Nemoc štěpu proti hostiteli (graft versus host disease, GvHD) stále představuje zásadní, život ohrožující komplikaci po alogenní transplantaci krvetvorných buněk (allogeneic stem cell transplantation, aloSCT). Reakce štěpu proti hostiteli obecně se rozvine až u 50 % pacientů po aloSCT, klinicky významná stadia (stadium III-IV akutní GvHD či extenzivní chronická GvHD) se vyskytují až u 20 % pacientů po aloSCT od HLA shodného dárce, incidence GvHD pak vzrůstá s každou další HLA neshodou. Uváděná mortalita GvHD se pohybuje kolem 10 % případů. Standardem léčby GvHD je systémová kortikoterapie, která je úspěšná u přibližně 60 % pacientů s lehkými formami GvHD a pouze u přibližně 30 % pacientů s těžkou GvHD obecně. Kortikoterapie v kombinaci s dalšími imunosupresivními léky po aloSCT prohlubuje imunodeficit fragilních transplantovaných pacientů, a kromě nesporných benefitů má četné závažné dlouhodobé nežádoucí účinky. V rámci snahy o zlepšení péče o pacienty s GvHD se tak do praxe dostávají nové molekuly, působící proti GvHD jinými, více zacílenými mechanismy. Zásadním reprezentantem těchto molekul je ruxolitinib, inhibitor Janusových kináz 1 a 2 (JAK1/2). Ruxolitinib je nyní standardem léčby u pacientů se steroid-refrakterní akutní i chronickou GvHD.
Graft versus host disease (GvHD) remains a major life-threatening complication after allogeneic hematopoietic cell transplantation (alloSCT). GvHD generally develops in up to 50% of patients after alloSCT and clinically significant stages (stage III-IV acute GvHD or extensive chronic GvHD) occur in up to 20% of patients after alloSCT from an HLA-matched donor. The incidence of GvHD increases with each additional HLA mismatch. The reported mortality rate of GvHD is around 10%. The standard treatment for GvHD is systemic corticotherapy, which is successful in approximately 60% of patients with mild forms of GvHD and only in approximately 30% of patients with severe GvHD in general. Corticotherapy in combination with other immunosuppressive drugs after alloSCT exacerbates immunodeficiency in fragile transplanted patients and has numerous serious long-term side effects in addition to its undeniable benefits. Thus, in an effort to improve the care of GvHD patients, new molecules that counteract GvHD by different, more targeted mechanisms are coming into use. A major representative of these molecules is ruxolitinib, a Janus tyrosine kinase 1/2 (JAK 1/2) inhibitor that interferes with GvHD mechanisms at multiple levels. Ruxolitinib is now the standard of care for patients with steroid-refractory acute and chronic GvHD.
- Keywords
- ruxolitinib,
- MeSH
- Molecular Targeted Therapy classification methods MeSH
- Transplantation, Homologous classification methods MeSH
- Immunosuppression Therapy MeSH
- Janus Kinase Inhibitors * pharmacology classification adverse effects therapeutic use MeSH
- Clinical Studies as Topic MeSH
- Humans MeSH
- Graft vs Host Disease * diagnosis drug therapy MeSH
- Hematopoietic Stem Cell Transplantation methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Imunoterapie znamená průlom v léčebných paradigmatech některých hematologických malignit. Umožňuje posun od vysoce dávkovaných nespecifických chemoterapeutických protokolů k terapiím specifičtěji cíleným proti jednotlivým maligním komponentám. Kromě toho v mnoha případech stimuluje/moduluje vlastní imunitní systém proti nádorovému procesu, a je tedy všeobecně méně imunosupresivní než chemoterapeutické protokoly. Imunoterapie představuje velmi široký pojem, hrubě ji můžeme dělit na protilátkovou a buněčnou. Tento text má za cíl uvést nejzásadnější a nejperspektivnější postupy buněčné imunoterapie, a to nejen ve smyslu široce skloňovaných CAR-T lymfocytů.
Immunotherapy shifts therapeutic paradigms of several hematological malignancies. It enables a switch from high-dose, non-specific chemotherapy protocols to therapies more specifically targeted against individual malignant components. In many cases it aims to stimulate/support the body’s own immune system against the tumor process and is therefore generally less immunosuppressive than chemotherapy protocols. Immunotherapy represents a very broad issue. It can be roughly divided into antibody mediated and cellular immunotherapy. This text aims to outline the most relevant and promising cell-based approaches, not only in the sense of the widely inflected CAR-T lymphocytes.
- MeSH
- Killer Cells, Natural immunology MeSH
- Receptors, Chimeric Antigen immunology drug effects MeSH
- Hematologic Neoplasms * drug therapy classification MeSH
- Immunotherapy, Adoptive * classification methods MeSH
- Humans MeSH
- Graft vs Host Disease drug therapy immunology MeSH
- Hematopoietic Stem Cell Transplantation classification methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Mnohočetný myelom je onemocnění krvetvorby charakterizované proliferací atypických plazmatických buněk a nadprodukcí abnormálních imunoglobulinů. Je to druhá nejčastější hematologická malignita.1 Z definice se stále jedná o nevyléčitelné onemocnění, nicméně vzhledem k velmi progresivnímu vědeckému vývoji v oblasti myelomu se hranice kontrolování a léčení nemoci pomalu stírá. Imunoterapie jako taková je zásadním milníkem ve změně paradigmatu léčby mnohočetného myelomu, a právě monoklonální protilátky byly prvním krokem v této oblasti. Tento článek podává přehled monoklonálních protilátek užívaných v současnosti v léčbě mnohočetného myelomu.
Multiple myeloma is a disorder of the hematopoietic system characterized by proliferation of atypical plasma cells and overproduction of abnormal immunoglobulins. It is the second most common haematological malignancy.1 By definition, it is still an incurable disease, but along with the very progressive scientific developments of myeloma, the frontier of controlling and treating the disease is slowly blurring. Immunotherapy, as such, has been the major milestone in the paradigm shift in the treatment of multiple myeloma, and monoclonal antibodies were the first step in this field. This article reviews the monoclonal antibodies currently used in the treatment of multiple myeloma.
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
- Adult MeSH
- Quality of Life MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Recurrence, Local MeSH
- Multiple Myeloma * therapy MeSH
- Graft vs Host Disease * MeSH
- Disease-Free Survival MeSH
- Transplantation Conditioning adverse effects MeSH
- Retrospective Studies MeSH
- Hematopoietic Stem Cell Transplantation * adverse effects MeSH
- Stem Cell Transplantation adverse effects MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
