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151. Bcor and bcorl1 mutations in pediatric acute myeloid leukemia

Author

Rooij, J.D. (Johan) de, Heuvel-Eibrink, M.M. (Marry) van den, Hermkens, M.C.H. (M. C H), Verboon, P. (Peter), Arentsen-Peters, T.C.J.M. (Susan), Fornerod, M.W.J. (Maarten), Baruchel, A. (André), Stary, J. (Jan), Reinhardt, D. (Dirk), Haas, V. (Valerie) de, Pieters, R. (Rob), Zwaan, C.M. (Michel), Rooij, J.D. (Johan) de, Heuvel-Eibrink, M.M. (Marry) van den, Hermkens, M.C.H. (M. C H), Verboon, P. (Peter), Arentsen-Peters, T.C.J.M. (Susan), Fornerod, M.W.J. (Maarten), Baruchel, A. (André), Stary, J. (Jan), Reinhardt, D. (Dirk), Haas, V. (Valerie) de, Pieters, R. (Rob), and Zwaan, C.M. (Michel)

Published
2015
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152. Transplantation in patients with SCID: mismatched related stem cells or unrelated cord blood?

Author

Fernandes, Jf, Rocha, V, Labopin, M, Neven, B, Moshous, D, Gennery, Ar, Friedrich, W, Porta, F, Diaz de Heredia, C, Wall, D, Bertrand, Y, Veys, P, Slatter, M, Schulz, A, Chan, Kw, Grimley, M, Ayas, M, Gungor, T, Ebell, W, Bonfim, C, Kalwak, K, Taupin, P, Blanche, S, Gaspar, Hb, Landais, P, Fischer, A, Gluckman, E, Cavazzana Calvo, M, Eurocord, Inborn Errors Working Party of European Group for Blood, Marrow Transplantation: Ahmed, A, Auiti, A, Biffi, A, Cant, A, Fasth, A, Gennery, A, Hassan, A, Lankester, A, O'Mera, A, Plabani, A, Rovelli, A, Salmon, A, Scarselli, A, Thrasher, A, Van Royen, A, Villa, A, Wawer, A, Wahadneh, A, Worth, A, Belohradsky, B, Wolska, B, Gaspar, B, Bonfirm, C, Booth, C, Klein, C, Messina, C, Peters, C, Steward, C, Lindemans, C, Schuetz, C, de Heredia Rubio CD, Bensoussan, D, Gleadow, D, Lilic, D, Gambineri, Eleonora, Smith, E, Aerts, F, Caracseghi, F, Roberts, G, Davies, G, Al Mousa, H, Jossanc, H, Ozsahim, H, Hirsch, I, Meyts, I, Tezcan, I, Mueller, I, Andresc, I, Boelens, J, Fernandes, J, Folloni, J, Keuhl, J, Reichenbach, J, Stary, J, Wachowiak, J, Xu Bayford, J, Cunha, Jm, Ehlert, J, Rao, K, Sykora, K, Andais, L, Brown, L, Dal Cortivo, L, Griffith, L, Notarangelo, L, Abinun, M, Albert, M, Bierings, M, Bouchet, M, Cavazzana, M, Hirschfield, M, Cowan, M, Hoenig, M, Loubser, M, Roncarolo, M, Sauer, M, Schneider, M, Verstegen, M, Schroeder, M, Essink, M, Yesilipek, M, Entz Werle, N, Mahlaoui, N, Schlautmann, N, Taylor, N, Vanroyen, N, Walffraat, N, Sanal, O, Amrolia, P, Bordigoni, P, De Coppi, P, Frange, P, Orchard, P, Sedlacek, P, Shaw, P, Stephensky, P, Bacchetta, R, Bredius, R, Formankova, R, Gale, R, Seger, R, Wynn, R, Corbacioglu, S, Ehl, S, Hacein Bey, S, Hambleton, S, Mohsen, S, Mueller, S, Pai, Sy, Espanol, T, Flood, T, Guengoer, T, Bordon, V, Ormoor, V, Pashano, V, Courteille, V, Czogala, W, Qasim, W, Camci, Y, and Nademi, Z.

Subjects
Male, medicine.medical_specialty, Transplantation Conditioning, medicine.medical_treatment, Immunology, Graft vs Host Disease, Kaplan-Meier Estimate, Cord Blood Stem Cell Transplantation, Hematopoietic stem cell transplantation, Biochemistry, Gastroenterology, SCID HSCT, Internal medicine, medicine, Humans, Proportional Hazards Models, Retrospective Studies, Preparative Regimen, Severe combined immunodeficiency, business.industry, Umbilical Cord Blood Transplantation, Incidence, Hematopoietic Stem Cell Transplantation, Infant, Newborn, Infant, Cell Biology, Hematology, medicine.disease, Surgery, Transplantation, Treatment Outcome, Child, Preschool, Histocompatibility, Cord blood, Female, Severe Combined Immunodeficiency, business
Abstract

Pediatric patients with SCID constitute medical emergencies. In the absence of an HLA-identical hematopoietic stem cell (HSC) donor, mismatched related-donor transplantation (MMRDT) or unrelated-donor umbilical cord blood transplantation (UCBT) are valuable treatment options. To help transplantation centers choose the best treatment option, we retrospectively compared outcomes after 175 MMRDTs and 74 UCBTs in patients with SCID or Omenn syndrome. Median follow-up time was 83 months and 58 months for UCBT and MMRDT, respectively. Most UCB recipients received a myeloablative conditioning regimen; most MMRDT recipients did not. UCB recipients presented a higher frequency of complete donor chimerism (P = .04) and faster total lymphocyte count recovery (P = .04) without any statistically significance with the preparative regimen they received. The MMRDT and UCBT groups did not differ in terms of T-cell engraftment, CD4+ and CD3+ cell recoveries, while Ig replacement therapy was discontinued sooner after UCBT (adjusted P = .02). There was a trend toward a greater incidence of grades II-IV acute GVHD (P = .06) and more chronic GVHD (P = .03) after UCBT. The estimated 5-year overall survival rates were 62% ± 4% after MMRDT and 57% ± 6% after UCBT. For children with SCID and no HLA-identical sibling donor, both UCBT and MMRDT represent available HSC sources for transplantation with quite similar outcomes.

Published
2012

153. Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study

Author

Strahm, B., Nollke, P., Zecca, M., Korthof, E.T., Bierings, M., Furlan, I., Sedlacek, P., Chybicka, A., Schmugge, M., Bordon, V., Peters, C., O'Marcaigh, A., Heredia, C.D. de, Bergstraesser, E., Moerloose, B.D., Heuvel-Eibrink, M.M. van den, Stary, J., Trebo, M., Wojcik, D., Niemeyer, C.M., Locatelli, F., EWOG-MDS Study Grp, University of Zurich, Strahm, B, and Pediatrics

Subjects
Oncology, Melphalan, Adult, Male, Cancer Research, medicine.medical_specialty, Cyclophosphamide, Adolescent, medicine.medical_treatment, 2720 Hematology, Graft vs Host Disease, 610 Medicine & health, children, myelodysplastic syndrome, stem cell transplantation, Hematopoietic stem cell transplantation, Disease-Free Survival, Recurrence, hemic and lymphatic diseases, Internal medicine, medicine, Humans, 1306 Cancer Research, Cumulative incidence, Child, Preparative Regimen, Juvenile myelomonocytic leukemia, business.industry, Hematopoietic Stem Cell Transplantation, Infant, Hematology, medicine.disease, Surgery, Leukemia, surgical procedures, operative, 10036 Medical Clinic, Child, Preschool, Myelodysplastic Syndromes, 2730 Oncology, Female, business, Busulfan, medicine.drug
Abstract

We report on the outcome of children with advanced primary myelodysplastic syndrome (MDS) transplanted from an HLA-matched sibling (MSD) or an unrelated donor (UD) following a preparative regimen with busulfan, cyclophosphamide and melphalan. Ninety-seven patients with refractory anemia with excess blasts (RAEB, n=53), RAEB in transformation (RAEB-T, n=29) and myelodysplasia-related acute myeloid leukemia (MDR-AML, n=15) enrolled in the European Working Group of MDS in Childhood (EWOG-MDS) 98 study and given hematopoietic stem cell transplantation (HSCT) were analyzed. Median age at HSCT was 11.1 years (range 1.4-19.0). Thirty-nine children were transplanted from an MSD, whereas 58 were given the allograft from a UD (n=57) or alternative family donor (n=1). Stem cell source was bone marrow (n=69) or peripheral blood (n=28). With a median follow-up of 3.9 years (range 0.1-10.9), the 5-year probability of overall survival is 63%, while the 5-year cumulative incidence of transplantation-related mortality (TRM) and relapse is 21% each. Age at HSCT greater than 12 years, interval between diagnosis and HSCT longer than 4 months, and occurrence of acute or extensive chronic graft-versus-host disease were associated with increased TRM. The risk of relapse increased with more advanced disease. This study indicates that HSCT following a myeloablative preparative regimen offers a high probability of survival for children with advanced MDS.

Published
2011

154. Outcome of relapsed infant acute lymphoblastic leukemia treated on the interfant-99 protocol

Author

Driessen, E M C, primary, de Lorenzo, P, additional, Campbell, M, additional, Felice, M, additional, Ferster, A, additional, Hann, I, additional, Vora, A, additional, Hovi, L, additional, Escherich, G, additional, Li, C K, additional, Mann, G, additional, Leblanc, T, additional, Locatelli, F, additional, Biondi, A, additional, Rubnitz, J, additional, Schrappe, M, additional, Silverman, L, additional, Stary, J, additional, Suppiah, R, additional, Szczepanski, T, additional, Valsecchi, M, additional, and Pieters, R, additional

Published
2015
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157. miR-139-5p controls translation in myeloid leukemia through EIF4G2

Author

Emmrich, S, primary, Engeland, F, additional, El-Khatib, M, additional, Henke, K, additional, Obulkasim, A, additional, Schöning, J, additional, Katsman-Kuipers, J E, additional, Michel Zwaan, C, additional, Pich, A, additional, Stary, J, additional, Baruchel, A, additional, de Haas, V, additional, Reinhardt, D, additional, Fornerod, M, additional, van den Heuvel-Eibrink, M M, additional, and Klusmann, J H, additional

Published
2015
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158. Systematic review of the addition of vincristine plus steroid pulses in maintenance treatment for childhood acute lymphoblastic leukaemia - an individual patient data meta-analysis involving 5659 children

Author

Yetgin, S, Olcay, L, Dibar, E, Conter, V, Masera, G, Valsecchi, MG, Dacou-Voutetakis, C, Henze, I, Loening, L, Schrappe, M, von Stackelberg, A, Zimmermann, M, Attarbaschi, A, Gadner, H, Mann, G, Brandalise, SR, Carroll, WL, Devidas, M, Gaynon, P, Hunger, S, Nachman, J, Janka, G, Stary, J, Gelber, RD, Bierings, M, Kamps, WA, Pieters, R, Otten, J, Suciu, S, Viana, MB, Baruchel, A, Ortega, JJ, Magyarosy, E, Perez, C, Steinberg, D, Tsurusawa, M, Zintl, F, Matsuzaki, A, Eden, TOB, Lilleyman, JS, Richards, S, Steinherz, PG, Kochupillai, V, de Toledo, JS, Appelbaum, FR, Campbell, M, Cheng, C, Pei, D, Pui, CH, Nakazawa, S, Elphinstone, T, Evans, V, Gettins, L, Hicks, C, MacKinnon, L, Morris, P, Wade, R, and Wise, C

Published
2010

159. 48 GATA2-RELATED MYELODYSPLASTIC SYNDROMES (MDS): PREVALENCE, CLINICAL CHARACTERISTICS AND PROGNOSIS

Author

Wlodarski, M., primary, Hirabayashi, S., additional, Pastor, V., additional, Stary, J., additional, Hasle, H., additional, Masetti, R., additional, Dworzak, M., additional, Schmugge, M., additional, van den Heuvel-Eibrink, M., additional, De Moerloose, B., additional, Ussowicz, M., additional, Catala, A., additional, Smith, O., additional, Goehring, G., additional, Schlegelberger, B., additional, Locatelli, F., additional, Makishima, H., additional, Maciejewski, J., additional, Strahm, B., additional, and Niemeyer, C., additional

Published
2015
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160. BCOR and BCORL1 mutations in pediatric acute myeloid leukemia

Author

de Rooij, J. D. E., primary, van den Heuvel-Eibrink, M. M., additional, Hermkens, M. C. H., additional, Verboon, L. J., additional, Arentsen-Peters, S. T. C. J. M., additional, Fornerod, M., additional, Baruchel, A., additional, Stary, J., additional, Reinhardt, D., additional, de Haas, V., additional, Pieters, R., additional, and Zwaan, C. M., additional

Published
2015
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161. Improved outcome for children and adolescent with acute lymphoblastic leukemia in the first decade of the 21st century: A report from the Slovak Republic

Author

KOLENOVA, A., primary, KAISEROVA, E., additional, MAKOHUSOVA,, M., additional, SUBOVA, Z., additional, BUBANSKA, E., additional, ORAVKINOVA, I., additional, SVEC, P., additional, FABRI, O., additional, HUNGER, S. P., additional, SUFLIARSKA, S., additional, HORAKOVA, S., additional, MRAZOVA, V., additional, and STARY, J., additional

Published
2015
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165. Homeobox gene expression in acute myeloid leukemia is linked to typical underlying molecular aberrations

Author

Kramarzova, K.S. (Karolina Skvarova), Fiser, K. (Karel), Mejstříková, E. (Ester), Rejlova, K. (Katerina), Zaliova, M. (Marketa), Fornerod, M.W.J. (Maarten), Drabkin, H.A. (Harry), Heuvel-Eibrink, M.M. (Marry) van den, Stary, J. (Jan), Trka, J. (Jan), Starkova, J. (Julia), Kramarzova, K.S. (Karolina Skvarova), Fiser, K. (Karel), Mejstříková, E. (Ester), Rejlova, K. (Katerina), Zaliova, M. (Marketa), Fornerod, M.W.J. (Maarten), Drabkin, H.A. (Harry), Heuvel-Eibrink, M.M. (Marry) van den, Stary, J. (Jan), Trka, J. (Jan), and Starkova, J. (Julia)

Abstract

__Background:__ Although distinct patterns of homeobox (HOX) gene expression have been described in defined cytogenetic and molecular subsets of patients with acute myeloid leukemia (AML), it is unknown whether these patterns are the direct result of transcriptional alterations or rather represent the differentiation stage of the leukemic cell. __Method:__ To address this question, we used qPCR to analyze mRNA expression of HOXA and HOXB genes in bone marrow (BM) samples of 46 patients with AML and sorted subpopulations of healthy BM cells. These various stages of myeloid differentiation represent matched counterparts of morphological subgroups of AML. To further study the transcriptional alterations of HOX genes in hematopoiesis, we also analyzed gene expression of epigenetic modifiers in the subpopluations of healthy BM and leukemic cells. __Results:__ Unsupervised hierarchical clustering divided the AMLs into five clusters characterized by the presence of prevalent molecular genetic aberrations. Notably, the impact of genotype on HOX gene expression was significantly more pronounced than that of the differentiation stage of the blasts. This driving role of molecular aberrations was best exemplified by the repressive effect of the PML-RARa fusion gene on HOX gene expression, regardless of the presence of the FLT3/ITD mutation. Furthermore, HOX gene expression was positively correlated with mRNA levels of histone demethylases (JMJD3 and UTX) and negatively correlated with gene expression of DNA methyltranferases. No such relationships were observed in subpopulations of healthy BM cells. __Conclusion:__ Our results demonstrate that specific molecular genetic aberrations, rather than differentiation per se, underlie the observed differences in HOX gene expression in AML. Moreover, the observed correlations between epigenetic modifiers and HOX ex pression that are specific to malignant hematopoiesis, suggest their potential causal relationships.

Published
2014
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166. Mapping epigenetic regulator gene mutations in cytogenetically normal pediatric acute myeloid leukemia

Author

Valerio, D.G., Katsman-Kuipers, J.E., Jansen, J.H., Verboon, L.J., Haas, V. de, Stary, J., Baruchel, A., Zimmermann, M., Pieters, R., Reinhardt, D., Heuvel-Eibrink, M.M. van den, Zwaan, C.M., Valerio, D.G., Katsman-Kuipers, J.E., Jansen, J.H., Verboon, L.J., Haas, V. de, Stary, J., Baruchel, A., Zimmermann, M., Pieters, R., Reinhardt, D., Heuvel-Eibrink, M.M. van den, and Zwaan, C.M.

Abstract

Contains fulltext : 137409.pdf (publisher's version ) (Open Access)

Published
2014

167. Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood

Author

Yoshimi, A. (Ayami), Heuvel-Eibrink, M.M. (Marry) van den, Baumann, I. (Irith), Schwarz, S. (Stephan), Simonitsch-Klupp, I. (Ingrid), Paepe, P. (Pascale) de, Campr, V. (Vit), Kerndrup, G. (Gitte), O'Sullivan, M.J. (Maureen), Devito, R. (Rita), Leguit, P. (Piet), Hernandez, M. (Manuel), Dworzak, M.N. (Michael), Moerloose, B. (Barbara) de, Stary, J. (Jan), Hasle, H. (Henrik), Smith, O.P. (Owen Patrick), Zecca, M. (Marco), Catala, F., Schmugge, M., Locatelli, F. (Franco), Führer, M. (Monika), Fischer, A. (Alexandra), Guderle, A. (Anne), Nöllke, P. (Peter), Strahm, B. (Brigitte), Niemeyer, C.M. (Charlotte), Yoshimi, A. (Ayami), Heuvel-Eibrink, M.M. (Marry) van den, Baumann, I. (Irith), Schwarz, S. (Stephan), Simonitsch-Klupp, I. (Ingrid), Paepe, P. (Pascale) de, Campr, V. (Vit), Kerndrup, G. (Gitte), O'Sullivan, M.J. (Maureen), Devito, R. (Rita), Leguit, P. (Piet), Hernandez, M. (Manuel), Dworzak, M.N. (Michael), Moerloose, B. (Barbara) de, Stary, J. (Jan), Hasle, H. (Henrik), Smith, O.P. (Owen Patrick), Zecca, M. (Marco), Catala, F., Schmugge, M., Locatelli, F. (Franco), Führer, M. (Monika), Fischer, A. (Alexandra), Guderle, A. (Anne), Nöllke, P. (Peter), Strahm, B. (Brigitte), and Niemeyer, C.M. (Charlotte)

Abstract

Refractory cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this study, we compared the outcome of immunosuppressive therapy using horse antithymocyte globulin (n=46) with that using rabbit antithymocyte globulin (n=49) in 95 patients with refractory cytopenia of childhood and hypocellular bone marrow. The response rate at 6 months was 74% for horse antithymocyte globulin and 53% for rabbit antithymocyte globulin (P=0.04). The inferior response in the rabbit antithymocyte globulin group resulted in lower 4-year transplantation-free (69% versus 46%; P=0.003) and failure-free (58% versus 48%; P=0.04) survival rates in this group compared with those in the horse antithymocyte globulin group. However, because of successful second-line hematopoietic stem cell transplantation, overall survival was comparable between groups (91% versus 85%; P=ns). The cumulative incidence of relapse (15% versus 9%; P=ns) and clonal evolution (12% versus 4%; P=ns) at 4 years was comparable between groups. Our results suggest that the outcome of immunosuppressive therapy with rabbit antithymocyte globulin is inferior to that of horse antithymocyte globulin. Although immunosuppressive therapy is an effective therapy in selected patients with refractory cytopenia of childhood, the long-term risk of relapse or clonal evolution remains.

Published
2014
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168. Mapping epigenetic regulator gene mutations in cytogenetically normal pediatric acute myeloid leukemia

Author

Valerio, D.G. (Daria), Katsman-Kuipers, J.E. (Jenny), Jansen, J.H. (Joop), Verboon, P. (Peter), Haas, V. (Valerie) de, Stary, J. (Jan), Baruchel, A. (André), Zimmermann, M. (Martin), Pieters, R. (Rob), Reinhardt, D. (Dirk), Heuvel-Eibrink, M.M. (Marry) van den, Zwaan, C.M. (Michel), Valerio, D.G. (Daria), Katsman-Kuipers, J.E. (Jenny), Jansen, J.H. (Joop), Verboon, P. (Peter), Haas, V. (Valerie) de, Stary, J. (Jan), Baruchel, A. (André), Zimmermann, M. (Martin), Pieters, R. (Rob), Reinhardt, D. (Dirk), Heuvel-Eibrink, M.M. (Marry) van den, and Zwaan, C.M. (Michel)

Published
2014
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169. Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood

Author

Yoshimi, A, Van den Heuvel - Eibrink, Marry, Baumann, I (Irith), Schwarz, S, Simonitsch-Klupp, I, de Paepe, P, Campr, V, Kerndrup, GB, O'Sullivan, M, Devito, R, Leguit, R, Hernandez, M, Dworzak, M, de Moerloose, B, Stary, J, Hasle, H, Smith, OP, Zecca, M, Catala, A, Schmugge, M, Locatelli, F (Franco), Fuhrer, M, Fischer, A, Guderle, A, Nollke, P, Strahm, B, Niemeyer, CM, Yoshimi, A, Van den Heuvel - Eibrink, Marry, Baumann, I (Irith), Schwarz, S, Simonitsch-Klupp, I, de Paepe, P, Campr, V, Kerndrup, GB, O'Sullivan, M, Devito, R, Leguit, R, Hernandez, M, Dworzak, M, de Moerloose, B, Stary, J, Hasle, H, Smith, OP, Zecca, M, Catala, A, Schmugge, M, Locatelli, F (Franco), Fuhrer, M, Fischer, A, Guderle, A, Nollke, P, Strahm, B, and Niemeyer, CM

Published
2014

170. Criteria for evaluating response and outcome in clinical trials for children with juvenile myelomonocytic leukemia

Author

Niemeyer, C. M., primary, Loh, M. L., additional, Cseh, A., additional, Cooper, T., additional, Dvorak, C. C., additional, Chan, R., additional, Xicoy, B., additional, Germing, U., additional, Kojima, S., additional, Manabe, A., additional, Dworzak, M., additional, De Moerloose, B., additional, Stary, J., additional, Smith, O. P., additional, Masetti, R., additional, Catala, A., additional, Bergstraesser, E., additional, Ussowicz, M., additional, Fabri, O., additional, Baruchel, A., additional, Cave, H., additional, Zwaan, M., additional, Locatelli, F., additional, Hasle, H., additional, van den Heuvel-Eibrink, M. M., additional, Flotho, C., additional, and Yoshimi, A., additional

Published
2014
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174. Identification of novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia

Author

Balgobind, BV, Raimondi, SC, Harbott, J, Zimmermann, M, Alonzo, TA, Auvrignon, A, Beverloo, HB, Chang, M, Creutzig, U, Dworzak, MN, Forestier, E, Gibson, B, Hasle, Henrik, Harrison, CJ, Heerema, NA, Kaspers, GJ, Leszl, A, Litvinko, N, Nigro, LL, Morimoto, A, Perot, C, Pieters, R, Reinhardt, D, Rubnitz, JE, Smith, FO, Stary, J, Stasevich, I, Strehl, S, Taga, T, Tomizawa, D, Webb, D, Zemanova, Z, Zwaan, CM, and van den Heuvel-Eibrink, MM

Published
2009

178. Prognosis of pediatric patients transplanted for Ph+ chronic myeloid leukemia in the period from 1989 to 2006 in the Czech Republic

Author

Krol, L., Formankova, R., Keslova, P., Vavra, V., Zemanova, Z., Kyra Michalova, Dobrovolna, M., Moravcova, J., Kobylka, P., Ivaskova, E., Navratilova, J., Stary, J., and Sedlacek, P.

Subjects
Male, Time Factors, Adolescent, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease, Prognosis, Piperazines, Pyrimidines, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Benzamides, Imatinib Mesylate, Humans, Female, Child
Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by clonal proliferation of primitive hematopoietic stem cell. The median age at diagnosis is 55 to 60 years with less than 10% of patients younger 20 years. Incidence of CML in children in the Czech Republic is 0.106 cases/100 thousands per year. Here we report outcome of 38 pediatric patients (median age 12.5 years; range 1.8 - 17.3) with Ph-positive CML diagnosed between years 1989 to 2006. Primarily chronic phase of the disease was diagnosed in 32 (84%) patients. 32 (84.2%) patients underwent hematopoietic stem cell transplantation (HSCT) with the median age at transplantation of 14.9 years (range 6.9 - 20.5 years). Out of transplanted patients 16 (50%) obtained graft from unrelated donor, 13 (41%) from matched sibling donor, 2 from haploidentical family donor and autologous transplantation has been performed in one case. 6 patients were not transplanted, 4 of them died (median 1.2 years from diagnosis), 2 are alive 0.6 and 17.8 years from the diagnosis. Overall survival (OS) in 25 patients after HSCT at our department during the whole period is 66.7% with 15/16 being in stable continuous molecular-genetic remission (94%). During the period of time results of transplantations have been significantly improved (p=0.0071). OS after HSCT until year 1997 is 25% while from year 1998 until now is 87.5%. All centers OS of patients after HSCT is 71%. Results of HSCT in children with CML obtained from the year 1998 at our center are fully comparable with results achieved in large and experienced centers. HSCT remains the only proven and effective method for the treatment of CML. Clinical studies assessing the role of tyrosine kinase inhibitors in children instead of early HSCT should be planned carefully in order to avoid sub-optimal outcomes.

Published
2008

183. Second allogeneic hematopoietic stem cell transplantation (HSCT) results in outcome similar to that of first HSCT for patients with juvenile myelomonocytic leukemia [4]

Author

Yoshimi, A., Mohamed, M., Bierings, M., Urban, C., Korthof, E., Zecca, M., Sykora, K. -W., Duffner, U., Trebo, M., Matthes-Martin, S., Sedlacek, P., Klingebiel, T., Lang, P., Fuhrer, M., Claviez, A., Wossmann, W., Pession, A., Arvidson, J., O'Marcaigh, A. S., van den Heuvel-Eibrink, M. M., Stary, J., Hasle, H., Nollke, P., Locatelli, F., and Niemeyer, C. M.

Published
2007

197. Sensitivity but not specificity of minimal residual disease by 4-color flow cytometry depends on the time point during the treatment of childhood B lineage ALL

Author

Mejstrikova, Ester, Fronkova, E, Pospisilova, K, Batinić, Drago, Dubravčić, Klara, Luria, D, Izraeli, S, Stark, B, Kappelmayer, J, Kiss, F, Ng, M, Leung, Y, Cheng, AS, Kalina, T, Vaskova, M, Stary, J, and Hrusak, O.

Subjects
4-color flow cytometry, MRD, ALL
Abstract

Several studies showed a good correlation between minimal residual disease (MRD) obtained by flow cytometry (FC) and by PCR (Ig/TCR rearrangements). However, before FC is widely applied for therapeutic decisions we need exact, objective and standardized criteria. Therefore, we pre-defined B-lineage cell subsets using 4- and 3-color FC and we established background levels for each subset in pre-defined time-points on therapy. Investigators’ subjective bias was minimized. Values above the background are compared to PCR- based MRD. Patients and methods. Children with ALL were treated by ALL IC BFM2002 protocol. This international flow cytometric trial MiniMini contained 4 laboratories (Croatia 36 patients, Israel 48, Hong Kong 33 and Czech Republic 136). 442 samples were measured simultaneously by PCR and 4color FC. Pre-defined subsets (28 values) were measured in all patients at 5 time points (d0, d8, d15, d33 and week 12). Cut off for positivity and negativity of individual subpopulations were assessed as follows: 1) negative samples by PCR for respective time point were randomly divided into training and testing cohort 2) 98.5 percentile of individual subpopulation in training cohort was selected as a cut off for positivity and negativity. 3) cut off values were tested on testing cohort and PCR positive samples (total 337 samples), sample was considered positive when having at least one value above cut off (when more values were above cut off, highest value was considered as MRD) Results. When all time points were analyzed together, sensitivity of FC MRD was 82% and specificity 88% There are no negative patients at day 8 in bone marrow by FC or by PCR. 5 samples at day 15 were positive by PCR (

Published
2006

198. Acute megakaryoblastic leukemia in children and adolescents, excluding Down's syndrome: improved outcome with intensified induction treatment

Author

André Schrauder, W.-D. Ludwig, Dirk Reinhardt, Stary J, Claudia Langebrake, Martin Zimmermann, S Diekamp, Michael Dworzak, U Creutzig, Gudrun Fleischhack, Jochen Harbott, and J. Ritter

Subjects
Male, Cancer Research, Pediatrics, medicine.medical_specialty, Adolescent, Treatment outcome, MEDLINE, Acute megakaryoblastic leukemia, Leukemia, Megakaryoblastic, Acute, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Child, Survival analysis, INDUCTION TREATMENT, Etoposide, Retrospective Studies, Clinical Trials as Topic, S syndrome, business.industry, Remission Induction, Cytarabine, Infant, Retrospective cohort study, Hematology, medicine.disease, Survival Analysis, Leukemia, Treatment Outcome, Oncology, Child, Preschool, Female, business, Idarubicin
Abstract

Acute megakaryoblastic leukemia in children and adolescents, excluding Down's syndrome: improved outcome with intensified induction treatment

Published
2005

200. 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

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