82 research outputs found
Mobilizacja krwiotwĂłrczych komĂłrek macierzystych â wczoraj i dziĆ
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 âa 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 krwiotwĂłrczych komĂłrek macierzystych (HSC) do krwi obwodowej umoĆŒliwiĆaich efektywne pobieranie z krwi, zamiast ze szpiku, w celu autologicznego lub allogenicznegoprzeszczepienia. ZaleĆŒnie od aktywnoĆci choroby, a takĆŒe od potrzeby stosowania leczeniachemioterapeutycznego, obecnie stosuje siÄ protokoĆy mobilizacji oparte na podawaniu czynnikastymulujÄ
cego wzrost kolonii granulocytĂłw (G-CSF) â samego lub w skojarzeniu z chemioterapiÄ
.Mobilizacje wedĆug tych protokoĆĂłw sÄ
na ogĂłĆ skuteczne, co udowodniono w ciÄ
guostatnich 15 lat. Ostatnio pojawiĆa siÄ kolejna moĆŒliwoĆÄ terapeutyczna, wynikajÄ
ca z zastosowaniapleryksaforu â swoistego antagonisty receptora chemokinowego CXCR4. Wyniki licznychbadaĆ wykazaĆy jego wysokÄ
skutecznoĆÄ w mobilizacji HSC, szczegĂłlnie jeĆli jest stosowanyw skojarzeniu z G-CSF, a niekiedy takĆŒe z chemioterapiÄ
. W niniejszym artykuleprzedstawiono rys historyczny strategii mobilizacji HSC oraz najnowsze obserwacje dotyczÄ
cezastosowania pleryksaforu
Gammapatie monoklonalne o znaczeniu nerkowym
Termin gammapatia monoklonalna o znaczeniu nerkowym (MGRS) w akronimie rĂłĆŒni siÄ jedynie jednÄ
literÄ
od gammapatii monoklonalnej o nieokreĆlonym znaczeniu (MGUS), jednakĆŒe w znaczeniu klinicznym jest to zupeĆnie inna jednostka. W przebiegu MGRS biaĆko produkowane przez klon komĂłrek uszkadza nerki, przez co moĆŒe prowadziÄ do ich niewydolnoĆci. W niniejszym artykule dokonano przeglÄ
du piĆmiennictwa dotyczÄ
cego jednostek chorobowych zaliczanych do grupy MGRS, ich podziaĆu ze wzglÄdu na typ uszkodzenia nerek i charakterystykÄ deponowanych w nich zĆogĂłw. W pracy omĂłwiono takĆŒe wspĂłĆczesne moĆŒliwoĆci leczenia w poszczegĂłlnych jednostkach chorobowych zaliczanych do MGRS
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
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 Ă 10(6)/kg (range: 0.3-13.4). The minimum required number of CD34+ cells (â„2.0 Ă 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 Ă 10(6)/kg (range: 1.1-14.8). The minimum required number of CD34+ cells (â„2.0 Ă 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
Organ complications after CD19 CAR T-cell therapy for large B cell lymphoma: a retrospective study from the EBMT transplant complications and lymphoma working party.
We investigated â„ grade 3 (CTC-AE) organ toxicities for commercial CD19 chimeric antigen receptor T cell (CAR-T cell) products in 492 patients (Axi-Cel; n = 315; Tisa-Cel; n = 177) with Large B-cell Lymphoma in the European Society for Blood and Marrow Transplantation (EBMT) CAR-T registry. The incidence of â„ grade 3 organ toxicities during the first 100 days after CAR-T was low and the most frequent were: renal (3.0%), cardiac (2.3%), gastro-intestinal (2.3%) and hepatic (1.8%). The majority occurred within three weeks after CAR-T cell therapy. Overall survival was 83.1% [79.8-86.5; 95% CI] at 3 months and 53.5% [49-58.4; 95% CI] at one year after CAR-T. The most frequent cause of death was tumour progression (85.1%). Non-relapse mortality was 3.1% [2.3-4.1; 95% CI] at 3 months and 5.2% [4.1-6.5; 95% CI] at one year after CAR-T. The most frequent causes of non-relapse mortality were cell-therapy-related toxicities including organ toxicities (6.4% of total deaths) and infections (4.4% of total deaths). Our data demonstrates good safety in the European real-world setting
ECP versus ruxolitinib in steroid-refractory acute GVHD â a retrospective study by the EBMT transplant complications working party
IntroductionExtracorporal Photophoresis (ECP) is in clinical use for steroid-refractory and steroid-dependent acute GVHD (SR-aGVHD). Based on recent Phase-III study results, ruxolitinib has become the new standard of care for SR-aGVHD. Our aim was to collect comparative data between ruxolitinib and ECP in SR-aGVHD in order to improve the evidence base for clinical decision making. MethodsWe asked EBMT centers if they were willing to participate in this study by completing a data form (Med-C) with detailed information on GVHD grading, -therapy, -dosing, -response and complications for each included patient.Results31 centers responded positively (14%) and we included all patients receiving alloSCT between 1/2017-7/2019 and treated with ECP or ruxolitinib for SR-aGVHD grades II-IV from these centers. We identified 53 and 40 patients with grades II-IV SR-aGVHD who were treated with ECP and ruxolitinib, respectively. We performed multivariate analyses adjusted on grading and type of SR-aGVHD (steroid dependent vs. refractory). At day+90 after initiation of treatment for SR-aGVHD we found no statistically significant differences in overall response. The odds ratio in the ruxolitinib group to achieve overall response vs. the ECP group was 1.13 (95% CI = [0.41; 3.22], p = 0.81). In line, we detected no statistically significant differences in overall survival, progression-free survival, non-relapse mortality and relapse incidence.DiscussionThe clinical significance is limited by the retrospective study design and the current data canât replace prospective studies on ECP in SR-aGVHD. However, the present results contribute to the accumulating evidence on ECP as an effective treatment option in SR-aGVHD
Hematopoietic stem cell mobilization with the reversible CXCR4 receptor inhibitor plerixafor (AMD3100)âPolish compassionate use experience
Recent developments in the field of targeted therapy have led to the discovery of a new drug, plerixafor, that is a specific inhibitor of the CXCR4 receptor. Plerixafor acts in concert with granulocyte colony-stimulating factor (G-CSF) to increase the number of stem cells circulating in the peripheral blood (PB). Therefore, it has been applied in the field of hematopoietic stem cell mobilization. We analyzed retrospectively data regarding stem cell mobilization with plerixafor in a cohort of 61 patients suffering from multiple myeloma (Nâ=â23), non-Hodgkinâs lymphoma (Nâ=â20), or Hodgkinâs lymphoma (Nâ=â18). At least one previous mobilization attempt had failed in 83.6% of these patients, whereas 16.4% were predicted to be poor mobilizers. The median number of CD34+ cells in the PB after the first administration of plerixafor was 22/ÎŒL (range of 0â121). In total, 85.2% of the patients proceeded to cell collection, and a median of two (range of 0â4) aphereses were performed. A minimum of 2.0âĂâ106 CD34+ cells per kilogram of the patientâs body weight (cells/kg b.w.) was collected from 65.6% of patients, and the median number of cells collected was 2.67âĂâ106 CD34+ cells/kg b.w. (0â8.0). Of the patients, 55.7% had already undergone autologous stem cell transplantation, and the median time to neutrophil and platelet reconstitution was 12 and 14 days, respectively. Cases of late graft failure were not observed. We identified the diagnosis of non-Hodgkinâs lymphoma and previous radiotherapy as independent factors that contributed to failure of mobilization. The current report demonstrates the satisfactory efficacy of plerixafor plus G-CSF for stem cell mobilization in heavily pre-treated poor or predicted poor mobilizers
Addition of Rituximab in Reduced Intensity Conditioning Regimens for B-Cell Malignancies Does Not Influence Transplant Outcomes: EBMT Registry Analyses Following Allogeneic Stem Cell Transplantation for B-Cell Malignancies
Rituximab (R) is increasingly incorporated in reduced intensity conditioning (RIC) regimens
for allogeneic hematopoietic cell transplantation (alloHCT) in patients with B-cell
malignancies, not only to improve disease control, but also to prevent graft-versus-host
disease (GVHD). There are no randomized prospective data to validate this practice,
although single center data and the CIBMTR analysis have shown promising results. We
aimed at validation of these findings in a large registry study. We conducted a
retrospective analysis using the EBMT registry of 3,803 adult patients with B-cell
malignancies undergoing alloHCT (2001â2013) with either rituximab (R-RIC-9%) or nonrituximab
(RIC-91%) reduced intensity regimens respectively. Median age and median
follow up were 55 years (range 19.1â77.3) and 43.2 months (range 0.3â179.8),
respectively. There was no difference in transplant outcomes (R-RIC vs RIC), including
1-year overall survival (69.9% vs 70.7%), 1-year disease-free survival (64.4% vs 62.2%),
1-year non-relapse mortality (21% vs 22%), and day-100 incidence of acute GVHD 2-4°
(12% vs 12%). In summary, we found that addition of rituximab in RIC regimens for B-cell
malignancies had no significant impact on major transplant outcome variables. Of note,
data on chronic GVHD was not available, limiting the conclusions that can be drawn from
the present study
Age-dependent determinants of infectious complications profile in children and adults after hematopoietic cell transplantation : lesson from the nationwide study
Incidence and outcome of microbiologically documented bacterial/viral infections and invasive fungal disease (IFD) in children and adults after hematopoietic cell transplantation (HCT) were compared in 650 children and 3200 adults in multicenter cross-sectional nationwide study. Infections were diagnosed in 60.8% children and 35.0% adults, including respectively 69.1% and 63.5% allo-HCT, and 33.1% and 20.8% auto-HCT patients. The incidence of bacterial infections was higher in children (36.0% vs 27.6%; pââ21 days were risk factors for death from infection. In conclusion, pediatric patients have 2.9-fold higher incidence and 2.5-fold better outcome of infections than adults after HCT
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