CAN A REDUCED DOSE OF CYTARABINE BE AS EFFECTIVE AS FULL DOSE IN THE TREATMENT OF PRIMARY DIFFUSE B-CELL LYMPHOMA IN MATRix PROTOCOL?

Primarni limfom središnjeg živčanog sustava rijetki je agresivan non-Hodgkinov limfom. Suvremeni pristup liječenju bolesnika podobnih za intenzivnu imuno-kemoterapiju uključuje faze indukcije i konsolidacije. IELSG32, randomizirano ispitivanje Međunarodne grupe za istraživanje ekstranodalnih limfoma (engl. International Extranodal Lymphoma Study Group) pokazalo je kako u indukcijskoj fazi kombinacija visokih doza metotreksata, citarabina, tiotepe i rituksimaba praćena konsolidacijom autolognom transplantacijom krvotvornih matičnih stanica znatno poboljšava ishode tih bolesnika. Retrospektivno je analizirano sedmero bolesnika s novo dijagnosticiranim primarnim limfomom mozga liječenih od listopada 2018. do veljače 2022. godine koji su primili MATRix protokol kemoterapije s reduciranom dozom citarabina. Primijenjena doza iznosila je 2000 mg/m2 svakih 12 sati trećeg dana ciklusa. Četvrtog dana ciklusa citarabin je izostavljen kod svih bolesnika. Pet bolesnika postiglo je kompletnu remisiju, a jedan parcijalnu remisiju. Kod većine bolesnika na indukcijsku fazu nastavljena je konsolidacija transplantacijom krvotvornih matičnih stanica. Kod jednog bolesnika zabilježena je progresija bolesti tri mjeseca nakon autologne transplantacije krvotvornim matičnim stanicama. Terapijske nuspojave su usporedive i slične s rezultatima IELSG32, s naglaskom da su se hematološke toksičnosti gradusa 4 javljale u malim brojevima. S obzirom na prikazane kliničke slučajeve postavlja se pitanje bi li niža doza citarabina u MATRix protokolu mogla biti jednako učinkovita kao i puna doza u postizanju remisije bolesti primarnog B-velikostaničnog limfoma mozga.Primary diffuse B-cell brain lymphoma is a rare, aggressive non-Hodgkin’s lymphoma. The modern approach to treatment involves two phases, induction and consolidation. IELSG32, a randomized trial by the International Extranodal Lymphoma Study Group, showed that in the induction phase, the combination of high doses of methotrexate, cytarabine, thiotepa, and rituximab followed by consolidation therapy with autologous hematopoietic stem cell transplantation signifi cantly improved outcomes in these patients. We aim here to present characteristics and outcomes of seven patients with newly diagnosed primary central nervous system lymphoma who were treated between November 2018 and February 2022. All of them received the MATRix reduced-dose cytarabine chemotherapy protocol. The dose of cytarabine was 2000 mg/ m2 every 12 hours on the third day of the cycle. On the fourth day of the cycle, cytarabine was completely omitted in all patients. Five patients achieved complete remission and one patient achieved partial remission after completion of the induction therapy at a reduced dose, followed by autologous hematopoietic stem cell transplantation in most patients. One patient had progression of the disease three months after autologous hematopoietic stem cell transplantation. Therapeutic toxicities were similar to IELSG32 results with emphasis on the fact that hematologic toxicities of grade 4 occurred in a low percentage. The above raises a question whether a reduced dose of cytarabine in MATRix protocol be as effective as full dose in achieving disease remission

CAN A REDUCED DOSE OF CYTARABINE BE AS EFFECTIVE AS FULL DOSE IN THE TREATMENT OF PRIMARY DIFFUSE B-CELL LYMPHOMA IN MATRix PROTOCOL?

Primarni limfom središnjeg živčanog sustava rijetki je agresivan non-Hodgkinov limfom. Suvremeni pristup liječenju bolesnika podobnih za intenzivnu imuno-kemoterapiju uključuje faze indukcije i konsolidacije. IELSG32, randomizirano ispitivanje Međunarodne grupe za istraživanje ekstranodalnih limfoma (engl. International Extranodal Lymphoma Study Group) pokazalo je kako u indukcijskoj fazi kombinacija visokih doza metotreksata, citarabina, tiotepe i rituksimaba praćena konsolidacijom autolognom transplantacijom krvotvornih matičnih stanica znatno poboljšava ishode tih bolesnika. Retrospektivno je analizirano sedmero bolesnika s novo dijagnosticiranim primarnim limfomom mozga liječenih od listopada 2018. do veljače 2022. godine koji su primili MATRix protokol kemoterapije s reduciranom dozom citarabina. Primijenjena doza iznosila je 2000 mg/m2 svakih 12 sati trećeg dana ciklusa. Četvrtog dana ciklusa citarabin je izostavljen kod svih bolesnika. Pet bolesnika postiglo je kompletnu remisiju, a jedan parcijalnu remisiju. Kod većine bolesnika na indukcijsku fazu nastavljena je konsolidacija transplantacijom krvotvornih matičnih stanica. Kod jednog bolesnika zabilježena je progresija bolesti tri mjeseca nakon autologne transplantacije krvotvornim matičnim stanicama. Terapijske nuspojave su usporedive i slične s rezultatima IELSG32, s naglaskom da su se hematološke toksičnosti gradusa 4 javljale u malim brojevima. S obzirom na prikazane kliničke slučajeve postavlja se pitanje bi li niža doza citarabina u MATRix protokolu mogla biti jednako učinkovita kao i puna doza u postizanju remisije bolesti primarnog B-velikostaničnog limfoma mozga.Primary diffuse B-cell brain lymphoma is a rare, aggressive non-Hodgkin’s lymphoma. The modern approach to treatment involves two phases, induction and consolidation. IELSG32, a randomized trial by the International Extranodal Lymphoma Study Group, showed that in the induction phase, the combination of high doses of methotrexate, cytarabine, thiotepa, and rituximab followed by consolidation therapy with autologous hematopoietic stem cell transplantation signifi cantly improved outcomes in these patients. We aim here to present characteristics and outcomes of seven patients with newly diagnosed primary central nervous system lymphoma who were treated between November 2018 and February 2022. All of them received the MATRix reduced-dose cytarabine chemotherapy protocol. The dose of cytarabine was 2000 mg/ m2 every 12 hours on the third day of the cycle. On the fourth day of the cycle, cytarabine was completely omitted in all patients. Five patients achieved complete remission and one patient achieved partial remission after completion of the induction therapy at a reduced dose, followed by autologous hematopoietic stem cell transplantation in most patients. One patient had progression of the disease three months after autologous hematopoietic stem cell transplantation. Therapeutic toxicities were similar to IELSG32 results with emphasis on the fact that hematologic toxicities of grade 4 occurred in a low percentage. The above raises a question whether a reduced dose of cytarabine in MATRix protocol be as effective as full dose in achieving disease remission

Interferencija biokemijskih testova u bolesnika liječenog eltrombopagom

46 godišnji bolesnik s ranije dijagnosticiranom imunom trombocitopenijom (ITP) hospitaliziran je zbog laboratorijskih i kliničkih znakova trombocitopenije tj. hematoma i hematurije.. Prethodno je liječen metilprednizolonom, imunoglobulinom, rituksimabom i romiplostinom. Ovog puta smo se odlučili za liječenje eltrombopagom, peroralnim agonistom trombopoetinskih receptora u dozi od 50mg dnevno prema smjernicama koje se koriste kao trajna terapija u drugoj ili kasnijoj liniji liječenja bolesnika s ITP-om. Prije početka liječenja eltrombopagom rutinski biokemijski nalazi su bili uredni izuzev vrijednosti triglicerida (3,5 mmol/L). Nakon primjene eltrombopaga ponavljali smo biokemijske nalaze svaka 2 tjedna, ukupno pet puta. Iz ponovljenih nalaza zapažamo značajan porast lipidograma i to kolesterola s 4,4 na 6–8,1 mmol/L, HDL-a s 1,1 na 1,1–1,6 mmol/L, LDL-a s 1,6 na 2,9–3,9 mmol/L i triglicerida s 3,5 na 5,0–8,9 mmol/L. Napominjemo da je isključen mogući utjecaj drugih lijekova te nije bilo promjena u količini i učestalosti konzumiranja masnoća i alkohola. Također nije bilo laboratorijskih niti kliničkih znakova oštećenja jetre ili poremećaja rada štitnjače. Isto tako, nije bilo promjena vrijednosti ukupnog bilirubina i kreatinina kao što se navodi u uputstvima lijeka. Prema navedenom kao i podatku iz laboratorija da serum ni u jednom slučaju nije bio lipemičan, smatram da je interferencija lijeka s biokemiskim testovima bio uzrok hiperlipidemije. Eltrombopag je inače vrlo obojena molekula zbog čega postoji interferencija s biokemijskim testovima. Do sada u literaturi nije bilo opisanog slučaja o utjecaju eltrombopaga na vrijednosti lipida. U svrhu dobivanja valjanih rezultata biokemijskih nalaza preporuča se korelacija s kliničkom slikom, ponovno testiranje, primjena drugih biokemijskih testova kao i metoda razrjeđivanja

Podnošljivost kombinacija obinutuzumaba i viših doza klorambucila u prvoj liniji liječenja kronične limfocitne leukemije

Podnošljivost kombinacija obinutuzumaba i viših doza klorambucila u prvoj liniji liječenja kronične limfocitne leukemij

Podnošljivost kombinacija obinutuzumaba i viših doza klorambucila u prvoj liniji liječenja kronične limfocitne leukemije

Podnošljivost kombinacija obinutuzumaba i viših doza klorambucila u prvoj liniji liječenja kronične limfocitne leukemij

Treatment-Related Risk Factors for Adverse Outcomes of COVID-19 in Patients Treated for Lymphoid Malignancies in the Pre-Omicron Era—A Study of KroHem, the Croatian Group for Hematologic Diseases

Patients with lymphoid malignancies are at increased risk of death or prolonged infection due to COVID-19. Data on the influence of different antineoplastic treatment modalities on outcomes are conflicting. Anti-CD20 monoclonal antibodies increase the risk of prolonged infection. It is unclear whether this risk is affected by the choice of the antibody (rituximab vs. obinutuzumab). To elucidate the role of antineoplastic therapy on COVID-19 outcomes, KroHem collected data on patients with lymphoid malignancies diagnosed with COVID-19 between October 2020 and April 2021. A total of 314 patients were identified, 75 untreated, 61 off treatment and 178 on treatment. The mortality rate in untreated and off-treatment patients was 15% and 16%; 9% and 10% had prolonged infection. In the on-treatment group, 3% were still prolonged positive at time of data collection, 62% recovered and 35% died; 42% had prolonged infection. Disease type, use of anti-CD20 monoclonal antibodies, prior autologous stem-cell transplantation (ASCT) and line of treatment did not significantly affect mortality. Mortality was higher in older patients (p = 0.0078) and those treated with purine analogues (p = 0.012). Prolonged COVID-19 was significantly more frequent in patients treated with anti-CD20 monoclonal antibodies (p = 0.012), especially obinutuzumab, and purine analogues (p = 0.012). Age, prior ASCT and treatment line did not significantly affect risk of prolonged infection. These data suggest that increased age and use of purine analogues are main risk factors for increased mortality of COVID-19 in patients with lymphoid malignancies. Obinutuzumab further increases the risk of prolonged disease, but not of death, in comparison to rituximab. Epidemiological considerations should be taken into account when choosing the appropriate antineoplastic therapy for patients with lymphoid malignancies