Despite lower virulence, the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) still poses a relevant threat for immunocompromised patients. A retrospective multicentric study was conducted to evaluate the efficacy of pre-exposure prophylaxis with tixagevimab/cilgavimab (Evusheld) with a 6-month follow-up for preventing severe COVID-19 in adult patients with hematology malignancy. Among the 606 patients in the cohort, 96 (16%) contracted COVID-19 with a median of 98.5 days after Evusheld administration. A total of 75% of patients had asymptomatic or mild severity of COVID-19, while just 25% of patients with SARS-CoV-2 positivity had to be hospitalized. Two patients (2%) died directly, and one patient (1%) in association with COVID-19. Eight patients (1.3%) of every cohort experienced adverse events related to Evusheld, mostly grade 1 and of reversible character. It was found that complete vaccination status or positive seroconversion was not associated with lower risk of COVID-19 infection. Previous treatment with an anti-CD20 monoclonal antibody was associated with higher rates of COVID-19, while previous treatment with anti-CD38 monoclonal antibody was not, as was the case for recipients of hematopoietic stem cell transplantation or CAR-T cell therapy. Presence of other comorbidities was not associated with more severe COVID-19. The results support the growing evidence for Evusheld's efficacy against severe COVID-19 in patients with hematology malignancies.
- MeSH
- COVID-19 * MeSH
- dospělí MeSH
- hematologické nádory * komplikace farmakoterapie epidemiologie MeSH
- lidé MeSH
- monoklonální protilátky MeSH
- preexpoziční profylaxe * MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Česká republika MeSH
Our observational study analysed fungal infection frequency within cohorts with versus without antifungal prophylaxis (AFP) among newly diagnosed first-line venetoclax and azacitidine (VEN + AZA)-treated acute myeloid leukaemias in Czech, Austrian and Slovak haematology centres. Among 186 patients, 85 (46%) received antifungal prophylaxis, while 101 (54%) received no prophylaxis. Fungal infections occurred in 1/85 patients with prophylaxis (1%) and 5/101 patients without prophylaxis (5%) (p = 0.222). No significant difference was recorded between cohorts with and without AFP in terms of death rate (p = 0.296) and overall survival (p = 0.844). In conclusion, most infections were not severe, developing during the first treatment-cycle and did not affect patients' overall outcome.
- MeSH
- akutní myeloidní leukemie * farmakoterapie komplikace MeSH
- antifungální látky * terapeutické užití aplikace a dávkování MeSH
- azacytidin * aplikace a dávkování terapeutické užití MeSH
- bicyklické sloučeniny heterocyklické * aplikace a dávkování terapeutické užití MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mykózy * prevence a kontrola etiologie MeSH
- protokoly protinádorové kombinované chemoterapie * škodlivé účinky terapeutické užití aplikace a dávkování MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sulfonamidy * aplikace a dávkování terapeutické užití 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
- multicentrická studie MeSH
- pozorovací studie MeSH
BACKGROUND: Older patients with AML/MDS have a poor prognosis with alloHCT as the only curative option. However alloHCT is challenging given its high TRM. Recently, a composite endpoint of GRFS was proposed to define transplant success. A single centre retrospective analysis was performed to determine the main variables influencing GRFS. PATIENTS AND METHODSMETHODS: 91 consecutive patients≥ 60 years (median 64 years, range 60-74) with AML/MDS who received reduced-intensity alloHCT during 2001-2017 analysed. Disease risk index (DRI) at HCT was low/intermediate in 47pts (52%) and high in 44 pts (48%). RESULTS: After median follow-up for survivors of 56 months (range 7-144), 37 (40.6%) patients were alive. The OS, LFS and GRFS were 61.4%, 58.1%, 49.1% at 1 year and 35.5%, 32.3% and 23.1% at 5 years, respectively. The 1-year and 5-year incidences of NRM and relapse were 26.9%, 21.3% and 47.9% and 35.4%, respectively. In univariate analysis, high DRI was the strongest factor for worse OS (HR 2.121; p = 0.049), LFS (HR 1.924; p = 0.0123) and GRFS (HR 2.319; p = 0.0005). The donor age ≥ 62 years had a negative impact on OS (HR 2.110; p = 0.0345) and GRFS (HR 2.014; p = 0.0341). High DRI (HR 2.652; p = 0.0003) and donor age (HR 2.304; p = 0.0257) retained its significance in multivariate analysis for GRFS. CONCLUSION: A significant portion of older patients with myeloid malignancies survive alloHCT without experiencing GRFS event with DRI as the main determinant of outcome. Negative impact of donor age≥ 62 years suggests preference of a young donor, regardless of being related or unrelated.
- MeSH
- akutní myeloidní leukemie * MeSH
- homologní transplantace škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- myeloproliferativní poruchy * komplikace MeSH
- nemoc štěpu proti hostiteli * etiologie MeSH
- příprava pacienta k transplantaci MeSH
- retrospektivní studie MeSH
- senioři MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The standard of care in multiple myeloma (MM) consists of induction chemotherapy followed by autologous stem cell transplant (autoSCT), but this setting doesn't present curative potential. Despite advances in new, efficient, and targeted drugs, allogeneic transplant (aloSCT) remains the modality with curative potential in MM. With the knowledge of high mortality and morbidity related to the treatment in comparison to treatment with novel drugs, there is no consensus in the indication of aloSCT in MM, also the choice of ideal patients profiting from this method is difficult. Therefore, we performed a retrospective unicentric study of 36 unselected consecutive patients transplanted for MM in the University Hospital in Pilsen between the years 2000-2020 in order to define possible variables influencing survival. The median age of the patients was 52 years (38-63) and the distribution of MM subtypes was standard. The majority of the patients were transplanted in the relapse setting, 3 (8.3%) patients in the 1st line setting, and in 7 (19%) patients elective auto-alo tandem transplant was performed. 18 patients (60% of patients with available cytogenetics (CG) had high-risk disease. 12 (33.3%) patients were transplanted with chemoresistant disease (at least PR not reached). With a median follow-up of 85 months, we observed median overall survival (OS) of 30 months (range 10-60) and median progression-free survival (PFS) of 15 months (11-175). 1- and 5-year Kaplan Meier survival probabilities for OS were 55% and 30.5% respectively. During the follow-up, 27 (75%) patients died, 11 (35%) due to treatment-related mortality (TRM), and 16 patients (44%) due to a relapse. 9 (25%) patients were still alive, 3 (8.3%) of them with complete remission (CR), and 6 (16.7%) patients with relapse/progression. Altogether 21 (58%) of the patients relapsed/progressed with a median of 11 months (3-175). Incidence of clinically significant acute graft versus host disease (aGvHD gr. >II) was low (8.3%) and extensive chronic GvHD (cGvHD) developed in 4 patients (11.1%). Univariant analysis proved marginal statistical significance in disease status before aloSCT (chemosensitive × chemoresistant) for OS, favoring patients with the chemosensitive disease (HR 0.43, 95% CI 0.18-1.01, p=0.05), there was no significant impact of high-risk cytogenetics (CG) on survival. No other analyzed parameter was found to be significant. Our findings support the conclusion that aloSCT is able to overcome high-risk CG and that aloSCT still remains a valid treatment choice with acceptable toxicity in well-selected high-risk patients with curative potential, even though often with active disease, but not derogating the quality of life significantly.
- MeSH
- dospělí MeSH
- kvalita života MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- mnohočetný myelom * terapie MeSH
- nemoc štěpu proti hostiteli * MeSH
- přežití bez známek nemoci MeSH
- příprava pacienta k transplantaci škodlivé účinky MeSH
- retrospektivní studie MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky MeSH
- transplantace kmenových buněk škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Jako standardní přípravný režim se před podáním autologní transplantace krvetvorných buněk (ASCT) u relabujících či refrakterních lymfomů používal BEAM, tedy carmustine (BCNU) v kombinaci s etoposidem, cytarabinem a melfalanem. Recentní nedostatek BCNU však vedl k nutnosti přechodu na alternativní režim, kterým se v našem centru stal od července 2018 režim obsahující thiotepu, tzv. TEAM. Rozhodli jsme se retrospektivně srovnat gastrointestinální (GIT) toxicitu obou přípravných režimů. Zahrnuli jsme 142 konsekutivně autologně transplantovaných pacientů (BEAM = 82, TEAM = 60), z nichž 31 % mělo difuzní velkobuněčný B-lymfom (DLBCL), 20 % Hodgkinův lymfom (HL), 15 % lymfom z plášťových buněk (MCL), 14 % T-buněčné lymfomy (T-NHL) a zbylých 20 % ostatní druhy non-Hodgkinových lymfomů (NHL). Obě kohorty byly srovnatelné stran věku pacientů, zastoupení diagnóz a stavu nemoci v době ASCT. V distribuci jednotlivých stupňů GIT toxicity nebyl mezi dvěma přípravnými režimy nalezen statisticky signifikantní rozdíl, a to ani po seskupení všech stupňů do dvou hlavních skupin pacientů (grade 0 + 1 vs. grade 2–4). Pacienti dostávající režim TEAM však častěji dospěli k potřebě parenterální výživy, a to ve 20 případech (33 %) oproti pouhým 13 případům (16 %) u režimu BEAM (p = 0,04). Nerelapsová mortalita (NRM) byla u obou režimů srovnatelně nízká, během hospitalizace byla 0 %, ve 3 měsících pak 2 % shodně pro oba přípravné režimy (p = 1,0). Nezaznamenali jsme statisticky signifikantní rozdíl v celkovém přežití (overal survival; OS) ani v přežití do známek progrese (progression free survival; PFS) (p = 0,59 pro OS, p = 0,1 pro PFS).
The BEAM regimen, i.e., carmustine (BCNU) in combination with etoposide, cytarabine, and melphalan was used as standard conditioning prior to autologous hematopoietic cell transplantation (ASCT) in relapsed or refractory lymphomas. However, the recent unavailability of BCNU necessitated the use of an alternative regimen, which in our centre became from July 2018 the so-called TEAM regimen containing thiotepa. We decided to retrospectively compare the gastrointestinal (GIT) toxicity of both conditioning regimens. We included 142 consecutive autologous transplant patients (BEAM = 82, TEAM = 60), of whom 31% had diffuse large B-cell lymphoma (DLBCL), 20% Hodgkin‘s lymphoma (HL), 15 % mantle cell lymphoma (MCL), 14% T-cell lymphomas (T-NHL) and the remaining 20% other types of non-Hodgkin lymphomas (NHL). Both cohorts were comparable in terms of patient age, prevalence of diagnoses, and disease status at the time of ASCT. There was no statistically significant difference in the distribution of the grades of GIT toxicity between the two cohorts, even after grouping all grades into two main groups of patients (grade 0+1 vs. grade 2–4). Patients receiving the TEAM regimen were more likely to require parenteral nutrition, namely in 20 cases (33%) versus only 13 cases (16%) in the BEAM regimen (P = 0.04). Non-relapse mortality (NRM) was comparably low for both regimens – 0% during hospitalization and 2% at 3 months for both conditioning regimens (P = 1.0). We also compared overall survival (OS) and progression-free survival (PFS): there was no statistically significant difference between the two cohorts (P = 0.59 for OS, P = 0.1 for PFS).
- MeSH
- autologní transplantace MeSH
- dospělí MeSH
- karmustin škodlivé účinky terapeutické užití MeSH
- kombinovaná farmakoterapie metody škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfom * farmakoterapie MeSH
- nežádoucí účinky léčiv epidemiologie MeSH
- příprava pacienta k transplantaci * metody škodlivé účinky statistika a číselné údaje MeSH
- protinádorové látky škodlivé účinky terapeutické užití MeSH
- senioři MeSH
- thiotepa škodlivé účinky terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P<0.001). Overall survival in patients with a diagnosis of COVID-19 between January 2020 and August 2020 was significantly lower than that in patients diagnosed between September 2020 and February 2021 and between March 2021 and September 2021 (39.8% vs. 60% vs. 61.9%, respectively; P=0.006). COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment, whenever possible.
