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1
المؤلفون: Ehud Even-Or, Bella Shadur, Adeeb NaserEddin, Irina Zaidman, Yael Dinur Schejter, Polina Stepensky
المصدر: Bone Marrow Transplantation
مصطلحات موضوعية: medicine.medical_specialty, Transplantation Conditioning, Cyclophosphamide, medicine.medical_treatment, Graft vs Host Disease, Hematopoietic stem cell transplantation, Graft-versus-host disease, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Child, Transplantation, Hemophagocytic lymphohistiocytosis, business.industry, Hematopoietic Stem Cell Transplantation, Osteopetrosis, Hematology, medicine.disease, Surgery, Stem-cell research, medicine.anatomical_structure, surgical procedures, operative, 030220 oncology & carcinogenesis, Congenital amegakaryocytic thrombocytopenia, Bone marrow, business, Busulfan, 030215 immunology, medicine.drug
الوصف: Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for a variety of nonmalignant disorders including osteopetrosis, bone marrow failures, and immune deficiencies. Haploidentical HSCT is a readily available option in the absence of a matched donor, but engraftment failure and other post-transplant complications are a concern. Post-transplant cyclophosphamide (PT-Cy) regimens are gaining popularity and recent reports show promising results. We report our experience with nine pediatric patients with nonmalignant diseases who were transplanted from a haploidentical donor with PT-Cy. From 2015 to 2019, nine children with nonmalignant diseases underwent haploidentical HSCT with PT-Cy, two as a second transplant and seven as primary grafts after upfront serotherapy and busulfan-based myeloablative conditioning. Patient’s diseases included osteopetrosis (n = 5), congenital amegakaryocytic thrombocytopenia (n = 2), hemophagocytic lymphohistiocytosis (n = 1), and Wiskott Aldrich syndrome (n = 1). Two patients failed to engraft following upfront PT-Cy transplants, one was salvaged with a second PT-Cy transplant, and the other with a CD34+ selected graft. None of the patients suffered from graft-versus-host disease. Three patients died from early posttransplant infectious complications and six patients are alive and well. In conclusion, haploidentical HSCT with PT-Cy is a feasible option for pediatric patients with nonmalignant diseases lacking a matched donor.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cd6ab755ef3dee592c740cfa78d23280Test
http://europepmc.org/articles/PMC7450679Test -
2
المؤلفون: Polina Stepensky, Fabian Hauck, Rajat Bhattacharyya, Ansgar Schulz, Catharina Schuetz, Elad Jacoby, Michael H. Albert, Tayfun Güngör, Mehtap Sirin, Manfred Hoenig, Rita Beier
المساهمون: University of Zurich, Albert, Michael H
المصدر: Bone Marrow Transplantation
مصطلحات موضوعية: medicine.medical_specialty, Transplantation Conditioning, Cyclophosphamide, Platelet Engraftment, 2747 Transplantation, medicine.medical_treatment, 2720 Hematology, Medizin, Graft vs Host Disease, 610 Medicine & health, Hematopoietic stem cell transplantation, Treosulfan, Biostatistics, Article, medicine, Humans, Retrospective Studies, Transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, Translational research, Fludarabine, Surgery, surgical procedures, operative, 10036 Medical Clinic, Alemtuzumab, Rituximab, business, medicine.drug
الوصف: Graft failure requires urgent salvage HSCT, but there is no universally accepted approach for this situation. We investigated T-cell replete haploidentical HSCT with post-transplantation cyclophosphamide following serotherapy-based, radiation-free, reduced intensity conditioning in children with non-malignant disorders who had rejected their primary graft. Twelve patients with primary or secondary graft failure received T-cell replete bone marrow grafts from haploidentical donors and post-transplantation cyclophosphamide. The recommended conditioning regimen comprised rituximab 375 mg/m2, alemtuzumab 0.4 mg/kg, fludarabine 150 mg/m2, treosulfan 20–24 g/m2 and cyclophosphamide 29 mg/kg. After a median follow-up of 26 months (7–95), eleven of twelve patients (92%) are alive and well with complete donor chimerism in ten. Neutrophil and platelet engraftment were observed in all patients after a median of 18 days (15–61) and 39 days (15–191), respectively. Acute GVHD grade I was observed in 1/12 patients (8%) and mild chronic GVHD in 1/12 patients (8%). Viral reactivations and disease were frequent complications at 75% and 42%, respectively, but no death from infectious causes occurred. In summary, this retrospective analysis demonstrates that a post-transplantation cyclophosphamide-based HLA-haploidentical salvage HSCT after irradiation-free conditioning results in excellent engraftment and overall survival in children with non-malignant diseases.
وصف الملف: s41409-021-01323-9.pdf - application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d16022076ea2a6d9489c9bee397d0a90Test
https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&origin=inward&scp=85105479238Test -
3
المؤلفون: Bella Shadur, Andrew R. Gennery, Nurcicek Padem, Anna Mukhina, Polina Stepensky, Svetlana O. Sharapova, Sara Sebnem Kilic, Magdalena Avbelj Stefanija, Luis I. Gonzales-Granado, Isabelle Meyts, Jacques G. Rivière, Filomeen Haerynck, Joachim Zobel, Benoit Florkin, Laura Gamez, Vedat Uygun, Nicolette Moes, Neslihan Edeer Karaca, Lennart Hammarström, Anke M.J. Peters, Bodo Grimbacher, Sevgi Köstel Bal, Aydan Ikinciogullari, Zahra Chavoshzadeh, Joris M. van Montfrans, Sule Haskologlu, Hassan Abolhassani, Necil Kutukculer, Safa Baris, Yuliya Mareika, Juan Luis Santos Perez, Elif Karakoc-Aydiner, Asghar Aghamohammadi, Mehdi Adeli, Antonio Marzollo, Hermann J. Girschick, Sevgi Keles, Amer Khojah, Shahrzad Bakhtiar, Victoria Katharina Tesch, Anna Shcherbina, Antonios G.A. Kolios, Marie Meeths, Mikko Seppänen, Austen Worth, Marina Garcia-Prat, Figen Dogu, Arjan C. Lankester, Markus G. Seidel
المساهمون: European Soc Blood, European Soc Immunodeficiencies, University of Zurich, Tesch, Victoria Katharina, Abolhassani, Hassan, Shadur, Bella, Zobel, Joachim, Mareika, Yuliya, Sharapova, Svetlana, Karakoc-Aydiner, Elif, Riviere, Jacques G., Garcia-Prat, Marina, Moes, Nicolette, Haerynck, Filomeen, Gonzales-Granado, Luis I., Santos Perez, Juan Luis, Mukhina, Anna, Shcherbina, Anna, Aghamohammadi, Asghar, Hammarstrom, Lennart, Dogu, Figen, Haskologlu, Sule, Ikinciogullari, Aydan I., Bal, Sevgi Kostel, Baris, Safa, Kilic, Sara Sebnem, Karaca, Neslihan Edeer, Kutukculer, Necil, Girschick, Hermann, Kolios, Antonios, Keles, Sevgi, Uygun, Vedat, Stepensky, Polina, Worth, Austen, van Montfrans, Joris M., Peters, Anke M. J., Meyts, Isabelle, Adeli, Mehdi, Marzollo, Antonio, Padem, Nurcicek, Khojah, Amer M., Chavoshzadeh, Zahra, Stefanija, Magdalena Avbelj, Bakhtiar, Shahrzad, Florkin, Benoit, Meeths, Marie, Gamez, Laura, Grimbacher, Bodo, Seppanen, Mikko R. J., Lankester, Arjan, Gennery, Andrew R., Seidel, Markus G., Ege Üniversitesi, Bursa Uludağ Üniversitesi/Tıp Fakültesi/Çocuk İmmünoloji., Kılıç, Sara Şebnem, AAH-1658-2021, Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, TRIMM - Translational Immunology Research Program, Research Programs Unit, University of Helsinki, HUS Inflammation Center
المصدر: The journal of allergy and clinical immunology
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Journal of Allergy and Clinical Immunology, 145(5), 1452-1463. MOSBY-ELSEVIERمصطلحات موضوعية: Male, Neurologic disease, medicine.medical_treatment, Autoimmunity, Hematopoietic stem cell transplantation, Treatment response, Eye disease, 0302 clinical medicine, Thrombotic thrombocytopenic purpura, Azathioprine, combined immunodeficiency, Disease activity, Treatment outcome, Disease course, Child, Inborn error of immunity (IEI), Immunodeficiency, combined, Hematopoietic Stem Cell Transplantation, combined immunodeficiency (CID), hematopoietic stem cell transplantation (HSCT), Tocilizumab, Signal transducing, Multicenter study, Immunologic deficiency syndromes, 3. Good health, Clinical trial, Retrospective study, sirolimus, Child, Preschool, Cyclosporine, 2723 Immunology and Allergy, Graft failure, Lung infection, hematopoietic stem, Cohort analysis, Longitudinal study, Rituximab, Infection, Human, Hepatomegaly, medicine.medical_specialty, Genotype, Immunology, Cause of death, Major clinical study, Article, 03 medical and health sciences, Signal transducing adaptor protein, Humans, Lipopolysaccharide responsive beige like anchor protein deficiency, cell transplantation, Aged, 2403 Immunology, MUTATIONS, Abatacept, Immunologic Deficiency Syndromes, Adalimumab, Failure to thrive, Follow up, Survival analysis, Immune dysregulation, medicine.disease, Survival Analysis, 030104 developmental biology, Disease activity score, Splenomegaly, 10033 Clinic for Immunology, School child, Human medicine, immunodeficiency, 0301 basic medicine, Thyroiditis, Allergy, Unclassified drug, Immune deficiency, Lipopolysaccharide responsive beige like anchor protein, Respiratory failure, Skin manifestation, medicine.disease_cause, Lymphocyte proliferation, Medicine and Health Sciences, Immunology and Allergy, Overall survival, Middle aged, performance scale, Interstitial pneumonia, Priority journal, CTLA4, Mycophenolate mofetil, Chloroquine, clinical score, Immunosuppression, Disease burden, Transplant-Related Mortality, Middle Aged, Acute graft versus host disease, Hospitalization, Immune deficiency and dysregulation activity score, Treatment Outcome, Phenotype, surgical procedures, operative, primary immunodeficiency disorder (PID), hematopoietic stem cell transplantation, Female, medicine.drug, Adult, dysregulation, Malabsorption, abatacept, Adolescent, Child, preschool, Pemission, Interstitial lung disease, 610 Medicine & health, LRBA, Young Adult, immune dysregulation, Internal medicine, Adaptor proteins, medicine, primary immunodeficiency disorder, Mycophenolic acid, Rapamycin, Mortality, Disease severity, Adaptor Proteins, Signal Transducing, Inborn error of immunity, Chimera, business.industry, Protein, Retrospective cohort study, LRBA protein, Multiple organ failure, Infliximab, Immunosuppressive treatment, Young adult, Preschool child, 3121 General medicine, internal medicine and other clinical medicine, Common Variable Immunodeficiency, Immunoglobulin Deficiency, immune, business, 030215 immunology
الوصف: Background: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant. Objective: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant. Method: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices. Results: of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. the overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). in contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome. Conclusion: the lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT.
Styrian Children's Cancer Aid Foundation; Slovenian Research AgencySlovenian Research Agency - Slovenia [P3-0343]; Jonas S_oderquist Foundation; Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [217S847, 318S202]; Deutsche Forschungsgemeinschaft under Germany's Excellence StrategyGerman Research Foundation (DFG) [390939984, 39087428]; E-Rare program of the European Union by the Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [GR1617/14-1/iPAD]; Netzwerke Seltener Erkrankungen of the German Ministry of Education and Research [GAIN_ 01GM1910A]; Finnish Foundation for Pediatric Research and Pediatric Research Center, HUS Helsinki University Hospital; Graduate Research Training Scholarship of the Australian government; Hadassah Australia; ERN-RITA network [739543]
M.G. Seidel and the Research Unit for Pediatric Hematology and Immunology are supported in part by the Styrian Children's Cancer Aid Foundation. M. Avbeli Stefanija was supported by the Slovenian Research Agency (grant P3-0343). H. Abolhassani was supported by the Jonas S_oderquist Foundation. S. Baris was supported by the Scientific and Technological Research Council of Turkey for the diagnosis of patients with LRBA deficiency (grants 217S847 and 318S202). B. Grimbacher receives support through the Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy (CIBSS-EXC-2189-Project ID 390939984 and RESIST-EXC 2155-Project ID 39087428); through the E-Rare program of the European Union, managed by the Deutsche Forschungsgemeinschaft (grant GR1617/14-1/iPAD); and through the Netzwerke Seltener Erkrankungen of the German Ministry of Education and Research (grant GAIN_ 01GM1910A). M.R.J. Sepp_anen was supported by the Finnish Foundation for Pediatric Research and Pediatric Research Center, HUS Helsinki University Hospital. I. Meyts is a member of the ERN-RITA network (project identification number 739543). B. Shadur is supported by a Graduate Research Training Scholarship of the Australian government and by Hadassah Australia.وصف الملف: 1-s2.0-S009167491932603X-main.pdf - application/pdf; application/pdf; Print-Electronic
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b609bdc323ed2eb41f327b418827ce5fTest
https://hdl.handle.net/10067/1695250151162165141Test -
4
المصدر: Pediatric Transplantation. 24
مصطلحات موضوعية: Male, medicine.medical_specialty, Transplantation Conditioning, medicine.medical_treatment, 030232 urology & nephrology, Hematopoietic stem cell transplantation, ThioTEPA, 030230 surgery, Treosulfan, 03 medical and health sciences, 0302 clinical medicine, medicine, Mucositis, Humans, Prospective Studies, Child, Busulfan, Transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Infant, Sequela, Prognosis, medicine.disease, Hyperpigmentation, Dermatology, Fludarabine, Child, Preschool, Pediatrics, Perinatology and Child Health, Toxicity, Drug Therapy, Combination, Female, Drug Eruptions, medicine.symptom, business, Immunosuppressive Agents, Thiotepa, Vidarabine, medicine.drug
الوصف: TBC regimens are considered as "reduced toxicity" and are increasingly employed in pediatric HSCT. In our center, we commonly use the combination of treosulfan-thiotepa-fludarabine and ATG for pediatric non-malignant diseases. As we often observe acute skin toxicities following this conditioning regimen, we conducted a prospective observational study to describe and characterize these toxicities. Fifteen pediatric patients undergoing HSCT for non-malignant diseases who were treated at Hadassah-Hebrew University Medical Center during 2015 were enrolled. A thorough dermatological assessment was done on days 0, 1, 7, and 14 from treatment initiation and included description of cutaneous reactions, measurement of BSA of affected skin, and response to local treatment. All the fifteen enrolled patients developed some degree of acute skin reaction. Cutaneous manifestations were variable and included erythematous patches in inguinal area and genitalia (80%), in neck and axillae (40%), diffuse hyperpigmentation (73%), erosions in inguinal area and buttock (47%), and xerosis and desquamation (40%). Average affected BSA reached 71.8%. Erosions were more prevalent in children younger than 2 years of age. The eruptions resolved without sequela in all patients and did not necessitate treatment other than topical agents. Observed extracutaneous toxicities included oral mucositis (40%), diarrhea (47%), and elevated liver enzymes (47%). TBC combined with thiotepa is highly toxic to the skin with various cutaneous manifestations. The toxicity resolves with no long-term sequela.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1b16866b59555f47208055be547a81cdTest
https://doi.org/10.1111/petr.13626Test -
5
المؤلفون: Noa Haggiag, Polina Stepensky, Nathalie Assayag-Asherie, Shlomit Kfir-Erenfeld, Eitan Yefenof, Moshe Biton
المصدر: Oncotarget
مصطلحات موضوعية: 0301 basic medicine, Dishevelled Proteins, Apoptosis, 0302 clinical medicine, Leukemia, Bcl-2-Like Protein 11, Gene Expression Regulation, Leukemic, High-Throughput Nucleotide Sequencing, Transfection, Up-Regulation, Haematopoiesis, Phosphotransferases (Alcohol Group Acceptor), Oncology, 030220 oncology & carcinogenesis, Glucocorticoid, medicine.drug, Research Paper, Transcriptional Activation, proliferation, Down-Regulation, Biology, Proto-Oncogene Proteins c-myc, 03 medical and health sciences, Proto-Oncogene Proteins c-myb, Receptors, Glucocorticoid, Cyclin-dependent kinase, Cell Line, Tumor, microRNA, medicine, Humans, Glucocorticoids, Cell Proliferation, Sequence Analysis, RNA, Cyclin-dependent kinase 2, Cyclin-Dependent Kinase 2, miR-103, Cell Cycle Checkpoints, medicine.disease, Introns, Cyclin E1, MicroRNAs, 030104 developmental biology, Gene Expression Regulation, Drug Resistance, Neoplasm, Immunology, Cancer research, biology.protein, glucocorticoid
الوصف: // Shlomit Kfir-Erenfeld 1, * , Noa Haggiag 1, * , Moshe Biton 1 , Polina Stepensky 2 , Nathalie Assayag-Asherie 1, * , Eitan Yefenof 1, * 1 The Lautenberg Center for Immunology and Cancer Research, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel 2 Pediatric Hemato-Oncology and Bone Marrow Transplantation Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel * These authors contributed equally to this work Correspondence to: Eitan Yefenof, email: eitany@ekmd.huji.ac.il Nathalie Assayag-Asherie, email: nathalie.asherie@mail.huji.ac.il Keywords: glucocorticoid, miR-103, leukemia, apoptosis, proliferation Received: June 01, 2016 Accepted: November 12, 2016 Published: November 18, 2016 ABSTRACT Glucocorticoid (GC) hormones are an important ingredient of leukemia therapy since they are potent inducers of lymphoid cell apoptosis. However, the development of GC resistance remains an obstacle in GC-based treatment. In the present investigation we found that miR-103 is upregulated in GC-sensitive leukemia cells treated by the hormone. Transfection of GC resistant cells with miR-103 sensitized them to GC induced apoptosis (GCIA), while miR-103 sponging of GC sensitive cells rendered them partially resistant. miR-103 reduced the expression of cyclin dependent kinase (CDK2) and its cyclin E1 target, thereby leading to inhibition of cellular proliferation. miR-103 is encoded within the fifth intron of PANK3 gene. We demonstrate that the GC receptor (GR) upregulates miR-103 by direct interaction with GC response element (GRE) in the PANK3 enhancer. Consequently, miR-103 targets the c-Myc activators c-Myb and DVL1, thereby reducing c-Myc expression. Since c-Myc is a transcription factor of the miR-17~92a poly-cistron, all six miRNAs of the latter are also downregulated. Of these, miR-18a and miR-20a are involved in GCIA, as they target GR and BIM, respectively. Consequently, GR and BIM expression are elevated, thus advancing GCIA. Altogether, this study highlights miR-103 as a useful prognostic biomarker and drug for leukemia management in the future.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::47852a196f04b1fdb6b6f456a19faebeTest
http://europepmc.org/articles/PMC5352135Test -
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المؤلفون: Klaus-Michael Debatin, Ingrid Furlan, Orly Elpeleg, Donald Bunjes, Meinrad Beer, Catharina Schuetz, Stephanie von Harsdorf, Batia Avni, Sigal Grisariu, Polina Stepensky, Bella Shadur, Ansgar Schulz, Irina Zaidman, Manfred Hoenig, Mehtap Sirin
مصطلحات موضوعية: 0301 basic medicine, Adult, Pediatrics, medicine.medical_specialty, Transplantation Conditioning, Adolescent, medicine.medical_treatment, Hematopoietic stem cell transplantation, Treosulfan, 03 medical and health sciences, Young Adult, 0302 clinical medicine, medicine, Humans, Child, Transplantation, biology, business.industry, Hematopoietic Stem Cell Transplantation, Osteopetrosis, Hematology, medicine.disease, Tissue Donors, Fludarabine, 030104 developmental biology, 030220 oncology & carcinogenesis, Cohort, Mutation, biology.protein, Quality of Life, CLCN7, business, Rare disease, medicine.drug, Follow-Up Studies
الوصف: Osteopetrosis (OP) is a rare disease caused by defective osteoclast differentiation or function. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment available in the infantile “malignant” form of OP. Improved clinical and genetic diagnosis of OP has seen the emergence of a cohort of patients with less severe and heterogeneous clinical presentations. This intermediate form of OP does not call for urgent intervention, but patients accumulate debilitating skeletal complications over years and decades, which are severe enough to require curative treatment and may also require intermittent transfusion of blood products. Here we present data from 7 patients with intermediate OP caused by mutations in TCIRG1 (n = 2), CLCN7 (n = 2), RANK (n = 1), SNX10 (n = 1), and CA2 (n = 1), who were transplanted between the ages of 5 to 30 years (mean, 15; median, 12). Donors were matched siblings or family (n = 4), matched unrelated (n = 2), or HLA haploidentical family donors (n = 1). Conditioning was fludarabine and treosulfan based. All 6 patients transplanted from matched donors are currently alive with a follow-up period between 1 and 8 years at time of publication (median, 4 years) and have demonstrated a significant improvement in symptoms and quality of life. Patients with intermediate OP should be considered for HSCT.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc4833fa953f1355081b779ead2182f1Test
https://europepmc.org/articles/PMC6436016Test/ -
7
المؤلفون: Sung-Yun Pai, Ahmed Aziz Bousfiha, Lilia Lycopoulou, Hassan Abolhassani, Sarah K. Nicholas, Martha M. Eibl, Jennifer M. Puck, Olga E. Pashchenko, Boglarka Ujhazi, Emma Westermann-Clark, Turkan Patiroglu, Beatriz Tavares Costa-Carvalho, Polina Stepensky, Jack J. Bleesing, Cullen M. Dutmer, Kaan Boztug, Asghar Aghamohammadi, Shanmuganathan Chandrakasan, Andreas Reiff, Jolan E. Walter, Gergely Kriván, Avni Y. Joshi, Paolo Palma, Gloria Pinero, Mehdi Adeli, Jocelyn R. Farmer, Ekrem Unal, Roshini S. Abraham, Caterina Cancrini, Marianna Tzanoudaki, John W. Sleasman, Zsofia Foldvari, Musa Karakukcu, Bernard M. Fischer, Carmem Bonfim, Meredith A. Dilley, Catharina Schuetz, Hermann M. Wolf, Robbert G. M. Bredius, Benedicte Neven, Suk See De Ravin, Harry R. Hill, Franco Locatelli, David Buchbinder, Polly J. Ferguson, Maria Kanariou, Ahmet Ozen, Elif Karakoc-Aydiner, Christoph B. Geier, Joseph D. Hernandez, Karin Chen, Raif S. Geha, Jean-Pierre de Villartay, Claire Booth, Luigi D. Notarangelo, Melissa M. Hazen, Vera Goda, Ayca Kiykim, Birgit Hoeger, Safa Baris, Ghassan Dbaibo, Waleed Al-Herz, Manish J. Butte, Maurizio Miano, Olajumoke Fadugba, Lauren A. Henderson, Khulood Khalifa Al-Saad, Sarah E. Henrickson, Steven M. Holland, Alice Bertaina, Beata Wolska-Kuśnierz, Erwin W. Gelfand, Gigliola Di Matteo, Suhag Parikh, Despina Moshous
المساهمون: Farmer, Jocelyn R., Foldvari, Zsofia, Ujhazi, Boglarka, De Ravin, Suk See, Chen, Karin, Bleesing, Jack J. H., Schuetz, Catharina, Al-Herz, Waleed, Abraham, Roshini S., Joshi, Avni Y., Costa-Carvalho, Beatriz T., Buchbinder, David, Booth, Claire, Reiff, Andreas, Ferguson, Polly J., Aghamohammadi, Asghar, Abolhassani, Hassan, Puck, Jennifer M., Adeli, Mehdi, Cancrini, Caterina, Palma, Paolo, Bertaina, Alice, Locatelli, Franco, Di Matteo, Gigliola, Geha, Raif S., Kanariou, Maria G., Lycopoulou, Lilia, Tzanoudaki, Marianna, Sleasman, John W., Parikh, Suhag, Pinero, Gloria, Fischer, Bernard M., Dbaibo, Ghassan, Unal, Ekrem, Patiroglu, Turkan, Karakukcu, Musa, Al-Saad, Khulood Khalifa, Dilley, Meredith A., Pai, Sung-Yun, Dutmer, Cullen M., Gelfand, Erwin W., Geier, Christoph B., Eibl, Martha M., Wolf, Hermann M., Henderson, Lauren A., Hazen, Melissa M., Bonfim, Carmem, Wolska-Kusnierz, Beata, Butte, Manish J., Hernandez, Joseph D., Nicholas, Sarah K., Stepensky, Polina, Chandrakasan, Shanmuganathan, Miano, Maurizio, Westermann-Clark, Emma, Goda, Vera, Krivan, Gergely, Holland, Steven M., Fadugba, Olajumoke, Henrickson, Sarah E., Ozen, Ahmet, Karakoc-Aydiner, Elif, Baris, Safa, Kiykim, Ayca, Bredius, Robbert, Hoeger, Birgit, Boztug, Kaan, Pashchenko, Olga, Neven, Benedicte, Moshous, Despina, de Villartay, Jean-Pierre, Bousfiha, Ahmed Aziz, Hill, Harry R., Notarangelo, Luigi D., Walter, Jolan E.
المصدر: The journal of allergy and clinical immunology. In practice, vol 7, iss 6
Journal of Allergy and Clinical Immunology: In Practice, 7(6), 1970-+. ELSEVIER SCIENCE BVمصطلحات موضوعية: Male, RECOMBINATION ACTIVITY, autoimmune cytopenias, hematopoietic stem cell transplantation (HSCT), immune dysregulation, recombination activating gene (RAG), severe combined immunodeficiency (SCID), Hematopoietic stem cell transplantation, Autoimmunity, medicine.disease_cause, SEVERE COMBINED IMMUNODEFICIENCY, Recombination activating gene, hemic and lymphatic diseases, Autoimmune cytopenias, Immunology and Allergy, Child, GRANULOMATOUS-DISEASE, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Treatment Outcome, Severe combined immunodeficiency, Autoimmune neutropenia, Child, Preschool, VACCINE-STRAIN, Rituximab, Female, Autoimmune hemolytic anemia, Immunosuppressive Agents, medicine.drug, Adult, Hyper IgM syndrome, Evans syndrome, Adolescent, Autoimmune Disease, Article, Young Adult, medicine, Genetics, recombinase activating gene (RAG), Humans, RITUXIMAB, Preschool, Homeodomain Proteins, Inflammation, Settore MED/38 - Pediatria Generale e Specialistica, MUTATIONS, business.industry, Inflammatory and immune system, OMENN SYNDROME, Immunologic Deficiency Syndromes, Infant, Immune dysregulation, medicine.disease, GENE, CLINICAL PHENOTYPES, Transplantation, Immunology, business, CYTOPENIAS
الوصف: BACKGROUND: Although autoimmunity and hyperinflammation secondary to recombination activating gene (RAG) deficiency have been associated with delayed diagnosis and even death, our current understanding is limited primarily to small case series. OBJECTIVE: Understand the frequency, severity, and treatment responsiveness of autoimmunity and hyperinflammation in RAG deficiency. METHODS: In reviewing the literature and our own database, we identified 85 patients with RAG deficiency, reported between 2001 and 2016, and compiled the largest case series to date of 63 patients with prominent autoimmune and/or hyperinflammatory pathology. RESULTS: Diagnosis of RAG deficiency was delayed a median of 5 years from the first clinical signs of immune dysregulation. Most patients (55.6%) presented with more than 1 autoimmune or hyperinflammatory complication, with the most common etiologies being cytopenias (84.1%), granulomas (23.8%), and inflammatory skin disorders (19.0%). Infections, including live viral vaccinations, closely preceded the onset of autoimmunity in 28.6% of cases. Autoimmune cytopenias had early onset (median, 1.9, 2.1, and 2.6 years for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively) and were refractory to intravenous immunoglobulin, steroids, and rituximab in most cases (64.7%, 73.7%, and 71.4% for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively). Evans syndrome specifically was associated with lack of response to first-line therapy. Treatment-refractory autoimmunity/ hyperinflammation prompted hematopoietic stem cell transplantation in 20 patients. CONCLUSIONS: Autoimmunity/hyperinflammation can be a presenting sign of RAG deficiency and should prompt further evaluation. Multilineage cytopenias are often refractory to immunosuppressive treatment and may require hematopoietic cell transplantation for definitive management. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::57333a5b4138191a75d42450eb190461Test
http://hdl.handle.net/2108/228513Test -
8
المؤلفون: Jolanta Gozdzik, Caroline A. Lindemans, Urs Schanz, Manfred Hoenig, Karl-Walter Sykora, Robert Chiesa, Benedicte Neven, Petr Sedlacek, Franco Locatelli, Henric-Jan Blok, Mary Slatter, Polina Stepensky, Michael H. Albert, Ansgar Schulz, Matthias Felber, Amal Al-Seraihy, Serap Aksoylar, Krzysztof Kałwak, Arjan C. Lankester, Marco Zecca, Andrew R. Gennery, Brigitte Strahm, Paul Veys, Fabian Hauck, Per Ljungman, Robert Wynn, Su Han Lum, Despina Moshous, Junfeng Wang, Tayfun Guengoer
المصدر: Blood, 132
مصطلحات موضوعية: medicine.medical_specialty, business.industry, Surrogate endpoint, Proportional hazards model, medicine.medical_treatment, Incidence (epidemiology), Immunology, Cell Biology, Hematology, Hematopoietic stem cell transplantation, ThioTEPA, 030204 cardiovascular system & hematology, medicine.disease, Biochemistry, Transplantation, 03 medical and health sciences, 0302 clinical medicine, Graft-versus-host disease, 030220 oncology & carcinogenesis, Internal medicine, Medicine, Cumulative incidence, business, medicine.drug
الوصف: Introduction: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disease characterized by impairment of the phagocyte NADPH-oxidase complex, resulting in deficient microbial killing and life-threatening bacterial and fungal infections. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative approach, but it can be complicated by graft failure, graft versus-host disease (GvHD) and transplant-related mortality (TRM). In order to define prognostic risk factors in this setting, the IEWP of the EBMT performed a large retrospective registry study on 600 pediatric and adult patients with CGD undergoing allo-HSCT. Patients and Methods: We analyzed the outcome of patients with CGD who received allo-HSCT in EBMT centers between 1993 and 2017. The main end-points of the study were overall survival (OS) and event-free survival (EFS; events were death and primary or secondary engraftment failure) according to patient's age, donor type, stem cell source and conditioning regimen. One patient died before allo-HSCT and was excluded from analysis. Results: We studied 536 children (aged < 18 years) and 63 adults (aged ≥ 18 years) affected by CGD. The median follow-up was 45.37 months (IQR 15.8-81.8). Genetic results were available for 307 patients: inheritance was X-linked (75%) or autosomal recessive (25%). Median age at transplant was 7.2 years (range: 0.12-48.56). Conditioning regimen was Busulfan/Fludarabine (n=244; 41%), Busulfan/Cyclophosphamide (n=104; 17%), Treosulfan/Fludarabine (n=76; 13%), Treosulfan/Fludarabine/Thiotepa (n=52; 9%) or other drug combinations (n=123; 20%). Donors were human leukocyte antigen (HLA) matched related (MFD, 10/10; n=211, 40%), matched unrelated (MUD, 10/10 or 6/6 in UCB; n=201; 38%), mismatched related (MMFD, ≥ 9/10; n= 27; 5%) or mismatched unrelated (MMUD, ≥ 9/10 or 5/6 in UCB; n= 83; 16%). Stem cell source was bone marrow (BM; n=408; 69%), peripheral blood (PB; n=153; 26%) or umbilical cord blood (UCB; n=27; 5%). Donor engraftment occurred in 516 evaluable patients (88%), while primary or secondary engraftment failure occurred in 68 patients (12%). Seventy-nine patients (13%) died after allo-HSCT. The 2 year Kaplan-Meier estimate of OS and EFS were 87.1% (95% CI, 84.2-89.9) and 77.8% (95% CI, 74.2-81.4), respectively (Fig A). The 2-year cumulative incidence of grade II-IV acute GvHD, chronic GvHD and extensive chronic GvHD was 18.6% (95%, 15.1-22.2), 16.2 % (95%, 18.8-19.7) and 5.5% (95%, 3.4-7.7), respectively. A univariate cox model with spline term demonstrated that older age at transplant was associated with an increased risk of death (p=0.002). Children undergoing allo-HSCT had a superior 2y OS (88.1%; 95% CI 85.2-91.0), compared to adults (78.2%; 95% CI, 67.7-88.7), p=0.03 (Fig B). Patients undergoing allo-HSCT from a MFD had a superior EFS (86.5%; 95% CI 81.5-91.4) compared to MUD (73.3%; 95% CI 66.7-79.9), MMUD (78.2%; 95% CI 69-87.5) and MMFD (59.7; 95% CI 40.4-79.1), p< 0.001 (Fig C). Patients receiving BM grafts had superior 2y EFS (81.0%; 95% CI 76.9-85.1) compared to PB (72.5%; 95% CI 64.7-80.4) and UCB (66.7%; 95% CI 48.9-84.4), p=0.04. The pattern of disease inheritance and the choice of conditioning regimen didn't have an impact on outcome (Fig D). Fifty-three patients with graft failure underwent a second allo-HSCT and the 2y OS in this group was 82.1% (95% CI, 71.5-92.7). Year of transplantation didn't have an influence on outcome. Conclusion: This is the largest study describing the outcome of allo-HSCT in children and adults affected by CGD. We demonstrate an excellent outcome, with a low incidence of graft failure, TRM and GvHD. Older patients with CGD have reduced survival after allo-HSCT, indicating that transplant should be considered at a younger age. The use of a MMFD is associated with poorer outcome; indication to transplant in this setting should be carefully evaluated by the treating physicians. Disclosures Chiesa: Bluebird Bio: Consultancy; Gilead: Consultancy. Kalwak:medac: Other: travel grants; Sanofi: Other: travel grants. Sykora:Aventis-Behring: Research Funding; medac: Research Funding. Locatelli:Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Honoraria; bluebird bio: Consultancy; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wynn:Orchard SAB: Membership on an entity's Board of Directors or advisory committees; Orchard Therapeutics: Equity Ownership; Chimerix: Research Funding; Genzyme: Honoraria; Bluebird Bio: Consultancy; Orchard Therapeutics: Consultancy; Chimerix: Consultancy. Zecca:Chimerix: Honoraria. Veys:Pfizer: Honoraria; Servier: Research Funding; Novartis: Honoraria. Slatter:Medac: Other: Travel assistance.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c523b2aef2ca2c0a96f9094e3334e298Test
http://hdl.handle.net/1887/3195443Test -
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المؤلفون: Natan Gorelik, Polina Stepensky, Juma Natsheh, Natalia Simanovsky, Michael Weintraub, Reuven Or, Ron Lamdan, Genady Drozdinsky, Odeya Erlich
المصدر: Pediatric Blood & Cancer. 63:535-540
مصطلحات موضوعية: medicine.medical_specialty, Hepatic veno-occlusive disease, business.industry, medicine.medical_treatment, Retrospective cohort study, Hematology, Hematopoietic stem cell transplantation, medicine.disease, Surgery, Fludarabine, Transplantation, 03 medical and health sciences, surgical procedures, operative, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, Pediatrics, Perinatology and Child Health, medicine, Transplantation Conditioning, Adverse effect, business, 030215 immunology, medicine.drug, Infantile malignant osteopetrosis
الوصف: Background Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for infantile malignant osteopetrosis (IMO), but is associated with a high incidence of adverse outcomes. In this study, we present our experience with HSCT for IMO patients comparing different types of conditioning regimens. Methods Thirty-eight patients with IMO (aged from 1 month to 6 years, median 0.66 years) who underwent allogeneic HSCT from 1983 in our hospital were included in this retrospective study. Fludarabine-based conditioning regimens were used in 26 patients and 12 patients were transplanted using other conditioning regimens. Results The overall survival after conditioning with fludarabine was 96% (25/26) versus 58% (7/12) for the alternative regimens (P = 0.004), with significantly fewer adverse effects including hypercalcemia and veno-occlusive disease of liver. All patients who survive are clinically well. Conclusions We conclude that fludarabine-based conditioning regimens are safe and effective in patients with IMO, improving morbidity and mortality related to HSCT.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::69650f25b9e6ef03d7764ee7140fa40bTest
https://doi.org/10.1002/pbc.25801Test -
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المؤلفون: Jakob Passweg, Stella Santarone, Polina Stepensky, Francesco Lanza, Gérard Socié, Eric Beohou, Ibrahim Yakoub-Agha, Mohamad Mohty, Benedetto Bruno, Francesco Saraceni, Myriam Labopin, Arnon Nagler, Pietro Pioltelli, Bipin N. Savani, Francesca Bonifazi, William Arcese, Mahmoud Aljurf
مصطلحات موضوعية: Oncology, Myeloid, Male, Transplantation Conditioning, Graft vs Host Disease, Adolescent, Adult, Allografts, Antineoplastic Combined Chemotherapy Protocols, Busulfan, Combined Modality Therapy, Confidence Intervals, Cyclophosphamide, Disease-Free Survival, Drug Evaluation, Female, Humans, Leukemia, Myeloid, Acute, Living Donors, Middle Aged, Myeloablative Agonists, Proportional Hazards Models, Retrospective Studies, Siblings, Survival Analysis, Thiotepa, Vidarabine, Young Adult, Bone Marrow Transplantation, Peripheral Blood Stem Cell Transplantation, 0302 clinical medicine, Leukemia, Hematology, Fludarabine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, medicine.drug, medicine.medical_specialty, ThioTEPA, Acute, NO, 03 medical and health sciences, Internal medicine, medicine, business.industry, medicine.disease, Regimen, business, Settore MED/15 - Malattie del Sangue, 030215 immunology
الوصف: Busulfan plus cyclophosphamide (BuCy) is the traditional conditioning regimen for allogeneic stem cell transplant (allo-SCT) for young, fit patients with acute myeloid leukemia (AML). The thiotepa-busulfan-fludarabine (TBF) protocol has recently demonstrated promising outcome in cord blood and haploidentical SCT; however, there is limited evidence about this regimen in transplant from matched siblings (MSD) and unrelated donors (UD). We retrospectively compared outcomes of 2523 patients aged 18-50 with AML in remission, undergoing transplant from MSD or UD prepared with either TBF or BuCy conditioning. A 1:3 pair-matched analysis was performed: 146 patients receiving TBF were compared with 438 patients receiving BuCy. Relapse risk was significantly lower in the TBF when compared with BuCy group (HR 0.6, P = .02), while NRM did not differ. No significant difference was observed in LFS and OS between the two regimens. TBF was associated with a trend towards higher risk of grades III-IV aGVHD (HR 1.8, P = .06) and inferior cGVHD (HR 0.7, P = .04) when compared with BuCy. In patients undergoing transplant in first remission, the advantage for TBF in terms of relapse was more evident (HR 0.4, P = .02), leading to a trend for better LFS in favor of TBF (HR 0.7, P = .10), while OS did not differ between the two cohorts. In conclusion, TBF represents a valid myeloablative conditioning regimen providing significantly lower relapse and similar survival when compared with BuCy. Patients in first remission appear to gain the most from this protocol, as in this subgroup a tendency for better LFS was observed when compared with BuCy.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::98d843ca1028a29d98f56c9751b58b0bTest
http://hdl.handle.net/11392/2415802Test