeSH
- dítě MeSH
- homologní transplantace metody MeSH
- lidé MeSH
- příprava pacienta k transplantaci metody MeSH
- retrospektivní studie MeSH
- transplantace hematopoetických kmenových buněk metody MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Graft-versus-host disease (GVHD) represents a significant cause of mortality after allogeneic hematopoietic stem cell transplantation (HSCT). NF-kB system is a master regulator of innate immunity responses. It controls the expression of various cytokines and chemokines many of which are involved in GVHD pathogenesis. Chemo(radio) therapy administered during conditioning induces DNA damage and activates DNA damage response (DDR) signaling resulting in irreversible cell cycle arrest - cellular senescence which has been described to be associated with robust pro-inflammatory secretion mostly controlled by NF-kB. The NFKB1 gene encodes the DNA-binding subunit of the NF-kB complex. Using the candidate gene approach, we analyzed possible association of two single-nucleotide polymorphisms (SNPs) rs3774937 C/T and rs3774959 A/G of the NFKB1 gene with GVHD and transplant-related mortality (TRM) occurrence in 109 recipients allografted from HLA-identical donor. Both SNPs in recipients were found to be strongly associated with acute GVHD. Nevertheless, no significant association with chronic GVHD and TRM was found. Presented pilot results contribute to pre-clinical observations and suggest that NF-kB may be an important regulator of HSCT-related inflammatory reactions such as acute GVHD. Novel pathogenic mechanisms of GVHD may arise from perspectives of DDR and cellular senescence where NF-kB plays an essential role.
- Klíčová slova
- Allogeneic hematopoietic stem cell transplantation, Cellular senescence, Graft-versus-host disease, NFKB1 gene, Senescence-associated secretory phenotype, Single-nucleotide polymorphism,
- MeSH
- alografty MeSH
- dospělí MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- nemoc štěpu proti hostiteli genetika mortalita terapie MeSH
- NF-kappa B - podjednotka p50 genetika MeSH
- pilotní projekty MeSH
- přežití bez známek nemoci MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Názvy látek
- NF-kappa B - podjednotka p50 MeSH
- NFKB1 protein, human MeSH Prohlížeč