Mobilizacja krwiotwórczych komórek macierzystych — wczoraj i dziś

The method of hematopoietic stem cells (HSC) mobilization to peripheral blood enabled theirefficient collection from peripheral blood instead of bone marrow, for the purpose of autologousor allogeneic transplantation. Depending on the activity of the disease and on the need ofchemotherapeutic treatment, the current protocols of mobilization consist of granulocyte-colonystimulating factor (G-CSF) alone, or in combination with chemotherapy. The mobilizationsthat use these protocols are usually efficient, as it has been documented for the last 15 years oftheir use. Recently, the new mobilization strategy arose based on the discovery of plerixafor —a specific antagonist of the CXCR4 receptor. The numerous studies revealed its high efficacy ofHSC mobilization, especially when used in combination with G-CSF, and eventually chemotherapy.The current review presents the historical perspective of HSC mobilization, focusingon the last observations regarding the use of plerixafor.Metoda mobilizacji krwiotwórczych komórek macierzystych (HSC) do krwi obwodowej umożliwiłaich efektywne pobieranie z krwi, zamiast ze szpiku, w celu autologicznego lub allogenicznegoprzeszczepienia. Zależnie od aktywności choroby, a także od potrzeby stosowania leczeniachemioterapeutycznego, obecnie stosuje się protokoły mobilizacji oparte na podawaniu czynnikastymulującego wzrost kolonii granulocytów (G-CSF) — samego lub w skojarzeniu z chemioterapią.Mobilizacje według tych protokołów są na ogół skuteczne, co udowodniono w ciąguostatnich 15 lat. Ostatnio pojawiła się kolejna możliwość terapeutyczna, wynikająca z zastosowaniapleryksaforu — swoistego antagonisty receptora chemokinowego CXCR4. Wyniki licznychbadań wykazały jego wysoką skuteczność w mobilizacji HSC, szczególnie jeśli jest stosowanyw skojarzeniu z G-CSF, a niekiedy także z chemioterapią. W niniejszym artykuleprzedstawiono rys historyczny strategii mobilizacji HSC oraz najnowsze obserwacje dotyczącezastosowania pleryksaforu

The current opinion on the place of plerixafor in hematopoietic stem cell mobilization

Pleryksafor jest swoistym antagonistą receptora chemokinowego CXCR4 wykorzystywanym do mobilizacji krwiotwórczych komórek macierzystych ze szpiku do krwi obwodowej w celu ich pobrania i następnie autologicznego przeszczepienia. Europejskie wskazania rejestracyjne obejmują stosowanie pleryksaforu u pacjentów ze szpiczakiem plazmocytowym i chłoniakami, którzy wykazują się niedostateczną mobilizacją. Ze względu na jego wysoką skuteczność w połączeniu z G-CSF (czynnik wzrostu kolonii granulocytowych) wykorzystuje się go głównie u chorych, u których nie powiodła się wcześniejsza mobilizacja (nieudani mobilizatorzy). Wskazania rejestracyjne umożliwiają stosowanie pleryksaforu również u pacjentów o tzw. przewidywanej nieskutecznej mobilizacji (przewidywani źli mobilizatorzy) oraz u tych, u których aktualnie prowadzona mobilizacja przebiega suboptymalnie (potwierdzeni źli mobilizatorzy). Istnieją dane, że nawet u pacjentów, u których skutecznie mobilizuje się komórki krwiotwórcze (dobrzy mobilizatorzy), stosowanie pleryksaforu mogłoby w przyszłości znaleźć swoje uzasadnienie. W artykule przedstawiono możliwości stosowania pleryksaforu w wyżej wymienionych przypadkach. Zasugerowano też algorytm tzw. „ratunkowego” stosowania pleryksaforu w trakcie mobilizacji komórek krwiotwórczych.Plerixafor is a specific antagonist of the CXCR4 chemokine receptor used for mobilization of hematopoietic stem cells from bone marrow to peripheral blood for their collection and subsequent transplantation. The European label indications include patients with lymphoma and multiple myeloma whose cells mobilise poorly. Because of its high efficacy when used in combination with G-CSF, it has been used mainly in patients with failed previous mobilization (“failed mobilizers”). However, label indications include plerixafor usage also in patients predicted to mobilize poorly (“predicted poor mobilizers”) as well as those with suboptimal current mobilization (“proven poor mobilizers”). Also patients who mobilize efficiently (“good mobilizers”) might benefit from mobilization with plerixafor. The paper demonstrates the use of plerixafor in above situations. Also a “rescue” strategy of plerixafor use during stem cell mobilization is presented

Investigation and Management of Bone Mineral Density Following Hematopoietic Cell Transplantation : A Survey of Current Practice by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation

Reduced bone mineral density (BMD) is a well-recognized complication of hematopoietic cell transplantation (HCT), with significant drops in BMD occurring within the first 12 months after HCT. Guidance on identifying and managing this complication is available in several published guidelines. In this study, we investigated current practices in the investigation and management of low BMD in centers registered with the European Society for Blood and Marrow Transplantation (EBMT). A questionnaire about bone health was sent to all registered centers, and responses were received from 99 centers in 25 countries (52%) currently registered with the EBMT. Our data highlight considerable heterogeneity in practices across European centers in relation to investigations, management, and use of guidelines. Our data demonstrate the need for better dissemination and implementation of existing guidelines and also for the development of multidisciplinary guidelines with input from all relevant stakeholders. (c) 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.Peer reviewe

Gammapatie monoklonalne o znaczeniu nerkowym

Termin gammapatia monoklonalna o znaczeniu nerkowym (MGRS) w akronimie różni się jedynie jedną literą od gammapatii monoklonalnej o nieokreślonym znaczeniu (MGUS), jednakże w znaczeniu klinicznym jest to zupełnie inna jednostka. W przebiegu MGRS białko produkowane przez klon komórek uszkadza nerki, przez co może prowadzić do ich niewydolności. W niniejszym artykule dokonano przeglądu piśmiennictwa dotyczącego jednostek chorobowych zaliczanych do grupy MGRS, ich podziału ze względu na typ uszkodzenia nerek i charakterystykę deponowanych w nich złogów. W pracy omówiono także współczesne możliwości leczenia w poszczególnych jednostkach chorobowych zaliczanych do MGRS

Which questionnaires should we use to evaluate quality of life in patients with chronic graft-vs-host disease?

Aim To investigate the ability of two standard quality of life (QOL) questionnaires – The Short Form (36-item) Health Survey (SF-36) and The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC QLQ C30) to evaluate QOL in patients with chronic graft-vs-host disease (cGVHD) graded according to National Institutes of Health (NIH) consensus criteria. Methods In this cross-sectional study, QOL was assessed in patients who underwent allogeneic stem cell transplantation (allo-SCT) at the University Hospital Centre Zagreb and were alive and in complete remission for more than one year after allo-SCT. Results The study included 58 patients, 38 patients with cGVHD and 20 controls, patients without cGVHD. Patients with cGVHD scored according to the NIH criteria had significantly lower scores of global health status and lower QOL on all SF-36 subscales and most of QLQ C30 functional subscales (P < 0.050 for all comparisons). Furthermore, patients with active cGVHD had significantly lower QOL scores than patients with inactive cGVHD, and this difference was most evident in physical functioning subscale of SF-36 (P = 0.0007) and social functioning subscale of QLQ C30 (P = 0.009). Conclusion cGVHD scored according to the NIH criteria is correlated with patient-reported QOL, particularly in the physical domains as detected by SF-36. QLQ C30 questionnaire adds more information on social functioning and should be used as a valuable tool in the evaluation of social domains in cGVHD patients

Single Positive Commensal Blood Culture in hospital setting is associated with higher mortality after hematopoietic stem cell transplantation

BackgroundSingle positive staphylococcal blood culture in a hematopoietic stem cell transplantation (HSCT) recipient is generally regarded as contamination. Such a blood culture (BC) does not fill the criteria for Laboratory-Confirmed Bloodstream Infection (LCBI) and could be described as Single Positive Commensal Blood Culture. The aim of this retrospective cohort analysis was to determine the clinical significance of SPCBC in HSCT recipients.Methods206 patients transplanted between 2007 and 2013 were followed until January 2015.ResultsThe 100-day survival for patients without positive BC was 99.6% compared with 83.9% for LCBI and 82.8% for SPCBC (p=0.0036). The 5-year overall survival (5yOS) was 67.1% for patients without positive BC, 44.9% for LCBI, 34.0% for SPCBC (

Reduced Calcium Signaling Is Associated With Severe Graft-Versus-Host Disease: Results From Preclinical Models and From a Prospective EBMT Study

Despite its involvement in various immune functions, including the allogeneic activation of T-lymphocytes, the relevance of calcium (Ca2+) for GVHD pathobiology is largely unknown. To elucidate a potential association between Ca(2+)and GVHD, we analyzed Ca2+-sensing G-protein coupled receptor 6a (GPRC6a) signaling in preclinical GVHD models and conducted a prospective EBMT study on Ca(2+)serum levels prior alloSCT including 363 matched sibling allogeneic peripheral blood stem cell transplantations (alloSCTs). In experimental models, we found decreasedGprc6aexpression during intestinal GVHD. GPRC6a deficient alloSCT recipients had higher clinical and histopathological GVHD scores leading to increased mortality. As possible underlying mechanism, we found increased antigen presentation potential in GPRC6a(-/-)alloSCT recipients demonstrated by higher proliferation rates of T-lymphocytes. In patients with low Ca(2+)serum levels (≤ median 2.2 mmol/l) before alloSCT, we found a higher incidence of acute GVHD grades II-IV (HR = 2.3 Cl = 1.45-3.85p= 0.0006), severe acute GVHD grades III-IV (HR = 3.3 CI = 1.59-7.14,p= 0.002) and extensive chronic GVHD (HR = 2.0 Cl = 1.04-3.85p= 0.04). In conclusion, experimental and clinical data suggest an association of reduced Ca(2+)signaling with increased severity of GVHD. Future areas of interest include the in depth analysis of involved molecular pathways and the investigation of Ca(2+)signaling as a therapeutic target during GVHD

Use of busulfan in conditioning for allogeneic hematopoietic stem cell transplantation in adults : a survey by the Transplant Complications Working Party of the EBMT

A survey was carried out among EBMT centers about the use of busulfan for conditioning in allogeneic stem cell transplantation. Of 109 responding centers, 106 used busulfan for conditioning, 102 in conventional myeloablative doses, and 93 in reduced doses (RIC). The route of administration was mostly intravenous, but similar to 10% of the centers gave the drug orally. The number of doses in i.v. administration varied and was in myeloablative conditioning mostly one (50 centers) or four (43 centers) doses a day. Seventeen of the 106 centers used pharmacokinetics for dose adjustment in myeloablative conditioning, nine in RIC. The details of pharmacokinetic monitoring varied markedly. Three quarters of the centers reported adjusting the dose based on obesity in myeloablative conditioning and about 60% in RIC. The most common method for dose calculation was ideal body weight + 0.25 x (actual body weight - ideal body weight). In conclusion, the present survey showed marked heterogeneity in the current practices of busulfan administration for conditioning. The impact of the heterogeneity is not well known. Due to this and the scarcity of support from controlled clinical studies, no clear guidelines can be presented, but some prevailing policies to be recommended were identified.Peer reviewe

Plerixafor for autologous peripheral blood stem cell mobilization in patients previously treated with fludarabine or lenalidomide.

Fludarabine and lenalidomide are essential drugs in the front-line treatment of non-Hodgkin lymphoma (NHL) and multiple myeloma (MM), respectively. Data suggests that fludarabine and lenalidomide therapy may have a deleterious effect on stem cell mobilization. In the European compassionate use program, 48 patients (median age 57 years) previously treated with fludarabine (median 5 cycles; range: 1-7 cycles) were given plerixafor plus granulocyte colony-stimulating factor (G-CSF) for remobilization following a primary mobilization attempt. The overall median number of CD34+ cells collected was 2.3 × 10(6)/kg (range: 0.3-13.4). The minimum required number of CD34+ cells (≥2.0 × 10(6)/kg) was collected from 58% of patients in a median of 2 days. Thirty-five patients (median age = 57 years) previously treated with lenalidomide (median 5 cycles; range: 1-10 cycles) were given plerixafor plus G-CSF for remobilization. The overall median number of CD34+ cells collected was 3.4 × 10(6)/kg (range: 1.1-14.8). The minimum required number of CD34+ cells (≥2.0 × 10(6) per kg) was collected from 69% of patients in a median of 2 days. In conclusion, salvage mobilization with plerixafor plus G-CSF is successful in the majority of patients with MM previously treated with lenalidomide. In fludarabine-exposed patients, only 58% of patients will achieve successful salvage mobilization with plerixafor plus G-CSF, suggesting the need for novel mobilization regimens algorithms in this subgroup of patients

Statins Impair Antitumor Effects of Rituximab by Inducing Conformational Changes of CD20

Jakub Golab and colleagues found that statins significantly decrease rituximab-mediated complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity against B cell lymphoma cells