Leczenie żywieniowe pacjentów poddawanych przeszczepieniu macierzystych komórek krwiotwórczych

Hematopoietic stem cell transplantation (HSCT) – the highly aggressive therapeutic process – is connected with high risk of side effects and complications, which influence nutritional management.Moreover, limitation of possibility of nutrients delivery is accompanied by simultaneous increase in requirement for nutritional elements. Thus, implementation of nutritional support as an element of supportive treatment is advisable or necessary in many of these patients.Unfortunately, there is a lack of uniform clinical nutrition guidelines for HSCT patients. Currently, special attention is paid to: suitable qualification for different form of nutritional support, consideration of routine implementation of nutritional support after myeloablative conditioning (especially with total body irradiation), avoidance of unjustified arrest of oral/enteral nutrition (probably higher risk of Graft-vs-Host disease – GvHD) and likely clinical advantages of the use of glutamine and/or omega-3 fatty acids in nutritional mixtures.Moreover, in the context of clinical nutrition, patients with severe gastro-intestinal toxicity and persons with GvHD grade > II with intestinal failure require special attention. For these patients, primary nutritional support is parenteral nutrition (PN).The indications of PN implementation include: impossible, ineffective (e.g. nutrients absorption <50% daily requirements) or contraindicated oral/enteral feeding and progressive undernutrition. In case of use of myeloablative conditioning with total body irradiation and high-dose chemotherapy, the routine PN initiation should be taken into consideration according to preemptive strategy.Composition of intravenous nutritional mixtures is also very important. Based on scientific references and own study, the addition of glutamine and omega-3 fatty acids seems to be advisable (e.g. positive influence of mucous membrane regeneration and hematopoietic recovery, less complications). However, not all clinical studies confirmed above mentioned advantages. Moreover, optimal daily dose of these substrates is currently unknown.     

Zakażenia wirusowe po transplantacji komórek krwiotwórczych

Infections remain one of the most serious problems in patients undergoing stem cell transplantation. With the progress concerning transplant techniques and the supportive treatment we observe decrease in the incidence of infectious complications early after transplant with extended duration and risks later. Viral infections constitute the specific group of complications, strictly related to the immunological reconstitution after the transplantation. Most often appearing infections caused by viruses of Herpesviridae family together with currently binding recommendations concerning the diagnostics, the prevention and the treatment are discussed in the paper.     

Transplantacje komórek krwiotwórczych w przewlekłej białaczce limfocytowej

Despite the significant progress that has been made in recent years in the treatment of chronic lymphocytic leukemia (CLL), mainly due to the introduction of monoclonal antibodies, allogeneic hematopoietic cell transplantation remains the only method that could potentially cure CLL. However, because of high peritransplant mortality, this method is reserved only for patients with high-risk CLL. Autologous transplantation is currently not recommended for patients with CLL due to the lack of advantage over the standard first-line FCR immunochemotherapy and the lack of efficacy in high-risk CLL.     

Diagnostyka i różnicowanie późnych nieinfekcyjnych powikłań płucnych u chorych po transplantacji allogenicznych komórek krwiotwórczych

The role of pulmonary function monitoring after allogeneic haematopoietic stem cell transplantation and the prognostic significance of detected airflow impairment are discussed by the authors. The purpose of the work is also to clarify the nomenclature and diagnostic criteria of non-infectious pulmonary complications after allotransplant. The incidence and diagnostic criteria of representative conditions, as bronchiolitis obliterans and cryptogenic organizing pneumonia are presented. The significance of radiologic findings, bronchoscopy and lung biopsy in diagnostic strategy is also discussed. We believe that the presented review of the current multidisciplinary knowledge on late non-infectious pulmonary complications in patients after stem cell transplantation may be useful in improving the quality of long-term care of those patients.     

Chłoniak z komórek płaszcza u pacjentów niekwalifikujących się do chemioterapii w wysokich dawkach

Mantle cell lymphoma typically occurs at the age of 65 or more, is usually a generalized neoplasm of B-cell origin involving lymph nodes, bone marrow, blood, and gastrointestinal tract. Initially, it is reasonably well responsive to treatment but relapses uniformly follow with increasing resistance to subsequent treatments. A diagnosis requires histopathologic examination by experienced hemato-pathologist, immunohistochemistry, and in cases of atypical morphology or immunophenotype – FISH and flow cytomtery. A clinical course is heterogenous due to variable sites of involvement, rate of disease progression, and a burden of comorbidities in individual patient. The optimal treatment is a combination of anti-CD20 antibody and chemotherapy that needs to be tailored to the patient's particular health conditions. Rational choices include R-CHOP, bendamustine, and chlorambucil. If complete or partial remission is achieved, maintenance rituximab may prolong remission duration significantly. In rare cases of limited disease, involved field radiotherapy may result in long-term remissions. At relapse, treatment should be guided by symptoms or complications and aimed at the best possible quality of life. The optimal option would be a clinical trial of a new agent.     

Ocena znaczenia ekspresji błonowej dipeptydylo-peptydazy IV na komórkach hematopoetycznych u chorych ze szpiczakiem plazmocytowym poddawanych mobilizacji komórek krwiotwórczych

Dipeptidyl peptidase IV is a membrane enzyme involved in intracellular interactions governing processes. Proven its effects on engraftment the transplanted allogeneic hematopoietic cells. The aim of this study was to analyze the expression of CD26 in the mobilization of hematopoietic cells for auto-transplantation in multiple myeloma patients. In 30 patients, who, during the 2011–2012, underwent the mobilization of hematopoietic cells, CD26 was determined on CD34 positive cells as well as on lymphocytes, monocytes and granulocytes, before mobilization procedures, as well as on the cells obtained after separation on cell separator. We found a statistically significant increase in the number of mononuclear cells expressing CD26, non-expression of CD26 on granulocytes, both before and during the mobilization procedures. Additionally we found a week expression of CD26 on CD34 positive cells. The obtained results seem to indicate an important role of bone matrix cells expressing CD26 in the process of mobilization of hematopoietic cells in myeloma multiplex patients.     

Wskazania do transplantacji komórek krwiotwórczych u dzieci i młodzieży – rekomendacje Polskiej Pediatrycznej Grupy ds. Transplantacji Komórek Krwiotwórczych – 2014

This article presents the current recommendations from the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation concerning the indications for hematopoietic stem cell transplantation (HSCT) in children and adolescents suffering from hematological malignancies, solid tumours, and congenital or acquired non-malignant disorders. Indications for HSCT are established in context of the recent results of conventional treatment, i.e. obtained with non-HSCT strategies; it means transplantation is justifiable exclusively, when it significantly increases individual patient's chances to be cured, despite of the risk of HSCT-related mortality. Hence, due to the advances of non-transplant treatment strategies as well as progress in the field of HSCT the indications for HSCT require to be regularly up-dated. The recommendations presented in this article are based on the current guidelines from the European Group for Blood and Bone Marrow Transplantation (EBMT), including those from the EBMT Pediatric Diseases Working Party and the EBMT Inborn Errors Working Party, and from the international treatment protocols currently applied in the centers of the Polish Pediatric Leukemia/Lymphoma Study Group and Polish Pediatric Solid Tumours Study Group. The recommendations are addressed not only to the Polish pediatric transplant centers, but first of all to the Polish pediatric centers involved in diagnostics and treatment of the malignancies and non-malignant disorders in children and adolescents with non-transplant strategies, because it is their responsibility to identify as soon as possible indications for HSCT and refer patient at the appropriate time to pediatric transplant center.     

Wysokie dawki cyklofosfamidu po niemieloablacyjnym haploidentycznym przeszczepieniu komórek krwiotwórczych u dziecka z nawrotową postacią nerwiaka zarodkowego: krok w kierunku rozdzielenia reakcji GVT i GVH

Allogeneic HSCT with graft versus tumor (GVT) effect is an accepted therapeutic option in pediatric solid tumors. Due to donor availability and logistic reasons, unmanipulated family haploidentical transplants are becoming increasingly used in patients lacking an HLA identical family donor, or a well matched unrelated donor. Recently nonmyeloablative, haplo-identical T-cell replete bone marrow transplantation using high-dose cyclophosphamide post-HSCT (PTCy) to control GVHD and prevent graft rejection by inducing bi-directional tolerance was described. The objective of this report is an analysis of case of a child treated for relapsed neuroblastoma with haploidentical HSCT with PTCy. In this case following therapeutic modalities were combined: haploidentical HSCT in pediatric solid tumor relapsing after autologous HSCT, non-myeloablative haploidentical HSCT with unmanipulated T-repleted graft, and post-transplant use of high-dose cyclophosphamide as GVHD prophylaxis. This strategy was safe and efficient, as we observed low toxicity, relatively fast hematological engraftment, and hyperacute GVHD followed by mild GVHD. Patient stayed in remission for 12 months. Based on published data, it seems possible, that PTCy selectively depletes T cells that react against host allo-antigens, yet preserves tumor-specific and pathogen reactive T cells.     

Dyskwalifikacja dawcy komórek krwiotwórczych w trakcie chemioterapii wysokodawkowanej u biorcy przygotowywanego do transplantacji: propozycja algorytmu postępowania ratunkowego

BackgroundA donor hematopoietic cells disqualification is an uncomfortable situation at each stage of the donor typing and qualification because of extended waiting time to transplant. The occurrence of such an event occurring after completed conditioning is a life-threatening situation for the patient. We present a case report where the donor was disqualified during conditioning of the patient.Case reportA 17-year-old girl suffering from secondary AML was referred to HSCT unit for a transplant from matched unrelated donor. Conditioning consisted of busulfan, melfalan, fludarabine, and anti-thymocyte globulin (ATG Genzyme). After 4 days of chemotherapy, an information has been received about severe adverse event during mobilization of peripheral blood stem cells (PBSC) at the donor and the lack of her agreement to harvest bone marrow. Hence there was a necessity to cancel the procedure of PBSC mobilization and apheresis.Rescue proceduresFollowing rescue procedures have been undertaken immediately: (1) cessation of conditioning; (2) an urgent new search for another unrelated donor; and (3) arrangement for a rescue haploidentical transplant from mother, who was qualified for the procedure of PBSC mobilization.ResultsAs a consequence of undertaken steps a new mismatched unrelated (8/10) donor was found within 4 days. The patient continued chemotherapy and dosage of ATG has been increased by 50%. The PBSC apheresis process from haploidentical donor was cancelled. The transplantation was performed with a three-day delay in comparison to initially scheduled protocol.ConclusionWe believe that the proposed algorithm of rescue procedures can facilitate the proceedings in the case of donor hematopoietic cells disqualification directly prior to transplantation. It seems reasonable to propose a discussion on the implementation of procedures to reduce the risk of similar events. To consider is typing for each patient two potential donors, collection of material for transplantation before proceeding to transplantation and collection from each patient's own material for transplantation to the rescue.     

Leczenie chorych na szpiczaka plazmocytowego w starszym wieku niebędących kandydatami do autologicznej transplantacji komórek krwiotwórczych (autoSCT)

Multiple myeloma is still incurable disease, despite significant advances made in therapy during last 10–14 years. The improvement of survival rate is mainly observed in younger patients but not in older. Thus the major problem is to improve survival of older patients.     

Terapia celowana i transplantacja komórek krwiotwórczych szansą na wyleczenie chorych z ostrą białaczką szpikową

Acute myeloid leukemia (AML) is a heterogeneous disorder with a diverse prognosis. About 70% of AML patients may achieve complete remission after conventional chemotherapy, but long-term outcome remains unsatisfactory. The development of molecular biology resulted in a better understanding of AML pathogenesis as well as it allowed us the introduction of targeted therapy. However, most AML patients still require the allogeneic hematopoietic stem cell transplantation (alloHSCT) to be cured. The long-term results of alloHSCT for AML depend on a variety of factors including the age at transplant, the presence of well-defined risk factors and disease status at transplant. It seems that the combination of targeted therapy with conventional chemotherapy and subsequent alloHSCT may be a chance for curing a significant proportion of AML patients.     

Osoczowe stężenie cytokin limfo-i angiogennych u chorych na chłoniaka rozlanego z dużych komórek B

Angiogenesis and lymphangiogenesis play an important role in the development of diffuse large B-cell lymphoma (DLBCL). Above phenomena are controlled by a number of cytokines among them the most important are vascular endothelial growth factor family members (VEGF), their receptors (VEGF-R) and basic fibroblast growth factor (bFGF). The aim of this study was to evaluate the plasma level of VEGF-C, VEGF-D, VEGF-R3 and bFGF in 55 patients with DLBCL before treatment as well as after chemotherapy with R-CHOP protocol. Control group consisted of 30 healthy subjects. The concentration of VEGF-R3 was significantly higher in patients before treatment than in control group. Concentrations of VEGF-R3 and VEGF-C were significantly higher in patients with higher risk (IPI 3-5) than in subjects with lower risk (IPI 0-2). Additionally, VEGF-R3 was positively correlated with β₂-microglobulin, whereas VEGF-D was correlated positively with LDH and β ₂-microglobulin, and negatively with platelets count and serum albumins concentration. We found no statistical differences between cytokine values after treatment as compared to initial ones. However, our results do not indicate a predictive value of the cytokines studied regarding the issue of DLBCL therapy, they may suggest a role of some lymphangiogesis-involved factors in the disease activity.     

Profilaktyka zakażeń grzybiczych u dzieci poddawanych transplantacjom komórek hematopoetycznych

Invasive fungal infections (IFI) remain a very important cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT) in children. The recent study from Polish pediatric transplant centers revealed that 27.3% of children transplanted in 2012–2013 developed IFI. The highest risk was observed among patients with AML and ALL after allogeneic HSCT. Such results warrant the use of extensive antifungal prophylaxis in this cohort of patients. ECIL-4 guidelines for antifungal prophylaxis in children undergoing HSCT along with clinical practice are presented in the review. Furthermore preventive measures for patients discharged home after HSCT are discussed.