The treatment of relapsed/refractory acute myeloid leukemia (AML) is associated with a dismal prognosis. The allogeneic hematopoietic cell transplantation (allo-HCT) is frequently performed as salvage therapy. Reduced intensity conditioning protocols have been developed with the aim of reducing the leukemia burden without increasing their toxicity. We compared the reduced intensity conditioning FM140 (fludarabine, 150 mg/m2; melphalan 140 mg/m2) with FBM110 (fludarabine 150 mg/m2; BCNU, also known as carmustine, 300-400 mg/m2; and melphalan 110 mg/m2). From the European Bone Marrow Transplantation (EBMT) Acute Leukemia Working Party registry, we identified 293 adult patients (FM140, n = 118 and FBM110, n = 175) with AML with relapsed/refractory disease prior to allo-HCT. There were some differences such as age (FM140 = 59.5 years vs. FBM110 = 65.1 years, p < 0.001) and graft-versus-host disease (GvHD) prophylaxis based on in vivo T-cell depletion (TCD, FM140 = 39% vs. FBM110 = 75%, p < 0.001). No differences were observed between FM140- and FBM110-treated patients regarding overall survival (OS) (2-year OS: 39.3% vs. 45.7%, p = 0.58), progression-free survival (PFS) (2-year PFS: 36.1% vs. 37.3%, p = 0.69), non-relapse mortality (NRM) (2-year NRM: 15.3% vs. 25.7%, p = 0.10) and relapse incidence (RI) (2-year RI: 48.6% vs. 37.0%, p = 0.7). In conclusion, despite differences in age and GvHD prophylaxis, AML patients with active disease undergoing allo-HCT after FBM110 conditioning showed similar outcomes compared to FM140.
- MeSH
- akutní myeloidní leukemie * terapie mortalita MeSH
- dospělí MeSH
- homologní transplantace metody MeSH
- karmustin terapeutické užití aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- melfalan * terapeutické užití aplikace a dávkování MeSH
- příprava pacienta k transplantaci metody MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- recidiva MeSH
- registrace * MeSH
- senioři MeSH
- transplantace hematopoetických kmenových buněk * metody MeSH
- vidarabin * analogy a deriváty terapeutické užití aplikace a dávkování 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
- srovnávací studie MeSH
AIMS: Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a vital treatment for various paediatric malignant and nonmalignant diseases. The conditioning treatment before allo-HSCT is crucial for successful engraftment. Treosulfan, a cytotoxic prodrug, has gained popularity due to its lower toxicity compared to traditional alkylating agents used for conditioning treatment. METHODS: We investigated the relationship between pharmacokinetics and pharmacodynamics of treosulfan in paediatric patients, in a substudy pooling from 2 multicentre phase 2 clinical trials. A total of 83 children with malignant and nonmalignant diseases received treosulfan-based conditioning. Treosulfan exposure and its relationship with clinical outcomes, including survival, graft failure and graft-vs.-host disease, were investigated. RESULTS: Our findings reveal no significant association between treosulfan exposure and the key clinical outcomes or toxicity (P-values between .22 and .99), if the dosing is based on the approved product information. CONCLUSION: These findings suggest that treosulfan exposure after standardized body surface area-based dosing is appropriate in paediatric allo-HSCT.
- MeSH
- alkylační protinádorové látky * škodlivé účinky aplikace a dávkování terapeutické užití farmakokinetika MeSH
- busulfan * analogy a deriváty aplikace a dávkování škodlivé účinky farmakokinetika MeSH
- dítě MeSH
- homologní transplantace * škodlivé účinky MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- nemoc štěpu proti hostiteli * prevence a kontrola MeSH
- předškolní dítě MeSH
- příprava pacienta k transplantaci * metody škodlivé účinky MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
Autologous hematopoietic cell transplants (auto-HCTs) remain the standard of care for transplant-eligible MM patients. The general practice has been to undergo upfront apheresis following induction to collect sufficient number of CD34+ cells to facilitate two auto-HCTs. However, 5-30% of MM patients do not initially mobilise a sufficient number of hematopoietic stem cells and are classified as poor mobilizers (PM). We compared the baseline characteristics and outcomes of 61 PMs and 816 non-PM patients who underwent a second auto-HCT and who were enrolled in the non-interventional CALM study (NCT01362972). Only patients who collected CD34+ prior to auto-HCT1 were included. Auto-HCT2 comprised both tandem and salvage transplants. PMs were re-mobilized with plerixafor (n = 24, 39.3%) or non-plerixafor-based regimens (n = 37, 60.7%). There were no significant differences in engraftment, progression-free survival (PFS) or overall survival (OS) after the second auto-HCT between PM and non-PM patients. There was a trend to shorter PFS in PM patients undergoing salvage auto-HCT (median 9.6 vs. 12.9 months; p = 0.08) but no significant difference in OS. The median OS was 41.1 months for PM and 41.2 months for non-PM patients (p = 0.86). These data suggest that salvage mobilization is effective and does not affect overall outcomes after a second auto-HCT.
- MeSH
- autologní transplantace * metody MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom * terapie mortalita MeSH
- mobilizace hematopoetických kmenových buněk * metody MeSH
- retrospektivní studie MeSH
- senioři MeSH
- transplantace hematopoetických kmenových buněk * metody MeSH
- výsledek terapie 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
The association of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects after allogeneic stem-cell transplantation (SCT) is well-established but was not confirmed in the modern era and following post-transplant cyclophosphamide (PTCy). We assessed GVHD/ GVL association in AML patients following HLA-matched SCT with standard calcineurin-based (n = 12,653, 57% with additional in-vivo T-cell depletion) or PTCy-based (n = 508) GVHD prophylaxis. Following standard prophylaxis, acute GVHD grade II-IV and III-IV, chronic GVHD, and extensive chronic GVHD rates were 23.8%, 7.5%, 37.0%, and 16.3%, respectively. Acute GVHD grade II and III-IV were associated with lower relapse [hazard-ratio (HR) 0.85, P = 0.002; HR 0.76, P = 0.003, respectively)], higher non-relapse mortality (NRM) (HR 1.5, P < 0.001; HR 6.21, P < 0.001) and lower overall survival (OS) (HR 1.49, P < 0.001; HR 6.1, P < 0.001). Extensive chronic GVHD predicted lower relapse (HR 0.69, P < 0.001), higher NRM (HR 2.83, P < 0.001), and lower OS (HR 2.74, P < 0.001). Following PTCy, GVHD rates were 22.8%, 6.2%, 35.5%, and 17.7%, respectively. Acute GVHD was not associated with relapse (HR 1.37, P = 0.15) but predicted higher NRM (HR 3.34, P < 0.001) and lower OS (HR 1.92, P = 0.001). Chronic GVHD was not prognostic for these outcomes. In conclusion, GVHD and GVL are strongly associated with contemporary SCT. However, following PTCy, GVHD is not associated with reduced relapse.
- MeSH
- akutní myeloidní leukemie * terapie MeSH
- cyklofosfamid * terapeutické užití MeSH
- dospělí MeSH
- HLA antigeny imunologie MeSH
- homologní transplantace MeSH
- imunosupresiva terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nemoc štěpu proti hostiteli * etiologie prevence a kontrola MeSH
- reakce štěpu proti leukémii * MeSH
- senioři MeSH
- testování histokompatibility MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Perianal fistulas of Crohn's disease (CD) create a significant burden on patients' lives. However, the efficacy and safety of adipose-derived mesenchymal stem cell treatment are contradicting, and real-world evidence is lacking. AIMS: To examine the usability of darvadstrocel therapy in managing perianal CD. METHODS: We enrolled patients with CD and perianal fistulas in this retrospective multicenter study. The primary outcome was perianal clinical remission (defined as all treated fistulas closed) at weeks 26 and 52. Secondary outcomes were clinical response rates (≥ 1 fistulas closed), perianal activity (PDAI), patient satisfaction, and adverse events. Data were recorded at baseline and weeks 12, 26 and 52. Prediction of primary outcomes was performed by logistic regression. RESULTS: Overall, among 223 patients (male/female ratio: 0.48), perianal clinical remission was achieved in 78.2% and 62.3% until weeks 26 and 52. Baseline PDAI score (OR 0.75), number of fistulas (OR 0.28) and the number of weeks after preparation for surgery (OR 0.98) were associated with treatment failure. The clinical response rates were 84.8% and 79.8% at weeks 26 and 52. Improvement of subjective perianal symptoms was achieved in 77.8% and 78.4% of patients, respectively. Adverse events occurred in 13.5% of patients; perianal abscesses and proctalgia were the most frequently reported. CONCLUSION: Effectiveness data were higher than in clinical trials. The safety profile was reassuring, and patients' satisfaction was high. Appropriate patient selection, fistula preparation and expertise may help to achieve treatment success.
- MeSH
- Crohnova nemoc * terapie komplikace MeSH
- dospělí MeSH
- indukce remise MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- rektální píštěl * terapie etiologie MeSH
- retrospektivní studie MeSH
- spokojenost pacientů MeSH
- transplantace mezenchymálních kmenových buněk * metody škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Minimal residual disease (MRD) is one of the most important prognostic factors in multiple myeloma (MM) and a valid surrogate for progression-free survival (PFS) and overall survival (OS). Recently, MRD negativity was approved as an early clinical endpoint for accelerated drug approval in MM. Nevertheless, there is limited evidence of MRD utility in real-world setting. In this retrospective multicenter study, we report outcomes of 331 newly diagnosed MM patients with MRD evaluation at Day+100 after autologous stem cell transplantation using flow cytometry with a median limit of detection of 0.001%. MRD negativity was reached in 47% of patients and was associated with significantly prolonged median PFS (49.2 months vs. 18.4 months; hazard ratios (HR) = 0.37; p < 0.001) and OS (not reached vs. 74.9 months; HR = 0.50; p = 0.007). Achieving MRD negativity was associated with PFS improvements regardless of age, International Staging System (ISS) stage, lactate dedydrogenase (LDH) level, or cytogenetic risk. Importantly, MRD positive patients benefited from lenalidomide maintenance versus no maintenance (18-months PFS: 81% vs. 46%; HR = 0.24; p = 0.002) while in MRD negative patients such benefit was not observed (p = 0.747). The outcomes of our real-world study recapitulate results from clinical trials including meta-analyses and support the idea that MRD positive patients profit more from lenalidomide maintenance than MRD negative ones.
- MeSH
- autologní transplantace MeSH
- dospělí MeSH
- lenalidomid aplikace a dávkování terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom * diagnóza mortalita terapie patologie MeSH
- prognóza MeSH
- průtoková cytometrie * metody MeSH
- retrospektivní studie MeSH
- reziduální nádor * diagnóza MeSH
- senioři MeSH
- staging nádorů MeSH
- transplantace hematopoetických kmenových buněk metody MeSH
- výsledek terapie 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
This article provides an up-to-date review of the management of chronic pancreatitis, highlighting advancements in medical therapy, nutritional support, endoscopic and surgical approaches, and emerging treatments. Nutritional management accentuates addressing malabsorption and nutrient deficiencies. Advances in endoscopy and parenchyma-sparing surgical techniques have opened new avenues for improved patient outcomes, with total pancreatectomy and islet autotransplantation offering the only definitive solution for selected patients. Additionally, emerging therapies, including anti-inflammatory and immune-modulating agents, show promise for future treatment options. Emphasizing a multidisciplinary approach, this review aims to equip health care professionals with a comprehensive overview of current management strategies and future directions.
- MeSH
- chronická pankreatitida * terapie MeSH
- lidé MeSH
- nutriční podpora * metody MeSH
- pankreatektomie * metody MeSH
- transplantace Langerhansových ostrůvků metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The eye represents a highly specialized organ, with its main function being to convert light signals into electrical impulses. Any damage or disease of the eye induces a local inflammatory reaction that could be harmful for the specialized ocular cells. Therefore, the eye developed several immunoregulatory mechanisms which protect the ocular structures against deleterious immune reactions. This protection is ensured by the production of a variety of immunosuppressive molecules, which create the immune privilege of the eye. In addition, ocular cells are potent producers of numerous growth and trophic factors which support the survival and regeneration of diseased and damaged cells. If the immune privilege of the eye is interrupted and the regulatory mechanisms are not sufficiently effective, the eye disease can progress and result in worsening of vision or even blindness. In such cases, external immunotherapeutic interventions are needed. One perspective possibility of treatment is represented by mesenchymal stromal/stem cell (MSC) therapy. MSCs, which can be administered intraocularly or locally into diseased site, are potent producers of various immunoregulatory and regenerative molecules. The main advantages of MSC therapy include the safety of the treatment, the possibility to use autologous (patient's own) cells, and observations that the therapeutic properties of MSCs can be intentionally regulated by external factors during their preparation. In this review, we provide a survey of the immunoregulatory and regenerative mechanisms in the eye and describe the therapeutic potential of MSC application for corneal damages and retinal diseases.
AIMS: This study aimed to examine changes in the repertoire of functional T-cells specific for six leukemia-associated antigens (LAA), including WT1, PRAME, MUC1, CCNA1, NPM1, and NPM1c, during immune reconstitution following allogeneic transplantation of hematopoietic stem cells (HSCT) in patients with acute myeloid leukemia. PATIENTS & METHODS: LAA-specific T cell response was measured by ELISPOT- IFNγ and intracellular cytokine staining in 47 patients before starting conditioning therapy (baseline) and 7 months after HSCT. RESULTS: The positive cumulative LAA-specific T cell response before HSCT was associated with a decreased risk of relapse after HSCT. The prevalent genetic aberration - an internal tandem duplication of Fms 3 - related receptor tyrosine kinase, which has been previously implicated in immune escape mechanisms, is presented here for the first time as a factor associated with the absence of an adaptive T cell response against multiple LAAs. T-cell specific responses against wild-type and mutated NPM1 antigens were less frequent in the study cohort and did not correlate with mutations in the NPM1 gene. CONCLUSIONS: Our results showed that the T-cell response to LAA can be reconstituted after HSCT. Measurement of functional pre-transplant T-cell responses against multiple LAAs could help to find patients with an increased risk of relapse.
- MeSH
- akutní myeloidní leukemie * terapie imunologie genetika MeSH
- antigeny nádorové imunologie MeSH
- dospělí MeSH
- homologní transplantace MeSH
- jaderné proteiny genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mucin 1 genetika imunologie MeSH
- mutace * MeSH
- nukleofosmin * MeSH
- proteiny WT1 imunologie genetika MeSH
- recidiva MeSH
- senioři MeSH
- T-lymfocyty * imunologie MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- tyrosinkinasa 3 podobná fms * genetika 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
IMPORTANCE: The current standard-of-care salvage therapy in relapsed/refractory classic Hodgkin lymphoma (cHL) includes consolidation high-dose chemotherapy (HDCT)/autologous stem cell transplant (aSCT). OBJECTIVE: To investigate whether presalvage risk factors and fludeoxyglucose-18 (FDG) positron emission tomography (PET) response to reinduction chemotherapy can guide escalation or de-escalation between HDCT/aSCT or transplant-free consolidation with radiotherapy to minimize toxic effects while maintaining high cure rates. DESIGN, SETTING, AND PARTICIPANTS: EuroNet-PHL-R1 was a nonrandomized clinical trial that enrolled patients younger than 18 years with first relapsed/refractory cHL across 68 sites in 13 countries in Europe between January 2007 and January 2013. Data were analyzed between September 2022 and July 2024. INTERVENTION: Reinduction chemotherapy consisted of alternating IEP (ifosfamide, etoposide, prednisolone) and ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). Patients with low-risk disease (late relapse after 2 cycles of first-line chemotherapy and any relapse with an adequate response after 1 IEP/ABVD defined as complete metabolic response on FDG-PET and at least 50% volume reduction) received a second IEP/ABVD cycle and radiotherapy (RT) to all sites involved at relapse. Patients with high-risk disease (all primary progressions and relapses with inadequate response after 1 IEP/ABVD cycle) received a second IEP/ABVD cycle plus HDCT/aSCT with or without RT. MAIN OUTCOMES AND MEASURES: The primary end point was 5-year event-free survival. Secondary end points were overall survival (OS) and progression-free survival (PFS). PFS was identical to event-free survival because no secondary cancers were observed. PFS data alone are presented for simplicity. RESULTS: Of 118 patients analyzed, 58 (49.2%) were female, and the median (IQR) age was 16.3 (14.5-17.6) years. The median (IQR) follow-up was 67.5 (58.5-77.0) months. The overall 5-year PFS was 71.3% (95% CI, 63.5%-80.1%), and OS was 82.7% (95% CI, 75.8%-90.1%). For patients in the low-risk group (n = 59), 41 received nontransplant salvage with a 5-year PFS of 89.7% (95% CI, 80.7%-99.8%) and OS of 97.4% (95% CI, 92.6%-100%). In contrast, 18 received HDCT/aSCT off protocol, with a 5-year PFS of 88.9% (95% CI, 75.5%-100%) and OS of 100%. All 59 patients with high-risk disease received HDCT/aSCT (and 23 received post-HDCT/aSCT RT) with a 5-year PFS of 53.3% (95% CI, 41.8%-67.9%) and OS of 66.5% (95% CI, 54.9%-80.5%). CONCLUSION AND RELEVANCE: In this nonrandomized clinical trial, FDG-PET response-guided salvage in relapsed cHL may identify patients in whom transplant-free salvage achieves excellent outcomes. HDCT/aSCT may be reserved for primary progression and relapsed cHL with inadequate response. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00433459.
- MeSH
- autologní transplantace MeSH
- dítě MeSH
- etoposid terapeutické užití aplikace a dávkování MeSH
- Hodgkinova nemoc * terapie farmakoterapie patologie MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- mladiství MeSH
- pozitronová emisní tomografie MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- transplantace hematopoetických kmenových buněk MeSH
- záchranná terapie * MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- komentáře MeSH
- multicentrická studie MeSH