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151. Mastocytosis: reactive or neoplastic?

Author

Krober, S M, Horny, H-P, Ruck, P, Kammerer, U, Geiselhart, A, Handgretinger, R, Griesser, H, Menke, D M, and Kaiserling, E

Published
1997

153. Survival after blinatumomab treatment in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia

Author

Gore, L., Locatelli, Franco, Zugmaier, G., Handgretinger, R., O'Brien, M. M., Bader, P., Bhojwani, D., Schlegel, P. -G., Tuglus, C. A., von Stackelberg, A., Locatelli F. (ORCID:0000-0002-7976-3654), Gore, L., Locatelli, Franco, Zugmaier, G., Handgretinger, R., O'Brien, M. M., Bader, P., Bhojwani, D., Schlegel, P. -G., Tuglus, C. A., von Stackelberg, A., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

NO ABSTRACT

Published
2018

154. The European Society for Blood and Marrow Transplantation (EBMT) Consensus Guidelines for the Detection and Treatment of Donor-specific Anti-HLA Antibodies (DSA) in Haploidentical Hematopoietic Cell Transplantation

Author

Ciurea, S. O., Cao, K., Fernadez-Vina, M., Kongtim, P., Malki, M. A., Fuchs, E., Luznik, L., Huang, X. -J., Ciceri, F., Locatelli, Franco, Aversa, F., Castagna, L., Bacigalupo, A., Martelli, M., Blaise, D., Handgretinger, R., Roy, D. -C., O'Donnell, P., Bashey, A., Lazarus, H. M., Ballen, K., Savani, B. N., Mohty, M., Nagler, A., Locatelli F. (ORCID:0000-0002-7976-3654), Ciurea, S. O., Cao, K., Fernadez-Vina, M., Kongtim, P., Malki, M. A., Fuchs, E., Luznik, L., Huang, X. -J., Ciceri, F., Locatelli, Franco, Aversa, F., Castagna, L., Bacigalupo, A., Martelli, M., Blaise, D., Handgretinger, R., Roy, D. -C., O'Donnell, P., Bashey, A., Lazarus, H. M., Ballen, K., Savani, B. N., Mohty, M., Nagler, A., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Haploidentical donors are now increasingly considered for transplantation in the absence of HLA-matched donors or when an urgent transplant is needed. Donor-specific anti-HLA antibodies (DSA) have been recently recognized as an important barrier against successful engraftment of donor cells, which can affect transplant survival. DSA appear more prevalent in this type of transplant due to higher likelihood of alloimmunization of multiparous females against offspring's HLA antigens, and the degree of mismatch. Here we summarize the evidence for the role of DSA in the development of primary graft failure in haploidentical transplantation and provide consensus recommendations from the European Society for Blood and Marrow Transplant Group on testing, monitoring, and treatment of patients with DSA receiving haploidentical hematopoietic progenitor cell transplantation.

Published
2018

159. The German PID-net registry

Author

El-Helou, S. M., Biegner, A. K., Bode, S., Ehl, S., Heeg, M., Ritterbusch, H., Rusch, S., Schmitt, R., Warnatz, K., Baerlecken, N. T., Baumann, U., Beider, R., Ernst, D., Gerschmann, S., Klemann, C., Mielke, G., Schmidt, R. E., Schuermann, G., Viemann, D., Albert, M., Eichinger, A., Eisl, E., Hauck, F., Klein, C., Sollinger, F., von Bernuth, H., Hanitsch, L., Krueger, R., Scheibenbogen, C., Avila, A., Borte, M., Borte, S., Fasshauer, M., Hauenherm, A., Kellner, N., Mueller, H., Uelzen, A., Bader, P., Bakhtiar, S., Hess, U., Lee, J. Y., Schubert, R., Voss, S., Zielen, S., Bienemann, K., Lankisch, P., Laws, H. J., Neubert, J., Dueckers, G., Lamers, B., Langemeyer, V., Niehues, T., Hoenig, M., Schulz, A., Schwarz, K., Steinmann, S., Graf, D., Haase, G., Liese, J. G., Morbach, H., Schwaneck, E., Tony, H. P., Foell, D., Hellige, A., Masjosthusmann, K., Mohr, M., Wittkowski, H., Fischer, J. C., Hedrich, C. M., Roesen-Wolff, A., Roesler, J., Behrends, U., Rieber, N., Schauer, U., Boesecke, C., Dilloo, D., Engelhardt, A., Huelsmann, B., Rockstroh, J., Scholtes, C., Schoenberger, S., Wasmuth, J. C., Handgretinger, R., Henes, J., Holzer, U., Kanz, L., Ankermann, T., von Bismarck, P., Schreiber, S., Zeuner, R., Huppertz, H. I., Kaiser-Labusch, P., Greil, J., Jakoby, D., Kulozik, A. E., Graf, N., Heine, S., Garwer, B., Kobbe, R., Lehmberg, K., Mueller, I., Herrmann, F., Horneff, G., Klein, A., Peitz, J., Schmidt, N., Apel, K., Bielack, S., Gross-Wieltsch, U., Deutz, P., Lassay, L., Kamitz, D., Stienen, A., Tenbrock, K., Wagner, N., Classen, C. F., Weiss, M., Bernbeck, B., Brummel, B., Lara-Villacanas, E., Muenstermann, E., Schneider, D., Tietsch, N., Westkemper, M., Naumann-Bartsch, N., Metzler, M., Sobik, B., Kuehnle, I., Kullmann, S., Kramm, C., Girschick, H., Elbe, S., Specker, C., Vinnemeier-Laubenthal, L., Haenicke, H., Schulz, C., Schweigerer, L., Mueller, T. G., Kindle, G., Grimbacher, B., El-Helou, S. M., Biegner, A. K., Bode, S., Ehl, S., Heeg, M., Ritterbusch, H., Rusch, S., Schmitt, R., Warnatz, K., Baerlecken, N. T., Baumann, U., Beider, R., Ernst, D., Gerschmann, S., Klemann, C., Mielke, G., Schmidt, R. E., Schuermann, G., Viemann, D., Albert, M., Eichinger, A., Eisl, E., Hauck, F., Klein, C., Sollinger, F., von Bernuth, H., Hanitsch, L., Krueger, R., Scheibenbogen, C., Avila, A., Borte, M., Borte, S., Fasshauer, M., Hauenherm, A., Kellner, N., Mueller, H., Uelzen, A., Bader, P., Bakhtiar, S., Hess, U., Lee, J. Y., Schubert, R., Voss, S., Zielen, S., Bienemann, K., Lankisch, P., Laws, H. J., Neubert, J., Dueckers, G., Lamers, B., Langemeyer, V., Niehues, T., Hoenig, M., Schulz, A., Schwarz, K., Steinmann, S., Graf, D., Haase, G., Liese, J. G., Morbach, H., Schwaneck, E., Tony, H. P., Foell, D., Hellige, A., Masjosthusmann, K., Mohr, M., Wittkowski, H., Fischer, J. C., Hedrich, C. M., Roesen-Wolff, A., Roesler, J., Behrends, U., Rieber, N., Schauer, U., Boesecke, C., Dilloo, D., Engelhardt, A., Huelsmann, B., Rockstroh, J., Scholtes, C., Schoenberger, S., Wasmuth, J. C., Handgretinger, R., Henes, J., Holzer, U., Kanz, L., Ankermann, T., von Bismarck, P., Schreiber, S., Zeuner, R., Huppertz, H. I., Kaiser-Labusch, P., Greil, J., Jakoby, D., Kulozik, A. E., Graf, N., Heine, S., Garwer, B., Kobbe, R., Lehmberg, K., Mueller, I., Herrmann, F., Horneff, G., Klein, A., Peitz, J., Schmidt, N., Apel, K., Bielack, S., Gross-Wieltsch, U., Deutz, P., Lassay, L., Kamitz, D., Stienen, A., Tenbrock, K., Wagner, N., Classen, C. F., Weiss, M., Bernbeck, B., Brummel, B., Lara-Villacanas, E., Muenstermann, E., Schneider, D., Tietsch, N., Westkemper, M., Naumann-Bartsch, N., Metzler, M., Sobik, B., Kuehnle, I., Kullmann, S., Kramm, C., Girschick, H., Elbe, S., Specker, C., Vinnemeier-Laubenthal, L., Haenicke, H., Schulz, C., Schweigerer, L., Mueller, T. G., Kindle, G., and Grimbacher, B.

Published
2017

160. Outcome of children with acute leukemia given HLA-haploidentical HSCT after ab T-cell and B-cell depletion

Author

Locatelli, Franco, Merli, P., Pagliara, D., Li Pira, G., Falco, M., Pende, D., Rondelli, R., Lucarelli, B., Brescia, L. P., Masetti, R., Milano, G. M., Bertaina, V., Algeri, M., Pinto, R. M., Strocchio, L., Meazza, R., Grapulin, L., Handgretinger, R., Moretta, A., Bertaina, A., Moretta, L., Locatelli F. (ORCID:0000-0002-7976-3654), Locatelli, Franco, Merli, P., Pagliara, D., Li Pira, G., Falco, M., Pende, D., Rondelli, R., Lucarelli, B., Brescia, L. P., Masetti, R., Milano, G. M., Bertaina, V., Algeri, M., Pinto, R. M., Strocchio, L., Meazza, R., Grapulin, L., Handgretinger, R., Moretta, A., Bertaina, A., Moretta, L., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-haploidentical relative (haplo-HSCT) is a suitable option for children with acute leukemia (AL) either relapsed or at high-risk of treatment failure. We developed a novel method of graft manipulation based on negative depletion of ab T and B cells and conducted a prospective trial evaluating the outcome of children with AL transplanted with this approach. Eighty AL children, transplanted between September 2011 and September 2014, were enrolled in the trial. All children were given a fully myeloablative preparative regimen. Anti–T-lymphocyte globulin from day 25 to 23 was used for preventing graft rejection and graft-versus-host disease (GVHD); no patient received any posttransplantation GVHD prophylaxis. Two children experienced primary graft failure. The cumulative incidence of skin-only, grade 1-2 acute GVHD was 30%; no patient developed extensive chronic GVHD. Four patients died, the cumulative incidence of nonrelapse mortality being 5%, whereas 19 relapsed, resulting in a 24% cumulative incidence of relapse. With a median follow-up of 46 months for surviving patients, the 5-year probability of chronic GVHD-free, relapse-free survival (GRFS) is 71%. Total body irradiation–containing preparative regimen was the only variable favorably influencing relapse incidence and GRFS. The outcomes of these 80 patients are comparable to those of 41 and 51 children given transplantation from an HLA-identical sibling or a 10/10 allelic-matched unrelated donor in the same period. These data indicate that haplo-HSCT after ab T- and B-cell depletion represents a competitive alternative for children with AL in need of urgent allograft. This trial was registered at www.clinicaltrials.gov as #NCT01810120.

Published
2017

161. Application of Interleukin 2 in Neuroblastoma

Author

Handgretinger, R., Bruchelt, G., Schneider, M., Niethammer, D., Treuner, J., Heimpel, H., editor, Huhn, D., editor, Mueller-Eckhardt, C., editor, Ruhenstroth-Bauer, G., editor, Neth, Rolf, editor, Gallo, Robert C., editor, Greaves, Melvyn F., editor, and Kabisch, Hartmut, editor

Published
1987
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162. ZUMA-4 preliminary results: phase 1 study of KTE-C19 chimeric antigen receptor T cell therapy in pediatric and adolescent patients (pts) with relapsed/refractory acute lymphoblastic leukemia (R/R ALL)

Author

Lee, D.W., primary, Wayne, A.S., additional, Huynh, V., additional, Handgretinger, R., additional, Pieters, R., additional, Michele, G., additional, Baruchel, A., additional, Feuchtinger, T., additional, Bertrand, Y., additional, Hemiston, M., additional, Brown, P.A., additional, Rossi, J., additional, Jiang, Y., additional, Navale, L., additional, Stout, S., additional, Aycock, J., additional, Mardiros, A., additional, Wiezorek, J., additional, and Jain, R., additional

Published
2017
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164. GLI Inhibition als neuer therapeutischer Ansatz für Patienten mit Rhabdomyosarkomen

Author

Böhme, KA, Riester, R, Zaborski, JJ, Hopp, U, Traub, F, Handgretinger, R, Kluba, T, and Schleicher, SB

Subjects
Arsen Trioxid, ddc: 610, Rhabdomyosarkom, 610 Medical sciences, Medicine, Hedgehog-Signalweg
Abstract

Fragestellung: Rhabdomyosarkome (RMS) sind seltene mesenchymale Tumoren, die überwiegend bei Kindern und Jugendlichen auftreten. Eine anomale Aktivierung des Hedgehog (Hh)-Signalwegs wird bei verschiedenen Tumorerkrankungen mit der Progression, Metastasierung und Chemoresistenz in Verbindung gebracht.[zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2015)

Published
2015
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165. Will Post-Transplantation Cell Therapies for Pediatric Patients Become Standard of Care?

Author

Lankester, A.C., Locatelli, F., Bader, P., Rettinger, E., Egeler, M., Katewa, S., Pulsipher, M.A., Nierkens, S., Schultz, K., Handgretinger, R., Grupp, S.A., Boelens, J.J., Bollard, C.M., and Westhafen Intercontinental Grp

Subjects
Graft Rejection, Male, medicine.medical_treatment, Adoptive cellular therapy, Cell- and Tissue-Based Therapy, Graft vs Host Disease, Hematopoietic stem cell transplantation, Disease, Pediatrics, NATURAL-KILLER-CELLS, 0302 clinical medicine, VERSUS-HOST-DISEASE, Medicine, Child, 0303 health sciences, Hematology, Graft vs Tumor Effect, adoptive cellular therapy, chimeric antigen receptor, pediatrics, stem cell transplantation, Hematopoietic Stem Cell Transplantation, Stem cell transplantation, ALLOGENEIC-DENDRITIC CELLS, Allografts, CHIMERIC ANTIGEN RECEPTOR, 3. Good health, surgical procedures, operative, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Child, Preschool, Hematologic Neoplasms, Lymphocyte Transfusion, Female, T-REGULATORY CELLS, medicine.medical_specialty, MINOR HISTOCOMPATIBILITY ANTIGENS, Adolescent, chemical and pharmacologic phenomena, MESENCHYMAL STROMAL CELLS, ACUTE MYELOID-LEUKEMIA, Donor lymphocyte infusion, 03 medical and health sciences, Immune system, Internal medicine, Humans, Intensive care medicine, 030304 developmental biology, ACUTE LYMPHOBLASTIC-LEUKEMIA, Transplantation, business.industry, Mesenchymal stem cell, Infant, BONE-MARROW-TRANSPLANTATION, Chimeric antigen receptor, Immunology, business, 030215 immunology
Abstract

Although allogeneic hematopoietic stem cell transplantation (HSCT) is a curative approach for many pediatric patients with hematologic malignancies and some nonmalignant disorders, some critical obstacles remain to be overcome, including relapse, engraftment failure, graft-versus-host disease (GVHD), and infection. Harnessing the immune system to induce a graft-versus-tumor effect or rapidly restore antiviral immunity through the use of donor lymphocyte infusion (DLI) has been remarkably successful in some settings. Unfortunately, however, the responses to DLI can be variable, and GVHD is common. Thus, manipulations to minimize GVHD while restoring antiviral immunity and enhancing the graft-versus-tumor effect are needed to improve outcomes after allogeneic HSCT. Cellular therapies, defined as treatment modalities in which hematopoietic or nonhematopoietic cells are used as therapeutic agents, offer this promise for improving outcomes post-HSCT. This review presents an overview of the field for pediatric cell therapies in the transplant setting and discusses how we can broaden applicability beyond phase I. (C) 2015 American Society for Blood and Marrow Transplantation.

Published
2015

166. Monocytes show immunoregulatory capacity on CD4+ T cells in a human in‐vitro model of extracorporeal photopheresis.

Author

Wiese, F., Reinhardt‐Heller, K., Volz, M., Gille, C., Köstlin, N., Billing, H., Handgretinger, R., and Holzer, U.

Subjects
MONOCYTES, HUMAN T cells, T cells
Abstract

Summary: Extracorporeal photopheresis (ECP) is a widely used immunomodulatory therapy for the treatment of various T cell‐mediated disorders such as cutaneous T cell lymphoma (CTCL), graft‐versus‐host disease (GvHD) or systemic sclerosis. Although clinical benefits of ECP are already well described, the underlying mechanism of action of ECP is not yet fully understood. Knowledge on the fate of CD14+ monocytes in the context of ECP is particularly limited and controversial. Here, we investigated the immunoregulatory function of ECP treated monocytes on T cells in an in‐vitro ECP model. We show that ECP‐treated monocytes significantly induce proinflammatory T cell types in co‐cultured T cells, while anti‐inflammatory T cells remain unaffected. Furthermore, we found significantly reduced proliferation rates of T cells after co‐culture with ECP‐treated monocytes. Both changes in interleukin secretion and proliferation were dependent on cell‐contact between monocytes and T cells. Interestingly, blocking interactions of programmed death ligand 1 (PD‐L1) to programmed death 1 (PD‐1) in the in‐vitro model led to a significant recovery of T cell proliferation. These results set the base for further studies on the mechanism of ECP, especially the regulatory role of ECP‐treated monocytes. Although clinical benefits of ECP are already well described, the underlying mechanism of action of ECP, which is commonly used for the treatment of various T cell‐mediated disorders, is not yet fully understood. In this study, we established an in‐vitro ECP model focusing on ECP‐treated monocytes in co‐culture with CD4+ T cells as knowledge on the role of monocytes in ECP is particularly controversial and should be further investigated. We found that in‐vitro ECP treatment of monocytes (1) significantly induced proinflammatory T cell types dependent on cell‐contact, whereas anti‐inflammatory T cells were unaffected, (2) significantly reduced proliferation rates of co‐cultured T cells in a cell‐contact‐dependent manner partially due to PD‐L1–PD‐1 interactions as (3) blockade of this interaction by antibodies led to a slight but significant recovery of T cell proliferation. [ABSTRACT FROM AUTHOR]

Published
2019
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167. Proceedings from the Second Haploidentical Stem Cell Transplantation Symposium-Haplo2014, San Francisco, California, December 4, 2014

Author

Al Malki, M. M., Horowitz, M., Handgretinger, R., Leung, W., Roy, D. -C., Huang, X. -J., Fuchs, E., Locatelli, Franco, Blaise, D., Mineishi, S., Martelli, M., Miller, J., June, C., Ai, H. -S., Luznik, L., Mavilio, D., Lugli, E., van den Brink, M. R. M., Champlin, R. E., Ciurea, S. O., Locatelli F. (ORCID:0000-0002-7976-3654), Al Malki, M. M., Horowitz, M., Handgretinger, R., Leung, W., Roy, D. -C., Huang, X. -J., Fuchs, E., Locatelli, Franco, Blaise, D., Mineishi, S., Martelli, M., Miller, J., June, C., Ai, H. -S., Luznik, L., Mavilio, D., Lugli, E., van den Brink, M. R. M., Champlin, R. E., Ciurea, S. O., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Significant progress has been made over the past decade in haploidentical transplantation, with the development of novel methods to control intense alloreactive reactions generated in the major HLA-mismatched setting. Application of post-transplantation cyclophosphamide has gained worldwide acceptance as an effective and low-cost way to perform this type of transplantation, with outcomes now similar to those from HLA-matched unrelated donors. These advances have resulted in improved treatment-related mortality, whereas disease relapse has emerged as the most common cause of treatment failure. In addition, improvements in immunologic reconstitution after transplantation are much needed, not only in haploidentical transplantation but in all forms of stem cell transplantation. This symposium has focused on some of the most promising methods to control alloreactivity in this form of transplantation and application of cellular therapy to prevent disease relapse after transplantation, as well as understanding immunologic reconstitution and foreseeable approaches to improve immune recovery after transplantation.

Published
2016

168. Phase I/Phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia

Author

Von Stackelberg, A., Locatelli, Franco, Zugmaier, G., Handgretinger, R., Trippett, T. M., Rizzari, C., Bader, P., O'Brien, M. M., Brethon, B., Bhojwani, D., Schlegel, P. G., Borkhardt, A., Rheingold, S. R., Cooper, T. M., Zwaan, C. M., Barnette, P., Messina, C., Michel, G., Dubois, S. G., Hu, K., Zhu, M., Whitlock, J. A., Gore, L., Locatelli F. (ORCID:0000-0002-7976-3654), Von Stackelberg, A., Locatelli, Franco, Zugmaier, G., Handgretinger, R., Trippett, T. M., Rizzari, C., Bader, P., O'Brien, M. M., Brethon, B., Bhojwani, D., Schlegel, P. G., Borkhardt, A., Rheingold, S. R., Cooper, T. M., Zwaan, C. M., Barnette, P., Messina, C., Michel, G., Dubois, S. G., Hu, K., Zhu, M., Whitlock, J. A., Gore, L., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. Weevaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children , 18 years old with relapsed/refractory BCP-ALL in a phase I dosage-escalation part and a phase II part, using 6-week treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II). Results We treated 49 patients in phase I and 44 patients in phase II. Four patients had dose-limiting toxicities in cycle 1 (phase I). Three experienced grade 4 cytokine-release syndrome (one attributed to grade 5 cardiac failure); one had fatal respiratory failure. The maximum-tolerated dosage was 15 mg/m2d. Blinatumomab pharmacokinetics was linear across dosage levels and consistent among age groups. On the basis of the phase I data, the recommended blinatumomab dosage for children with relapsed/refractory ALL was 5 mg/m2d for the first 7 days, followed by 15 mg/m2d thereafter. Among the 70 patients who received the recommended dosage, 27 (39%; 95% CI, 27% to 51%) achieved complete remission within the first two cycles, 14 (52%) of whom achieved complete minimal residual disease response. The most frequent grade $ 3 adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%). Three patients (4%) and one patient (1%) had cytokine-release syndrome of grade 3 and 4, respectively. Two patients (3%) interrupted treatment after grade 2 seizures. Conclusion This trial, which to the best of our knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL. Blinatumomab may represent an important new t

Published
2016

175. Better Outcome With Maintenance Therapy : Pediatric Patients With Stage Iv Soft Tissue Sarcoma Benefit From Long Term Therapy Compared To Sct Or No Further Therapy

Author

Bochennek, K., Dantonello, T., Borkhardt, A., Dirksen, U., Eggert, A., Greiner, J., Handgretinger, R., Kazanowska, B., Kratz, C., Ladenstein, R., Ljungman, Gustaf, Hallmen, E., Koscielniak, E., Klingebiel, T., Bochennek, K., Dantonello, T., Borkhardt, A., Dirksen, U., Eggert, A., Greiner, J., Handgretinger, R., Kazanowska, B., Kratz, C., Ladenstein, R., Ljungman, Gustaf, Hallmen, E., Koscielniak, E., and Klingebiel, T.

Published
2015

177. Will Post-Transplantation Cell Therapies for Pediatric Patients Become Standard of Care?

Author

Lankester, A. C., Locatelli, Franco, Bader, P., Rettinger, E., Egeler, M., Katewa, S., Pulsipher, M. A., Nierkens, S., Schultz, K., Handgretinger, R., Grupp, S. A., Boelens, J. J., Bollard, C. M., Locatelli F. (ORCID:0000-0002-7976-3654), Lankester, A. C., Locatelli, Franco, Bader, P., Rettinger, E., Egeler, M., Katewa, S., Pulsipher, M. A., Nierkens, S., Schultz, K., Handgretinger, R., Grupp, S. A., Boelens, J. J., Bollard, C. M., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Although allogeneic hematopoietic stem cell transplantation (HSCT) is a curative approach for many pediatric patients with hematologic malignancies and some nonmalignant disorders, some critical obstacles remain to be overcome, including relapse, engraftment failure, graft-versus-host disease (GVHD), and infection. Harnessing the immune system to induce a graft-versus-tumor effect or rapidly restore antiviral immunity through the use of donor lymphocyte infusion (DLI) has been remarkably successful in some settings. Unfortunately, however, the responses to DLI can be variable, and GVHD is common. Thus, manipulations to minimize GVHD while restoring antiviral immunity and enhancing the graft-versus-tumor effect are needed to improve outcomes after allogeneic HSCT. Cellular therapies, defined as treatment modalities in which hematopoietic or nonhematopoietic cells are used as therapeutic agents, offer this promise for improving outcomes post-HSCT. This review presents an overview of the field for pediatric cell therapies in the transplant setting and discusses how we can broaden applicability beyond phase I.

Published
2015

178. Distinct Aspergillus fumigatus morphotypes induce neutrophilic CXCR4high myeloid-derived suppressor cells through a Dectin-1-mediated mechanism

Author

Rieber, N., Bouzani, M., Ost, M., Hofer, L., Schäfer, I., Mezger, M., Pfeiffer, M., Einsele, H., Handgretinger, R., Löffler, J., and Hartl, D.

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Introduction: The coordinated action of both innate and adaptive immunity is essential to protect the host against Aspergillus fumigatus. Innate myeloid cells recognize the fungus, while T cells orchestrate long-term immune responses. However, overreactive T cell responses drive hyperinflammation with[for full text, please go to the a.m. URL], 21. Jahrestagung der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI)

Published
2013

179. Adoptiver T-Zelltransfer als Therapieoption bei refraktären Virusinfektionen mit Adenovirus nach allogener Stammzelltransplantation

Author

Feucht, J., Opherk, K., Kayser, S., Handgretinger, R., Lang, P., and Feuchtinger, T.

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Systemische Virusinfektionen nach allogener Stammzelltransplantation sind mit einer hohen Morbiditäts- und Mortalitätsrate verbunden. Dabei führen bei Kindern insbesondere Virämien mit Adenovirus (ADV) zu lebensbedrohlichen Manifestationen und schwerwiegenden Verläufen. Aufgrund[for full text, please go to the a.m. URL], 21. Jahrestagung der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI)

Published
2013

180. A phase I/II study of CY and topotecan in patients with high-risk malignancies undergoing autologous hematopoietic cell transplantation: the St Jude long-term follow-up

Author

Wright, N. L., Horwitz, E. M., Handgretinger, R., Stewart, C. F., Srivastava, D. K., Hale, G. A., Leung, W., Bowman, L. C., Kasow, K. A., Li, C., and Barfield, R. C.

Abstract

Fifty-eight consecutive children with high-risk malignancies were treated with CY, and targeted topotecan followed by autologous hematopoietic cell transplantation (AHCT) in a phase I/II Institutional Review Board-approved study. Twelve participants enrolled in phase I; 5 received dose level 1 of topotecan 3 mg/m(2) per day, with subsequent doses targeted to total systemic exposure of 100±20 ng h/mL and CY 750 mg/m(2) per day. Seven participants received dose level 2. CY dose escalation to 1 g/m(2) per day was considered excessively toxic; one died from irreversible veno-occlusive disease and two experienced reversible hepatotoxicity. These adverse events halted further dose escalation. A total of 46 participants were enrolled in phase II; results are on the 51 participants who received therapy at dose level 1, the maximum tolerated dose. Diagnoses included neuroblastoma (26), sarcoma (9), lymphoma (8), brain tumors (5), Wilms (2) and retinoblastoma (1). Twenty participants (39.3%) were in CR1 at enrollment; median age was 5.1 years. Most common non-hematological grade III-IV toxicity was gastrointestinal (n=37). Neutrophil and platelet engraftment occurred at a median of 15 and 24 days, respectively. Twenty-six (51%) participants remain alive at a median of 6.4 years after AHCT. CY 3.75 g/m(2), and targeted topotecan followed by AHCT are feasible and produce acceptable toxicity in children with high-risk malignancies.Bone Marrow Transplantation advance online publication, 19 March 2012; doi:10.1038/bmt.2012.51.

Published
2012
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182. Pediatric T-cell lymphoblastic leukemia evolves into relapse by clonal selection, acquisition of mutations and promoter hypomethylation

Author

Kunz, J. B., primary, Rausch, T., additional, Bandapalli, O. R., additional, Eilers, J., additional, Pechanska, P., additional, Schuessele, S., additional, Assenov, Y., additional, Stutz, A. M., additional, Kirschner-Schwabe, R., additional, Hof, J., additional, Eckert, C., additional, von Stackelberg, A., additional, Schrappe, M., additional, Stanulla, M., additional, Koehler, R., additional, Avigad, S., additional, Elitzur, S., additional, Handgretinger, R., additional, Benes, V., additional, Weischenfeldt, J., additional, Korbel, J. O., additional, Muckenthaler, M. U., additional, and Kulozik, A. E., additional

Published
2015
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183. Consensus of German Transplant Centers on Hematopoietic Stem Cell Transplantation in Fanconi Anemia

Author

Chao, M., additional, Ebell, W., additional, Bader, P., additional, Beier, R., additional, Burkhardt, B., additional, Feuchtinger, T., additional, Handgretinger, R., additional, Hanenberg, H., additional, Koehl, U., additional, Kratz, C., additional, Kremens, B., additional, Lang, P., additional, Meisel, R., additional, Mueller, I., additional, Roessig, C., additional, Sauer, M., additional, Schlegel, P., additional, Schulz, A., additional, Strahm, B., additional, Thol, F., additional, and Sykora, K., additional

Published
2015
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184. Immunotherapy in the Context of Hematopoietic Stem Cell Transplantation: The Emerging Role of Natural Killer Cells and Mesenchymal Stromal Cells

Author

Lankester, A.C., Ball, L.M., Lang, P., and Handgretinger, R.

Subjects
Immunotherapy Hematopoietic stem cell transplantation Natural killer cells Mesenchymal stromal cells versus-host-disease bone-marrow-transplantation umbilical-cord blood acute myeloid-leukemia inhibit lymphocyte-proliferation kir-ligand incompatibility breast-cancer patients suppress t-lymphocyte allogeneic nk cells class-i expression
Abstract

Immunotherapy in the context of hematopoietic stem cell transplantation has been dominated for many years by T-cell- and dendritic-cell-based treatment modalities. During the last decade, insight into the biology of natural killer (NK) cells and mesenchymal stromal cells (MSC) has rapidly increased and resulted in NK- and MSC-based therapeutic strategies in clinical practice. This article reviews current knowledge of the biology and clinical aspects of NK cells and MSC.

Published
2010

188. Combined PET/MR: Where Are We Now? Summary Report of the Second International Workshop on PET/MR Imaging April 8–12, 2013, Tubingen, Germany

Author

Bailey, D. L., Barthel, H., Beuthien-Baumann, B., Beyer, T., Bisdas, S., Boellaard, R., Czernin, J., Drzezga, A., Ernemann, U., Franzius, C., Gückel, B., Handgretinger, R., Hartenbach, M., Hellwig, D., Nadel, H., Nekolla, S. G., Pfluger, T., Pichler, B. J., Quick, H. H., Sabri, O., Sattler, B., Schäfer, J., Schick, F., Siegel, B. A., Schlemmer, H. P., Schwenzer, N. F., Hoff, J., Veit-Haibach, P., Wehrl, H. F., Bailey, D. L., Barthel, H., Beuthien-Baumann, B., Beyer, T., Bisdas, S., Boellaard, R., Czernin, J., Drzezga, A., Ernemann, U., Franzius, C., Gückel, B., Handgretinger, R., Hartenbach, M., Hellwig, D., Nadel, H., Nekolla, S. G., Pfluger, T., Pichler, B. J., Quick, H. H., Sabri, O., Sattler, B., Schäfer, J., Schick, F., Siegel, B. A., Schlemmer, H. P., Schwenzer, N. F., Hoff, J., Veit-Haibach, P., and Wehrl, H. F.

Abstract

This workshop was held a year after the initial positron emission tomography/magnetic resonance (PET/MR) workshop in Tübingen, which was recently reported in this journal. The discussions at the 2013 workshop, however, differed substantially from those of the initial workshop, attesting to the progress of combined PET/MR as an innovative imaging modality. Discussions were focused on the search for truly novel, unique clinical and research applications as well as technical issues such as reliable and accurate approaches for attenuation and scatter correction of PET emission data. The workshop provided hands-on experience with PET and MR imaging. In addition, structured and moderated open discussion sessions, including six dialogue boards and two roundtable discussions, provided input from current and future PET/MR imaging users. This summary provides a snapshot of the current achievements and challenges for PET/MR.

Published
2014

190. 1008PD - ZUMA-4 preliminary results: phase 1 study of KTE-C19 chimeric antigen receptor T cell therapy in pediatric and adolescent patients (pts) with relapsed/refractory acute lymphoblastic leukemia (R/R ALL)

Author

Lee, D.W., Wayne, A.S., Huynh, V., Handgretinger, R., Pieters, R., Michele, G., Baruchel, A., Feuchtinger, T., Bertrand, Y., Hemiston, M., Brown, P.A., Rossi, J., Jiang, Y., Navale, L., Stout, S., Aycock, J., Mardiros, A., Wiezorek, J., and Jain, R.

Published
2017
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192. Statement by members of the Ponte di Legno group on the right of children with leukemia to have full access to essential treatment for acute lymphoblastic leukemia

Author

Arico, M, Basso, Giuseppe, Biondi, A, Conter, V, Masera, G, Rognoni, G, Valsecchi, Mg, Cario, G, Gadner, H, Haas, O, Harbott, J, Panzer, R, Riehm, H, Shrappe, M, Stackelberg, A, Stanulla, M, Zimmermann, M, Camita, B, Caroll, W, Gaynon, P, Hunger, S, Nachman, J, Schultz, K, Winick, N, Horstmann, M, JANKA SCHAUB, G, Stary, J, Trka, J, Sallan, S, Silverman, L, Pieters, R, Veerman, A, Bertrand, Y, Suciu, S, Leverger, G, Horibe, K, Eden, Ob, Harrison, C, Gibson, B, Forestier, E, Schmiegelow, K, Vettenranta, K, Campana, D, COUSTON SMITH, E, Evans, We, Handgretinger, R, Pui, Ch, Relling, Mv, Lang, Dc, Manabe, A, Tsuchida, M, Pinkel, D., Tognoni, G, Masera, G, Pui, C, Eden, T, Nachman, J, Gadner, H, Gaynon, P, Evans, W, and Schrappe, M

Subjects
Pediatrics, medicine.medical_specialty, Clinical Trials as Topic, Statement (logic), business.industry, Lymphoblastic Leukemia, Health Policy, International Cooperation, Child Welfare, Hematology, Patient Advocacy, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Health Services Accessibility, Precursor Cell Lymphoblastic Leukemia Lymphoma, Leukemia, Oncology, Acute lymphocytic leukemia, medicine, Humans, business, Child
Published
2004

193. Glycosylation and lectins-examples of immunesurveillance and immune evasion

Author

Müller, I., Jenner, J., Handgretinger, R., Riberdy, J., and Kerst, G.

Subjects
Immune system, Tumor, 6 - Ciencias aplicadas::61 - Medicina [CDU]
Abstract

Cell surface proteins are posttranslationally modified by tightly regulated enzymes of glycosylation. Typical patterns of glycosylation may signal pathological situations to the immune system. Here, carbohydrate receptors on the surface of cells in the immune system are involved in regulation of effector cells. Moreover, some lectins are circulating in the plasma and take part in host defense. The code of carbohydrate modifications is impaired in malignant cells and yet they are not eliminated. In this review, we focus on recent experimental evidence for regulatory functions of lectins and carbohydrate derivatives in the immune system and tumours.

Published
2004

195. The activating STAT5B N642H mutation is a common abnormality in pediatric T-cell acute lymphoblastic leukemia and confers a higher risk of relapse

Author

Bandapalli, O. R., primary, Schuessele, S., additional, Kunz, J. B., additional, Rausch, T., additional, Stutz, A. M., additional, Tal, N., additional, Geron, I., additional, Gershman, N., additional, Izraeli, S., additional, Eilers, J., additional, Vaezipour, N., additional, Kirschner-Schwabe, R., additional, Hof, J., additional, von Stackelberg, A., additional, Schrappe, M., additional, Stanulla, M., additional, Zimmermann, M., additional, Koehler, R., additional, Avigad, S., additional, Handgretinger, R., additional, Frismantas, V., additional, Bourquin, J. P., additional, Bornhauser, B., additional, Korbel, J. O., additional, Muckenthaler, M. U., additional, and Kulozik, A. E., additional

Published
2014
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196. ATYPICAL TERATOID RHABDOID TUMOUR

Author

Bertozzi, A. I., primary, Munzer, C., additional, Fouyssac, F., additional, Andre, N., additional, Boetto, S., additional, Leblond, P., additional, Bourdeaut, F., additional, Dufour, C., additional, Deshpande, R. K., additional, Bhat, K. G., additional, Mahalingam, S., additional, Muscat, A., additional, Cain, J., additional, Ferguson, M., additional, Popovski, D., additional, Algar, E., additional, Rossello, F. J., additional, Jayasekara, S., additional, Watkins, D. N., additional, Hodge, J., additional, Ashley, D., additional, Hishii, M., additional, Saito, M., additional, Arai, H., additional, Han, Z. Y., additional, Richer, W., additional, Lucchesi, C., additional, Freneaux, P., additional, Nicolas, A., additional, Grison, C., additional, Pierron, G., additional, Delattre, O., additional, Epari, S., additional, TS, N., additional, Gupta, T., additional, Chinnaswamy, G., additional, Sastri, J. G., additional, Shetty, P., additional, Moiyadi, A., additional, Jalali, R., additional, Fay-McClymont, T., additional, Johnston, D., additional, Janzen, L., additional, Guger, S., additional, Scheinemann, K., additional, Fleming, A., additional, Fryer, C., additional, Hukin, J., additional, Mabbott, D., additional, Huang, A., additional, Bouffet, E., additional, Lafay-Cousin, L., additional, Kawamura, A., additional, Yamamoto, K., additional, Nagashima, T., additional, Bartelheim, K., additional, Benesch, M., additional, Buchner, J., additional, Gerss, J., additional, Hasselblatt, M., additional, Kortmann, R.-D., additional, Fleischack, G., additional, Quiroga, E., additional, Reinhard, H., additional, Schneppenheim, R., additional, Seeringer, A., additional, Siebert, R., additional, Timmermann, B., additional, Warmuth-Metz, M., additional, Schmid, I., additional, Fruhwald, M. C., additional, Kerl, K., additional, Klingebiel, T., additional, Al-Kofide, A., additional, Khafaga, Y., additional, Al-Hindi, H., additional, Dababo, M., additional, Ul-Haq, A., additional, Anas, M., additional, Barria, M. G., additional, Siddiqui, K., additional, Hassounah, M., additional, Ayas, M., additional, Al-Shail, E., additional, Jeibmann, A., additional, Eikmeier, K., additional, Linge, A., additional, Johann, P., additional, Koos, B., additional, Kool, M., additional, Pfister, S. M., additional, Paulus, W., additional, Schuller, U., additional, Junckerstorff, R., additional, Rosenblum, M. K., additional, Alassiri, A. H., additional, Rossi, S., additional, Gottardo, N., additional, Toledano, H., additional, Viscardi, E., additional, Witkowski, L., additional, Nagel, I., additional, Oyen, F., additional, Foulkes, W. D., additional, Schrey, D., additional, Malietzis, G., additional, Chi, S., additional, Marshall, L., additional, Carceller, F., additional, Moreno, L., additional, Zacharoulis, S., additional, Bhardwaj, R., additional, Chakravadhanula, M., additional, Ozals, V., additional, Hampton, C., additional, Metpally, R., additional, Grillner, P., additional, Asmundsson, J., additional, Gustavsson, B., additional, Holm, S., additional, Johann, P. D., additional, Korshunov, A., additional, Ryzhova, M., additional, Milde, T., additional, Witt, O., additional, Jones, D. T. W., additional, Hovestadt, V., additional, Gajjar, A., additional, Fruhwald, M., additional, Pfister, S., additional, Finetti, M., additional, Pons, A. d. C., additional, Selby, M., additional, Smith, A., additional, Crosier, S., additional, Wood, J., additional, Skalkoyannis, B., additional, Bailey, S., additional, Clifford, S., additional, Williamson, D., additional, Rutkowski, S., additional, Kortmann, R. D., additional, Graf, N., additional, Boos, J., additional, Nysom, K., additional, Moreno, N., additional, Holsten, T., additional, Ahlfeld, J., additional, Mertins, J., additional, Hotfilder, M., additional, Schleicher, S., additional, Handgretinger, R., additional, Meisterernst, M., additional, Schmidt, C., additional, Dittmar, S., additional, Chan, G. C. F., additional, Shing, M. M. K., additional, Yuen, H. L., additional, Li, R. C. H., additional, Ling, S. L., additional, Slavc, I., additional, Peyrl, A., additional, Chocholous, M., additional, Azizi, A., additional, Czech, T., additional, Dieckmann, K., additional, Haberler, C., additional, Leiss, U., additional, Gotti, G., additional, Biassoni, V., additional, Schiavello, E., additional, Spreafico, F., additional, Pecori, E., additional, Gandola, L., additional, Massimino, M., additional, Kornelius, K., additional, Yano, H., additional, Nakayama, N., additional, Ohe, N., additional, Ozeki, M., additional, Kanda, K., additional, Kimura, T., additional, Hori, T., additional, Fukao, T., additional, Iwama, T., additional, Weil, A. G., additional, Diaz, A., additional, Gernsback, J., additional, Bhatia, S., additional, Ragheb, J., additional, Niazi, T., additional, Khatib, Z., additional, Zoghbi, A., additional, Meisterernst, a. M., additional, Birks, D., additional, Griesinger, A., additional, Amani, V., additional, Donson, A., additional, Posner, R., additional, Dunham, C., additional, Kleinschmidt-DeMasters, B. K., additional, Handler, M., additional, Vibhakar, R., additional, Foreman, N., additional, Zhou, L., additional, Catchpoole, D., additional, Kakkar, A., additional, Biswas, A., additional, Suri, V., additional, Sharma, M., additional, Kale, S., additional, Mahapatra, A., additional, Sarkar, C., additional, Torchia, J., additional, Picard, D., additional, Ho, K. C., additional, Khuong-Quang, D.-A., additional, Louterneau, L., additional, Bourgey, M., additional, Chan, T., additional, Golbourn, B., additional, Cousin, L.-L., additional, Taylor, M. D., additional, Dirks, P., additional, Rutka, J. T., additional, Hawkins, C., additional, Majewski, J., additional, Kim, S.-K., additional, Jabado, N., additional, Chang, J. H.-C., additional, Confer, M., additional, Chang, A., additional, Goldman, S., additional, Dunn, M., additional, and Hartsell, W., additional

Published
2014
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197. Pediatric posttransplant relapsed/refractory B-precursor acute lymphoblastic leukemia shows durable remission by therapy with the T-cell engaging bispecific antibody blinatumomab

Author

Schlegel, P., primary, Lang, P., additional, Zugmaier, G., additional, Ebinger, M., additional, Kreyenberg, H., additional, Witte, K.-E., additional, Feucht, J., additional, Pfeiffer, M., additional, Teltschik, H.-M., additional, Kyzirakos, C., additional, Feuchtinger, T., additional, and Handgretinger, R., additional

Published
2014
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