Transplantacija autolognih matičnih stanica u liječenju ne-Hodgkinovog limfoma

Substantial number of patients who present with non-Hodgkin’s lymphoma cannot be cured of their disease by conventional dose therapy. New data on treatment results in the past decade elucidate the role of high-dose therapy (HDT) and autologous bone marrow or peripheral blood stem cells in the treatment of malignant lymphomas. There is evidence from randomized studies that high-dose therapy followed by autografting for relapsed chemosensitive patients is superior to conventional chemotherapy in terms of disease-free and overall survival. For this group of patients autografting became a standard approach to therapy. Also the increasing evidences indicate that high-dose therapy and autotransplantation in first remission improves survival in high-risk patients. The toxicity of the procedure is substantially reduced in recent years. Several new methods are under investigation, like various forms of immunotherapy and radioimmunotherapy, with the aim to reduce the incidence of relapse following transplantation.Brojne bolesnike s ne-Hodgkinovim limfomom nije moguće izliječiti terapijom konvencionalnih doza. Novi podaci o rezultatima liječenja u posljednjem desetljeću rasvjetljavaju ulogu terapije velikim dozama i matičnih stanica autlogne koštane srži ili periferne krvi u liječenju zloćudnih limfoma. U randomiziranim je ispitivanjima dokazano da je terapija velikim dozama nakon koje slijedi autotransplantacija primijenjena u kemosenzitivnih bolesnika s relapsom uspješnija od konvencionalne kemoterapije s obzirom na sveukupno preživljenje bez znakova bolesti. Za tu je skuppinu bolesnika autotransplantacija postala standardna terapijska metoda. Sve je više dokaza koji pokazuju da se terapijom velikim dozama i autotransplantacijom kod prve remisije bolesti postiže bolje preživljenje u bolesnika izloženim velikom riziku. Toksičnost postupka posljednjih je godina znatno smanjena. Ispituje se nekoliko novih metoda, poput raznih oblika imunoterapije i radioimunoterapije, s ciljem da se pojavnost relapsa nakon transplantacije smanji

Transplantacija autolognih matičnih stanica u liječenju ne-Hodgkinovog limfoma

Substantial number of patients who present with non-Hodgkin’s lymphoma cannot be cured of their disease by conventional dose therapy. New data on treatment results in the past decade elucidate the role of high-dose therapy (HDT) and autologous bone marrow or peripheral blood stem cells in the treatment of malignant lymphomas. There is evidence from randomized studies that high-dose therapy followed by autografting for relapsed chemosensitive patients is superior to conventional chemotherapy in terms of disease-free and overall survival. For this group of patients autografting became a standard approach to therapy. Also the increasing evidences indicate that high-dose therapy and autotransplantation in first remission improves survival in high-risk patients. The toxicity of the procedure is substantially reduced in recent years. Several new methods are under investigation, like various forms of immunotherapy and radioimmunotherapy, with the aim to reduce the incidence of relapse following transplantation.Brojne bolesnike s ne-Hodgkinovim limfomom nije moguće izliječiti terapijom konvencionalnih doza. Novi podaci o rezultatima liječenja u posljednjem desetljeću rasvjetljavaju ulogu terapije velikim dozama i matičnih stanica autlogne koštane srži ili periferne krvi u liječenju zloćudnih limfoma. U randomiziranim je ispitivanjima dokazano da je terapija velikim dozama nakon koje slijedi autotransplantacija primijenjena u kemosenzitivnih bolesnika s relapsom uspješnija od konvencionalne kemoterapije s obzirom na sveukupno preživljenje bez znakova bolesti. Za tu je skuppinu bolesnika autotransplantacija postala standardna terapijska metoda. Sve je više dokaza koji pokazuju da se terapijom velikim dozama i autotransplantacijom kod prve remisije bolesti postiže bolje preživljenje u bolesnika izloženim velikom riziku. Toksičnost postupka posljednjih je godina znatno smanjena. Ispituje se nekoliko novih metoda, poput raznih oblika imunoterapije i radioimunoterapije, s ciljem da se pojavnost relapsa nakon transplantacije smanji

Thrombotic Thrombocytopenic Purpura – The Role of ADAMTS13 Assay in Clinical Practice

Thrombotic thrombocytopenic purpura (TTP) is a disorder characterized by disseminated thrombotic occlusions of the microcirculation. Identification of ADAMTS13 protease and its place in the pathophysiology of TTP led to better understanding of the disease and better survival for the diseased. Here we show a case report of a patient that had a normal ADAMTS13 protease activity and an unusual clinical presentation and utilize that case to highlight how the absence of a severe ADAMTS13 protease deficiency does not preclude a diagnosis of TTP and how early initiation and continuation of plasma exchange therapy can lead to a positive outcome, even in a severely ill patient. Even though ADAMTS13 protease determination has no immediate influence on the decision whether or not to start the plasma exchange therapy, it has great impact on future management of the patient and should be determined whenever possible

Učinkovitost venetoklaksa u liječenju relapsirajuće i refraktorne akutne mijeloične leukemije

The most common acute leukemia in adults is acute myeloid leukemia (AML) and it is mainly treated with cytarabine and anthracyclines. Although this combination of drugs is effective for most patients, some of them experience relapse and require new strategies. Recently venetoclax, a drug that blocks B-cell lymphoma-2 (Bcl-2) protein and leads to programmed cell death, was approved for use in the treatment of AML. Here we present a patient with relapsed AML after allogeneic hematopoietic stem cell transplantation (HSCT) who was successfully treated with venetoclax.Najčešća leukemija u odraslih je akutna mijeloična leukemija (AML) i poglavito se liječi citarabinom i antraciklinima. Iako je ova kombinacija lijekova učinkovita za većinu pacijenata, neki od njih dožive relaps i zahti- jevaju nove strategije. U posljednje vrijeme je venetoklaks, lijek koji blokira B-stanični limfom-2 (Bcl-2) protein i vodi u programiranu staničnu smrt, odobren za liječenje AML-a. U ovom prikazu, prezentiramo pacijenta s relapsom AML-a nakon transplantacije alogenih hematopoetskih matičnih stanica koji je uspješno liječen venetoklaksom

The Importance of a Watchful Eye: Multiple Infections in Immunocompromised Patient

Immunocompromised patients are a unique subset of the population that requirespecial attention and care. These individuals are susceptible to a wide range of infections and illnesses, and even minor symptoms can be indicative of a more serious underlying condition. Unfortunately, due to the immunocompromised state, symptoms can often be less severe or easily overlooked, leading to delayed diagnosis and treatment

Kompleksna varijantna translokacija Philadelphia kromosoma koja uključuje kromosome 1, 9, 12 i 22 u slučaju kronične mijeloične leukemije (KML)

Aim: Chronic myeloid leukemia (CML) is characterized by the Philadelphia (Ph) chromosome created by the reciprocal translocation t(9;22)(q34;q11), resulting in the hybrid gene breakpoint cluster region - Abelson (BCR-ABL1). Around 5–10% of CML cases develop complex variant Ph translocations involving one or more chromosomal regions besides 9 and 22. We report in this study a case of acute lymphoblastic leukemia (ALL) developed from CML displaying a novel four-way translocation. Case report: Complete blood analysis of 46-year-old male patient showed an increase in white blood cells, lower levels of red blood cells and platelets. Bone-marrow sample was subjected to conventional cytogenetic (Giemsa-banding) and fluorescence in situ hybridization methods and four - way translocation was identified. Considering hepatosplenomegaly and breakpoint cluster region that was characterized as major (M-bcr) on quantitative real-time polymerase chain reaction (RQ-PCR), ALL was diagnosed as a transformation from CML. Conclusion: This study reports new four-way translocation ins(22;1)(q11.2;q31q32)t(1;9;12;22)(q32;q34;q13;q11.2) in an ALL patient developed from the CML and was cross-checked in Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer.Cilj: Kronična mijeloična leukemija (KML) karakterizirana je Philadelphia kromosomom (Ph), koji nastane recipročnom translokacijom t(9;22)(q34;q11.2), i rezultira fuzijskim genom BCR-ABL1. Kompleksna varijantna translokacija uključuje jos jedan ili više kromosoma uz kromosome 9 i 22, te se javlja u 5-10% svih slučajeva KML. U ovoj studiji prijavljujemo novi slučaj varijantne akutne limfoblastične leukemije (ALL) koja se transformirala iz KML. Prikaz slučaja: Kompletna krvna slika 46-godišnjeg pacijenta pokazala je povećane vrijednosti bijelih krvnih stanica, a snižene vrijednosti crvenih krvih stanica i trombocita. Uzorak koštane srži (KS) poslan je na klasičnu citogenetičku (Giemsa-pruganje) i fluorescentu in situ hibridizacijsku (FISH) analizu kojima je potvrđena nova varijantna translokacija između četiri kromosoma. Obzirom na hepatosplenomegaliju i područje prijelomne točke koja je karakterizirana kao „major“ (M-bcr) korištenjem kvantitativne polimerazne lančane reakcije u stvarnom vremenu, dijagnosticirana je ALL u transformaciji iz KML. Zaključak: Ova studija prijavljuje novu varijantnu translokaciju koja obuhvaća 4 kromosoma ins(22;1)(q11.2;q31q32)t(1;9;12;22)(q32;q34;q13;q11.2) kod pacijenta sa ALL transformiranom iz KML, na temelju provjere u bazama podataka „Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer“

Amniotic membrane transplantation for severe ocular graft-versus-host disease following allogeneic hematopoietic stem cell transplantation

Allogeneic stem cell transplantation (allo-SCT) offers cure to otherwise incurable hematologic malignancies, but can also lead to many infectious and immune complications, most importantly graft-versus-host disease (GVHD). Ocular GVHD (oGVHD) occurs in 40-60% of allo-SCT patients and can result in severe ocular surface disease causing vision impairment and deterioration of quality of life. Amniotic membrane transplantation (AMT) is an established technique in the treatment of various diseases of the ocular surface. This method could provide new options in the management of otherwise disabling severe oGVHD We describe a young female patient with myeloproliferative neoplasm who underwent allo-SCT from an unrelated donor and suffered from numerous post-transplant complications. In the early post-transplant period she developed acute skin and liver GVHD, requiring introduction of immunosupressive treatment with steroids. Steroid treatment was then complicated with miopathy, iatrogenic diabetes and many infections. She developed serious herpes virus (HSV) ophtalmitis followed by severe GVHD of the eye. Despite multiagent local therapy, oGVHD progressed to ocular ulcers with threatening corneal perforation. We hesitated from increasing systemic immunosupression due to severity of previous HSV reactivation. Therefore we decided to perform AMT which led to complete corneal healing and full clinical recovery. Moreover, there was no recurrence of severe oGVHD and the patient resumed her daily activities In conclusion, this case report serves as a foundation for further research of AMT possibilities. This procedure could become beneficial in the treatment of severe oGVHD, especially in patients at high risk for infectious complications and contraindication for systemic immunosuppression

Febrilne reakcije nakon infuzije krvotvornih matičnih stanica češće su ukoliko se ne primijeni premedikacija kortikosteroidima što rezultira većom upotrebom antibiotika rano nakon transplantacije

Background: There is no consensus as to the need for steroid premedication before fresh product hematopoietic stem cell (HSC) infusion. In case of febrile reaction post-HSC infusion, on-call staff frequently prescribe antibiotics empirically. Considering the recent data on the value of microbiota and its influence on GVHD incidence, we analysed the frequency of febrile reactions and the use of antibiotic after HSC infusion in 149 consecutive patients. Methods: In the time period between 1/2018 and 10/2019, 149 patients were subject to transplantation in our institution. Per institutional standard operating procedure (SOP), all the patients received premedication before hematopoietic stem cell infusion consisting of 20 mg chloropyramine-chlorid iv, and in case of ABO incompatible graft 1 mg/kg methylprednisolone iv. Retrospective data was collected by using patient charts. Survival probability was calculated by applying Kaplan-Meier method. Results: Fifty-two patients received steroids, 12 patients (23%) developing fever after graft infusion, 46 patients received no steroids, 26 of them (57%) developed fever (p<0.001). There was no difference in the number of patients having positive blood cultures. Nine (17%) and 16 (35%) patients received IV antibiotics in the “steroid” and no-steroid” group, respectively (p<0.05). There was no difference in survival between “steroid” and “no-steroid” group. Conclusions: Even with no difference in the frequency of febrile episodes caused by systemic infection, a significantly more patients not receiving steroid premedication develop fever and are treated with IV antibiotics, which could potentially have further implications on transplantation outcomes due to its influence on microbiota early post-transplant.Uvod: Trenutno ne postoji konsenzus o potrebi primjene premedikacije kortikosteroidima prije infuzije svježih krvotvornih matičnih stanica (KMS). U slučaju febrilne reakcije nakon infuzije KMS-a, dežurno osoblje često propiše antibiotike empirijski. Uzimajući u obzir nedavne podatke o vrijednosti mikrobiote i njezinom utjecaju na incidenciju GVHD-a, analizirali smo učestalost febrilnih reakcija i uporabu antibiotika nakon infuzije KMS-a u 149 uzastopna bolesnika. Metode: U razdoblju između 1/2018. i 10/2019. u našoj je ustanovi transplantirano ukupno 149 pacijenata. Prema institucionalnom standardnom operativnom postupku (SOP), svi su pacijenti primali premedikaciju prije infuzije krvotvornih matičnih stanica koja se sastojala od 20 mg kloropiramin-klorida iv, a u slučaju ABO inkompatibilnog presatka i 1 mg / kg metilprednizolona iv. Retrospektivno su prikupljeni podaci koristeći povijesti bolesti pacijenata. Vjerojatnost preživljavanja izračunata je Kaplan-Meierovom metodom. Rezultati: Pedeset i dva bolesnika su primila kortikosteroide, od njih je 12 bolesnika (23%) razvilo vrućicu nakon infuzije presatka, dok 46 bolesnika nije primilo kortikosteroide, a od njih je 26 (57%) razvilo vrućicu (p <0,001). Nije bilo razlike u broju bolesnika koji su imali pozitivne hemokulture. U skupini koja je primila kortikosteroide, 9 (17%) bolesnika je liječeno iv antibioticima, dok je u skupini koja nije primala kortikosteroide, 16 (35%) bolesnika liječeno iv antibioticima (p <0,05). Nije bilo razlike u preživljenju između te dvije skupine. Zaključci: Čak i bez razlike u učestalosti febrilnih epizoda uzrokovanih sistemskom infekcijom, znatno više pacijenata koji nisu dobili premedikaciju je razvilo vrućicu i liječilo se iv antibioticima, što bi potencijalno moglo imati daljnje implikacije na ishode transplantacije zbog utjecaja na mikrobiotu rano nakon transplantacije