561 results on '"Leukemia therapy"'
Search Results
2. Enhancing CAR-T cells: unleashing lasting impact potential with phytohemagglutinin activation in in vivo leukemia model.
- Author
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Sert B, Gulden G, Teymur T, Ay Y, Turan RD, Unaldi OM, Guzenge E, Erdil HE, Isik S, Oz P, Bozkurt I, Ozer S, Yurdakul T, Kamali O, Ovali E, Tarhan N, and Tastan C
- Subjects
- Mice, Animals, Phytohemagglutinins pharmacology, T-Lymphocytes, Immunotherapy, Adoptive methods, CD28 Antigens, Antigens, CD19, Receptors, Antigen, T-Cell, Leukemia therapy, Neoplasms
- Abstract
Chimeric antigen receptor T (CAR-T) cell therapy holds great promise as an innovative immunotherapeutic approach for cancer treatment. To optimize the production and application of CAR-T cells, we evaluated the in vivo stability and efficacy capacities of CAR-T cells developed under different conditions. In this study, CAR-T cells were activated using Phytohemagglutinin (PHA) or anti-CD3&anti-CD28 and were compared in an in vivo CD19+B-cell cancer model in mouse groups. Our results demonstrated that CAR-T cells activated with PHA exhibited higher stability and anti-cancer efficacy compared to those activated with anti-CD3&anti-CD28. Specifically, CAR19BB-T cells activated with PHA exhibited continuous proliferation and long-term persistence without compromising their anti-cancer efficacy. Kaplan-Meier survival analysis revealed prolonged overall survival in the CAR-T cell-treated groups compared to the only tumor group. Furthermore, specific LTR-targeted RT-PCR analysis confirmed the presence of CAR-T cells in the treated groups, with significantly higher levels observed in the CAR19BB-T (PHA) group compared to other groups. Histopathological analysis of spleen, kidney, and liver tissue sections indicated reduced inflammation and improved tissue integrity in the CAR-T cell-treated groups. Our findings highlight the potential benefits of using PHA as a co-stimulatory method for CAR-T cell production, offering a promising strategy to enhance their stability and persistence. These results provide valuable insights for the development of more effective and enduring immunotherapeutic approaches for cancer treatment. CAR-T cells activated with PHA may offer a compelling therapeutic option for advancing cancer immunotherapy in clinical applications., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2024
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3. Unmanipulated haploidentical hematopoietic stem cell transplantation for mixed phenotype acute leukemia: a single center study.
- Author
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Huang J, Feng B, Cheng Y, Xu L, Zhang X, Huang X, and Wang Y
- Subjects
- Humans, Acute Disease, Phenotype, Transplantation Conditioning, Retrospective Studies, Hematopoietic Stem Cell Transplantation, Leukemia therapy, Graft vs Host Disease
- Published
- 2024
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4. Super-precise CRISPR tool enters US clinical trials for the first time.
- Author
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Ledford H
- Subjects
- Humans, Immunotherapy, Adoptive methods, Immunotherapy, Adoptive standards, Leukemia therapy, United States, Clinical Trials as Topic, CRISPR-Cas Systems, Gene Editing methods, Gene Editing standards
- Published
- 2023
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5. Effect of graft cell dose on second transplantation from a haploidentical donor with post-transplantation cyclophosphamide for relapsed/refractory acute leukemia.
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Nakaya Y, Nakamae H, Harada N, Okamura H, Sakatoku K, Ido K, Makuuchi Y, Kuno M, Takakuwa T, Hirose A, Nakamae M, Nishimoto M, Nakashima Y, Koh H, and Hino M
- Subjects
- Humans, Cyclophosphamide therapeutic use, Acute Disease, Transplantation Conditioning, Retrospective Studies, Leukemia therapy, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy
- Published
- 2023
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6. Label-free testing strategy to evaluate packed red blood cell quality before transfusion to leukemia patients.
- Author
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Dybas J, Wajda A, Alcicek FC, Kaczmarska M, Bulat K, Szczesny-Malysiak E, Martyna A, Perez-Guaita D, Sacha T, and Marzec KM
- Subjects
- Humans, Blood Transfusion, Erythrocytes, Erythrocyte Transfusion adverse effects, Leukemia diagnosis, Leukemia therapy, Leukemia etiology
- Abstract
Patients worldwide require therapeutic transfusions of packed red blood cells (pRBCs), which is applied to the high-risk patients who need periodic transfusions due to leukemia, lymphoma, myeloma and other blood diseases or disorders. Contrary to the general hospital population where the transfusions are carried out mainly for healthy trauma patients, in case of high-risk patients the proper quality of pRBCs is crucial. This leads to an increased demand for efficient technology providing information on the pRBCs alterations deteriorating their quality. Here we present the design of an innovative, label-free, noninvasive, rapid Raman spectroscopy-based method for pRBCs quality evaluation, starting with the description of sample measurement and data analysis, through correlation of spectroscopic results with reference techniques' outcomes, and finishing with methodology verification and its application in clinical conditions. We have shown that Raman spectra collected from the pRBCs supernatant mixture with a proper chemometric analysis conducted for a minimum one ratio of integral intensities of the chosen Raman marker bands within the spectrum allow evaluation of the pRBC quality in a rapid, noninvasive, and free-label manner, without unsealing the pRBCs bag. Subsequently, spectroscopic data were compared with predefined reference values, either from pRBCs expiration or those defining the pRBCs quality, allowing to assess their utility for transfusion to patients with acute myeloid leukemia (AML) and lymphoblastic leukemia (ALL)., (© 2022. The Author(s).)
- Published
- 2022
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7. RASA2 ablation in T cells boosts antigen sensitivity and long-term function.
- Author
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Carnevale J, Shifrut E, Kale N, Nyberg WA, Blaeschke F, Chen YY, Li Z, Bapat SP, Diolaiti ME, O'Leary P, Vedova S, Belk J, Daniel B, Roth TL, Bachl S, Anido AA, Prinzing B, Ibañez-Vega J, Lange S, Haydar D, Luetke-Eversloh M, Born-Bony M, Hegde B, Kogan S, Feuchtinger T, Okada H, Satpathy AT, Shannon K, Gottschalk S, Eyquem J, Krenciute G, Ashworth A, and Marson A
- Subjects
- Animals, Bone Marrow, CRISPR-Cas Systems, Disease Models, Animal, Gene Knockdown Techniques, Humans, Immunotherapy, Adoptive, Leukemia immunology, Leukemia pathology, Leukemia therapy, Mice, Receptors, Antigen, T-Cell immunology, Receptors, Chimeric Antigen immunology, Time Factors, Xenograft Model Antitumor Assays, Antigens, Neoplasm immunology, Neoplasms immunology, Neoplasms pathology, Neoplasms therapy, T-Lymphocytes immunology, T-Lymphocytes metabolism, ras GTPase-Activating Proteins deficiency, ras GTPase-Activating Proteins genetics
- Abstract
The efficacy of adoptive T cell therapies for cancer treatment can be limited by suppressive signals from both extrinsic factors and intrinsic inhibitory checkpoints
1,2 . Targeted gene editing has the potential to overcome these limitations and enhance T cell therapeutic function3-10 . Here we performed multiple genome-wide CRISPR knock-out screens under different immunosuppressive conditions to identify genes that can be targeted to prevent T cell dysfunction. These screens converged on RASA2, a RAS GTPase-activating protein (RasGAP) that we identify as a signalling checkpoint in human T cells, which is downregulated upon acute T cell receptor stimulation and can increase gradually with chronic antigen exposure. RASA2 ablation enhanced MAPK signalling and chimeric antigen receptor (CAR) T cell cytolytic activity in response to target antigen. Repeated tumour antigen stimulations in vitro revealed that RASA2-deficient T cells show increased activation, cytokine production and metabolic activity compared with control cells, and show a marked advantage in persistent cancer cell killing. RASA2-knockout CAR T cells had a competitive fitness advantage over control cells in the bone marrow in a mouse model of leukaemia. Ablation of RASA2 in multiple preclinical models of T cell receptor and CAR T cell therapies prolonged survival in mice xenografted with either liquid or solid tumours. Together, our findings highlight RASA2 as a promising target to enhance both persistence and effector function in T cell therapies for cancer treatment., (© 2022. The Author(s).)- Published
- 2022
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8. Myeloablative conditioning with thiotepa-busulfan-fludarabine does not improve the outcome of patients transplanted with active leukemia: final results of the GITMO prospective trial GANDALF-01.
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Bonifazi F, Pavoni C, Peccatori J, Giglio F, Arpinati M, Busca A, Bernasconi P, Grassi A, Iori AP, Patriarca F, Brunello L, Di Grazia C, Carella AM, Cilloni D, Picardi A, Proia A, Santarone S, Sorasio R, Carluccio P, Chiusolo P, Cupri A, Luppi M, Nozzoli C, Baronciani D, Casini M, Grillo G, Musso M, Onida F, Palazzo G, Parma M, Tringali S, Vacca A, Vallisa D, Sacchi N, Oldani E, Masciulli A, Gheorghiu A, Girmenia C, Martino M, Bruno B, Rambaldi A, and Ciceri F
- Subjects
- Busulfan therapeutic use, Humans, Prospective Studies, Recurrence, Thiotepa therapeutic use, Transplantation Conditioning methods, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation methods, Leukemia therapy
- Abstract
The outcome of refractory/relapsed (R/R) acute leukemias is still dismal and their treatment represents an unmet clinical need. However, allogeneic transplantation (allo-HSCT) remains the only potentially curative approach in this setting. A prospective study (GANDALF-01, NCT01814488; EUDRACT:2012-004008-37) on transplantation with alternative donors had been run by GITMO using a homogeneous myeloablative conditioning regimen with busulfan, thiotepa and fludarabine while GVHD prophylaxis was stratified by donor type. The study enrolled 101 patients; 90 found an alternative donor and 87 ultimately underwent allo-HSCT. Two-year overall survival of the entire and of the transplant population (primary endpoint) were 19% and 22%, without significant differences according to disease, donor type and disease history (relapsed vs refractory patients). Two-year progression-free survival was 19% and 17% respectively. The cumulative incidences of relapse and non-relapse mortality were 49% and 33% at two years. Acute grade II-IV and chronic GVHD occurred in 23 and 10 patients. Dose intensification with a myeloablative two-alkylating regimen as sole strategy for transplanting R/R acute leukemia does seem neither to improve the outcome nor to control disease relapse. A pre-planned relapse prevention should be included in the transplant strategy in this patient population., (© 2022. The Author(s).)
- Published
- 2022
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9. Decade-long leukaemia remissions with persistence of CD4 + CAR T cells.
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Melenhorst JJ, Chen GM, Wang M, Porter DL, Chen C, Collins MA, Gao P, Bandyopadhyay S, Sun H, Zhao Z, Lundh S, Pruteanu-Malinici I, Nobles CL, Maji S, Frey NV, Gill SI, Loren AW, Tian L, Kulikovskaya I, Gupta M, Ambrose DE, Davis MM, Fraietta JA, Brogdon JL, Young RM, Chew A, Levine BL, Siegel DL, Alanio C, Wherry EJ, Bushman FD, Lacey SF, Tan K, and June CH
- Subjects
- Antigens, CD19 immunology, CD8-Positive T-Lymphocytes cytology, CD8-Positive T-Lymphocytes immunology, Cell Separation, Humans, Time Factors, CD4-Positive T-Lymphocytes cytology, CD4-Positive T-Lymphocytes immunology, Immunotherapy, Adoptive, Leukemia immunology, Leukemia therapy, Receptors, Chimeric Antigen immunology
- Abstract
The adoptive transfer of T lymphocytes reprogrammed to target tumour cells has demonstrated potential for treatment of various cancers
1-7 . However, little is known about the long-term potential and clonal stability of the infused cells. Here we studied long-lasting CD19-redirected chimeric antigen receptor (CAR) T cells in two patients with chronic lymphocytic leukaemia1-4 who achieved a complete remission in 2010. CAR T cells remained detectable more than ten years after infusion, with sustained remission in both patients. Notably, a highly activated CD4+ population emerged in both patients, dominating the CAR T cell population at the later time points. This transition was reflected in the stabilization of the clonal make-up of CAR T cells with a repertoire dominated by a small number of clones. Single-cell profiling demonstrated that these long-persisting CD4+ CAR T cells exhibited cytotoxic characteristics along with ongoing functional activation and proliferation. In addition, longitudinal profiling revealed a population of gamma delta CAR T cells that prominently expanded in one patient concomitant with CD8+ CAR T cells during the initial response phase. Our identification and characterization of these unexpected CAR T cell populations provide novel insight into the CAR T cell characteristics associated with anti-cancer response and long-term remission in leukaemia., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2022
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10. Disruption of the oral microbiota is associated with a higher risk of relapse after allogeneic hematopoietic stem cell transplantation.
- Author
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de Molla VC, Heidrich V, Bruno JS, Knebel FH, Miranda-Silva W, Asprino PF, Tucunduva L, Rocha V, Novis Y, Camargo AA, Fregnani ER, and Arrais-Rodrigues C
- Subjects
- Adult, Aged, Brazil epidemiology, Female, Humans, Leukemia microbiology, Male, Middle Aged, Mouth Mucosa pathology, Neoplasm Recurrence, Local microbiology, Neoplasm Recurrence, Local pathology, Risk Factors, Survival Rate, Transplantation, Homologous, Treatment Outcome, Young Adult, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia therapy, Microbiota genetics, Mouth Mucosa microbiology, Neoplasm Recurrence, Local epidemiology, Transplantation Conditioning methods
- Abstract
Intestinal microbiota (IM) diversity and composition regulates host immunity and affects outcomes after allogeneic stem cell transplantation (allo-HSCT). We evaluated if the oral mucosa microbiota (OM) could impact the outcomes in patients who underwent allo-HSCT. Samples from the oral mucosa of 30 patients were collected at three time points: before the conditioning regimen, at aplasia, and at engraftment. We analyzed the associations of OM diversity and composition with allo-HSCT outcomes. Lower OM diversity at preconditioning was associated with a higher risk of relapse at 3 years (68% versus 33%, respectively; P = 0.04). Dominance (relative abundance ≥ 30%) by a single genus at preconditioning was also associated with a higher risk of relapse (63% versus 36% at 3 years, respectively; P = 0.04), as well as worse progression-free survival (PFS; 19% versus 55%, respectively; P = 0.01), and overall survival (OS) at 3 years (38% versus 81%, respectively; P = 0.02). In our study we observed that OM dysbiosis is associated with a higher risk of relapse and worse survival after allo-HSCT., (© 2021. The Author(s).)
- Published
- 2021
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11. Granulocyte transfusions in haematopoietic cell transplants and leukaemia: the phoenix or beating a dead horse?
- Author
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Gale RP, Schiffer CA, and Lazarus HM
- Subjects
- Granulocytes, Humans, Leukocyte Transfusion, Hematopoietic Stem Cell Transplantation, Leukemia therapy
- Published
- 2021
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12. Venous thrombosis and predictors of relapse in eosinophil-related diseases.
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Réau V, Vallée A, Terrier B, Plessier A, Abisror N, Ackermann F, Benainous R, Bohelay G, Chabi-Charvillat ML, Cornec D, Desbois AC, Faguer S, Freymond N, Gaillet A, Hamidou M, Killian M, Le Jeune S, Marchetti A, Meyer G, Osorio-Perez F, Panel K, Rautou PE, Rohmer J, Simon N, Tcherakian C, Vasse M, Zuelgaray E, Lefevre G, Kahn JE, and Groh M
- Subjects
- Adult, Aged, Churg-Strauss Syndrome epidemiology, Churg-Strauss Syndrome pathology, Eosinophilia complications, Eosinophilia epidemiology, Eosinophilia pathology, Eosinophils pathology, Female, Humans, Hypereosinophilic Syndrome epidemiology, Hypereosinophilic Syndrome genetics, Hypereosinophilic Syndrome pathology, Leukemia epidemiology, Leukemia genetics, Leukemia pathology, Male, Middle Aged, Portal Vein pathology, Pulmonary Embolism epidemiology, Pulmonary Embolism pathology, Pulmonary Embolism therapy, Recurrence, Retrospective Studies, Treatment Outcome, Venous Thrombosis epidemiology, Venous Thrombosis genetics, Venous Thrombosis pathology, mRNA Cleavage and Polyadenylation Factors genetics, Churg-Strauss Syndrome therapy, Eosinophilia therapy, Hypereosinophilic Syndrome therapy, Leukemia therapy, Venous Thrombosis therapy
- Abstract
Eosinophils have widespread procoagulant effects. Eosinophilic cardiovascular toxicity mostly consists of endomyocardial damage or eosinophilic vasculitis, while reported cases of venous thrombosis (VT) are scarce. We aimed to report on the clinical features and treatment outcomes of patients with unexplained VT and eosinophilia, and to identify predictors of relapse. This retrospective, multicenter, observational study included patients aged over 15 years with VT, concomitant blood eosinophilia ≥ 1G/L and without any other moderate-to-strong contributing factors for VT. Fifty-four patients were included. VT was the initial manifestation of eosinophil-related disease in 29 (54%) patients and included pulmonary embolism (52%), deep venous thrombosis (37%), hepatic (11%) and portal vein (9%) thromboses. The median [IQR] absolute eosinophil count at VT onset was 3.3G/L [1.6-7.4]. Underlying eosinophil-related diseases included FIP1L1-PDGFRA-associated chronic myeloid neoplasm (n = 4), Eosinophilic Granulomatosis with Polyangiitis (n = 9), lymphocytic (n = 1) and idiopathic (n = 29) variants of hypereosinophilic syndrome. After a median [IQR] follow-up of 24 [10-62] months, 7 (13%) patients had a recurrence of VT. In multivariate analysis, persistent eosinophilia was the sole variable associated with a shorter time to VT relapse (HR 7.48; CI95% [1.94-29.47]; p = 0.015). Long-term normalization of eosinophil count could prevent the recurrence of VT in a subset of patients with unexplained VT and eosinophilia ≥ 1G/L.
- Published
- 2021
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13. Management of patients with acute leukemia during the COVID-19 outbreak: practical guidelines from the acute leukemia working party of the European Society for Blood and Marrow Transplantation.
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Brissot E, Labopin M, Baron F, Bazarbachi A, Bug G, Ciceri F, Esteve J, Giebel S, Gilleece MH, Gorin NC, Lanza F, Peric Z, Ruggeri A, Sanz J, Savani BN, Schmid C, Shouval R, Spyridonidis A, Versluis J, Nagler A, and Mohty M
- Subjects
- Europe epidemiology, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Myeloid, Acute complications, Leukemia, Myeloid, Acute therapy, Pandemics, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Risk Factors, Societies, Medical, Tissue and Organ Procurement, COVID-19 complications, COVID-19 epidemiology, Leukemia complications, Leukemia therapy, SARS-CoV-2
- Published
- 2021
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14. Occurrence of long-term effects after hematopoietic stem cell transplantation in children affected by acute leukemia receiving either busulfan or total body irradiation: results of an AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) retrospective study.
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Saglio F, Zecca M, Pagliara D, Giorgiani G, Balduzzi A, Calore E, Favre C, Faraci M, Prete A, Tambaro FP, Quarello P, Locatelli F, and Fagioli F
- Subjects
- Busulfan adverse effects, Child, Cyclophosphamide, Humans, Retrospective Studies, Transplantation Conditioning adverse effects, Whole-Body Irradiation adverse effects, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia therapy
- Abstract
Patients given allogeneic hematopoietic stem cell transplantation (alloHSCT) present an increased incidence of long-term toxicities that can be attributed to the preparative regimen. We retrospectively analyzed in a population of 670 children receiving allo-HSCT for acute leukemia the occurrence of different late effects in function of the choice made between total body irradiation (TBI) and busulfan, as part of the preparative regimen. In univariable analysis, we found that patients treated with TBI developed cataract in 24% of the cases compared with 4% in patients treated with BU (p = 0.0001) and that the incidence of secondary malignant neoplasia (SMN) was higher in patients treated with TBI (18%) as compared with those prepared to the allograft with a Bu-based regimen (0%) (p = 0.019). Conditioning regimen did not show a statistically significant correlation with the occurrence of all the other investigated late effects. In multivariable analysis, TBI remained associated with the occurrence of cataracts (Relative Risk: 0.33 p = 0.012) and secondary malignancies (Relative Risk 3.96 × 10e-6 p < 0.001); however, other variables, as GvHD and disease type, were also correlated with these long-term sequels, indicating that in our study population the preparative regimen is not the only factor influencing the incidence of these complications.
- Published
- 2020
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15. Adult peripheral blood and umbilical cord blood NK cells are good sources for effective CAR therapy against CD19 positive leukemic cells.
- Author
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Herrera L, Santos S, Vesga MA, Anguita J, Martin-Ruiz I, Carrascosa T, Juan M, and Eguizabal C
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- Aged, Aged, 80 and over, Antigens, CD19 immunology, Cord Blood Stem Cell Transplantation methods, Female, Fetal Blood immunology, Graft vs Host Disease etiology, Humans, Killer Cells, Natural immunology, Leukemia immunology, Leukemia, Lymphocytic, Chronic, B-Cell immunology, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma immunology, Receptors, Antigen, T-Cell immunology, Receptors, Chimeric Antigen immunology, Remission Induction, Immunotherapy, Adoptive methods, Killer Cells, Natural transplantation, Leukemia therapy
- Abstract
Among hematological cancers, Acute Lymphoblastic Leukemia (ALL) and Chronic Lymphocytic Leukemia (CLL) are the most common leukemia in children and elderly people respectively. Some patients do not respond to chemotherapy treatments and it is necessary to complement it with immunotherapy-based treatments such as chimeric antigen receptor (CAR) therapy, which is one of the newest and more effective treatments against these cancers and B-cell lymphoma. Although complete remission results are promising, CAR T cell therapy presents still some risks for the patients, including cytokine release syndrome (CRS) and neurotoxicity. We proposed a different immune cell source for CAR therapy that might prevent these side effects while efficiently targeting malignant cells. NK cells from different sources are a promising vehicle for CAR therapy, as they do not cause graft versus host disease (GvHD) in allogenic therapies and they are prompt to attack cancer cells without prior sensitization. We studied the efficacy of NK cells from adult peripheral blood (AB) and umbilical cord blood (CB) against different target cells in order to determine the best source for CAR therapy. AB CAR-NK cells are slightly better at killing CD19 presenting target cells and CB NK cells are easier to stimulate and they have more stable number from donor to donor. We conclude that CAR-NK cells from both sources have their advantages to be an alternative and safer candidate for CAR therapy.
- Published
- 2019
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16. Targeting REGNASE-1 programs long-lived effector T cells for cancer therapy.
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Wei J, Long L, Zheng W, Dhungana Y, Lim SA, Guy C, Wang Y, Wang YD, Qian C, Xu B, Kc A, Saravia J, Huang H, Yu J, Doench JG, Geiger TL, and Chi H
- Subjects
- Animals, Basic-Leucine Zipper Transcription Factors deficiency, Basic-Leucine Zipper Transcription Factors metabolism, CD8-Positive T-Lymphocytes cytology, CRISPR-Cas Systems genetics, Disease Models, Animal, Female, Gene Deletion, Humans, Leukemia genetics, Leukemia metabolism, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating metabolism, Melanoma genetics, Melanoma metabolism, Mice, Mitochondria metabolism, Protein Tyrosine Phosphatase, Non-Receptor Type 2 genetics, Protein Tyrosine Phosphatase, Non-Receptor Type 2 metabolism, Reproducibility of Results, Ribonucleases deficiency, Ribonucleases genetics, Ribonucleases immunology, Suppressor of Cytokine Signaling 1 Protein genetics, Suppressor of Cytokine Signaling 1 Protein metabolism, Tumor Microenvironment immunology, CD8-Positive T-Lymphocytes immunology, Immunotherapy, Adoptive methods, Leukemia immunology, Leukemia therapy, Melanoma immunology, Melanoma therapy, Molecular Targeted Therapy, Ribonucleases metabolism
- Abstract
Adoptive cell therapy represents a new paradigm in cancer immunotherapy, but it can be limited by the poor persistence and function of transferred T cells
1 . Here we use an in vivo pooled CRISPR-Cas9 mutagenesis screening approach to demonstrate that, by targeting REGNASE-1, CD8+ T cells are reprogrammed to long-lived effector cells with extensive accumulation, better persistence and robust effector function in tumours. REGNASE-1-deficient CD8+ T cells show markedly improved therapeutic efficacy against mouse models of melanoma and leukaemia. By using a secondary genome-scale CRISPR-Cas9 screening, we identify BATF as the key target of REGNASE-1 and as a rheostat that shapes antitumour responses. Loss of BATF suppresses the increased accumulation and mitochondrial fitness of REGNASE-1-deficient CD8+ T cells. By contrast, the targeting of additional signalling factors-including PTPN2 and SOCS1-improves the therapeutic efficacy of REGNASE-1-deficient CD8+ T cells. Our findings suggest that T cell persistence and effector function can be coordinated in tumour immunity and point to avenues for improving the efficacy of adoptive cell therapy for cancer.- Published
- 2019
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17. Safety and efficacy of fresh whole blood donor lymphocyte infusion in children.
- Author
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Swaminathan VV, Uppuluri R, Patel S, Sivashankaran M, Ravichandran N, Ramanan KM, Ramakrishnan B, Vaidhyanathan L, and Raj R
- Subjects
- Allografts, Child, Chimerism, Disease-Free Survival, Female, Humans, Male, Retrospective Studies, Survival Rate, Blood Donors, Graft vs Host Disease mortality, Graft vs Host Disease therapy, Graft vs Leukemia Effect, Hematopoietic Stem Cell Transplantation, Leukemia mortality, Leukemia therapy, Lymphocyte Transfusion, Transplantation Conditioning
- Abstract
Donor lymphocyte infusion (DLI) is a form of cellular immunotherapy which is known to be effective in preventing relapse in leukemia by inducing graft versus leukemia (GVL) effect. In hematopoietic stem cell transplantation (HSCT) for benign hematological conditions including primary immune deficiency, mixed chimerism is seen with the use of reduced intensity conditioning. DLI can help prevent graft rejection by boosting the existing graft in these situations. There is scant data on the use of DLI in children who have undergone HSCT for benign hematological disorders. We present our case series with early withdrawal of immunosuppression and DLI as a means to mitigate relapse of leukemia and prevent graft rejection in mixed chimerism in children transplanted for benign hematological disorders. Donor lymphocyte infusion was given in a graded regimen with the cell dose of 1 × 10
5 CD3 cells/kg (1 × 104 /kg in haploidentical transplant), 5 × 105 CD3 cells/kg, 1 × 106 CD3 cells/kg depending on the graft kinetics and the clinical status of the children. A total of fifty eight children including those with haploidentical donors underwent DLI with an overall survival of 81.1%. The use of fresh whole blood in very small aliquots from the donor has made this technique cost effective and an attractive form of immunotherapy.- Published
- 2019
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18. ADCC can improve graft vs leukemia effect after T- and B-cell depleted haploidentical stem cell transplantation in pediatric B-lineage ALL.
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Schlegel P, Jung G, Lang AM, Döring M, Schulte JH, Ebinger M, Holzer U, Heubach F, Seitz C, Lang B, Hundsdörfer P, Eggert A, Eichholz T, Kreyenberg H, Lang P, and Handgretinger R
- Subjects
- Adolescent, Child, Child, Preschool, Cohort Studies, Disease-Free Survival, Female, Humans, Treatment Outcome, Antibody-Dependent Cell Cytotoxicity physiology, Graft vs Leukemia Effect physiology, Hematopoietic Stem Cell Transplantation methods, Leukemia therapy, Transplantation Conditioning methods
- Abstract
Posttransplant relapsed B-cell precursor ALL can be cured by 2nd hematopoietic stem cell transplantation (HSCT) in 20% of patients. The major cause of death after second HSCT is leukemic relapse. One reliable predictor for survival after 2nd-HSCT are posttransplant MRD levels. Patients with detectable or increase of MRD are likely to relapse. Patients in complete molecular remission show the best leukemia-free survival and lowest cumulative incidence (CI) of relapse. As patients who undergo second or subsequent HSCT are high-risk patients, we evaluated the prophylactic use of the chimeric Fc-optimized CD19-4G7SDIE-mAb. Posttransplant relapsed CD19
+ BCP-ALL patients, who underwent a second or subsequent haplo-HSCT from a T- and B-cell depleted graft received posttransplant prophylactic CD19-4G7SDIE-mAb treatment on compassionate use in complete molecular remission, to increase the antileukemic activity of the new reconstituting immune system by recruiting Fc-expressing effector cells. NK cells recovered early and robust. The 3 year overall survival in 15 evaluable patients was 56%, the 3 year event-free survival was 55% and the CI of relapse 38%. Compared to a historical control group, the CI of relapse was markedly lower and consecutively the EFS higher. Posttransplant-targeted therapy may overcome the need for unspecific GvL effect of undesired GvHD, that can cause severe morbidity and mortality. Due to a low adverse event profile the CD19-4G7SDIE-mAb may be suitable for broad administration to consolidate posttransplant MRD negativity.- Published
- 2019
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19. Controversies and challenges in HLA-haplotype-matched transplants for leukaemia.
- Author
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Gale RP
- Subjects
- Humans, Bone Marrow Transplantation methods, Haplotypes immunology, Leukemia therapy
- Abstract
Many typescripts in this issue describe increasing use of HLA-haplotype-matched transplants in persons with leukaemia and report outcomes. Consequently, my goal is not to repeat these data but to focus on controversies and challenges relevant to this topic including: (1) what is the best technique for performing these transplants; (2) who is the best donor; (3) who should receive this type of transplant; (4) how do results compare with transplants from other donors; and (5) how can results be improved.
- Published
- 2019
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20. Pre-transplant recovery of microbiome diversity without recovery of the original microbiome.
- Author
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Rashidi A, Kaiser T, Holtan SG, Weisdorf DJ, Khoruts A, and Staley C
- Subjects
- Acute Disease, Allografts, Female, Humans, Male, Gastrointestinal Microbiome, Hematopoietic Stem Cell Transplantation, Leukemia microbiology, Leukemia therapy
- Published
- 2019
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21. The safety and efficacy of clofarabine in combination with high-dose cytarabine and total body irradiation myeloablative conditioning and allogeneic stem cell transplantation in children, adolescents, and young adults (CAYA) with poor-risk acute leukemia.
- Author
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Hochberg J, Zahler S, Geyer MB, Chen N, Krajewski J, Harrison L, Militano O, Ozkaynak MF, Cheerva AC, Talano J, Moore TB, Gillio AP, Walters MC, Baxter-Lowe LA, Hamby C, and Cairo MS
- Subjects
- Acute Disease, Adolescent, Child, Child, Preschool, Clofarabine therapeutic use, Cytarabine therapeutic use, Female, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation mortality, Humans, Infant, Leukemia complications, Leukemia mortality, Leukemia, Myeloid, Acute therapy, Male, Myeloablative Agonists adverse effects, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Transplantation Conditioning adverse effects, Transplantation Conditioning mortality, Transplantation, Homologous, Treatment Outcome, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation methods, Leukemia therapy, Myeloablative Agonists therapeutic use, Transplantation Conditioning methods, Whole-Body Irradiation methods
- Abstract
Acute leukemias in children with CR3, refractory relapse, or induction failure (IF) have a poor prognosis. Clofarabine has single agent activity in relapsed leukemia and synergy with cytarabine. We sought to determine the safety and overall survival in a Phase I/II trial of conditioning with clofarabine (doses 40 - 52 mg/m
2 ), cytarabine 1000 mg/m2 , and 1200 cGy TBI followed by alloSCT in children, adolescents, and young adults with poor-risk leukemia. Thirty-seven patients; Age 12 years (1-22 years); ALL/AML: 34:3 (18 IF, 10 CR3, 13 refractory relapse); 15 related, 22 unrelated donors. Probabilities of neutrophil, platelet engraftment, acute GvHD, and chronic GvHD were 94%, 84%, 49%, and 30%, respectively. Probability of day 100 TRM was 8.1%. 2-year EFS (event free survival) and OS (overall survival) were 38.6% (CI95 : 23-54%), and 41.3% (CI95 : 25-57%). Multivariate analysis demonstrated overt disease at time of transplant (relative risk (RR) 3.65, CI95 : 1.35-9.89, P = 0.011) and umbilical cord blood source (RR 2.17, CI95 : 1.33-4.15, P = 0.019) to be predictors of worse EFS/OS. This novel myeloablative conditioning regimen followed by alloSCT is safe and well tolerated in CAYA with very poor-risk ALL or AML. Further investigation in CAYA with better risk ALL and AML undergoing alloSCT is warranted.- Published
- 2019
- Full Text
- View/download PDF
22. Impact of graft-versus-host disease on relapse and survival after allogeneic stem cell transplantation for pediatric leukemia.
- Author
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Kato M, Kurata M, Kanda J, Kato K, Tomizawa D, Kudo K, Yoshida N, Watanabe K, Shimada H, Inagaki J, Koh K, Goto H, Kato K, Cho Y, Yuza Y, Ogawa A, Okada K, Inoue M, Hashii Y, Teshima T, Murata M, and Atsuta Y
- Subjects
- Adolescent, Allografts, Child, Child, Preschool, Chronic Disease, Disease-Free Survival, Female, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Humans, Infant, Infant, Newborn, Male, Recurrence, Survival Rate, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Leukemia mortality, Leukemia therapy, Stem Cell Transplantation
- Abstract
Graft-versus-host disease (GVHD) occasionally leads to morbidity and mortality but is thought to reduce the risk of relapses in patients with a hematological malignancy. However, information on the effect of GVHD in pediatric leukemia is limited. Using a nationwide registry, we retrospectively analyzed 1526 children who underwent allogeneic stem cell transplantation for leukemia. Grades 0-I acute GVHD were associated with a higher relapse rate at three years after transplantation, at 25.4 and 24.3%, respectively, than grades II, III, or IV acute GVHD at 18.9%, 21.2%, and 2.6%, respectively. In contrast, the overall survival curve of the grades 0 and I GVHD groups (79.0% and 79.5%, respectively) approximated that of the grade II GVHD group (76.3%), and the probability of survival was worst in the severe GVHD groups (66.9% for grade III and 42.5% for grade IV). Chronic GVHD also reduced the relapse risk but conferred no survival advantage. Acute lymphoblastic leukemia was more sensitive to acute GVHD than acute myeloid leukemia (AML) while AML was more sensitive to chronic GVHD. Our study reproduced the preventive effects of GVHD against pediatric leukemia relapses but failed to demonstrate a significant survival advantage.
- Published
- 2019
- Full Text
- View/download PDF
23. Polo-like kinases and acute leukemia.
- Author
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Goroshchuk O, Kolosenko I, Vidarsdottir L, Azimi A, and Palm-Apergi C
- Subjects
- Acute Disease, Adult, Animals, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cell Cycle Proteins antagonists & inhibitors, Cell Cycle Proteins genetics, Cell Cycle Proteins physiology, Child, Clinical Trials as Topic, Combined Modality Therapy, Drug Screening Assays, Antitumor, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Leukemic, Hematopoietic Stem Cell Transplantation, Humans, Leukemia drug therapy, Leukemia therapy, Mice, Multigene Family, Neoplasm Proteins antagonists & inhibitors, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Protein Serine-Threonine Kinases antagonists & inhibitors, Protein Serine-Threonine Kinases genetics, Proto-Oncogene Proteins antagonists & inhibitors, RNA Interference, Survival Rate, Tumor Suppressor Proteins genetics, Polo-Like Kinase 1, Leukemia enzymology, Molecular Targeted Therapy, Neoplasm Proteins physiology, Protein Serine-Threonine Kinases physiology, Tumor Suppressor Proteins physiology
- Abstract
Acute leukemia is a common malignancy among children and adults worldwide and many patients suffer from chronic health issues using current therapeutic approaches. Therefore, there is a great need for the development of novel and more specific therapies with fewer side effects. The family of Polo-like kinases (Plks) is a group of five serine/threonine kinases that play an important role in cell cycle regulation and are critical targets for therapeutic invention. Plk1 and Plk4 are novel targets for cancer therapy as leukemic cells often express higher levels than normal cells. In contrast, Plk2 and Plk3 are considered to be tumor suppressors. Several small molecule inhibitors have been developed for targeting Plk1 inhibition. Despite reaching phase III clinical trials, one of the ATP-competitive Plk1 inhibitor, volasertib, did not induce an objective clinical response and even caused lethal side effects in some patients. In order to improve the specificity of the Plk1 inhibitors and reduce off-target side effects, novel RNA interference (RNAi)-based therapies have been developed. In this review, we summarize the mechanisms of action of the Plk family members in acute leukemia, describe preclinical studies and clinical trials involving Plk-targeting drugs and discuss novel approaches in Plk targeting.
- Published
- 2019
- Full Text
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24. Favorable immune recovery and low rate of GvHD in children transplanted with partially T cell-depleted PBSC grafts.
- Author
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Seitz CM, Eyrich M, Greil J, Schlegel P, Feuchtinger T, Bader P, Ebinger M, Schwarze CP, Schlegel PG, Schumm M, Handgretinger R, and Lang P
- Subjects
- Acute Disease, Adolescent, Adult, Allografts, Child, Child, Preschool, Disease-Free Survival, Female, Humans, Infant, Male, Survival Rate, Graft vs Host Disease immunology, Graft vs Host Disease mortality, Immune Reconstitution, Leukemia immunology, Leukemia mortality, Leukemia therapy, Lymphocyte Depletion, Peripheral Blood Stem Cell Transplantation, T-Lymphocytes immunology, Unrelated Donors
- Abstract
Transplantation of peripheral blood stem cells (PBSC) from matched unrelated donors (MUD) is still associated with a significant risk for graft vs. host disease (GvHD), especially in pediatric patients receiving grafts from adult donors containing high amounts of T cells. Here, we present long-term follow-up results on 25 pediatric patients, (acute leukemia n = 15, NHL n = 3, CML n = 3, MDS n = 5), transplanted with CD34 or CD133 positively selected PBSC from MUDs supplemented with an add-back of 1 × 10
7 /kg body weight (kgBW) unselected T cells resulting in a median T-cell depletion (TCD) of 1.97 log. A total of 24/25 (96%) patients had primary engraftment. Early T-cell recovery was significantly improved compared to patients receiving CD34-selected grafts without T-cell add-back and similar to patients receiving unmanipulated bone marrow. GvHD incidence was low with 8/4% aGvHD grade II/III, no grade IV and 13% limited cGvHD. In total, 16/25 (64%) patients are alive after a median follow-up of 10 years. Five-year event-free survival (EFS) was 68%, relapse probability 24% and transplantation-related mortality (TRM) 12%. Thus, in PBSC allotransplants from MUD, partial TCD with serotherapy and CSA/MTX prophylaxis, can effectively reduce GvHD without hampering engraftment and immune reconstitution.- Published
- 2019
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- View/download PDF
25. Risk factors associated with development and mortality by invasive fungal diseases in pediatric allogeneic stem cell transplantation. A pediatric subgroup analysis of data from a prospective study of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO).
- Author
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Castagnola E, Bagnasco F, Menoni S, Muraca M, Prete A, Belotti T, Iori AP, Barberi W, Severino A, Proia A, Raiola AM, Vacca A, Cudillo L, Rambaldi A, and Girmenia C
- Subjects
- Acute Disease, Adolescent, Child, Data Analysis, Female, Graft vs Host Disease, Humans, Invasive Fungal Infections mortality, Italy, Leukemia therapy, Male, Post-Exposure Prophylaxis, Prospective Studies, Risk Factors, Tissue Donors, Transplantation, Homologous adverse effects, Hematopoietic Stem Cell Transplantation adverse effects, Invasive Fungal Infections etiology
- Published
- 2018
- Full Text
- View/download PDF
26. Comparable survival using a CMV-matched or a mismatched donor for CMV+ patients undergoing T-replete haplo-HSCT with PT-Cy for acute leukemia: a study of behalf of the infectious diseases and acute leukemia working parties of the EBMT.
- Author
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Cesaro S, Crocchiolo R, Tridello G, Knelange N, Van Lint MT, Koc Y, Ciceri F, Gülbas Z, Tischer J, Afanasyev B, Bruno B, Castagna L, Blaise D, Mohty M, Irrera G, Diez-Martin JL, Pierelli L, Pioltelli P, Arat M, Delia M, Fagioli F, Ehninger G, Aljurf M, Carella AM, Ozdogu H, Mikulska M, Ljungman P, Nagler A, and Styczynski J
- Subjects
- Acute Disease, Adolescent, Adult, Aged, Child, Child, Preschool, Cytomegalovirus Infections transmission, Female, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Infant, Leukemia complications, Leukemia microbiology, Male, Middle Aged, Serologic Tests, Transplantation, Haploidentical adverse effects, Transplantation, Haploidentical methods, Young Adult, Cyclophosphamide therapeutic use, Cytomegalovirus isolation & purification, Hematopoietic Stem Cell Transplantation methods, Leukemia therapy, Survival Analysis, Tissue Donors
- Abstract
The role of donor CMV serostatus in the setting of non T-cell depleted haplo-HSCT with post-transplant cyclophosphamide (PT-Cy) has not been specifically addressed so far. Here we analyzed the impact of the donor CMV serological status on the outcome of 983 CMV seropositive (CMV+), acute leukemia patients receiving a first, non T-cell depleted haplo-HSCT registered in the EBMT database. The 1-year NRM was 21.3% (95% CI: 18.4-24.8) and 18.8% (95% CI: 13.8-25.5) in the CMV D+/R+ and D-/R+ pairs, respectively (p = 0.40). Similarly, 1-year OS was 55.1% (95% CI: 50.1-58.0) and 55.7% (95% CI: 48.0-62.8) in the same groups (p = 0.50). The other main outcomes were comparable. No difference in NRM nor OS was observed after stratification for the intensity of conditioning and multivariate anaysis confirmed the lack of significant association with NRM or OS. In conclusion, the choice of a CMV-seronegative donor did not impair early survival of CMV-seropositive patients with acute leukemia after a first, non T-cell depleted haploidentical HSCT and PT-Cy among this series of 983 consecutive patients. Future research may focus on the assessment of the hierarchy of all the donor variables.
- Published
- 2018
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27. No association between donor telomere length and outcomes after allogeneic unrelated hematopoietic cell transplant in patients with acute leukemia.
- Author
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Gadalla SM, Wang T, Loftus D, Friedman L, Dagnall C, Haagenson M, Spellman SR, Buturovic L, Blauwkamp M, Shelton J, Fleischhauer K, Hsu KC, Verneris MR, Krstajic D, Hicks B, Jones K, Lee SJ, and Savage SA
- Subjects
- Acute Disease, Adolescent, Adult, Aged, Child, Child, Preschool, Female, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation standards, Humans, Infant, Infant, Newborn, Leukemia diagnosis, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute therapy, Male, Middle Aged, Neutrophils, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Prognosis, Recurrence, Transplantation, Homologous, Treatment Outcome, Young Adult, Hematopoietic Stem Cell Transplantation methods, Leukemia therapy, Telomere Homeostasis, Unrelated Donors
- Abstract
Recent studies suggest improved survival in patients with severe aplastic anemia receiving hematopoietic cell transplant (HCT) from unrelated donors with longer telomeres. Here, we tested whether this effect is generalizable to patients with acute leukemia. From the Center for International Blood and Marrow Transplant Research (CIBMTR
® ) database, we identified 1097 patients who received 8/8 HLA-matched unrelated HCT for acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) between 2004 and 2012 with myeloablative conditioning, and had pre-HCT blood sample from the donor in CIBMTR repository. The median age at HCT for recipients was 40 years (range ≤1-68), and 32 years for donors (range = 18-61). We used qPCR for relative telomere length (RTL) measurement, and Cox proportional hazard models for statistical analyses. In a discovery cohort of 300 patients, longer donor RTL (>25th percentile) was associated with reduced risks of relapse (HR = 0.62, p = 0.05) and acute graft-versus-host disease II-IV (HR = 0.68, p = 0.05), and possibly with a higher probability of neutrophil engraftment (HR = 1.3, p = 0.06). However, these results did not replicate in two validation cohorts of 297 and 488 recipients. There was one exception; a higher probability of neutrophil engraftment was observed in one validation cohort (HR = 1.24, p = 0.05). In a combined analysis of the three cohorts, no statistically significant associations (all p > 0.1) were found between donor RTL and any outcomes.- Published
- 2018
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28. Access to alternative donor hematopoietic search and transplantation for acute leukemia in different macro-regions of Italy. A GITMO/IBMDR study.
- Author
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Milone G, Sacchi N, Gallina A, Leotta S, Picardi A, Guidi S, Tripepi G, Rambaldi A, and Bonifazi F
- Subjects
- Acute Disease, Adolescent, Adult, Europe, Female, Hematopoietic Stem Cell Transplantation, Humans, Italy, Male, Middle Aged, Registries, Leukemia therapy, Tissue Donors supply & distribution
- Abstract
Hematopoietic Stem Cell Transplantation activity levels vary across European countries. No data are available on the homogeneity of access to the transplant procedure for patient with leukaemia, within any European country. We measured homogeneity of the rate of alternative donor search in patients affected by acute leukaemia resident in each Italian region and macro-region during years 2010-2013. A total of 2747 alternative donor searches were studied. Twenty-one percent of all donor searches were made through extra-regional migration. Rate of alternative donor searches varied among the country's regions and macro-regions. The rate of donor searches was 38% lower in South Italy than in North Italy, and the rate of alternative donor transplantations performed was 45% lower. A reduced rate of alternative donor search in South macro-region was observed in all age cohorts. Despite the overall allogeneic transplant rate in Italy is relatively high, there are wide regional differences in access to transplant from alternative donor. Extra-regional migration cannot completely compensate for the lower access to transplant of acute leukaemia patients living in those regions where transplant activity is low.
- Published
- 2018
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29. 2017 in news: The science events that shaped the year.
- Author
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Callaway E, Castelvecchi D, Cyranoski D, Gibney E, Ledford H, Lee JJ, Morello L, Phillips N, Schiermeier Q, Tollefson J, Van Noorden R, and Witze A
- Subjects
- Animals, Antarctic Regions, Child, Chimera, Drug Approval organization & administration, Embryo Research, European Union organization & administration, Female, Forestry legislation & jurisprudence, Genome-Wide Association Study, Gravitation, Humans, Ice Cover, Leukemia therapy, Machine Learning, Male, National Institutes of Health (U.S.) economics, Patents as Topic legislation & jurisprudence, Planets, Quantum Theory, Reproductive Techniques, Assisted, Research Personnel, Saturn, Spacecraft, Stars, Celestial, Swine, Synchrotrons, United Kingdom, United States, United States Environmental Protection Agency economics, Young Adult, Astronomy, Cell- and Tissue-Based Therapy methods, Environmental Policy legislation & jurisprudence, Gene Editing legislation & jurisprudence, Gene Editing methods, Politics, Research Support as Topic economics, Research Support as Topic legislation & jurisprudence, Sexual Harassment
- Published
- 2017
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30. Patient perspectives on physical function after allogeneic hematopoietic stem cell transplantation: a qualitative study.
- Author
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Freeman AT, Stover AM, Grover NS, Shea TC, Reeve BB, and Wood WA
- Subjects
- Adult, Aged, Allografts, Female, Humans, Male, Middle Aged, Exercise, Hematopoietic Stem Cell Transplantation, Leukemia physiopathology, Leukemia therapy, Lymphoma physiopathology, Lymphoma therapy
- Published
- 2017
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31. Association between pretransplant iron overload determined by bone marrow pathological analysis and bacterial infection.
- Author
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Ohmoto A, Fuji S, Miyagi-Maeshima A, Kim SW, Tajima K, Tanaka T, Okinaka K, Kurosawa S, Inamoto Y, Taniguchi H, and Fukuda T
- Subjects
- Acute Disease, Adult, Allografts, Female, Humans, Male, Bacterial Infections blood, Bacterial Infections etiology, Bacterial Infections microbiology, Bacterial Infections pathology, Bone Marrow metabolism, Bone Marrow microbiology, Bone Marrow pathology, Hematopoietic Stem Cell Transplantation, Iron Overload blood, Iron Overload microbiology, Iron Overload pathology, Iron Overload therapy, Leukemia blood, Leukemia microbiology, Leukemia pathology, Leukemia therapy, Myelodysplastic Syndromes blood, Myelodysplastic Syndromes microbiology, Myelodysplastic Syndromes pathology, Myelodysplastic Syndromes therapy
- Published
- 2017
- Full Text
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32. Effect of body mass index on overall survival of patients with allogeneic hematopoietic stem cell transplantation.
- Author
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Yang J, Xue SL, Zhang X, Zhou YN, Qin LQ, Shen YP, and Wu DP
- Subjects
- Acute Disease, Adult, Body Weight, Female, Follow-Up Studies, Humans, Leukemia therapy, Male, Obesity, Overweight, Proportional Hazards Models, Retrospective Studies, Risk Factors, Survival Rate, Thinness, Transplantation, Homologous, Body Mass Index, Hematopoietic Stem Cell Transplantation mortality
- Abstract
Background/objectives: The present work was performed to investigate the association between body mass index (BMI) before transplantation and the overall survival (OS) of patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT)., Subjects/methods: Data from 310 adults who were diagnosed with acute leukemia and underwent allo-HSCT between March 2001 and December 2011 were analyzed. According to the suggested BMI categories for Asian population, patients with BMIs of ⩾23 and ⩾25 kg/m
2 were identified as overweight and obese, respectively. Cox proportional hazards models was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs)., Results: The median follow-up time among the patients was 19.7 months (interquartile range=8.1-37.7). A total of 93 (34.8%) people died within the follow-up period. After adjusting for the potential confounders, normal-weight, overweight and obese patients showed significantly lower HRs than those of underweight patients, with a significant trend of OS improvement upon increasing BMI (P=0.019). Overweight and obese patients survived longer, with a significantly decreased HR by ~40% (HR=0.60; 95% CI: 0.38-0.95) compared with underweight and normal-weight patients., Conclusions: An increased OS was seen in allo-HSCT patients with BMI⩾23 kg/m2 compared to those with lower BMI. Further work are still needed to investigate of the effects of BMI or body composition on the survival of allo-HSCT patients.- Published
- 2017
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33. Outcome after failure of allogeneic hematopoietic stem cell transplantation in children with acute leukemia: a study by the société Francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).
- Author
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Roux C, Tifratene K, Socié G, Galambrun C, Bertrand Y, Rialland F, Jubert C, Pochon C, Paillard C, Sirvent A, Nelken B, Vannier JP, Freycon C, Beguin Y, Raus N, Yakoub-Agha I, Mohty M, Dalle JH, Michel G, Pradier C, Peffault de Latour R, and Rohrlich PS
- Subjects
- Acute Disease, Child, Disease Progression, Hematopoietic Stem Cell Transplantation mortality, Humans, Leukemia mortality, Leukemia, Biphenotypic, Acute mortality, Leukemia, Biphenotypic, Acute therapy, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Lymphocyte Transfusion, Palliative Care, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Retrospective Studies, Survival Rate, Transplantation, Homologous, Treatment Failure, Treatment Outcome, Hematopoietic Stem Cell Transplantation methods, Leukemia therapy
- Abstract
Allogeneic hematopoietic stem cell transplantation (SCT) contributes to improved outcome in childhood acute leukemia (AL). However, therapeutic options are poorly defined in the case of post-transplantation relapse. We aimed to compare treatment strategies in 334 consecutive children with acute leukemia relapse or progression after SCT in a recent 10-year period. Data could be analyzed in 288 patients (157 ALL, 123 AML and 8 biphenotypic AL) with a median age of 8.16 years at transplantation. The median delay from first SCT to relapse or progression was 182 days. The treatment consisted of chemotherapy alone (n=108), chemotherapy followed by second SCT (n=70), supportive/palliative care (n=67), combination of chemotherapy and donor lymphocyte infusion (DLI; n=30), or isolated reinfusion of donor lymphocytes (DLI; n=13). The median OS duration after relapse was 164 days and differed according to therapy: DLI after chemotherapy=385 days, second allograft=391 days, chemotherapy=174 days, DLI alone=140 days, palliative care=43 days. A second SCT or a combination of chemotherapy and DLI yielded similar outcome (hazard ratio (HR)=0.85, P=0.53) unlike chemotherapy alone (HR=1.43 P=0.04), palliative care (HR=4.24, P<0.0001) or isolated DLI (HR=1,94, P<0.04). Despite limitations in this retrospective setting, strategies including immunointervention appear superior to other approaches, mostly in AML.
- Published
- 2017
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34. Risk of sinusoidal obstruction syndrome in allogeneic stem cell transplantation after prior gemtuzumab ozogamicin treatment: a retrospective study from the Acute Leukemia Working Party of the EBMT.
- Author
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Battipaglia G, Labopin M, Candoni A, Fanin R, El Cheikh J, Blaise D, Michallet M, Ruggeri A, Contentin N, Ribera JM, Stadler M, Sierra J, von dem Borne PA, Bloor A, Socié G, Nagler A, and Mohty M
- Subjects
- Acute Disease, Adult, Aged, Aminoglycosides therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Female, Gemtuzumab, Graft vs Host Disease, Hepatic Veno-Occlusive Disease mortality, Hepatic Veno-Occlusive Disease prevention & control, Humans, Leukemia mortality, Leukemia therapy, Male, Middle Aged, Premedication mortality, Retrospective Studies, Survival Analysis, Transplantation, Homologous, Young Adult, Aminoglycosides toxicity, Antibodies, Monoclonal, Humanized toxicity, Hematopoietic Stem Cell Transplantation adverse effects, Hepatic Veno-Occlusive Disease etiology, Leukemia complications, Premedication methods
- Abstract
Gemtuzumab ozogamicin (GO) may increase the risk of sinusoidal obstruction syndrome (SOS) when used prior to allogeneic stem cell transplantation (HSCT). We assessed SOS incidence and outcomes after HSCT of 146 adults, with a median age of 50 years, previously receiving GO. SOS prophylaxis was used in 69 patients (heparin n=57, ursodeoxycholic acid n=8, defibrotide n=4). Cumulative incidence (CI) of SOS was 8% (n=11), with death in 3 patients. Median interval between last GO dose and HSCT was 130 days. Overall survival (OS) and SOS incidence did not differ for patients receiving GO ⩽3.5 months before HSCT and the others. CI of acute and chronic GVHD was 31% and 25%, respectively. Probability of OS and leukemia-free survival (LFS) at 5 years was 40% and 37%, respectively. Relapse incidence and non-relapse mortality were 42% and 21%, respectively. In multivariate analysis, active disease at HSCT was associated with relapse and worse LFS and OS (P<0.03). Liver abnormalities before HSCT correlated with worse OS (P<0.03). Use of low-dose GO prior to HSCT is associated with an acceptable SOS incidence. Prospective studies investigating the role and the utility of SOS prophylaxis are warranted.
- Published
- 2017
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35. GvHD after umbilical cord blood transplantation for acute leukemia: an analysis of risk factors and effect on outcomes.
- Author
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Chen YB, Wang T, Hemmer MT, Brady C, Couriel DR, Alousi A, Pidala J, Urbano-Ispizua A, Choi SW, Nishihori T, Teshima T, Inamoto Y, Wirk B, Marks DI, Abdel-Azim H, Lehmann L, Yu L, Bitan M, Cairo MS, Qayed M, Salit R, Gale RP, Martino R, Jaglowski S, Bajel A, Savani B, Frangoul H, Lewis ID, Storek J, Askar M, Kharfan-Dabaja MA, Aljurf M, Ringden O, Reshef R, Olsson RF, Hashmi S, Seo S, Spitzer TR, MacMillan ML, Lazaryan A, Spellman SR, Arora M, and Cutler CS
- Subjects
- Acute Disease, Adolescent, Antilymphocyte Serum administration & dosage, Child, Child, Preschool, Chronic Disease, Disease-Free Survival, Female, Graft vs Host Disease etiology, Humans, Infant, Infant, Newborn, Male, Registries, Survival Rate, Transplantation Conditioning, Cord Blood Stem Cell Transplantation, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Leukemia mortality, Leukemia therapy
- Abstract
Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1404 umbilical cord blood transplantation (UCBT) patients (single (<18 years)=810, double (⩾18 years)=594) with acute leukemia to define the incidence of acute GvHD (aGvHD) and chronic GvHD (cGvHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grade II-IV aGvHD was 39% (95% confidence interval (CI), 36-43%), grade III-IV aGvHD was 18% (95% CI, 15-20%) and 1-year cGvHD was 27% (95% CI, 24-30%). After double UCBT, 100-day incidence of grade II-IV aGvHD was 45% (95% CI, 41-49%), grade III-IV aGvHD was 22% (95% CI, 19-26%) and 1-year cGvHD was 26% (95% CI, 22-29%). For single UCBT, multivariate analysis showed that absence of antithymocyte globulin (ATG) was associated with aGvHD, whereas prior aGvHD was associated with cGvHD. For double UCBT, absence of ATG and myeloablative conditioning were associated with aGvHD, whereas prior aGvHD predicted for cGvHD. Grade III-IV aGvHD led to worse survival, whereas cGvHD had no significant effect on disease-free or overall survival. GvHD is prevalent after UCBT with severe aGvHD leading to higher mortality. Future research in UCBT should prioritize prevention of GvHD.
- Published
- 2017
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36. Pretransplant chest computed tomography screening in asymptomatic patients with leukemia and myelodysplastic syndrome.
- Author
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El Boghdadly Z, Oran B, Jiang Y, Rondon G, Champlin R, and Kontoyiannis DP
- Subjects
- Adolescent, Adult, Aged, Allografts, Aspergillus fumigatus, Female, Humans, Male, Middle Aged, Mycobacterium avium Complex, Mycobacterium avium-intracellulare Infection diagnostic imaging, Mycobacterium avium-intracellulare Infection mortality, Pneumonia diagnostic imaging, Pneumonia mortality, Pneumonia therapy, Pulmonary Aspergillosis diagnostic imaging, Pulmonary Aspergillosis mortality, Pulmonary Aspergillosis therapy, Retrospective Studies, Hematopoietic Stem Cell Transplantation, Leukemia diagnostic imaging, Leukemia mortality, Leukemia therapy, Myelodysplastic Syndromes diagnostic imaging, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes therapy, Thorax diagnostic imaging, Tomography, X-Ray Computed
- Published
- 2017
- Full Text
- View/download PDF
37. One or two umbilical cord blood cell units? Caveat emptor.
- Author
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Sanz J and Gale RP
- Subjects
- Allografts, HLA Antigens, Humans, Cord Blood Stem Cell Transplantation methods, Leukemia therapy
- Published
- 2017
- Full Text
- View/download PDF
38. Low-dose alemtuzumab for GvHD prevention followed by prophylactic donor lymphocyte infusions in high-risk leukemia.
- Author
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Tsirigotis P, Liga M, Gkirkas K, Stamouli M, Triantafyllou E, Marangos M, Pessach I, Sarantopoulos A, Spyridis N, and Spyridonidis A
- Subjects
- Adolescent, Adult, Aged, Disease-Free Survival, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Survival Rate, Time Factors, Alemtuzumab administration & dosage, Allografts, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Leukemia mortality, Leukemia therapy, Lymphocyte Transfusion, Siblings, Unrelated Donors
- Abstract
We analyzed the use of low-dose alemtuzumab in a cohort of 158 consecutive patients who underwent allogeneic PBSC transplantation. Patients with high-risk acute leukemia were prospectively screened for prophylactic donor lymphocyte infusion (pDLI). Lymphocytes were administered repeatedly at low and non-escalating doses (0.5-1 × 10
6 /kg). Low-dose alemtuzumab was effective in prevention of acute GvHD after sibling or well-matched unrelated transplantation, whereas a more intensified approach was needed after mismatched transplantation. The cumulative incidence of chronic moderate/severe chronic-GvHD (cGvHD) was 15.6%. In total, 63 high-risk leukemia patients were eligible for pDLI. Only 1 out of the 39 pDLI recipients relapsed as compared with 7 out of the 24 recipients, who did not receive pDLI due to logistical hurdles. In multivariate analysis, the use of adjuvant lymphocyte therapy was significantly associated with reduced incidence of relapse and improved disease-free survival. In summary, low-dose alemtuzumab confers to a low cGvHD incidence and the administration of pDLIs in this context is very likely to reduce relapse risk in high risk leukemia patients. This is translated in an estimated 5-year probability of GvHD-free and relapse-free survival of 43.3% for the 136 leukemia patients.- Published
- 2017
- Full Text
- View/download PDF
39. 2017 sneak peek: What the new year holds for science.
- Author
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Gibney E
- Subjects
- Animals, Antarctic Regions, Anthozoa, Astronomy trends, CRISPR-Cas Systems, China, Climate Change, Computers trends, Ecology trends, France, Gene Editing legislation & jurisprudence, Germany, Human Embryonic Stem Cells, Humans, Immunotherapy trends, Leukemia immunology, Leukemia therapy, Lymphoma immunology, Lymphoma therapy, Microbiota, Oceans and Seas, Planets, Politics, Quantum Theory, Solar Energy, Stem Cell Research, United Kingdom, United States, Science trends
- Published
- 2016
- Full Text
- View/download PDF
40. Comparable outcomes with marrow or peripheral blood as stem cell sources for hematopoietic cell transplantation from haploidentical donors after non-ablative conditioning: a matched-pair analysis.
- Author
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O'Donnell PV, Eapen M, Horowitz MM, Logan BR, DiGilio A, Brunstein C, Fuchs EJ, Flowers ME, Salit R, Raj K, Pagliuca A, Bradstock K, Granata A, Castagna L, Furst S, and Blaise D
- Subjects
- Adolescent, Adult, Age Factors, Aged, Clinical Trials, Phase II as Topic, Cohort Studies, Female, Hematopoietic Stem Cell Transplantation, Humans, Leukemia therapy, Male, Matched-Pair Analysis, Middle Aged, Multicenter Studies as Topic, Myelodysplastic Syndromes therapy, Time Factors, Transplantation, Homologous, Treatment Outcome, Bone Marrow Transplantation, Peripheral Blood Stem Cell Transplantation, Stem Cells cytology, Transplantation Conditioning
- Abstract
Competing Interests: There are no conflicts of interest to report.
- Published
- 2016
- Full Text
- View/download PDF
41. Pre-transplant emotional support is associated with longer survival after allogeneic hematopoietic stem cell transplantation.
- Author
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Ehrlich KB, Miller GE, Scheide T, Baveja S, Weiland R, Galvin J, Mehta J, and Penedo FJ
- Subjects
- Adult, Female, Hematopoietic Stem Cell Transplantation mortality, Humans, Leukemia mortality, Leukemia therapy, Lymphoma mortality, Lymphoma therapy, Male, Middle Aged, Prognosis, Stress, Psychological psychology, Survival Rate, Caregivers psychology, Leukemia psychology, Lymphoma psychology, Social Support
- Abstract
Emerging evidence suggests that psychosocial factors pre-transplant predict survival in cancer patients undergoing hematopoietic stem cell transplantation (HSCT). These studies, however, typically have small sample sizes, short-term follow ups or a limited panel of medical covariates. We extend this research in a large, well-characterized sample of transplant patients, asking whether patients' perceived emotional support and psychological distress predict mortality over 2 years. Prior to transplant, 400 cancer patients (55.5% males; 82.8% White; M
age =50.0 years; 67.0% leukemia, 20.0% lymphoma) were interviewed by a social caseworker, who documented the patients' perceived emotional support and psychological distress. Subsequently, patients received an allogeneic HSCT (51.0% matched-related donor, 42.0% matched-unrelated donor and 7.0% cord blood). HSCT outcomes were obtained from medical records. Controlling for demographic characteristics (age, sex, race/ethnicity and marital status) and medical confounders (disease type, conditioning regimen, remission status, cell dosage, donor and recipient CMV seropositivity, donor sex, comorbidities and disease risk), ratings of good emotional support pre-transplant predicted longer overall survival (hazard ratio (HR)=0.61, 95% confidence interval (CI), 0.42-0.91; P=0.013). Pre-transplant psychological distress was unrelated to survival, however (Ps>0.58). Emotional support was marginally associated with lower rates of treatment-related mortality (HR=0.58, CI, 0.32-1.05; P=0.073). These findings are consistent with the hypothesis that emotional support contributes to better outcomes following HSCT. Future studies should examine whether intervention efforts to optimize emotional resources can improve survival in cancer patients.- Published
- 2016
- Full Text
- View/download PDF
42. Focused extracorporeal shock wave for osteonecrosis of the femoral head with leukemia after allo-HSCT: a case series.
- Author
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Sun W, Gao F, Guo W, Wang B, Li Z, Cheng L, and Wang W
- Subjects
- Adult, Female, Femur Head Necrosis etiology, Femur Head Necrosis therapy, Humans, Leukemia therapy, Male, Osteonecrosis etiology, Retrospective Studies, Transplantation, Homologous, Treatment Outcome, Extracorporeal Shockwave Therapy methods, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia complications, Osteonecrosis therapy
- Published
- 2016
- Full Text
- View/download PDF
43. Is there really a specific graft-versus-leukaemia effect?
- Author
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Gale RP and Fuchs EJ
- Subjects
- HLA Antigens, Histocompatibility, Humans, Transplantation, Homologous, Graft vs Leukemia Effect immunology, Hematopoietic Stem Cell Transplantation methods, Leukemia therapy
- Published
- 2016
- Full Text
- View/download PDF
44. Safety concerns blight promising cancer therapy.
- Author
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Ledford H
- Subjects
- Antigens, Neoplasm immunology, Clinical Trials as Topic, Humans, Immunotherapy economics, Immunotherapy legislation & jurisprudence, Leukemia therapy, Lymphoma, Non-Hodgkin therapy, Melanoma therapy, Neoplasms immunology, T-Lymphocytes immunology, United States, United States Food and Drug Administration legislation & jurisprudence, Immunotherapy adverse effects, Neoplasms therapy, Patient Safety legislation & jurisprudence, T-Lymphocytes transplantation
- Published
- 2016
- Full Text
- View/download PDF
45. The molecular mechanics of mixed lineage leukemia.
- Author
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Slany RK
- Subjects
- Animals, Gene Expression Regulation, Neoplastic drug effects, Humans, Leukemia genetics, Leukemia pathology, Methyltransferases antagonists & inhibitors, Mice, Molecular Targeted Therapy, Neoplasm Proteins biosynthesis, Oncogene Proteins, Fusion antagonists & inhibitors, Small Molecule Libraries therapeutic use, Histone-Lysine N-Methyltransferase genetics, Leukemia therapy, Methyltransferases genetics, Myeloid-Lymphoid Leukemia Protein genetics, Oncogene Proteins, Fusion genetics
- Abstract
Mixed lineage leukemia caused by MLL fusion proteins is still a mostly incurable disease. Research on novel treatment strategies has gained momentum in the last years with the elucidation of the molecular mechanisms underlying the transforming potential of these powerful oncoproteins. This review summarizes the recent developments in this area including new attempts to treat MLL in a rational way by exploiting the biochemical vulnerabilities of the leukemogenic process.
- Published
- 2016
- Full Text
- View/download PDF
46. Pre-transplant diastolic but not systolic dysfunction has a negative prognostic impact after allogeneic stem cell transplantation.
- Author
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Sarmiento M, Parody R, Márquez-Malaver F, Espigado I, Falantes J, Caballero T, Calderón C, Carmona M, López Haldon J, and Pérez-Simón JA
- Subjects
- Adolescent, Adult, Aged, Blood Pressure, Diastole, Echocardiography, Female, Humans, Leukemia diagnosis, Male, Middle Aged, Preoperative Period, Prognosis, Retrospective Studies, Risk Factors, Systole, Time Factors, Transplantation, Homologous, Treatment Outcome, Ventricular Function, Left, Young Adult, Heart physiopathology, Leukemia therapy, Stem Cell Transplantation
- Published
- 2016
- Full Text
- View/download PDF
47. Clinical outcome and adverse events associated with empiric and pre-emptive use of amphotericin B lipid complex in a single center in lebanon.
- Author
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Moghnieh R, Fawaz I, Mugharbil A, Jisr T, Abdallah D, and Ibrahim A
- Subjects
- Adult, Aged, Allografts, Humans, Lebanon, Middle Aged, Amphotericin B administration & dosage, Hematopoietic Stem Cell Transplantation, Leukemia therapy, Neutropenia therapy
- Published
- 2016
- Full Text
- View/download PDF
48. New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT.
- Author
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Chang X, Zang X, and Xia CQ
- Subjects
- Allografts, Graft vs Host Disease prevention & control, Graft vs Leukemia Effect, Humans, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation methods, Leukemia therapy, Lymphocyte Transfusion methods
- Abstract
DLI is an effective strategy for patients with recurrent hematological malignancies after allogeneic hematopoietic SCT (allo-HSCT). DLI has been widely applied to boost the graft vs tumor (GVT) or GVL effects. However, given the potentially severe complications associated with conventional DLI and transient GVL effect, new strategies for DLI are emerging. In this review, we have discussed the recent important studies on DLI as a prophylactic or therapeutic modality for relapsed hematological disorders after allo-HSCT. The strategies to separate GVL from GVHD have also been discussed. Leukemia-targeting therapy and lymphodepletion combined with DLI, and prophylactic DLI after allo-HSCT are often employed for patients with high risk of relapse, which has been reviewed as well. In addition, we have also discussed the issues on DLI to be further addressed, such as the doses, timing and frequency of DLI in different clinical settings, leukemic antigen-specific DLI as well as how to augment GVL effect while attenuating GVHD.
- Published
- 2016
- Full Text
- View/download PDF
49. Influence of pre-existing invasive aspergillosis on allo-HSCT outcome: a retrospective EBMT analysis by the Infectious Diseases and Acute Leukemia Working Parties.
- Author
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Penack O, Tridello G, Hoek J, Socié G, Blaise D, Passweg J, Chevallier P, Craddock C, Milpied N, Veelken H, Maertens J, Ljungman P, Cornelissen J, Thiebaut-Bertrand A, Lioure B, Michallet M, Iacobelli S, Nagler A, Mohty M, and Cesaro S
- Subjects
- Acute Disease, Adolescent, Adult, Aged, Allografts, Child, Child, Preschool, Chronic Disease, Disease-Free Survival, Female, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Humans, Infant, Male, Middle Aged, Survival Rate, Aspergillosis complications, Aspergillosis mortality, Aspergillosis therapy, Hematopoietic Stem Cell Transplantation, Leukemia mortality, Leukemia therapy
- Abstract
Historically, invasive aspergillosis (IA) has been a major barrier for allogeneic hematopoietic stem cell transplantation (allo-HSCT). The influence of invasive IA on long-term survival and on transplant-related complications has not been investigated in a larger patient cohort under current conditions. Our aim was to analyze the long-term outcome of patients undergoing allo-HSCT with a history of prior IA. We used European Society for Blood and Marrow Transplantation database data of first allo-HSCTs performed between 2005 and 2010 in patients with acute leukemia. One thousand one hundred and fifty patients with data on IA before allo-HSCT were included in the analysis. The median follow-up time was 52.1 months. We found no significant impact of IA on major transplant outcome variables such as overall survival, relapse-free survival, non-relapse mortality, cumulative incidence of acute GvHD grade II-IV, chronic GvHD, pulmonary complications and leukemia relapse. However, we found a trend toward lower overall survival (P=0.078, hazard ratio (HR) (95% confidence interval (CI)): 1.16 (0.98, 1.36)) and higher non-relapse mortality (P=0.150, HR (95% CI): 1.19 (0.94, 1.50)) in allo-HSCT recipients with pre-existing IA. Our data suggest that a history of IA should not generally be a contraindication when considering the performance of allo-HSCT in patients with acute leukemia.
- Published
- 2016
- Full Text
- View/download PDF
50. Leukaemia success heralds wave of gene-editing therapies.
- Author
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Reardon S
- Subjects
- Animals, Clinical Trials as Topic, Factor IX genetics, Female, HIV Infections genetics, HIV Infections therapy, Hemoglobinopathies genetics, Hemoglobinopathies therapy, Hemophilia B genetics, Hemophilia B therapy, Humans, Infant, Leukemia immunology, London, T-Lymphocytes immunology, T-Lymphocytes metabolism, T-Lymphocytes transplantation, beta-Thalassemia genetics, beta-Thalassemia therapy, Genetic Engineering, Genetic Therapy, Leukemia genetics, Leukemia therapy
- Published
- 2015
- Full Text
- View/download PDF
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