Graft versus host disease (GVHD) is a major complication of haematopoietic SCT (HSCT). A number of inflammatory cytokines/chemokines are implicated in GVHD and have been identified in numerous single centre studies as potential biomarkers for acute and/or chronic GVHD. In this study, we analysed candidate inflammatory biomarkers (B-cell activating factor (BAFF), interleukin 33 (IL-33), CXCL10 and CXCL11) in a two-centre study. Biomarkers were evaluated pre-transplant and at serial time points post transplant in acute and chronic GVHD patient sera with time-matched control samples from patients without GVHD. Further validation was performed using the human skin explant assay, clinical GVHD biopsies and mRNA expression analysis. BAFF was significantly increased pre-transplant. BAFF, IL-33, CXCL10 and CXCL11 showed increased levels in acute GVHD patient sera and high protein expression in grades II-III of the in vitro skin explant graft versus host reaction (GVHR) group. BAFF, CXCL10 and CXCL11 also showed increased mRNA expression levels in clinical biopsies compared with the no/low-grade GVHD group. BAFF, CXCL10 and CXCL11 levels were increased in chronic GVHD patient sera. The results identify BAFF and CXCL10 as predictive biomarkers for acute GVHD and BAFF, CXCL10 and CXCL11 as useful diagnostic biomarkers for acute GVHD and chronic GVHD.

• MeSH
• akutní nemoc MeSH
• alografty MeSH
• biologické markery krev   MeSH
• chronická nemoc MeSH
• cytokiny MeSH
• hematologické nádory krev   terapie   MeSH
• lidé MeSH
• nemoc štěpu proti hostiteli krev   diagnóza   etiologie   MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• cytokiny MeSH

Corticosteroid-resistant graft-versus-host disease (GvHD) is difficult to manage and is associated with high morbidity and mortality. The purpose of our study was to evaluate the safety and efficacy of mycophenolate mofetil (MMF) as the salvage therapy for steroid-refractory GvHD. Twenty one patients (10 with acute GvHD and 11 with chronic GvHD) were studied retrospectively. Steroid-resistant GvHD was defined as acute or chronic GvHD not responding to a first-line regimen of cyclosporine A and corticosteroids in a dose equivalent to 2 mg/kg methylprednisolone for at least 7 days. MMF was added at a dose of 2 g daily, and corticosteroids were tapered. Thirteen (62%) of 21 patients responded to the treatment with MMF, including 6 (60%) of 10 patients with acute refractory GvHD and 7 (64%) of 11 patients with chronic refractory GvHD. The most common adverse effects were infectious complications (67%, 14 of 21 patients) and hematological toxicity (29%, 6 of 21 patients). Median duration of MMF administration was 6 months (range 1-27 months). Sixteen of 21 patients were alive after the median follow-up of 27 months (range 1-72 months) after the initiation of MMF therapy. All 16 surviving patients were in good clinical condition and in remission of their hematological malignancy. Five patients died--two of relapses of leukemia and three of refractory intestinal GvHD. These results suggest that MMF can be an effective treatment for some cases of steroid-refractory GvHD.

• MeSH
• akutní nemoc MeSH
• chronická nemoc MeSH
• dospělí MeSH
• hodnocení léčiv MeSH
• homologní transplantace MeSH
• imunosupresiva aplikace a dávkování   MeSH
• kyselina mykofenolová aplikace a dávkování   analogy a deriváty   MeSH
• leukemie terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoc štěpu proti hostiteli farmakoterapie   mortalita   prevence a kontrola   MeSH
• recidiva MeSH
• transplantace periferních kmenových buněk * metody   MeSH
• záchranná terapie * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imunosupresiva MeSH
• kyselina mykofenolová MeSH

Since 2006, combined graft-versus-host disease (GVHD) prophylaxis with ATG Grafalon has been our department's base of peri-transplant supportive care. This recent retrospective study included 398 patients who underwent their first allogeneic hematopoietic stem cell transplantation after receiving a defined dose of ATG Grafalon. Our observations recorded reduced incidence of severe acute and chronic GVHD without negative impact on overall survival in a nonselected group with standard and uniform GVHD prophylaxis.

• Klíčová slova
• ATG Grafalon, Acute and chronic GVHD, AlloHSCT,
• MeSH
• antilymfocytární sérum terapeutické užití   MeSH
• homologní transplantace škodlivé účinky   MeSH
• incidence MeSH
• lidé MeSH
• nemoc štěpu proti hostiteli * epidemiologie   etiologie   prevence a kontrola   MeSH
• příprava pacienta k transplantaci škodlivé účinky   MeSH
• retrospektivní studie MeSH
• syndrom bronchiolitis obliterans * MeSH
• transplantace hematopoetických kmenových buněk * škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antilymfocytární sérum 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 po terapii bez příznaků 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

BACKGROUND: Oral graft-versus-host disease (GVHD) is a significant complication after allogeneic stem cell transplantation (SCT) and there is no consistent information about its characteristics in patients after reduced-intensity conditioning regimen FLU/MEL (fludarabine 120 mg/m² and melphalan 140 mg/m²). MATERIAL/METHODS: This was a single-centre prospective observational study of patients after allogeneic SCT with FLU/MEL conditioning performed during the period 1/2005-12/2007. Characteristics of oral GVHD were observed in 71 patients. The observation was discontinued due to death, donor lymphocyte infusion (DLI) or new chemotherapy administration. RESULTS: In 10/2010, the median duration of the observation of the cohort of the patients was 13 (0.2-69) months, and 42 (35-69) months in the still-ongoing 20/71 (28%) patients. Oral acute GVHD had sporadic 7% incidence, whereas oral chronic GVHD was observed in 33% of patients and persisted with median duration of 188 (11-665) days. Clinical and histopathological features were similar in both acute and chronic oral GVHD and included mucosal lichenoid changes, erythema, ulcerations and pseudomembranes, satellite necrosis, apoptotic bodies and lichenoid interface inflammation. CONCLUSIONS: It is necessary to consider complex clinical symptomatology and pathological correlations when classifying the oral GVHD, because local oral symptoms and histopathological features in both acute and chronic oral GVHD forms can be similar. Even though the oral chronic GVHD was mild in the majority of patients, it can be considered as clinically significant due to its incidence, duration and symptomatology. The FLU/MEL conditioning regimen should not be considered as low-risk protocol in this context.

• MeSH
• akutní nemoc MeSH
• chronická nemoc MeSH
• dospělí MeSH
• homologní transplantace MeSH
• lidé středního věku MeSH
• lidé MeSH
• melfalan terapeutické užití   MeSH
• mladý dospělý MeSH
• nemoc štěpu proti hostiteli etiologie   patologie   MeSH
• nemoci úst etiologie   patologie   MeSH
• příprava pacienta k transplantaci škodlivé účinky   MeSH
• senioři MeSH
• transplantace kmenových buněk škodlivé účinky   MeSH
• vidarabin analogy a deriváty   terapeutické užití   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
• fludarabine MeSH Prohlížeč
• melfalan MeSH
• vidarabin MeSH

BACKGROUND: Chronic graft-versus-host disease (cGVHD) represents a major cause of morbidity and mortality after allogeneic bone marrow transplantation (BMT). Extracorporeal photochemotherapy (ECP), a technique used in the treatment of cutaneous T-cell lymphoma, has also shown clinical efficacy in the treatment of refractory cGVHD. STUDY DESIGN AND METHODS: In this study, the dynamics of dendritic cell (DC) activation were investigated during the process of photopheresis in patients treated for refractory cGVHD. RESULTS: It is reported that myeloid DCs can be isolated from the photopheretic products before retransfusion to the patient. It is shown that DCs in ECP product are in the immature state with respect to the phenotypic and functional characteristics. In contrast to the in vitro-generated monocyte-derived DCs and DCs not treated by 8-methoxypsoralen and UVA, they produce significant amounts of interleukin-10 (IL-10). They efficiently capture apoptotic lymphocytes and do not induce proliferation of T lymphocytes. They preserve the capacity to be activated by polyriboinosinic polyribocytidylic acid and lipopolysaccharide, however. ECP also induces rapid and massive apoptosis of alloreactive lymphocytes. A model of the potential implication of IL-10-producing DCs in the down regulation of harmful alloreactive immune reaction is presented. CONCLUSION: It is believed that this study provides a novel insight into the mechanisms of action of ECP in the control of cGVHD.

• MeSH
• apoptóza MeSH
• chronická nemoc MeSH
• dendritické buňky metabolismus   MeSH
• fotoferéza * MeSH
• homologní transplantace MeSH
• interleukin-10 metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• monocyty metabolismus   MeSH
• nemoc štěpu proti hostiteli metabolismus   terapie   MeSH
• proliferace buněk MeSH
• T-lymfocyty MeSH
• transplantace kostní dřeně * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interleukin-10 MeSH

Corticosteroid-resistant GVHD is difficult to manage and is associated with high morbidity and mortality. Cyclophosphamide (Cy) is an established immunosuppressive and cytotoxic drug widely used as part of pretransplant conditioning regimens. In a retrospective study of 15 patients who had not responded to corticosteroids (nine with acute GVHD, three with GVHD after donor leukocyte infusion, and three progressive chronic GVHD), pulse Cy at a median dose of 1 g/m(2) was very effective in the treatment of skin (100% response), liver (70% response), and the oral cavity (100% response). Severe intestinal GVHD responded poorly. The toxicity profile was acceptable, with manageable, short-term myelosuppression in some patients. The risk of opportunistic infections, mixed chimerism, relapses, or post-transplant lymphoproliferative disease was not increased. Overall survival was 57%, with median and maximum follow-up of 9 and 37 months, respectively. The cost of the drug was negligible, especially when compared to monoclonal antibodies. Pulse Cy requires further investigation in corticosteroid-resistant GVHD.

• MeSH
• analýza přežití MeSH
• autoimunita MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• dospělí MeSH
• hodnocení léčiv MeSH
• hormony kůry nadledvin farmakologie   MeSH
• kožní nemoci farmakoterapie   MeSH
• léková rezistence * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• nemoc štěpu proti hostiteli farmakoterapie   mortalita   patologie   MeSH
• nemoci jater farmakoterapie   MeSH
• nemoci úst farmakoterapie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cyklofosfamid MeSH
• hormony kůry nadledvin MeSH

BACKGROUND: Both mismatched unrelated donor (MMUD) and haploidentical (haplo) transplantation are valid options in patients with high-risk acute lymphoblastic leukemia (ALL) lacking a matched donor. METHODS: The study compared the outcomes of adult patients with ALL in complete remission (CR) who underwent 9/10 MMUD versus haplo transplantation with posttransplant cyclophosphamide (PTCy) as graft-vs-host disease (GVHD) prophylaxis in 2010-2020. RESULTS: The study included 781 patients (MMUD, 103; haplo, 678). The median age was 40 (19-73) and 38 (18-75) years, respectively (p = .51). The most frequent immunosuppression agents added to PTCy were mycophenolate mofetil (MMF)/cyclosporine A and MMF/tacrolimus. In vivo T-cell depletion (anti-thymocyte globulin) was administered to 21% and 8% of the transplants, respectively (p < .0001). Neutrophil (absolute neutrophil count >0.5 × 109 /L) recovery was achieved in 97.1% versus 96.7% versus (p = 1) in MMUD and haplo, respectively. Nonrelapse mortality and relapse incidence were not significantly different between MMUD and haplo, hazard ratio (HR) = 1.45 (95% confidence interval [CI], 0.81-2.62; p = .21) and HR = 0.81 (95% CI, 0.52-1.28, p = .38), respectively. HRs for leukemia-free survival, overall survival, and GVHD-free, relapse-free survival were respectively, HR = 1.05 (95% CI, 0.73-1.50, p = .8), HR = 1.17 (95% CI, 0.77-1.76, p = .46), and HR = 1.07 (95% CI, 0.78-1.46, p = .7) for haplo compared to MMUD. Acute (a)GVHD grade 2-4 was significantly higher with haplo, HR = 1.73 (95% CI, 1.08-2.76, p = .023), whereas aGVHD grade 3-4 and chronic GVHD did not differ significantly between the two transplant groups. CONCLUSION: Outcomes of MMUD and haplo transplants with PTCy-based GVHD prophylaxis for ALL patients in CR are similar, apart from a higher incidence of aGVHD with haplo transplants.

• Klíčová slova
• acute lymphoblastic leukemia, allogeneic stem cell transplantation, graft versus host disease, haploidentical, mismatched unrelated donors, posttransplant cyclophosphamide,
• MeSH
• akutní lymfatická leukemie * farmakoterapie   MeSH
• akutní nemoc MeSH
• cyklofosfamid terapeutické užití   MeSH
• dospělí MeSH
• HLA antigeny MeSH
• kyselina mykofenolová terapeutické užití   MeSH
• lidé MeSH
• nemoc štěpu proti hostiteli * prevence a kontrola   MeSH
• nepříbuzný dárce MeSH
• příprava pacienta k transplantaci škodlivé účinky   MeSH
• retrospektivní studie MeSH
• transplantace hematopoetických kmenových buněk * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cyklofosfamid MeSH
• HLA antigeny MeSH
• kyselina mykofenolová MeSH

Chronic granulomatous disease (CGD) can be cured by allogeneic hemopoietic stem cell transplantation (HSCT). Complications include graft failure, graft-versus-host disease (GVHD), infection, and transplant-related mortality; therefore, reduced-intensity conditioning regimens are being used to improve outcomes. In this retrospective study, the aim was to determine the outcome of treosulfan-based conditioning in HSCT for pediatric patients with CGD. The following data were collected: risk features pre-HSCT, additional conditioning agents, donor type and stem cell source, toxicity, engraftment, GVHD, chimerism, viral reactivation, post-HSCT complications, length of follow-up, and outcome. Seventy patients (median age, 107 months; interquartile range [IQR], 46-232 months) from 16 centers worldwide were transplanted between 2006 and 2015. Ninety-one percent had high-risk features. Fifty-seven HLA-matched donors, 12 HLA-mismatched donors, and 1 CD3(+)TCR αβ/CD19 depleted parental haploidentical transplants were performed. No major toxicity was reported. Median times to neutrophil and platelet engraftment were 17 (IQR, 15-35) and 16 (IQR, 13-50) days. At a median follow-up of 34 months (IQR, 13-102 months), the overall survival was 91.4%, and event-free survival was 81.4%. The cumulative incidence of acute grade III-IV GVHD was 12%. Nine patients developed chronic GVHD. When split cell chimerism was available, 95% or more myeloid donor chimerism was documented in 80% of surviving patients. Secondary graft failure occurred in 12% of patients. Treosulfan-containing conditioning regimens can be used safely in HSCT for children with CGD and high-risk clinical features, achieving excellent survival with high myeloid chimerism. Further studies are needed to compare with other regimens and evaluate the long-term outcome, particularly on fertility.

• MeSH
• akutní nemoc MeSH
• alografty MeSH
• busulfan aplikace a dávkování   analogy a deriváty   MeSH
• chronická granulomatózní nemoc * krev   mortalita   terapie   MeSH
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• míra přežití MeSH
• mladiství MeSH
• následné studie MeSH
• nemoc štěpu proti hostiteli krev   mortalita   MeSH
• neutrofily metabolismus   MeSH
• předškolní dítě MeSH
• přežití po terapii bez příznaků nemoci MeSH
• přežívání štěpu účinky léků   MeSH
• příprava pacienta k transplantaci metody   MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• trombocyty metabolismus   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• busulfan MeSH
• treosulfan MeSH Prohlížeč

Eligibility criteria for hematopoietic stem cell transplantation (HSCT) in acute lymphoblastic leukemia (ALL) vary according to disease characteristics, response to treatment, and type of available donor. As the risk profile of the patient worsens, a wider degree of HLA mismatching is considered acceptable. A total of 138 children and adolescents who underwent HSCT from HLA-identical sibling donors (MSDs) and 210 who underwent HSCT from matched donors (MDs) (median age, 9 years; 68% male) in 10 countries were enrolled in the International-BFM ALL SCT 2007 prospective study to assess the impact of donor type in HSCT for pediatric ALL. The 4-year event-free survival (65 ± 5% vs 61 ± 4%; P = .287), overall survival (72 ± 4% versus 68 ± 4%; P = .235), cumulative incidence of relapse (24 ± 4% versus 25 ± 3%; P = .658) and nonrelapse mortality (10 ± 3% versus 14 ± 3%; P = .212) were not significantly different between MSD and MD graft recipients. The risk of extensive chronic (cGVHD) was lower in MD graft recipients than in MSD graft recipients (hazard ratio [HR], .38; P = .002), and the risks of severe acute GVHD (aGVHD) and cGVHD were higher in peripheral blood stem cell graft recipients than in bone marrow graft recipients (HR, 2.06; P = .026). Compared with the absence of aGVHD, grade I-II aGVHD was associated with a lower risk of graft failure (HR, .63; P = .042) and grade III-IV aGVHD was associated with a higher risk of graft failure (HR, 1.85; P = .020) and nonleukemic death (HR, 8.76; P < .0001), despite a lower risk of relapse (HR, .32; P = .021). Compared with the absence of cGVHD, extensive cGVHD was associated with a higher risk of nonleukemic death (HR, 8.12; P < .0001). Because the outcomes of transplantation from a matched donor were not inferior to those of transplantation from an HLA-identical sibling, eligibility criteria for transplantation might be reviewed in pediatric ALL and possibly in other malignancies as well. Bone marrow should be the preferred stem cell source, and the addition of MTX should be considered in MSD graft recipients.

• Klíčová slova
• Acute lymphoblastic leukemia, Chronic graft-versus-host disease, Hematopoietic stem cell transplantation, Pediatric, Transplantation-related mortality,
• MeSH
• akutní lymfatická leukemie * mortalita   terapie   MeSH
• alografty MeSH
• dítě MeSH
• dospělí MeSH
• HLA antigeny * MeSH
• lidé MeSH
• míra přežití MeSH
• mladiství MeSH
• následné studie MeSH
• nemoc štěpu proti hostiteli etiologie   mortalita   MeSH
• nepříbuzný dárce * MeSH
• předškolní dítě MeSH
• přežití po terapii bez příznaků nemoci MeSH
• prospektivní studie MeSH
• retrospektivní studie MeSH
• sourozenci * MeSH
• transplantace periferních kmenových buněk * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• HLA antigeny * MeSH