Autologous stem cell transplantation with myeloablative conditioning is still a powerful weapon that can be used against this entity. Methods: We have evaluated retrospectively patients with AML where autologous stem cell transplantation was performed in the period from till Our group consisted of 94 patients; male patients 45 Median age at diagnosis was 44 years The average period from time of diagnosis to autologous SCT was 7.
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Results: In the majority of our group, we used myeloablative conditioning regimen with Busulphan-Cyclophosphamide, 60 patients As auto graft we used peripheral blood stem cells PBSC in 78 patients The mean number od apheresis procedures done in our group was 1. The mean time to engraftment was The transplant related mortality TRM was 2. The 5 year Overall Survival of our patients was All patients were transplanted in Complete Remission. Conclusions: Autologous stem cell transplantation could be an acceptable therapeutic solution for patients with AML as a consolidation therapy, where neither suitable compatible donor is available nor allogeneic stem cell transplantation could not be performed from various reasons depending on the bone marrow transplant unit.
Relapse after transplantation is still an important factor affecting survival. The three years cumulative incidence of relapse was Additional targeted and coordinated interventions are needed to maintain durable remission after allo-HSCT in this high-risk population.
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Background: One of the most potent prognostic factors affecting outcomes in AML is the presence of cytogenetic and molecular markers which can guide the selection of post-remission therapies. However, the role of allo-HCT compared to consolidation chemotherapy has not yet been elucidated. Methods: The data of 88 patients who were diagnosed with AML and received intensive induction therapy from March to July were included in the current study.
To address the time dependence of the allo-HCT, the Simon and Makuch method was used in the graphical representation and the Mantel-Byar test and Andersen and Gill methods for identifying risk factors for long-term survival. With median follow-up duration of Therefore, the implication of allo-HCT to this group needs to be carefully considered considering other high risk factors. Therapy with hypomethylating agents may reverse the abnormal epigenetic silencing to modify the malignant phenotype. Decitabine incorporates into DNA after phosphorylation and forms irreversible covalent bonds with DNA methyltransferase-1, leading to genome-wide global DNA hypomethylation.
However, allogeneic hematopoietic stem cell transplantation HSCT remains the only curative therapy for high-risk AML, but disease relapse is the principal cause of treatment failure for these patients, depending on the diagnosis characteristics and status of disease at the time of transplantation. The outcomes of salvage treatments are very poor. Therefore, early maintenance therapy, directed at eliminating minimal residual disease and promoting a graft versus-leukemia GVL effect, could be an effective method to improve outcome after allo-HSCT.
Our study, open-label and prospective, aims to expand the current knowledge about the use of low-dose decitabine as maintenance therapy in high-risk AML patients after allo-HSCT. Methods: Seven patients with high-risk AML 2 with secondary AML, 5 with cytogenetics or molecular adverse factor in complete remission, were enrolled in the study between day 50 and 80 after allo-HSCT to evaluate the prophylactic effect of decitabine.
All patient received a myelo-ablative conditioning regimen with busulfan The source of graft was peripheral blood in six patients and bone marrow in one patient. The mean follow-up time was 22 months 16 - 35 months. Five patients are alive and in complete remission, while two patients relapsed one after 19 months, and 1 after 20 months from allo-HSCT ; of the two relapsed patients, one died and the other is alive with active disease. Conclusions: Our study shows that post-transplant decitabine is safe and may play a role in the maintenance of remission in high-risk AML patients.
Background: Reduced-intensity conditioning RIC allowed selected patients pts , with acute myeloid leukemia AML and over 60 years old y. We calculated the OS using Kaplan-Meyer curves.
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Results: We identified 15 pts, median age 62 y. The median follow-up was 25 months. One patient pt had CML blast crisis and was on first major molecular remission. Thirteen pts were infused with peripheral blood HSC and 2 with bone marrow. The median time to neutrophil and platelet engraftment for the whole cohort was 14 and 11 days, respectively. Ten pts presented with mild acute skin GVHD. Eleven pts had chronic GVHD, 2 classified as severe; 7 required systemic therapy, 5 of those beyond 1 year. The median time on immunosuppressants was days. At 2 years the OS was Other relevant complications were hypoxemic pneumonia in 5 pts, 1 urinary sepsis, CMV and EBV reactivation respectively in 8 and 4 pts; pulmonary and renal toxicity either in 2 pts.
Pts maintaining or achieving MRD negativity after transplant had better survival. Although with only 15 pts, these results suggest that allo-HSCT is feasible as consolidation strategy in selected AML pts over 60 years. Overall Survival]. Background: Hematopoietic stem cell transplantation HSCT is the only curative option for Fanconi anaemia FA ; an inherited disorder characterized by congenital anomalies, progressive bone marrow failure BMF and a predisposition to develop malignancies. Methods: We retrospectively analysed the data of 27 consecutive patients that underwent HSCT at this centre from till June The data was analysed for variables affecting the outcome in terms of overall survival OS.
Results: Median age at diagnosis was 10 years years. Median age at transplant was All patients at transplant were in aplastic phase. Male to female ratio was 1. Twenty-four Twenty-three Eleven Mean time to neutrophil and platelets engraftment was Average hospital stay was Four patients Post-transplant mortality is 12 The major causes of mortality include; respiratory infections 04 , Primary graft failure 03 , grade IV gut GVHD 02 , diffused alveolar haemorrhage 01 , CMV disease 01 and acute myeloid leukaemia 01 4. Background: Paroxysmal nocturnal hemoglobinuria PNH is a rare clonal non-neoplastic hematopoietic stem cell disease whose incidence is 1.
Disease characteristics and natural history have been mostly analyzed by multicenter, retrospective studies, with the limit of heterogeneous approaches. Herein we report the incidence of severe complications and outcome in a real life setting scenario of PNH patients consecutively diagnosed and managed at our PNH referral Center between January and June Methods: Patients received a homogeneous diagnostic and treatment approach according to the period of observation availability of diagnostic tests and eculizumab.
All patients treated with eculizumab received vaccination with conjugated anti-meningococcus ACWY-serotypes and, since , conjugated anti-meningococcus B-serotype. In the event of any complication, patients could refer to dedicated Hematology Emergency Rooms ER 24 hours daily. The occurrence of renal failure and pulmonary hypertension was specifically evaluated.
The renal function was studied according to the Cockcroft-Gault formula and the lung function was prospectively monitored by daytime-on exertion, nocturnal pulsoximetric profiles and complete spirometric tests, with DLCO measurement. Results: Overall,48 PNH patients, median age 36 years range , were analyzed. One patient showed a spontaneous disappearance of the PNH clone. Since , eculizumab was administered in 28 patients. During eculizumab treatment no thrombotic event was observed while two severe infectious episodes respiratory tract and urinary tract infection were observed in only one of the 28 patients.
No patient showed a significant reduction of the renal function. Out of 24 patients prospectively monitored for lung function no pathological alteration in any diurnal or nocturnal pulseoximetric test was observed. No patient showed obstructive or restrictive ventilatory deficiency, nor reduced DLCO values. Conclusions: Our study reports a better OS and lower rate of severe complications in PNH compared to previous experiences.
Although renal failure and lung hypertension have been reported by other groups, we did not observe these complications along a prolonged follow-up. We can assume that the availability of a dedicated ER service enabled an early diagnosis and prompt treatment in case of hemoglobinuria crises reducing the risk or organ damage or other complications. The use of eculizumab, together with improved supportive approaches, presumably accounts for the trend towards a better survival witnessed over the last decade in the management of PNH patients.
Background: Aplastic anemia is a syndrome of bone marrow failure characterized by peripheral pancytopenia and marrow hypoplasia. Allogeneic stem cell transplantation from HLA-matched sibling is performed in the firstline setting in young aplastic anemia patients and in elderly patients who are refractory to immunosuppressive treatment.
But if the patient does not have a HLA-matched sibling, allogeneic stem cell transplantation is performed from unrelated and haploidentical donors. In this study, we analyzaed and compared the results of aplastic anemia patients who had undergone allogeneic stem cell transplantation either from matched unrelated or haploidentical donors.
Methods: We collected and analyzed data of aplastic anemia patients who had undergone allogeneic stem cell transplantation from matched unrelated or haploidentical donor between and Results: There were 10 patients who had received allogeneic stem cell transplantation from unrelated donors and there were 10 patients who had undergone haploidentical transplantation. But in 4 patients who had undergone haploidentical transplantation, engraftment failure had occurred and they were transplanted from different haploidentical donors fort he second time.
So a total of 10 unrelated and 14 haploidentical transplants were performed. The median age of patients who had undergone unrelated transplantation was 29 and the median age of patients who had undergone unrelated transplantation was 22 The results of the haploidentical and unrelated transplantations are shown in Table 1. Conclusions: Although the number of patients are low in this study, we can conclude that urelated and haploidentical transplantation in aplastic anemia have comparable toxicity and efficacy.
Table 1: Results of transplantation groups].
Figure 1:Overall Survival]. Background: Aplastic anaemia AA is a rare and serious hematologic disorder. Immunosuppression and allogeneic hematologic stem cell transplantation ASCT are two main treatment options. Overall and progression free survival was calculated. Results: In six years, 13 AA patients were transplanted. One of the patients was Fanconi AA. Paroxysmal nocturnal hemoglobinuria clone detected in two patient's follow-ups, they received eculizumab until ASCT. Mean age in ASCT was The source of stem cells was peripheral blood in all donors. Patients conditioning regimen and clinical course after ASCT summarized in table 1.
In our group mortality rate was Other patients are alive Background: Autologous stem cells transplantation aHSCT is an effective treatment for very aggressive autoimmune diseases such as multiple sclerosis MS. However, toxicity remains the major concern to a wide application of this approach.
Post transplant viral reactivations may induce severe complications and a rigorous monitoring of peripheral blood viral load for a prompt and effective therapy is required. We report here the policy of our Center about both monitoring and treatment of such side effect. Methods: A series of 37 consecutive patients with MS, transplanted between and is included in this analysis. All patients promptly responded to treatment within 2 weeks.
Six patients spontaneously recovered the EBV reactivation. Previous treatments were not predictive of any higher risk of viral reactivation. No impact on engraftment related to the reactivation was observed. Conclusions: This policy shows that, despite a high rate of CMV and EBV reactivation, no grade III-IV adverse events were observed, suggesting the key role of viral monitoring in these patients and the efficacy of the preemptive treatment. EBV reactivation at low titers should be monitored to identify those cases that could achieve a spontaneous resolution and avoid the induction of further immunosuppression by Rituximab.
These data confirm that patients diagnosed with AD undergoing autologous HSCT need a more intense pattern of care than hematological patients. Innocenti1, R. Saccardi EBMT Other with VenatorX strains sold by the department. Background: Autoimmune diseases are chronic serious conditions that are often refractory to standard therapies.
Since , autologous haematopoietic stem cell transplantation HSCT has been a very promising alternative that has shown satisfactory long-term results. The aim of this study is to evaluate immune reconstitution and mortality following HSCT in patients with autoimmune disease. Methods: A retrospective study was conducted on patients with diagnosis of autoimmune diseases that underwent autologous HSCT between July and January at a tertiary referral center in Colombia, South America.
Descriptive statistics were used to analyze patient's demographic and clinic characteristics. Results: Seven patients were included, with a mean age of 37 years range Median time of hospitalization was 21 days range ; longer in-patient management was due to infectious complications. Infectious complications included bacteremia caused by E. Coli and pneumocystis pneumonia that resulted in septic shock and acute respiratory failure, respectively. Regarding B-cell immune reconstitution, In the 10 months to 6 years of post-HSCT follow-up, there has not been evidence of disease relapse in any of the patients.
There were no deaths in the present cohort. Conclusions: Autologous HSCT has proved to be a successful treatment alternative in patients with severe refractory autoimmune disease, achieving sustained remissions for more than 5 years. Background: Multiple sclerosis MS is an inflammatory disease caused by autoimmune reactivity of T cells against myelin. There is accumulating evidence of the efficacy of high-dose chemotherapy followed by autologous haematopoietic stem cell transplantation aHSCT in MS patients who failed response to standard immunotherapy, despite a variability in eligibility criteria, conditioning regimens and outcome.
Patient eligibility criteria were active relapsing remitting RRMS or secondary-progressive MS SPMS , with prior failure to treatment with disease-modifying therapies and evidence of disease activity clinical relapse or new active lesions in magnetic resonance [MR]. Median age at MS diagnosis was Pre-aHSCT relapse rate per year was 2 Median baseline EDSS was 6. Median number of previous DMTs was 6 All patients had been treated with corticosteroids and copaxone, 5 Median inpatient stay during aHSCT was 28 days All patients developed febrile neutropenia, one was admitted to intensive care unit due to sepsis.
One patient developed an anaphylactic reaction to transfusion and another a self-limited encephalopathy. Two Patients were transfused with a median of 1 unit for erythrocytes and 3 for platelets. There was no treatment-related mortality and no long term side effects have been observed so far. For a median post-aHSCT follow-up of 8. The absence of evidence of disease activity at 6-months was Although there was no variation concerning EDSS punctuation, 4 The failure in reporting benefits in EDSS punctuation is probably due to a small sample size and short follow-up.
More studies are needed to establish the best patient selection criteria and define the ideal time to include these patients in transplantation programs, as well as to evaluate its long term outcome. Background: The development of oncohematological diseases may be complicated by the autoimmune pathology, including the production of antibodies to own red blood cells. The direct antiglobulin test DAT is used to detect antibodies and complement components on the surface of red blood cells.
A differentiated DAT allows to semi-quantitatively assess the immunoglobulins fixed on red blood cells and determine their subclass. The frequency of positive DAT in patients was compared with the same in healthy residents of the region - donors of blood components. Results: All blood donors were DAT-negative. Autoantibodies in the plasma of patients can interact not only with their own red blood cells, but also with test and donors red blood cells, being detected in an indirect antiglobulin test IAT.
These patients had difficulties in donors due to non-specific agglutination. Conclusions: Despite the fact that the development of oncohematological diseases is often accompanied by the production of autoantibodies, not in every case a positive result of DAT should be regarded as a sign of autoimmune hemolysis. To correctly assess the risk of hemolysis, the physicians should analyze other laboratory and clinical data. Positive DAT may be correlated with the difficulties of selection of the donor for such patient. However, the expansion of virus-specific T cells relies on a pre-existing virus-specific memory compartment in the stem cell donor.
In virus-seronegative donors, no expansion can be achieved. The repertoires indicate an antigen-directed oligoclonal expansion. Meanwhile, sequence comparison between an in vitro and in vivo expansion after EBV reactivation in one patient revealed the presence of several identical sequences. The translation of defined sets of TCRs into cellular products for adoptive transfer will help to overcome unmet clinical needs in the treatment and prophylaxis of virus reactivation, primary infection, and EBV-associated malignancies such as post-transplant lymphoproliferative disease PTLD and Hodgkin lymphoma.
Background: Lymphoid and myeloid acute leukemia are the most frequent cause of cancer related death in children.
Interactions between NKG2D receptor, expressed in cytotoxic immune cells, and its ligands NKG2DL , that are upregulated in many types of tumor cells including leukemic blasts, are important for anti-tumor immune surveillance. Results: NKG2D ligands were expressed in leukemia cell lines and leukemic blasts. The changes observed in NKG2DL surface expression at the different stages of the disease could be related to ligands release and immune escape. Background: For patients with high-risk leukaemia, allogeneic haematopoietic stem cell transplantation is the only curative treatment.
The presence of alloreactive T cells in the donor graft, however, leads to a high probability of developing graft-versus-host disease GVHD. T-cell depletion minimises the presence of GVHD-causing alloreactive cells, but often results in an increased incidence of infections and disease relapse. Photodepletion treatment PDT can specifically deplete activated alloreactive T cells while conserving resting T cells. PDT-treated cells have been utilised after T-cell-depleted haploidentical transplant to help reduce infection and relapse.
TH, a photoactive rhodamine derivative, was added and cells were exposed to visible light to deplete the THcontaining activated alloreactive cells. An ex vivo expansion protocol was exploited to evaluate the impact of PDT on reactivity to tumour and viral antigenic peptides. PDT-treated cells showed a significant increase in the frequency and number of WT1 -specific T cells on Day 14 of culture, greater than the increase seen in untreated cells, with some cultures continuing expansion on Day 21 Figure A.
These results corroborate the low infection and relapse rates observed in patients treated with PDT-treated cells. Disclosure: Funding for this study and medical writing support was provided by Kiadis Pharma. Denis-Clauide Roy also discloses travel support and consultancy with Kiadis Pharma.
No other authors have conflicts of interest to declare. Background: Acute lymphoblastic leukemia ALL is the most common childhood cancer and relapsed or refractory ALL is still difficult to treat. As the use of viral vector generated CAR NK cells is limited by theire genotoxicity, cost and regulatory demands, we are developing an innovative protocol using non-viral Sleeping Beauty SB transposition of third party NK cells as a source to produce 'off the shelf' CAR-engineered cell products.
They are successfully expanded ex vivo with IL cytokine stimulation under feeder-cell free conditions. Transfection efficiency and percent of living cells after electroporation is analyzed by flow cytometry. The transient MC-Venus longtime expansion and the viability after SBX based nucleofection is measured over two weeks.
Conclusions: The Sleeping Beauty based nucleofection of NK cells is a very promising non-viral method to generate more easy, safer and higher amounts of genetically modified third party NK cells for therapy of ALL and has also a broad range of clinical applications. Disclosure: Winfried S. Wels is an inventor on a patent describing chimeric antigen receptors with an optimized hinge region. Axel Schambach is an inventor on a patent describing alpharetroviral SIN vectors.
Michael Hudecek and Zoltan Ivics are inventors on patents related to Sleeping Beaut gene transfer technology. The remaining authors have nothing to disclose. Background: Mature immune cells from the stem cell graft are essential for the graft-versus-tumor GVT effect to eliminate residual malignant cells after hematopoietic stem cell transplantation HSCT , but donor cells are also involved in complications such as graft-versus-host disease GVHD.
Methods: We performed a prospective study of the detailed graft composition in recipients of peripheral blood stem cells PBSC or bone marrow BM in order to identify correlations to clinical outcomes, table 1. Table 1]. Conclusions: Our observations suggest that a more detailed graft characterization could benefit in risk assessment in HSCT and that donor selection, graft manipulation and additional cell infusions could optimize graft compositions regarding doses of cells beneficial for the transplantation.
Background: Extracorporeal photopheresis ECP is an immunomodulatory treatment that has shown efficacy in steroid refractory acute GvHD, but the mechanism of action is only partially understood. The objective of the study was to analyse the relationship between the infused subpopulation cellularity and response. Methods: 65 patients from 7 different centers with a total of ECP procedures were retrospectively analized.
ECP procedures were performed from January to June All ECP procedures were performed with the off-line system. For analytic purposes, the median number of cells infused per procedure until response or until the median number of procedures until response for non-responding patients and the cumulative number of cells infused until response or until the median in non-responders were calculated for all the subgroups. Same procedures were performed with the number cells infused until day 30 of ECP. Finally, the response and survival impact of infusing a number of cells above or below the median and in different tertiles was assessed until the median number of procedures needed to achieve a response.
Table 1: Patient and ECP characteristics]. Results: The median number of procedures until response was 3. We observed a trend towards a higher median number of monocytes per procedure and cumulative infused monocytes in responding patients median number infused None of the other analysed parameters showed a significant impact in overall survival.
Also the patients who received higher numbers of lymphocytes in the first procedures achieved a higher response rate. These findings suggest the possibility that higher number of treated and infused cells could influence the response to ECP, but specifically designed prospective studies are need to asses this possibility. However, administration of immunosuppressive drugs is still one of the major limitations of long-term allograft survival. Therefore, strategies for induction of donor-specific tolerance are highly desirable. To this aim, a clinical phase I study with donor-derived modulated immune cells MICs was conducted.
Potency of MICs was tested by different in vitro bio-assays. MICs were administered to patients with an escalation from 1. Frequency of adverse events AE was assessed from day 30 until day post-transplant. Dynamic changes of various lymphocyte subsets in patients after MIC therapy were detected by multicolor flow cytometry. Donor-specific immunosuppression was assessed by measuring anti-donor antibodies and mixed lymphocyte reaction MLR against donor and third-party cells.
Results: In all kidney transplant recipients, we observed a median serum creatinine of 1.
None of patients experienced rejection episode. Most importantly, none of them was associated with MICs transfusion. Besides two infectious complications, no post-transplant positive cross match results against the donor or titers of de novo donor-specific antibodies were recorded.
Notably, immunosuppressive therapy could be reduced without signs of rejection in group C. Moreover, in vitro MICs product demonstrated their immunomodulatory potency by inducing tolerogenic dendritic cells tDCs characterized by low expression of co-stimulatory CD80, CD86 and maturation CD83 as well as high expression of inhibitory marker CD Conclusions: MIC cell therapy modulates the immune system of kidney transplant recipients by increasing the ratio of regulatory B cells and facilitates the reduction of conventional immunosuppressive therapy without allograft injury or rejection episodes.
Therefore, MIC cell therapy represents a promising strategy in transplantation medicine. The low risk of transplant-related mortality and acute or chronic graft-versus-host disease GvHD render this approach more and more appealing. However, additional treatments need to be developed to further reduce the frequency of relapse. We use bioinformatics and targeted deep sequencing to evaluate the specificity of the genome editing process. Our preclinical data demonstrate that the non-target fraction can be efficiently engineered by genome editing to manufacture a new cell product characterized by high antileukemic activity and without the risk for GvHD.
However, CAR-T cell production requires specialized infrastructure and operators, which implies high cost and centralized production. At day 0 cells were activated with T Cell TransAct for 24h. No microbiological contamination was observed in final CAR T cells products. CGH and karyotype showed no genetic alterations. Free viral particles were undetectable in the supernatants. Reconstitution of adaptive immunity may take up to 2 years to recover T-Lymphocytes LT.
Delay in early LT recovery increases the risk of relapse, viral infections and transplant related mortality. Adoptive transfer of selected T cell subset with low alloreactivity potential is emerging as a strategy to improve IR. All infusions were well-tolerated and did not develop or worsen GvHD.
None of the DLI administered in cases of mixed chimerism, graft failure or relapse were effective in reverting those situations. However, to determine the real efficacy of this strategy, prospective studies are required. The research protocol was approved by the institutional review boards of the first affiliated hospital of Soochow University and both patients gave written informed consent.
Results: Both cases responded well with transient and reversible toxicities. Case 1 presented with grade 1 cytokine release syndrome CRS , manifested by intermittent fever and chill from day 4 after CAR-T infusion for half months associated with neutropenia. CAR-T cells expansion were observed in blood without obvious increase of cytokines. After infusion, Case 1 achieved and maintained molecular complete remission CR for more than 10 months. Case 2 presented with grade 3 CRS manifested by continuous high fever, hypotension and grade 1 liver disfunction from day 1 after CAR-T cell infusion for 1 week.
Obvious cytokines releasing peak IL-6 serum concentration After infusion, case 2 achieved hematological CR and cytogenetic CR and got 3 months disease free survival. Background: Chimeric antigen receptor engineered T CAR-T cells have emerged as a powerful cellular therapy to treat malignant disease, which is currently revolutionizing field of cancer immunotherapy.
A cryopreservation step post-manufacture is not only a logistical necessity for large scale cell manufacturing processes but also a mandatory request by regulatory authorities. In case relapse after 1 st CAR-T cell transplantation, a second application, maybe at a higher dose constitutes a therapeutical option. However, data concerning clinical grade CAR-T cell stability and functionality after months of cryopreservation have not been released by companies so far.
To investigate the effect of cryopreservation on CAR-T cells, we performed this study. Quality control tests for sterility, endotoxin and mycoplasma were performed for each batch according to European Pharmacopoeia and United States Pharmacopoeia guidelines. Stability of CD19 CAR-T cells in terms of viability, recovery, transduction efficiency and functional capacity were determined by microscopy, multi-parametric flow cytometry as well as chromium release tests following our SOPs.
Results: All the results of quality controls fully met the requirements of the regulatory authorities. Duration of cryopreservation up to 90 days had no negative influence on cell viability, recovery of viable CD19 CAR-T cells and transduction efficiency. However, the cell concentration for cryopreservation has a significant impact on the post-thawing viability low batches vs.
Moreover, we observed four transient side-effects of cryopreservation on the amount of cytokines released by CAR-T cells, the cytokine release on a per-cell basis, the multifunctionality of CAR-T cells and the killing capacity. The multi-functionality of CAR-T cells could be preserved.
Conclusions: Cryopreservation up to 90 days has no harmful effect on transduction efficiency and functionalities of CAR-T cells. However, the cell number per milliliter freezing medium matters. For the conduction of in vitro bio-assays to determine the function of CAR-T cells, an overnight resting process could mimic the situation after clinical application and eliminate the transient side-effects of cryopreservation to fully regain the functional potency of CAR-T cells.
We could already show that allogeneic donor- or autologous T-cells obtained from AML-patients can be stimulated by DC leu , resulting in a very efficient lysis of naive blasts. In persisting disease, a higher serum-release of CCL5 and at relapse a significantly higher CCL2-release were found compared to first diagnosis - pointing to a change of 'disease activity' on a chemokine level.
Whereas chemokine-levels in DC-culture supernatants compared to serum were variable, clear correlations with lateron after stimulating T-cells with DCleu in MLC improved antileukemic T-cell activity were seen: higher values of all chemokines in DC-culture supernatants always correlated with improved T-cells' antileukemic activity compared to stimulation with blast-containing MNC as control - whereas with respect to the corresponding serum values higher release of CXCL8, -9, and but lower values of CCL5 and -2 correlated with higher probabilities to improve antileukemic activity of DCleu-stimulated vs.
Predictive significant cut-off-values could be evaluated separating the groups compared. Predictive cut-off-values could be evaluated separating the groups compared in 'responders' and 'non-responders'. Since in DC-culture supernatants higher values of all chemokines correlated with improved antileukemic T-cell reactivity we conclude a change of functionality of CCL5 and -2 from an 'inflammatory' or 'tumor-promoting' to an 'antitumor'-reactive function.
This knowledge can contribute to develop immune-modifying strategies that promote antileukemic adaptive immune-responses. Background: Allogeneic hematopoietic cell transplantation allo-HCT is a curative treatment option for patients suffering from hematologic malignancies. Infusion of donor lymphocytes DLIs can induce sustained remission in case of minimal residual disease or relapse through potent graft-versus-leukemia GVL effects, although graft-versus-host disease GVHD represents a common dose-limiting toxicity.
Methods: We analyzed DLI samples by flow cytometry. Culture-expanded and purified DLI-iNKTs were then tested against tumor cell lines and primary leukemia cells in an ex vivo tumor control model. Results: iNKT cells represent 0. In this study, we generated WT1-specific cytotoxic T lymphocytes to confirm if activated B cells can act as a cancer antigen presenting cell and induce CTLs. Results: Cells expanded about 3 times after 17 days of culture. Killing assays were also performed to determine the immunogenicity of induced CTLs.
Conclusions: In this study, we can induce antigen-specific CTLs that specifically react to WT1 using activated B cells as antigen-presenting cells. Our results demonstrate that these in vitro expanded WT1-specific CTLs using activated B cells can be a promising candidate for adoptive immunotherapy against cancer. Background: T cells with chimeric antigen receptors CARs on their surface facilitate to target specific surface expressed antigens.
Research and clinical trials with CDCAR T cells show impressive remission induction rates and increased survival in heavily pretreated patients. Therefore, CAR T cells are introduced as new potent cellular therapeutics in the clinical routine. Results: Total volumes of leukaphereses were between 60 and ml with 2. Cells were harvested on day The final cell counts of the cellular products were 6. The final count of CAR T cells was therefore 2. Conclusions: The CliniMACS Prodigy T cell transduction process has been shown to run a fully-automated manufacturing process over 12 days without any deviations in a clean room environment on a single device.
The user interaction was reduced to activities at only 3 days to set up the system and provide fresh medium and reagents. The results were comparable for both unmobilized leukaphereses from healthy donors and showed expected slightly lower results in the patient. Background: Allogeneic hematopoietic stem cell transplantation alloHCT is an effective strategy in the long term control of several hematologic diseases, however, patients could experience complications, as graft versus host disease GVHD and disease relapse.
Recently, the introduction of post-transplant Cyclophosphamide ptCy allowed to significantly reduce GVHD, but disease relapse remains an important issue. Donor-lymphocyte infusion DLI is an established adoptive cell therapy for disease relapse after alloHSCT, but, in order to be efficient and safe, patients have to be off immunosuppression treatments and GVDH-free. Published by Vergara, Barcelona About this Item: Vergara, Barcelona, Condition: Bueno.
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