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

Většina pacientů s mnohočetným myelomem (MM) je starší 50 let, což je věk, kdy jsou kardiovaskulární nemoci běžné. Proto je třeba být si vědom nežádoucích kardiovaskulárních vlivů protimyelomových léků. Z klasických cytostatik má známý kardiotoxický vliv doxorubicin. Kardiovaskulární komplikace však mohou způsobit také vysoké dávky cyklofosfamidu, používané pro sběr kmenových krvetvorných buněk. Proto se při poškození srdce AL-amyloidózou doporučuje sběr kmenových buněk po G-CSF. Dávky melfalanu, které jsou obvyklé při transplantaci krvetvorné tkáně, mohou taktéž působit negativně na srdce a indukovat arytmie. Ze skupiny inhibitorů proteazomu má nejvíce kardiovaskulárních nežádoucích účinků karfilzomib, po bortezomibu byly popsány v podstatně menší míře, u ixazomibu se kardiotoxicita nepopisuje. U léků ze skupiny IMiD dominuje prokoagulační účinek, vyžadují cílenou profylaxi trombóz a plicních embolií, ale popsány byly i poruchy rytmu. Léčba novými anti-CD38 monoklonálními protilátkami není spojena s evidentní kardiotoxicitou, nežádoucí účinek v oblasti kardiovaskulární se však popisuje u glukokortikoidů, které jsou standardní premedikací při podání anti-CD protilátek. Cílem textu je informovat o incidenci těchto komplikací asociovaných s protimyelomovou léčbou.

Most patients with multiple myeloma (MM) are over 50 years old, which is an age when cardiovascular diseases are common. Therefore, it is important to be aware of the potential adverse cardiovascular effects of anti-myeloma drugs. Among conventional cytostatics, doxorubicin is known for its cardiotoxic effects. High doses of cyclophosphamide, used for stem cell collection, can also cause cardiovascular complications. Therefore, in cases where the heart is affected by AL amyloidosis, stem cell collection after G-CSF is recommended. The doses of melphalan typically used during haematopoietic stem cell transplantation may also have a negative impact on the heart and induce arrhythmias. Among proteasome inhibitors, carfilzomib is associated with the highest number of cardiovascular side effects, while those reported with bortezomib are significantly less frequent, and ixazomib is not associated with cardiotoxicity. In the group of IMiD drugs, procoagulant effects dominate, requiring targeted prophylaxis for thrombosis and pulmonary embolism; however, rhythm disorders have also been reported. Treatment with new anti-CD38 monoclonal antibodies is not linked to evident cardiotoxicity, but adverse cardiovascular effects are associated with glucocorticoids, which are standard premedications for administering anti-CD antibodies. The aim of this text is to inform about the incidence of these complications associated with anti-myeloma treatment.

• MeSH
• cyklofosfamid škodlivé účinky   toxicita   MeSH
• inhibitory proteasomu škodlivé účinky   toxicita   MeSH
• kardiotoxicita * etiologie   MeSH
• lidé MeSH
• melfalan škodlivé účinky   toxicita   MeSH
• mnohočetný myelom * farmakoterapie   komplikace   MeSH
• monoklonální protilátky škodlivé účinky   toxicita   MeSH
• nežádoucí účinky léčiv MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Postižení ledvin v rámci Light Chain Depositon Disease (LCDD) je velmi vzácně diagnostikovanou jednotkou. Popisuje- me případ, kdy tato diagnóza byla morfologicky stanovena až v biopsii transplantované ledviny a retrospektivně byla dohledána i v předchozí biopsii ledvin, kde však změny nebyly správně klasifikovány. Biopsie transplantované ledviny byla provedena pro postupně se horšící funkce štěpu. Následné vyšetření, cílené na monoklonální gamapatii, prokázalo zvýšenou sérovou koncentraci volných lehkých řetězců kappa (free light chain – FLC) s maximální hodnotou FLC kappa 226 mg/l a FLC lambda jen 6 mg/l. Poměr FLC kappa / FLC lambda byl jasně patologický, 37 (normalní rozmezí 0,26–1,65). Imunofixační elektroforéza séra a moče byla opakovaně negativní. Cytologické vyšetření kostní dřeně popsalo 8 % patolo- gických plazmatických buněk. Flow-cytometrické vyšetření kostní dřeně prokázalo 0,7 % plazmocytů ze všech jaderných buněk kostní dřeně. Tyto plazmocyty byly ve 100 % klonální, abnormálního fenotypu kappa+. Diagnóza byla uzavřena jako nemaligní gamapatie typu „monoklonální gamapatie renálního významu“ s poškozením ledvin v morfologické formě odpovídající LCDD. Pro léčbu byla zvolena kombinace daratumumabu, bortezomibu, cyklofosfamidu a dexametazonu. Současně pacientka dostávala imunosupresivní léčbu nutnou k zachování funkce transplantované ledviny. Sérová hladina volných lehkých řetězců kappa v průběhu prvních dvou měsíců léčby poklesla pod dolní hranici normy. LCDD je jednou z mnoha forem poškození ledvin, k němuž může dojít při nemaligních gamapatiích. Proto by vyšetření FLC mělo být provedeno vždy v rámci diferenciální diagnostiky každého renálního selhání. Pro poškození ledvin mono- klonálním imunoglobulinem byla akceptována klasifikace vytvořená mezinárodní skupinou The International Kidney and Monoclonal Gammopathy Research Group. Morfology, hodnoticí biopsie ledvin, je vhodné informovat o případné přítomnosti patologické koncentrace FLC anebo M-Ig, aby

Light Chain Deposition Disease (LCDD) is a very rarely diagnosed condition affecting the kidneys. We describe a case where this diagnosis was morphologically confirmed in a biopsy of a transplanted kidney, and retrospectively identified in a previous kidney biopsy where the changes were not correctly classified. The biopsy of the transplanted kidney was performed due to worsening graft function. Subsequent testing focused on monoclonal gammopathy, revealing elevated serum concentrations of free kappa light chains (FLC) with a maximum FLC kappa value of 226 mg/l and FLC lambda at only 6 mg/l. The FLC kappa / FLC lambda ratio was clearly pathological at 37 (normal range 0.26-1.65). Serum and urine immunofixation electrophoresis were repeatedly negative. Bone marrow cytology described 8% pathological plasma cells, and flow cytometry demonstrated 0.7% plasma cells among all nuclear bone marrow cells. These plasma cells were 100% clonal, of the abnormal kappa + phenotype. The diagnosis was thus concluded as a non-malignant gammopathy of the type "monoclonal gammopathy of clinical significance" with renal damage in a morphological form corresponding to LCDD. A combination of daratumumab, bortezomib, cyclophosphamide and dexamethasone was chosen for treatment LCDD. Free light kappa chains decreased below the lower limit of the norm during the first two months of anti-CD38 therapy. LCDD is one of the many forms of kidney damage that can occur in non-malignant gammopathies. Therefore, FLC testing should always be performed as part of the differential diagnosis of renal failure. For kidney damage by monoclonal immunoglobulin, a classification created by The International Kidney and Monoclonal Gammopathy Research Group was accepted. It is advisable to inform the evaluating morphologists of the possible presence of pathological concentrations of FLC and/or M-Ig so that they can focus the diagnosis in this direction, otherwise these rare forms of kidney injury may remain unrecognized.

• Klíčová slova
• daratumumab,
• MeSH
• bortezomib aplikace a dávkování   terapeutické užití   MeSH
• cyklofosfamid aplikace a dávkování   terapeutické užití   MeSH
• dexamethason aplikace a dávkování   terapeutické užití   MeSH
• lehké řetězce imunoglobulinů krev   MeSH
• lidé MeSH
• monoklonální protilátky aplikace a dávkování   terapeutické užití   MeSH
• paraproteinemie diagnóza   patologie   terapie   MeSH
• primární amyloidóza * diagnóza   farmakoterapie   MeSH
• renální insuficience etiologie   MeSH
• senioři MeSH
• transplantace ledvin MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

We retrospectively analyzed the impact of conditioning intensity on transplant outcomes according to their cytogenetic/molecular risk in a cohort of 1823 patients with acute myeloid leukemia (AML) and intermediate- or adverse-risk cytogenetics in first complete remission (CR1). These patients received their first hematopoietic stem cell transplantation (HSCT) using post-transplant cyclophosphamide (PTCy). The intermediate-risk cytogenetic group included 1386 (76%) patients, and 608 (34%) had mutated FLT3-ITD. Myeloablative conditioning was used in 930 patients (51%), while 1130 (62%) received an intensified conditioning (score ≥2.5) based on the transplant conditioning intensity (TCI) score. Conditioning intensity using the myeloablative/reduced intensity stratification did not impact transplant outcomes across the entire cohort. However, a higher TCI score was associated with a lower risk of relapse, with no effect on survival. In specific cytogenetic risk groups, a higher TCI score did not influence outcomes in the adverse-risk group. In the intermediate-risk group, the impact varied with FLT3-ITD status. Patients with FLT3-ITD mutation who received a higher TCI showed a beneficial effect on relapse, leukemia-free survival (LFS), and overall survival. Conversely, in FLT3-ITD wild-type patients, more intense conditioning had a detrimental effect on graft-versus-host disease-free, and relapse-free survival with no effect on other outcomes. In conclusion, for AML patients in CR1 undergoing HSCT with PTCy, it is crucial to consider cytogenetic risk and molecular status when selecting the conditioning regimen. Intensive conditioning should be considered for patients with intermediate-risk cytogenetics and mutated FLT3-ITD but should probably be avoided for those with wild-type FLT3-ITD.

• MeSH
• akutní myeloidní leukemie * terapie   genetika   mortalita   MeSH
• cyklofosfamid * terapeutické užití   aplikace a dávkování   farmakologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• příprava pacienta k transplantaci * metody   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk * 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

Post-transplant cyclophosphamide (PTCY) is increasingly used as effective graft-versus-host disease (GvHD) prophylaxis in allogeneic hematopoietic-cell transplantation (allo-HCT). However, PTCY is associated with toxicities. Whether patients with specific comorbidities are more vulnerable to cyclophosphamide-induced toxicity is unclear. We retrospectively evaluated the impact of individual organ dysfunctions for non-relapse mortality (NRM) risk and overall survival (OS) among 5888 adults who underwent PTCY-based allo-HCT for acute myeloid leukemia between 2010 and 2023. In multivariable analyses 5 of the comorbidities (renal, moderate/severe hepatic, cardiac including arrhythmia/valvular disease, severe pulmonary, infection) were independently associated with adverse NRM and OS without influencing relapse rate. A simplified model using the absence (n = 4390), presence of 1 (n = 1229) or presence of 2 or 3 (n = 269) of the comorbidities which were determined individually to contribute to NRM stratified patients into 3 NRM risk (16.2% vs. 21.6% vs. 36%, retrospectively) and OS categories (64% vs. 56% vs. 36.4%, retrospectively). In Cox model, recipients with 2 or 3 comorbidities had an increased hazard ratio for NRM of 2.38 (95% confidence interval [CI], 1.89-3) and for OS of 1.96 (95% CI 1.64-2.33). Whether patients with concomitant diagnoses, as determined here, may benefit from a reduced PTCY dose remains to be evaluated in prospective clinical trials.

• MeSH
• akutní myeloidní leukemie * terapie   mortalita   MeSH
• cyklofosfamid * terapeutické užití   škodlivé účinky   farmakologie   aplikace a dávkování   MeSH
• dospělí MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoc štěpu proti hostiteli prevence a kontrola   mortalita   MeSH
• příjemce transplantátu MeSH
• retrospektivní studie MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Whether fixed-duration acalabrutinib-venetoclax (with or without obinutuzumab) would result in better progression-free survival than chemoimmunotherapy in patients with untreated chronic lymphocytic leukemia (CLL) is unknown. METHODS: In this phase 3, open-label trial, we included patients 18 years of age or older who had an Eastern Cooperative Oncology Group performance-status score of 0 to 2 (range, 0 to 5, with higher numbers indicating greater disability) and who did not have a 17p deletion or TP53 mutation. Patients were randomly assigned, in a 1:1:1 ratio, to receive acalabrutinib-venetoclax (acalabrutinib, cycles 1 to 14; venetoclax, cycles 3 to 14), acalabrutinib-venetoclax-obinutuzumab (as above, plus obinutuzumab, cycles 2 to 7), or chemoimmunotherapy with the investigator's choice of fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab (cycles 1 to 6). The primary end point was progression-free survival (acalabrutinib-venetoclax vs. chemoimmunotherapy) in the intention-to-treat population, assessed by blinded independent central review. RESULTS: A total of 867 patients underwent randomization: 291 were assigned to receive acalabrutinib-venetoclax, 286 acalabrutinib-venetoclax-obinutuzumab, and 290 chemoimmunotherapy (of whom 143 received fludarabine-cyclophosphamide-rituximab and 147 bendamustine-rituximab). The median age of the patients was 61 years (range, 26 to 86), 64.5% were men, and 58.6% had unmutated IGHV. Estimated 36-month progression-free survival at a median follow-up of 40.8 months was 76.5% with acalabrutinib-venetoclax, 83.1% with acalabrutinib-venetoclax-obinutuzumab, and 66.5% with chemoimmunotherapy (hazard ratio for disease progression or death with acalabrutinib-venetoclax vs. chemoimmunotherapy, 0.65 [95% confidence interval {CI}, 0.49 to 0.87], P = 0.004; for the comparison of acalabrutinib-venetoclax-obinutuzumab with chemoimmunotherapy, P<0.001). Estimated 36-month overall survival was 94.1% with acalabrutinib-venetoclax, 87.7% with acalabrutinib-venetoclax-obinutuzumab, and 85.9% with chemoimmunotherapy. Neutropenia, the most common adverse event of clinical interest of grade 3 or higher, was reported in 32.3%, 46.1%, and 43.2% in the three groups, respectively; death from coronavirus disease 2019 was reported in 10, 25, and 21 patients in the three groups. CONCLUSIONS: Acalabrutinib-venetoclax with or without obinutuzumab significantly prolonged progression-free survival as compared with chemoimmunotherapy in fit patients with previously untreated CLL. (Funded by AstraZeneca; AMPLIFY ClinicalTrials.gov number, NCT03836261.).

• MeSH
• benzamidy * škodlivé účinky   aplikace a dávkování   MeSH
• bicyklické sloučeniny heterocyklické * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• chronická lymfatická leukemie * farmakoterapie   mortalita   MeSH
• cyklofosfamid * aplikace a dávkování   škodlivé účinky   MeSH
• doba přežití bez progrese choroby * MeSH
• dospělí MeSH
• humanizované monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• pyraziny * škodlivé účinky   aplikace a dávkování   MeSH
• rituximab * aplikace a dávkování   škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sulfonamidy * aplikace a dávkování   škodlivé účinky   MeSH
• vidarabin analogy a deriváty   aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

• MeSH
• benigní pemfigoid sliznice * diagnostické zobrazování   farmakoterapie   patologie   MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• hyperemie farmakoterapie   MeSH
• kombinovaná farmakoterapie MeSH
• kyselina mykofenolová aplikace a dávkování   MeSH
• lidé MeSH
• nemoci spojivky * diagnostické zobrazování   farmakoterapie   patologie   MeSH
• prednisolon aplikace a dávkování   MeSH
• rituximab aplikace a dávkování   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND: The rate of immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays the principal role in the development of serious post-transplant complications. However, the post-transplantation course has a significant impact on shaping the immune system of the recipient, per se, thus representing risk factors for subsequent unfavorable outcomes. The predictive power of an interferon gamma (IFNγ) release assay (IGRA) on graft-versus-host disease (GVHD) or hematological relapse in recipients of allo-HSCT treated with post-transplantation cyclophosphamide and the impact of these complications on the restoration of cellular immune responsiveness was evaluated. STUDY DESIGN: A prospective observational study in which 62 adult patients with myeloid hematological malignancies who underwent allo-HSCT with a myeloablative conditioning regimen combined with post-transplantation cyclophosphamide were enrolled. Clinical data were collected and the IGRA was performed before commencement of the conditioning regimen and for 12 months post-allo-HSCT. Multivariate Cox regression and logistic regression models with backward stepwise analyses were used to calculate the predictive values for acute or chronic GVHD, or hematological relapse. RESULTS: Pre-transplantation and early post-transplantation IGRA values and other selected covariables (age, diagnosis, relapse risk, conditioning type, pre-T lymphocyte count, and donor sex), enabled prediction of the 12-month incidence of chronic GVHD with positive and negative predictive values of 75 % and 88 %, respectively. However, the IGRA did not improve the predictive value for acute GVHD or hematological relapse. Patients with myelodysplastic syndrome (MDS) had a significantly lower pre-transplant IGRA value (p = 0.021) and a delayed IFNγ response in IGRA, post-HSCT, than patients with acute myeloid leukemia (AML) (p = 0.015 and p = 0.0063 for 3 and 4 months post-HSCT, respectively). CONCLUSIONS: The IGRA can be used to monitor the recovery of total cellular immunity, post-HSCT and it has shown potential for use in personalized post-transplantation care. In the multivariate backward stepwise logistic regression model, pre-and early post-transplantation IGRA values showed potential for predicting chronic GVHD. Patients with MDS had a significantly lower pre-transplantation IGRA value and delayed IFNγ response in IGRA, post-HSCT, than patients with AML.

• MeSH
• chronická nemoc MeSH
• cyklofosfamid * terapeutické užití   MeSH
• dospělí MeSH
• hematologické nádory terapie   MeSH
• homologní transplantace MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• myeloablativní agonisté terapeutické užití   MeSH
• nemoc štěpu proti hostiteli * diagnóza   prevence a kontrola   etiologie   MeSH
• příprava pacienta k transplantaci * metody   MeSH
• prospektivní studie MeSH
• senioři MeSH
• test pomocí interferonu gama MeSH
• transplantace hematopoetických kmenových buněk * škodlivé účinky   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
• pozorovací studie MeSH

PURPOSE: We report an analysis of minimal residual/detectable disease (MRD) as a predictor of outcome in previously untreated patients with follicular lymphoma (FL) from the randomized, multicenter GALLIUM (ClinicalTrials.gov identifier: NCT01332968) trial. PATIENTS AND METHODS: Patients received induction with obinutuzumab (G) or rituximab (R) plus bendamustine, or cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or cyclophosphamide, vincristine, prednisone (CVP) chemotherapy, followed by maintenance with the same antibody in responders. MRD status was assessed at predefined time points (mid-induction [MI], end of induction [EOI], and at 4-6 monthly intervals during maintenance and follow-up). Patients with evaluable biomarker data at diagnosis were included in the survival analysis. RESULTS: MRD positivity was associated with inferior progression-free survival (PFS) at MI (hazard ratio [HR], 3.03 [95% CI, 2.07 to 4.45]; P < .0001) and EOI (HR, 2.25 [95% CI, 1.53 to 3.32]; P < .0001). MRD response was higher after G- versus R-chemotherapy at MI (94.2% v 88.9%; P = .013) and at EOI (93.1% v 86.7%; P = .0077). Late responders (MI-positive/EOI-negative) had a significantly poorer PFS than early responders (MI-negative/EOI-negative; HR, 3.11 [95% CI, 1.75 to 5.52]; P = .00011). The smallest proportion of MRD positivity was observed in patients receiving bendamustine at MI (4.8% v 16.0% in those receiving CHOP; P < .0001). G appeared to compensate for less effective chemotherapy regimens, with similar MRD response rates observed across the G-chemo groups. During the maintenance period, more patients treated with R than with G were MRD-positive (R-CHOP, 20.7% v G-CHOP, 7.0%; R-CVP, 21.7% v G-CVP, 9.4%). Throughout maintenance, MRD positivity was associated with clinical relapse. CONCLUSION: MRD status can determine outcome after induction and during maintenance, and MRD negativity is a prerequisite for long-term disease control in FL. The higher MRD responses after G- versus R-based treatment confirm more effective tumor cell clearance.

• MeSH
• bendamustin hydrochlorid MeSH
• cyklofosfamid MeSH
• doxorubicin MeSH
• folikulární lymfom * MeSH
• galium * terapeutické užití   MeSH
• lidé MeSH
• prednison MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   MeSH
• reziduální nádor farmakoterapie   MeSH
• rituximab MeSH
• vinkristin MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

INTRODUCTION: ANCA-associated vasculitis (AAV) is a rare, life-threatening disease which may result in serious pulmonary and kidney damage. Cyclophosphamide or rituximab and high-dose glucocorticoids significantly improved patient outcomes, but at the expense of severe complications. Moreover, many patients still relapse and bear a significant burden of both disease- and treatment-related complications. Alternative complement pathway and C5a receptor signaling were demonstrated to play an important role in AAV pathogenesis. Avacopan is selective C5a receptor inhibitor successfully tested in renal AAV as glucocorticoid-sparing agent. AREAS COVERED: Pharmacokinetic/pharmacodynamic properties, clinical efficacy and safety of avacopan, available clinical trials and real-world experience with avacopan. EXPERT OPINION: In the phase 3 trial avacopan was shown to be non-inferior at six and superior at 12 months compared to high-dose glucocorticoids and either cyclophosphamide or rituximab in patients with active AAV. Treatment with avacopan was well tolerated and associated with improved quality of life. In patients with severe renal AAV, renal function improved more in avacopan-treated than in high-dose glucocorticoid-treated patients. Avacopan could thus replace high-dose glucocorticoids to avoid glucocorticoid-related toxicity and to improve long term renal outcome. As avacopan is CYP 3A4 inhibitor and substrate, drug-drug interactions must be considered during the treatment.

• MeSH
• ANCA-asociované vaskulitidy * farmakoterapie   MeSH
• aniliny MeSH
• cyklofosfamid aplikace a dávkování   škodlivé účinky   farmakologie   MeSH
• glukokortikoidy * aplikace a dávkování   farmakologie   škodlivé účinky   MeSH
• imunosupresiva aplikace a dávkování   škodlivé účinky   farmakologie   MeSH
• kombinovaná farmakoterapie MeSH
• kvalita života * MeSH
• kyseliny nipekotinové MeSH
• lidé MeSH
• receptor pro anafylatoxin C5a antagonisté a inhibitory   MeSH
• rituximab škodlivé účinky   aplikace a dávkování   farmakologie   MeSH
• stupeň závažnosti nemoci MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• srovnávací studie MeSH