Zastosowanie infuzyjnego schematu chemioterapii DA-EPOCH w leczeniu chłoniaków agresywnych

WstępStandardowe leczenie chłoniaków nie-Hodgkinowskich (non-Hodgkin lymphoma, NHL) oparte jest na stosowanym od ponad 30 lat schemacie CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). W przypadku niektórych podtypów NHL, wyniki leczenia schematami CHOP-podobnymi są niewystarczające lub wymagają zastosowania uzupełniającej radioterapii. W latach 90-tych XX wieku wprowadzono do praktyki schematy leczenia polegające na podawaniu cytostatyków w długotrwałych wlewach i dawkach dostosowanych do parametrów farmakodynamicznych.Celem pracy było przedstawienie doświadczenia jednego ośrodka w stosowaniu schematu DA-EPOCH (dose adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) w leczeniu NHL. Materiały i metodyPoddano obserwacji 13 chorych leczonych z powodu trzech różnych podtypów NHL: pierwotnego chłoniaka śródpiersia, chloniaka „szarej strefy“ oraz anaplastycznego chłoniaka z dużych limfocytów T. Chory z NHL z komórek T otrzymał schemat DA-EPOCH, chorzy z NHL B-komórkowymi DA-EPOCH z dodatkiem rituximabu. Ocenę odpowiedzi przeprowadzono metodą pozytonowej tomografii emisyjnej. WynikiW okresie 22 miesięcy podano łącznie 94 cykle DA-EPOCH (+/-R). U wszystkich pacjentów w czasie leczenia zaobserwowano neutropenię poniżej 0,5 G/l. Spośród 13 pacjentów, u 12 oceniono odpowiedź po zakończeniu leczenia. Całkowitą odpowiedź metaboliczną uzyskano u 9 chorych, a u 2 odpowiedź częściową. Całkowity odsetek odpowiedzi wyniósł 91%. U 1 pacjentki zaobserwowano progresję NHL. Obserwowano nieznaczną toksyczność leczenia, głównie hematologiczną. Nie zaobserwowano zgonów związanych z chemioterapią. WnioskiZebrane doświadczenia pozwalają uznać schemat DA-EPOCH za bezpieczny, skuteczny i łatwy do stosowania w warunkach oddziału szpitalnego

The beneficial role of allogenic hematopoietic cell transplantation in blastic plasmacytoid dendritic cell neoplasm

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare aggressive hematopoietic malignancy. The median survival is approximately 12 months, and for patients >65 years the survival rate is 7 months, when only chemotherapy is administered. Clinically, it is characterized by skin involvement and most often bone marrow lesions accompanied by lymphadenopathy and in some cases hepato- and/or splenomegaly. The diagnosis is based on histopathological examination of the skin or bone marrow lesions and tumor cell immunophenotyping. The etiopathogenesis of the disease is not fully understood. Therapeutic decisions are based only on the results of a few retrospective analyses and case reports. This article presents the important role of allogeneic hematopoietic cell transplantation in the treatment of BPDCN

Treatment of Graft-versus-Host Disease with Naturally Occurring T Regulatory Cells

A significant body of evidence suggests that treatment with naturally occurring CD4(+)CD25(+) T regulatory cells (Tregs) is an appropriate therapy for graft-versus-host disease (GvHD). GvHD is a major complication of bone marrow transplantation in which the transplanted immune system recognizes recipient tissues as a non-self and destroys them. In many cases, this condition significantly deteriorates the quality of life of the affected patients. It is also one of the most important causes of death after bone marrow transplantation. Tregs constitute a population responsible for dominant tolerance to self-tissues in the immune system. These cells prevent autoimmune and allergic reactions and decrease the risk of rejection of allotransplants. For these reasons, Tregs are considered as a cellular drug in GvHD. The results of the first clinical trials with these cells are already available. In this review we present important experimental facts which led to the clinical use of Tregs. We then critically evaluate specific requirements for Treg therapy in GvHD and therapies with Tregs currently under clinical investigation, including our experience and future perspectives on this kind of cellular treatment

The molecular profile in patients with polycythemia vera and essential thrombocythemia is dynamic and correlates with disease’s phenotype

IntroductionPolycythemia vera (PV) and essential thrombocythemia (ET) are diseases driven by canonical mutations in JAK2, CALR, or MPL gene. Previous studies revealed that in addition to driver mutations, patients with PV and ET can harbor other mutations in various genes, with no established impact on disease phenotype. We hypothesized that the molecular profile of patients with PV and ET is dynamic throughout the disease.MethodsIn this study, we performed a 37-gene targeted next-generation sequencing panel on the DNA samples collected from 49 study participants in two-time points, separated by 78-141 months. We identified 78 variants across 37 analyzed genes in the study population.ResultsBy analyzing the change in variant allele frequencies and revealing the acquisition of new mutations during the disease, we confirmed the dynamic nature of the molecular profile of patients with PV and ET. We found connections between specific variants with the development of secondary myelofibrosis, thrombotic events, and response to treatment. We confronted our results with existing conventional and mutation-enhanced prognostic systems, showing the limited utility of available prognostic tools.DiscussionThe results of this study underline the significance of repeated molecular testing in patients with PV and ET and indicate the need for further research within this field to better understand the disease and improve available prognostic tools

Clinical characteristics of essential thrombocythemia patients depend on the mutation status

The impact of the mutation status on the clinical course and the outcome of essential thrombocythemia (ET) patients has not yet been completely established. A total of 171 patients with diagnosed ET were tested and subsequently grouped, according to their mutation status – Janus Kinase 2 () – 112 patients, calreticulin () – 36 patients, and thrombopoietin receptor () – 5 patients. Moreover, 18 individuals were triple-negative (with non-mutated , , and ). -mutated patients preferentially were male, with higher platelets (PLT) counts (mean PLT = 1 002.3) and lower hemoglobin and hematocrit levels at the diagnosis, compared to the (mean PLT = 933.6), (mean PLT = 940.8) and triple-negative patients (mean PLT = 822.6) ( = 0.0035). The patients with mutated, and the triple-negative ones had a lower risk of arterial and venous thrombosis (3% and 5.6% cases at the time of diagnosis, respectively) than the patients with mutation (7.2%) ( = 0.9210). The overall survival rate did not differ statistically between the groups

Opieka ginekologiczna po transplantacji komórek krwiotwórczych – zalecenia na podstawie piśmiennictwa i własnych doświadczeń

Transplantacja komórek krwiotwórczych ( – HCT ) jest ugruntowaną metodą leczenia zarówno nienowotworowych, jak i rozrostowych chorób układu krwiotwórczego. U kobiet wiąże się jednak z występowaniem powikłań wczesnych i późnych dotyczących układu moczowo-płciowego. Konsekwencją gonadotoksycznego postępowania przygotowawczego (chemioterapii i radioterapii) jest przedwczesne wygaśnięcie funkcji jajników. U biorczyń allogenicznych przeszczepów ( HCT, allo-HCT) dodatkowo występują powikłania związane z występowaniem przewlekłej choroby przeczep przeciw gospodarzowi ( cGvHD) w istotny sposób upośledzające jakość życia kobiet w przypadku zajęcia strefy anogenitalnej (GvHDgyn). Dodatkowo przewlekła immunosupresja sprzyja występowaniu wtórnych nowotworów układu moczowo-płciowego. Pacjentki po HCT, szczególnie obciążone cGvHD, wymagają długoletniej interdyscyplinarnej opieki, włączając opiekę ginekologiczną. W pracy przedstawiono problemy ginekologiczne pacjentek po HCT oraz zaproponowano schemat standardu opieki ginekologicznej po transplantacji na podstawie piśmiennictwa i własnych doświadczeń

Antifungal management in adults and children with hematological malignancies or undergoing hematopoietic cell transplantation: recommendations of Polish Society of Hematology and Blood Transfusion, Polish Society of Pediatric Oncology and Hematology, and Polish Adult Leukemia Study Group, 2020

Invasive fungal disease (IFD) is one of the most serious complications of therapy in patients with immune suppression. It particularly concerns patients treated for malignant hematological diseases, immune deficiencies, or undergoing hematopoietic cell transplantation (HCT). Development of IFD can abrogate the effect of previous therapy and contributes to dismal outcome of the underlying disease. The Working Group consisting of members of the Polish Society of Hematology and Blood Transfusion, the Polish Society of Pediatric Oncology and Hematology, and the Polish Adult Leukemia Study Group has prepared recommendations for the diagnostic and therapeutic management of IFD in adults and children. This paper presents the current recommendations for patients in immune suppression treated in Polish pediatric and adult hematology and HCT centers, based on the guidelines of the European Conference on Infections in Leukaemia (ECIL) 2015–2019. Levels of diagnosis of IFD (possible, probable, and proven) and antifungal management (prophylaxis, as well as empirical and targeted therapies) are declared according to updated international criteria of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) 2019. Patients with primary diagnosis of acute lymphoblastic leukemia, acute myeloblastic leukemia, severe aplastic anemia, chronic granulomatous disease, and severe combined immunodeficiency, as well as patients after allogeneic HCT, are included in the high-risk groups for development of IFD. For these patients, antifungal prophylaxis based on azoles or micafungin is recommended. In empirical therapy, caspofungin or liposomal/lipid formulas of amphotericin B are recommended. The Working Group has discouraged the use of itraconazole in capsules and amphotericin deoxycholate. Detailed guidelines for first- and second-line targeted therapies for invasive candidiasis, aspergillosis, mucormycosis, fusariosis, and scedosporiosis, as well as the principles of the recommended dosing of antifungals, are presented in this paper

Long-term allogeneic hematopoietic cells transplantation survivors proinflammatory cytokine profile compared to their respective donors and immunophenotype differences depending on GvHD history and infection status

Background In the course of allogeneic hematopoietic cell transplantation (allo-HCT) the donor’s hematopoietic progenitor cells are exposed to immense proliferative stress to reconstitute in the recipient the functional hematopoiesis. Moreover, recipients who develop infections or chronic GvHD are subjected to further proliferative stress, especially in the lymphocyte subset. We hypothesized that allo-HCT may induce changes in proinflammatory cytokines profile and immunophenotype in the allo-HCT recipients, especially in patients with cGVHD history. We compared the cytokine profile (Il-6, Il-10, and TNF-) between long-term allo-HCT recipients and their respective donors and we analyzed cytokines profile and the immunophenotype of lymphocytes in long-term recipients grouped according to the infection and GvHD history. Results We have found no differences in the proinflammatory cytokines between allo-HCT recipients and their respective donors, as well as between recipients grouped according to infectious risk status. Immunophenotyping of recipients grouped according to GvHD status revealed an increased percentage of B-cell presenting PD-1 in recipients without a history of GvHD. Conclusions Lack of differences in proinflammatory cytokines concentrations between recipients and donors of allo-HCT would suggest that allo-HCT does not induce acceleration of the inflammageing-resembling phenomenon. No differences in the cytokine profile and immunophenotype between recipients grouped according to infectious risk status suggest that infectious risk is not reflected by the immunophenotype and cytokine profile. Furthermore, the lack of significant differences in immunophenotype of the recipients grouped according to the history of GvHD may suggest that in long-term survivors the immune system tends to stabilize with time

Pancreatic islet transplantation in a simultaneous pancreas and kidney transplant recipient — a case report

Beta cell replacement allows for adequate blood glucose control, reduced progression or even reversal of microvascular complications, and improves the quality of life. Simultaneous pancreas and kidney transplantation is the best therapeutic option for patients with type 1 diabetes and end-stage renal disease resulting from diabetic nephropathy. However, when pancreas transplantation is contraindicated or unavailable, pancreatic islet transplantation is an alternative minimally invasive procedure. We report a patient after earlier simultaneous kidney and pancreas transplantation with a failed pancreas graft, and no option for pancreas retransplantation. In this patient pancreatic islet transplantation was performed. The latter resulted in an improved blood glucose control, restoration of hypoglycaemia awareness, and improved quality of life with stable good function of the kidney allograft.Beta cell replacement allows for adequate blood glucosecontrol, reduced progression or even reversal ofmicrovascular complications, and improves the qualityof life. Simultaneous pancreas and kidney transplantationis the best therapeutic option for patients withtype 1 diabetes and end-stage renal disease resultingfrom diabetic nephropathy. However, when pancreastransplantation is contraindicated or unavailable, pancreaticislet transplantation is an alternative minimallyinvasive procedure. We report a patient after earliersimultaneous kidney and pancreas transplantationwith a failed pancreas graft, and no option for pancreasretransplantation. In this patient pancreatic islettransplantation was performed. The latter resultedin an improved blood glucose control, restoration ofhypoglycaemia awareness, and improved quality oflife with stable good function of the kidney allograft