Kwalifikacja do opieki paliatywnej pacjentów leczonych przeszczepieniem komórek krwiotwórczych

Wszystkie działania podejmowane przez zespół prowadzący leczenie za pomocą przeszczepienia komórek krwiotwórczych (PKK) są nakierowane na prowadzenie agresywnej i bardzo dynamicznej terapii, której celem jest ratowanie życia i zdrowia. Zdarza się jednak, że w trakcie tej terapii, a nawet jeszcze przed jej wdrożeniem, mogą wystąpić wskazania do objęcia pacjenta opieką paliatywną (np. odrzucenie przeszczepu, ciężkie niepoddające się leczeniu powikłania przeszczepienia, nasilona oporna na terapię choroba przeszczep przeciwko biorcy). W prezentowanej pracy podjęto próbę zintegrowania dwóch całkowicie odrębnych działów medycyny i przedstawiono możliwe wskazania do opieki paliatywnej u pacjentów leczonych przeszczepieniem komórek krwiotwórczych.Medycyna Paliatywna w Praktyce 2014; 8, 3: 103–10

Evidence that platelet-derived microvesicles may transfer platelet-specific immunoreactive antigens to the surface of endothelial cells and CD34^+ hematopoietic stem/progenitor cells : implication for the pathogenesis of immune thrombocytopenias

The pathogenesis and tissue damage that accompanies destruction of platelets in immune thrombocytopenias (IT) is still not understood very well and in addition to platelets, other cells (e.g. endothelial cells, CD34+ hematopoietic stem/progenitors) may also become affected. Based on our previous work that platelet antigens (e.g., CD41) may be transferred by platelet-derived microvesicles (PMV) to the surface of other cells, we asked if platelet derived-antigens, especially those that are involved in the formation of anti-platelet antibodies in IT (e.g., against antigen HPA 1 a) could be also transferred by similar mechanism. To address this issue normal human CD34+ cells, human umbilical vein-endothelial cells (HUVEC) and monocytic cell line THP-1 were incubated with PMV derived from HPA1a+ donors. We noticed that the HPA1a antigen is highly expressed on PMV-derived from the HPAla positive platelets and is transferred in PMV-dependent manner to the surface of CD34+ cells, HUVEC and monocytic THP-1 cells. These cells covered with HPA1a positive PMV but not by PMV derived from HPAla negative platelets reacted with anti-HPA1a antibodies derived from the alloimmunized pregnant women. More importantly, human hematopoietic cells that were preincubated with HPA1a+ PMV and subsequently exposed to anti-HPA 1 a serum and human NK cells, become subject to elimination by antibody dependent cell cytotoxicity ADCC. Thus, we postulate that PMV-dependent transfer of antigens may playing an important role in "expanding" the population of target cells that may be affected by anti-platelet antibodies and explain several pathologies that accompany IT (e.g. damage of endothelium, cytopenias)

Chemokine receptors and chemokine production by CD34+ stem cell-derived monocytes in response to cancer cells

Background: The chemokine-chemokine receptor (CR) network is involved in the regulation of cellular infiltration of tumours. Cancer cells and infiltrating macrophages produce a whole range of chemokines. This study explored the expression of some CR and chemokine production by cord blood stem cell-derived CD34+ monocytes and their novel CD14++CD16+ and CD14+CD16– subsets in response to tumour cells. Material and Methods: CR expression was determined by flow cytometry and their functional activity by migration to chemoattractants. Monocytes were cultured with tumour cells and the chemokine content was assessed in culture supernatants. Results: CD14++CD16+ monocytes exhibited increased expression of chemokine (C-C) receptor (CCR) 1, while CD14+CD16– of CCR2, chemokine (C-X-C) receptor (CXCR) 1, 2 and 4. The increased expression of CCR2 on CD14+CD16– monocytes was associated with their enhanced migration to monocyte chemoattractant protein–1 (CCL2), MCP-3 (CCL7), MCP-2 (CCL8) and MCP-4 (CCL13), while that of CXCR1 and 2 to interleukin 8 (CXCL8), and CXCR4 to stromal cell-derived factor-1 (CXCL12). Tumour cells induced production of macrophage inflammatory protein-1α (CCL3) MIP-1β and regulated on activation normal T-cells expressed and secreted (CCL5) but not CCL2 or CXCL8, monokine induced by gamma interferon (CXCL9), interferon gamma-induced protein 10 (CXCL10). Conclusion: The studied monocyte subsets, in comparison to those from blood, exhibit different expression of CRs and response to the stimuli that occur from tumour cells

Anthropometric profile of pediatric patients undergoing allogeneic hematopoietic stem cell transplantation: a single center one-year follow-up study

Introduction: Hematopoietic stem cell transplantation (HSCT) is an aggressive form of therapy which leads to malnutri­tion requiring nutritional support. The aim of our study was to evaluate if the growth of children is affected by HSCT and what the relevant factors are. Methods: We analyzed changes in anthropometric measures of 79 pediatric patients who underwent allogeneic HSCT. Nutritional status was assessed based on weight and height measurements collected prior to HSCT and within 12 months post-transplantation. Body weight and height were referred to the age of patients using available z-score calculators. Results: Compared to the first measurement, the weight-for-age and height-for-age z-scores were significantly reduced in all following measurements within a 1-year follow-up. The most severe weight loss occurred on the last day of hospitalization related to HSCT, while the height gain declined progressively after HSCT. The presence of acute graft versus host disease (GvHD) and the use of a total body irradiation-based regimen were found to be risk factors for a severe slowdown of weight gain, while acute GvHD of the gastrointestinal tract, chronic GvHD and the use of parenteral nutri­tion were risk factors for a decline in height gain. Conclusions: Patients treated with allogeneic HSCT demonstrate a reduction in the pace of growth. HSCT recipients complicated by GvHD require prolonged and close weight and height monitorin

Low seroprevalence and low incidence of infection with "Toxoplasma gondii" (Nicolle et Manceaux, 1908) in pediatric hematopoietic cell transplantation donors and recipients : polish nationwide study

Czyzewski, Krzysztof, Fraczkiewicz, Jowita, Salamonowicz, Malgorzata, Pieczonka, Anna, Zajac-Spychala, Olga, Zaucha-Prazmo, Agnieszka, Gozdzik, Jolanta, Styczynski, Jan (2019): Low seroprevalence and low incidence of infection with Toxoplasma gondii (Nicolle et Manceaux, 1908) in pediatric hematopoietic cell transplantation donors and recipients: Polish nationwide study. Folia Parasitologica (019) 66: 1-6, DOI: 10.14411/fp.2019.019, URL: http://dx.doi.org/10.14411/fp.2019.01

Allogeneic Haematopoietic Stem Cell Transplantation as Therapy for Chronic Granulomatous Disease—Single Centre Experience

Chronic granulomatous disease (CGD) is phagocytic cell metabolic disorder resulting in recurrent infections and granuloma formation. This paper reports the favourable outcome of allogeneic transplantation in six high-risk CGD patients. The following donors were used: HLA-matched, related (two) and unrelated (three), and HLA-mismatched, unrelated (one). One patient was transplanted twice using the same sibling donor because of graft rejection at 6 months after reduced-intensity conditioning transplant (fludarabine and melphalan). Myeloablative conditioning regimen consisted of busulphan and cyclophosphamide. Stem cell source was unmanipulated bone marrow containing: 5.2 (2.6–6.5) × 108 nucleated cells, 3.8 (2.0–8.0) × 106 CD34+ cells and 45 (27–64) × 106 CD3+ cells per kilogramme. Graft-versus-host disease prophylaxis consisted of cyclosporine A and, for unrelated donors, short course of methotrexate and anti-T-lymphocyte globulin. Mean neutrophile and platelet engraftments were observed at day 22 (20–23) and day 20 (16–29), respectively. Pre-existing infections and inflammatory granulomas resolved. With the follow-up of 4–35 months (mean, 20 months), all patients are alive and well with full donor chimerism and normalized superoxide production