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1. P557: HEMATOLOGIC IMPROVEMENTS WITH IVOSIDENIB + AZACITIDINE COMPARED WITH PLACEBO + AZACITIDINE IN PATIENTS WITH NEWLY-DIAGNOSED ACUTE MYELOID LEUKEMIA

Author

Dohner, H., primary, Montesinos, P., additional, Vives Polo, S., additional, Zarzycka, E., additional, Wang, J., additional, Bertani, G., additional, Heuser, M., additional, Calado, R., additional, Schuh, A., additional, Yeh, S.-P., additional, de la Fuente, A., additional, Cerchione, C., additional, Daigle, S., additional, Hui, J., additional, Pandya, S., additional, Gianolio, D., additional, Recher, C., additional, and de Botton, S., additional

Published
2022
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2. P430: MOLECULAR CHARACTERIZATION OF CLINICAL RESPONSE IN NEWLY-DIAGNOSED ACUTE MYELOID LEUKEMIA PATIENTS TREATED WITH IVOSIDENIB + AZACITIDINE COMPARED TO PLACEBO + AZACITIDINE

Author

de Botton, S., primary, Choe, S., additional, Marchione, D., additional, Montesinos, P., additional, Recher, C., additional, Vives Polo, S., additional, Zarzycka, E., additional, Wang, J., additional, Bertani, G., additional, Heuser, M., additional, Calado, R., additional, Schuh, A., additional, Yeh, S.-P., additional, Hui, J., additional, Pandya, S., additional, Gianolio, D., additional, Daigle, S., additional, DiNardo, C., additional, and Dohner, H., additional

Published
2022
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3. P556: CHANGES IN HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH NEWLY-DIAGNOSED ACUTE MYELOID LEUKEMIA RECEIVING IVOSIDENIB + AZACITIDINE OR PLACEBO + AZACITIDINE

Author

Schuh, A., primary, de Botton, S., additional, Recher, C., additional, Vives Polo, S., additional, Zarzycka, E., additional, Wang, J., additional, Bertani, G., additional, Heuser, M., additional, Calado, R., additional, Yeh, S.-P., additional, Hui, J., additional, Pandya, S., additional, Gianolio, D., additional, Chamberlain, C., additional, Dohner, H., additional, and Montesinos, P., additional

Published
2022
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4. Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial

Author

Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, Lo-Coco F., Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, and Lo-Coco F.

Published
2020

5. Oral azacitidine prolongs survival of patients with AML in remission independently of measurable residual disease status

Author

Roboz, GJ, Ravandi, F, Wei, AH, Dombret, H, Thol, F, Voso, MT, Schuh, AC, Porkka, K, La Torre, I, Skikne, B, Zhong, J, Beach, CL, Risueno, A, Menezes, DL, Ossenkoppele, G, Dohner, H, Roboz, GJ, Ravandi, F, Wei, AH, Dombret, H, Thol, F, Voso, MT, Schuh, AC, Porkka, K, La Torre, I, Skikne, B, Zhong, J, Beach, CL, Risueno, A, Menezes, DL, Ossenkoppele, G, and Dohner, H

Abstract

Measurable residual disease (MRD) in patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy is predictive of early relapse and poor survival. Postremission maintenance therapy that prolongs MRD negativity or converts MRD+ patients to MRD- status may delay or prevent relapse and improve overall survival (OS). In the phase 3 QUAZAR AML-001 trial, oral azacitidine (oral-AZA; formerly CC-486), a hypomethylating agent, significantly prolonged OS and relapse-free survival (RFS) compared with placebo in patients aged ≥55 years with AML in first remission after intensive chemotherapy who were not candidates for hematopoietic stem cell transplantation. In this trial, MRD (≥0.1% leukemic cells in bone marrow) was assessed by multiparameter flow cytometry in serial samples collected at baseline and on day 1 of every 3 cycles. As expected, baseline MRD status was significantly associated with both OS and RFS. Multivariate analyses showed oral-AZA significantly improved OS and RFS vs placebo independent of baseline MRD status. Oral-AZA treatment also extended the duration of MRD negativity by 6 months vs placebo and resulted in a higher rate of conversion from MRD+ at baseline to MRD- during treatment: 37% vs 19%, respectively. In the oral-AZA arm, 24% of MRD responders achieved MRD negativity >6 months after treatment initiation. Although presence or absence of MRD was a strong prognostic indicator of OS and RFS, there were added survival benefits with oral-AZA maintenance therapy compared with placebo, independent of patients' MRD status at baseline. Registered at clinicaltrials.gov as #NCT01757535.

Published
2022

6. A phase 3 study of Enasidenib (ENA) versus conventional care regimens (CCR) in older patients with late-stage mutant-IDH2 (MIDH2) relapsed/refractory acute myeloid leukemia (R/R AML)

Author

CRISTINA PAPAYANNIDIS, Dinardo, C., Montesinos, P., Schuh, A., Vyas, P., Wei, A., Ommen, H., Semochkin, S., Kim, H., Larson, R., Koprivnikar, J., Frankfurt, O., Thol, F., Chromik, J., Byrne, J., Pigneux, A., Thomas, X., Salamero, O., Vidriales, M., Doronin, V., Dohner, H., Fathi, A., Laille, E., Yu, X., Hasan, M., Martin-Regueira, P., and Botton, S.

Published
2021

7. VERY LONG-TERM RESULTS OF ALL-TRANS RETINOIC ACID AND ARSENIC TRIOXIDE IN NON-HIGH RISK ACUTE PROMYELOCYTIC LEUKEMIA: LATEST UPDATE OF THE ITALIAN-GERMAN APL0406 RANDOMIZED TRIAL

Author

Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, Lo-Coco F., Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, and Lo-Coco F.

Published
2019

8. The EHA Research Roadmap: Malignant Myeloid Diseases

Author

Dohner, H., Malcovati, Luca, Ossenkoppele, Gert J., Hochhaus, Andreas, Vannucchi, Alessandro Maria, Bullinger, Lars, Witte, T.J.M. de, Skoda, Radek, Wierzbowska, Agnieszka, Dohner, H., Malcovati, Luca, Ossenkoppele, Gert J., Hochhaus, Andreas, Vannucchi, Alessandro Maria, Bullinger, Lars, Witte, T.J.M. de, Skoda, Radek, and Wierzbowska, Agnieszka

Abstract

Contains fulltext : 237321.pdf (Publisher’s version ) (Open Access)

Published
2021

9. Midostaurin reduces relapse in FLT3-mutant acute myeloid leukemia: the Alliance CALGB 10603/RATIFY trial

Author

Larson, RA, Mandrekar, SJ, Huebner, LJ, Sanford, BL, Laumann, K, Geyer, S, Bloomfield, CD, Thiede, C, Prior, TW, Dohner, K, Marcucci, G, Voso, MT, Klisovic, RB, Galinsky, I, Wei, AH, Sierra, J, Sanz, MA, Brandwein, JM, de Witte, T, Niederwieser, D, Appelbaum, FR, Medeiros, BC, Tallman, MS, Krauter, J, Schlenk, RF, Ganser, A, Serve, H, Ehninger, G, Amadori, S, Gathmann, I, Dohner, H, Stone, RM, Larson, RA, Mandrekar, SJ, Huebner, LJ, Sanford, BL, Laumann, K, Geyer, S, Bloomfield, CD, Thiede, C, Prior, TW, Dohner, K, Marcucci, G, Voso, MT, Klisovic, RB, Galinsky, I, Wei, AH, Sierra, J, Sanz, MA, Brandwein, JM, de Witte, T, Niederwieser, D, Appelbaum, FR, Medeiros, BC, Tallman, MS, Krauter, J, Schlenk, RF, Ganser, A, Serve, H, Ehninger, G, Amadori, S, Gathmann, I, Dohner, H, and Stone, RM

Abstract

The prospective randomized, placebo-controlled CALGB 10603/RATIFY trial (Alliance) demonstrated a statistically significant overall survival benefit from the addition of midostaurin to standard frontline chemotherapy in a genotypically-defined subgroup of 717 patients with FLT3-mutant acute myeloid leukemia (AML). The risk of death was reduced by 22% on the midostaurin-containing arm. In this post hoc analysis, we analyzed the cumulative incidence of relapse (CIR) on this study and also evaluated the impact of 12 4-week cycles of maintenance therapy. CIR analyses treated relapses and AML deaths as events, deaths from other causes as competing risks, and survivors in remission were censored. CIR was improved on the midostaurin arm (HR = 0.71 (95% CI, 0.54-0.93); p = 0.01), both overall and within European LeukemiaNet 2017 risk classification subsets when post-transplant events were considered in the analysis as events. However, when transplantation was considered as a competing risk, there was overall no significant difference between the risks of relapse on the two randomized arms. Patients still in remission after consolidation with high-dose cytarabine entered the maintenance phase, continuing with either midostaurin or placebo. Analyses were inconclusive in quantifying the impact of the maintenance phase on the overall outcome. In summary, midostaurin reduces the CIR.

Published
2021

10. Management of adverse events in patients with acute myeloid leukemia in remission receiving oral azacitidine: experience from the phase 3 randomized QUAZAR AML-001 trial

Author

Ravandi, F, Roboz, GJ, Wei, AH, Dohner, H, Pocock, C, Selleslag, D, Montesinos, P, Sayar, H, Musso, M, Figuera-Alvarez, A, Safah, H, Tse, W, Sohn, SK, Hiwase, D, Chevassut, T, Pierdomenico, F, La Torre, I, Skikne, B, Bailey, R, Zhong, J, Beach, CL, Dombret, H, Ravandi, F, Roboz, GJ, Wei, AH, Dohner, H, Pocock, C, Selleslag, D, Montesinos, P, Sayar, H, Musso, M, Figuera-Alvarez, A, Safah, H, Tse, W, Sohn, SK, Hiwase, D, Chevassut, T, Pierdomenico, F, La Torre, I, Skikne, B, Bailey, R, Zhong, J, Beach, CL, and Dombret, H

Abstract

BACKGROUND: Most older patients with acute myeloid leukemia (AML) who attain morphologic remission with intensive chemotherapy (IC) will eventually relapse and post-relapse prognosis is dismal. In the pivotal QUAZAR AML-001 trial, oral azacitidine maintenance therapy significantly prolonged overall survival by 9.9 months (P < 0.001) and relapse-free survival by 5.3 months (P < 0.001) compared with placebo in patients with AML in first remission after IC who were not candidates for transplant. Currently, the QUAZAR AML-001 trial provides the most comprehensive safety information associated with oral azacitidine maintenance therapy. Reviewed here are common adverse events (AEs) during oral azacitidine treatment in QUAZAR AML-001, and practical recommendations for AE management based on guidance from international cancer consortiums, regulatory authorities, and the authors' clinical experience treating patients in the trial. METHODS: QUAZAR AML-001 is an international, placebo-controlled randomized phase 3 study. Patients aged ≥ 55 years with AML and intermediate- or poor-risk cytogenetics at diagnosis, who had attained first complete remission (CR) or CR with incomplete blood count recovery (CRi) within 4 months before study entry, were randomized 1:1 to receive oral azacitidine 300 mg or placebo once-daily for 14 days in repeated 28-day cycles. Safety was assessed in all patients who received ≥ 1 dose of study drug. RESULTS: A total of 469 patients received oral azacitidine (n = 236) or placebo (n = 233). Median age was 68 years. Patients received a median of 12 (range 1-80) oral azacitidine treatment cycles or 6 (1-73) placebo cycles. Gastrointestinal AEs were common and typically low-grade. The most frequent grade 3-4 AEs during oral azacitidine therapy were hematologic events. AEs infrequently required permanent discontinuation of oral azacitidine (13%), suggesting they were effectively managed with use of concomitant medications and oral azacitidine dosing modifi

Published
2021

11. VERY LONG-TERM RESULTS OF ALL-TRANS RETINOIC ACID AND ARSENIC TRIOXIDE IN NON-HIGH RISK ACUTE PROMYELOCYTIC LEUKEMIA: LATEST UPDATE OF THE ITALIAN-GERMAN APL0406 RANDOMIZED TRIAL

Author

Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, Lo-Coco F., Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, and Lo-Coco, F

Subjects
Hematology
Published
2019

12. Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia

Author

Dohner, K., Thiede, C., Jahn, N., Panina, E., Gambietz, A., Larson, R.A., Prior, T.W., Marcucci, G., Jones, Dan, Krauter, J., Heuser, M., Voso, M.T., Ottone, T., Nomdedeu, J.F., Mandrekar, S.J., Klisovic, R.B., Wei, A.H., Sierra, J., Sanz, Mariano, Brandwein, J.M., Witte, T.J. de, Jansen, J.H., Niederwieser, D., Appelbaum, F.R., Medeiros, B.C., Tallman, M.S., Schlenk, R.F., Ganser, A., Serve, H., Ehninger, G., Amadori, S., Gathmann, I., Benner, A., Pallaud, C., Stone, R.M., Dohner, H., Bloomfield, C.D., Dohner, K., Thiede, C., Jahn, N., Panina, E., Gambietz, A., Larson, R.A., Prior, T.W., Marcucci, G., Jones, Dan, Krauter, J., Heuser, M., Voso, M.T., Ottone, T., Nomdedeu, J.F., Mandrekar, S.J., Klisovic, R.B., Wei, A.H., Sierra, J., Sanz, Mariano, Brandwein, J.M., Witte, T.J. de, Jansen, J.H., Niederwieser, D., Appelbaum, F.R., Medeiros, B.C., Tallman, M.S., Schlenk, R.F., Ganser, A., Serve, H., Ehninger, G., Amadori, S., Gathmann, I., Benner, A., Pallaud, C., Stone, R.M., Dohner, H., and Bloomfield, C.D.

Abstract

Contains fulltext : 218279.pdf (Publisher’s version ) (Open Access), Patients with acute myeloid leukemia (AML) harboring FLT3 internal tandem duplications (ITDs) have poor outcomes, in particular AML with a high (>/=0.5) mutant/wild-type allelic ratio (AR). The 2017 European LeukemiaNet (ELN) recommendations defined 4 distinct FLT3-ITD genotypes based on the ITD AR and the NPM1 mutational status. In this retrospective exploratory study, we investigated the prognostic and predictive impact of the NPM1/FLT3-ITD genotypes categorized according to the 2017 ELN risk groups in patients randomized within the RATIFY trial, which evaluated the addition of midostaurin to standard chemotherapy. The 4 NPM1/FLT3-ITD genotypes differed significantly with regard to clinical and concurrent genetic features. Complete ELN risk categorization could be done in 318 of 549 trial patients with FLT3-ITD AML. Significant factors for response after 1 or 2 induction cycles were ELN risk group and white blood cell (WBC) counts; treatment with midostaurin had no influence. Overall survival (OS) differed significantly among ELN risk groups, with estimated 5-year OS probabilities of 0.63, 0.43, and 0.33 for favorable-, intermediate-, and adverse-risk groups, respectively (P < .001). A multivariate Cox model for OS using allogeneic hematopoietic cell transplantation (HCT) in first complete remission as a time-dependent variable revealed treatment with midostaurin, allogeneic HCT, ELN favorable-risk group, and lower WBC counts as significant favorable factors. In this model, there was a consistent beneficial effect of midostaurin across ELN risk groups.

Published
2020

13. Clinical practice recommendation on hematopoietic stem cell transplantation for acute myeloid leukemia patients with FLT3-internal tandem duplication: a position statement from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Author

Bazarbachi, A, Bug, G, Baron, F, Brissot, E, Ciceri, F, Abou Dalle, I, Dohner, H, Esteve, J, Floisand, Y, Giebel, S, Gilleece, M, Gorin, NC, Jabbour, E, Aljurf, M, Kantarjian, H, Kharfan-Dabaja, M, Labopin, M, Lanza, F, Malard, F, Peric, Z, Prebet, T, Ravandi, F, Ruggeri, A, Sanz, J, Schmid, C, Shouval, R, Spyridonidis, A, Versluis, Jurjen, Vey, N, Savani, BN, Nagler, A, Mohty, M, Bazarbachi, A, Bug, G, Baron, F, Brissot, E, Ciceri, F, Abou Dalle, I, Dohner, H, Esteve, J, Floisand, Y, Giebel, S, Gilleece, M, Gorin, NC, Jabbour, E, Aljurf, M, Kantarjian, H, Kharfan-Dabaja, M, Labopin, M, Lanza, F, Malard, F, Peric, Z, Prebet, T, Ravandi, F, Ruggeri, A, Sanz, J, Schmid, C, Shouval, R, Spyridonidis, A, Versluis, Jurjen, Vey, N, Savani, BN, Nagler, A, and Mohty, M

Published
2020

14. Chromosome aberrations in B-cell chronic lymphocytic leukemia: reassessment based on molecular cytogenetic analysis

Author

Dohner, H., Stilgenbauer, Stephan, Dohner, Konstanze, Bentz, Martin, and Lichter, Peter

Subjects
Science and technology
Abstract

Byline: H. Dohner (1), Stephan Stilgenbauer (1), Konstanze Dohner (1), Martin Bentz (1), Peter Lichter (2) Keywords: Key words B-cell chronic lymphocytic leukemia; Fluorescence in situ hybridization; TP53; 11q22-q23; Comparative genomic hybridization Abstract: In B-cell chronic lymphocytic leukemia (B-CLL) clonal chromosome aberrations are detected in approximately 40--50% of tumors when using conventional chromosome banding analysis. Most studies find trisomy 12 to be the most frequent chromosome aberration, followed by structural aberrations of the long arm of chromosomes 13 and 14. Trisomy 12 and the '14q+' marker are associated with shorter survival times, while the patients with 13q abnormalities have a favorable outcome, similar to those with a normal karyotype. The development of molecular cytogenetic techniques has greatly improved our ability to detect chromosome aberrations in tumor cells. Using fluorescence in situ hybridization, chromosome aberrations can be detected not only in dividing cells but also in interphase nuclei, an approach referred to as interphase cytogenetics. The prevalence of specific aberrations in B-CLL is currently being reassessed by interphase cytogenetics. By far the most frequent abnormality are deletions involving chromosome band 13q14, followed by deletions of the genomic region 11q22.3-q23.1, trisomy 12, deletions of 6q21-q23, and deletions/mutations of the TP53 tumor suppressor gene at 17p13. The evaluation of the true incidence of these aberrations now provides the basis for more accurate correlations with clinical characteristics and outcome. Deletions/mutations of the TP53 gene have been shown to be associated with resistance to treatment and to be an independent marker for poor survival. 11q deletions have been associated with extensive nodal involvement, rapid disease progression, and short survival times. Whether trisomy 12, 13q14, and 6q deletions have a prognostic impact awaits further study. The application of these molecular cytogenetic techniques will also contribute to the identification of the pathogenetically relevant genes that are affected by the chromosome aberrations in B-CLL. Author Affiliation: (1) Medizinische Klinik and Poliklinik V, Universitat Heidelberg, Hospitalstrasse 3, D-69115 Heidelberg, Germany, DE (2) Abteilung 'Organisation komplexer Genome,' Deutsches Krebsforschungszentrum, Heidelberg, Germany, DE Article note: Received: 2 February 1998 / Accepted: 31 March 1998

Published
1999

21. Analysis of a four-level laser system: investigations of the output power characteristics of a He-Ne laser

Author

Dohner, H.-J. and Elsasser, W.

Subjects
Physics -- Research, Optical pumping -- Research, Helium-neon lasers -- Usage, Physics
Abstract

The output power characteristics of a He-Ne laser are studied as an illustration of a four-level gas laser excitation scheme. A linear dependence of the output power on the pumping rate is deduced from measurements of the output power as a function of the excitation current for various cavity lifetimes. These investigations are suitable for a laboratory course for advanced physics students.

Published
1991

23. Endogenous Tumor Suppressor microRNA-193b: Therapeutic and Prognostic Value in Acute Myeloid Leukemia

Author

Bhayadia, R, Krowiorz, K, Haetscher, N, Jammal, R, Emmrich, S, Obulkasim, Askar, Fiedler, J, Schwarzer, A, Rouhi, A, Heuser, M, Wingert, S, Bothur, S, Dohner, K, Matzig, T, Ng, M, Reinhardt, D, Dohner, H, Zwaan, C.M., Van den Heuvel - Eibrink, Marry, Heckl, D, Fornerod, M.W.J., Thum, T, Humphries, RK, Rieger, MA, Kuchenbauer, F, Klusmann, JH, Bhayadia, R, Krowiorz, K, Haetscher, N, Jammal, R, Emmrich, S, Obulkasim, Askar, Fiedler, J, Schwarzer, A, Rouhi, A, Heuser, M, Wingert, S, Bothur, S, Dohner, K, Matzig, T, Ng, M, Reinhardt, D, Dohner, H, Zwaan, C.M., Van den Heuvel - Eibrink, Marry, Heckl, D, Fornerod, M.W.J., Thum, T, Humphries, RK, Rieger, MA, Kuchenbauer, F, and Klusmann, JH

Published
2018

24. Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation

Author

Stone, R.M., Mandrekar, S.J., Sanford, B.L., Laumann, K., Geyer, S., Bloomfield, C.D., Thiede, C., Prior, T.W., Dohner, K., Marcucci, G., Lo-Coco, F., Klisovic, R.B., Wei, A., Sierra, J., Sanz, M.A., Brandwein, J.M., Witte, T.J. de, Niederwieser, D., Appelbaum, F.R., Medeiros, B.C., Tallman, M.S., Krauter, J., Schlenk, R.F., Ganser, A., Serve, H., Ehninger, G., Amadori, S., Larson, R.A., Dohner, H., Stone, R.M., Mandrekar, S.J., Sanford, B.L., Laumann, K., Geyer, S., Bloomfield, C.D., Thiede, C., Prior, T.W., Dohner, K., Marcucci, G., Lo-Coco, F., Klisovic, R.B., Wei, A., Sierra, J., Sanz, M.A., Brandwein, J.M., Witte, T.J. de, Niederwieser, D., Appelbaum, F.R., Medeiros, B.C., Tallman, M.S., Krauter, J., Schlenk, R.F., Ganser, A., Serve, H., Ehninger, G., Amadori, S., Larson, R.A., and Dohner, H.

Abstract

Item does not contain fulltext, BACKGROUND: Patients with acute myeloid leukemia (AML) and a FLT3 mutation have poor outcomes. We conducted a phase 3 trial to determine whether the addition of midostaurin - an oral multitargeted kinase inhibitor that is active in patients with a FLT3 mutation - to standard chemotherapy would prolong overall survival in this population. METHODS: We screened 3277 patients, 18 to 59 years of age, who had newly diagnosed AML for FLT3 mutations. Patients were randomly assigned to receive standard chemotherapy (induction therapy with daunorubicin and cytarabine and consolidation therapy with high-dose cytarabine) plus either midostaurin or placebo; those who were in remission after consolidation therapy entered a maintenance phase in which they received either midostaurin or placebo. Randomization was stratified according to subtype of FLT3 mutation: point mutation in the tyrosine kinase domain (TKD) or internal tandem duplication (ITD) mutation with either a high ratio (>0.7) or a low ratio (0.05 to 0.7) of mutant to wild-type alleles (ITD [high] and ITD [low], respectively). Allogeneic transplantation was allowed. The primary end point was overall survival. RESULTS: A total of 717 patients underwent randomization; 360 were assigned to the midostaurin group, and 357 to the placebo group. The FLT3 subtype was ITD (high) in 214 patients, ITD (low) in 341 patients, and TKD in 162 patients. The treatment groups were well balanced with respect to age, race, FLT3 subtype, cytogenetic risk, and blood counts but not with respect to sex (51.7% in the midostaurin group vs. 59.4% in the placebo group were women, P=0.04). Overall survival was significantly longer in the midostaurin group than in the placebo group (hazard ratio for death, 0.78; one-sided P=0.009), as was event-free survival (hazard ratio for event or death, 0.78; one-sided P=0.002). In both the primary analysis and an analysis in which data for patients who underwent transplantation were censored, the benefit of mi

Published
2017

25. Circular RNAs of the nucleophosmin (NPM1) gene in acute myeloid leukemia

Author

Hirsch, S, Blatte, TJ, Grasedieck, S, Cocciardi, S, Rouhi, A, Jongen - Lavrencic, Mojca, Paschka, P, Kronke, J, Gaidzik, VI, Dohner, H, Schlenk, RF, Kuchenbauer, F, Dohner, K, Dolnik, A, Bullinger, L, Hirsch, S, Blatte, TJ, Grasedieck, S, Cocciardi, S, Rouhi, A, Jongen - Lavrencic, Mojca, Paschka, P, Kronke, J, Gaidzik, VI, Dohner, H, Schlenk, RF, Kuchenbauer, F, Dohner, K, Dolnik, A, and Bullinger, L

Published
2017

26. MEIS2 Is an Oncogenic Partner in AML1-ETO-Positive AML

Author

Vegi, N.M., Klappacher, J., Oswald, F., Mulaw, M.A., Mandoli, A., Thiel, V.N., Bamezai, S., Feder, K., Martens, J.H.A., Rawat, V.P.S., Mandal, T., Quintanilla-Martinez, L., Spiekermann, K., Hiddemann, W., Dohner, K., Dohner, H., Stunnenberg, H.G., Feuring-Buske, M., Buske, C., Vegi, N.M., Klappacher, J., Oswald, F., Mulaw, M.A., Mandoli, A., Thiel, V.N., Bamezai, S., Feder, K., Martens, J.H.A., Rawat, V.P.S., Mandal, T., Quintanilla-Martinez, L., Spiekermann, K., Hiddemann, W., Dohner, K., Dohner, H., Stunnenberg, H.G., Feuring-Buske, M., and Buske, C.

Abstract

Contains fulltext : 159977.pdf (publisher's version ) (Open Access)

Published
2016

27. The European Hematology Association Roadmap for European Hematology Research: a consensus document

Author

Engert, A, Balduini, C, Brand, A, Coiffier, B, Cordonnier, C, Dohner, H, de Wit, TD, Eichinger, S, Fibbe, W, Green, T, de Haas, F, Iolascon, A, Jaffredo, T, Rodeghiero, F, Salles, G, Schuringa, JJ, Andre, M, Andre-Schmutz, I, Bacigalupo, A, Bochud, PY, den Boer, Monique, Bonini, C, Camaschella, C, Cant, A, Cappellini, MD, Cazzola, M, Lo Celso, C, Dimopoulos, M, Douay, L, Dzierzak, Elaine, Einsele, H, Ferreri, A, De Franceschi, L, Gaulard, P, Gottgens, B, Greinacher, A, Gresele, P, Gribben, J, de Haan, G, Hansen, JB, Hochhaus, A, Kadir, R, Kaveri, S, Kouskoff, V, Kuhne, T, Kyrle, P, Ljungman, P, Maschmeyer, G, Mendez-Ferrer, S, Milsom, M, Mummery, C, Ossenkoppele, G, Pecci, A, Peyvandi, F, Philipsen, Sjaak, Reitsma, P, Ribera, JM, Risitano, A, Rivella, S, Ruf, W, Schroeder, T, Scully, M, Socie, G, Staal, F, Stanworth, S, Stauder, R, Stilgenbauer, S, Tamary, H, Theilgaard-Monch, K, Thein, SL, Tilly, H, Trneny, M, Vainchenker, W, Vannucchi, AM, Viscoli, C, Vrielink, H, Zaaijer, H, Zanella, A, Zolla, L, Zwaginga, JJ, Martinez, PA, van den Akker, E, Allard, S, Anagnou, N, Andrau, JC, Angelucci, E, Anstee, D, Aurer, I, Avet-Loiseau, H, Aydinok, Y, Bakchoul, T, Balduini, A, Barcellini, W, Baruch, D, Baruchel, A, Bayry, J, Bento, C, van den Berg, A (Andrea), Bernardi, R, Bianchi, P, Bigas, A, Biondi, A, Bohonek, M, Bonnet, D, Borchmann, P, Borregaard, N, Braekkan, S, ten Brink, M (Mirian), Brodin, E, Bullinger, L, Buske, C, Butzeck, B, Cammenga, J, Campo, E, Carbone, A, Cervantes, F, Cesaro, S, Charbord, P, Claas, F, Cohen, H, Conard, J, Coppo, P, Corrons, JLV, da Costa, L, Davi, F, Delwel, Ruud, Dianzani, I, Domanovic, D, Donnelly, P, Drnovsek, TD, Dreyling, M, Du, MQ, Durand, CML (Charles), Efremov, D, Eleftheriou, A, Elion, J, Emonts, Marieke, Engelhardt, M, Ezine, S, Falkenburg, F, Favier, R, Federico, M, Fenaux, P, Fitzgibbon, J, Flygare, J, Foa, R, Forrester, L, Galacteros, F, Garagiola, I, Gardiner, C, Garraud, O, van Geet, C, Geiger, H, Geissler, J, Germing, U, Ghevaert, C, Girelli, D, Godeau, B, Gokbuget, N, Goldschmidt, H, Goodeve, A, Graf, T, Graziadei, G, Griesshammer, M, Gruel, Y, Guilhot, F, von Gunten, S, Gyssens, I, Halter, J, Harrison, C, Harteveld, C, Hellstrom-Lindberg, E, Hermine, O, Higgs, D, Hillmen, P, Hirsch, H, Hoskin, P, Huls, G, Inati, A, Johnson, P, Kattamis, A, Kiefel, V, Kleanthous, M, Klump, H, Krause, D, Hovinga, JK, Lacaud, G, Lacroix-Desmazes, S, Landman-Parker, J, LeGouill, S, Lenz, G, von Lilienfeld-Toal, M, Lindern, Marieke, Lopez-Guillermo, A, Lopriore, E, Lozano, M, Macintyre, E, Makris, M, Martens, John, Mathas, S, Matzdorff, A, Medvinsky, A, Menendez, P, Migliaccio, AR, Miharada, K, Mikulska, M, Minard, V, Montalban, C, de Montalembert, M, Montserrat, E, Morange, PE, Mountford, J, Muckenthaler, M, Muller-Tidow, C, Mumford, A, Nadel, B, Navarro, JT, el Nemer, W, Noizat-Pirenne, F, O'Mahony, B, Oldenburg, J, Olsson, M, Oostendorp, R, Palumbo, A, Passamonti, F, Patient, R, de Latour, RP, Pflumio, F, Pierelli, L, Piga, A, Pollard, D, Raaijmakers, M, Radford, J, Rambach, R, Rao, AK, Raslova, H, Rebulla, P, Rees, D, Ribrag, V, Rijneveld, Anita, Rinalducci, S, Robak, T, Roberts, I, Rodrigues, C, Rosendaal, F, Rosenwald, A, Rule, S, Russo, R, Saglio, G, Sanchez, M, Scharf, RE, Schlenke, P, Semple, J, Sierra, J, So-Osman, C, Soria, JM, Stamatopoulos, K, Stegmayr, B, Stunnenberg, H, Swinkels, D, Barata, JPT, Taghon, T, Taher, A, Terpos, E, Thachil, J, Tissot, JD, Touw, Ivo, Toye, A, Trappe, R, Traverse-Glehen, A, Unal, S, Vaulont, S, Viprakasit, V, Vitolo, U, van Wijk, R, Wojtowicz, A, Zeerleder, S, Zieger, B, Engert, A, Balduini, C, Brand, A, Coiffier, B, Cordonnier, C, Dohner, H, de Wit, TD, Eichinger, S, Fibbe, W, Green, T, de Haas, F, Iolascon, A, Jaffredo, T, Rodeghiero, F, Salles, G, Schuringa, JJ, Andre, M, Andre-Schmutz, I, Bacigalupo, A, Bochud, PY, den Boer, Monique, Bonini, C, Camaschella, C, Cant, A, Cappellini, MD, Cazzola, M, Lo Celso, C, Dimopoulos, M, Douay, L, Dzierzak, Elaine, Einsele, H, Ferreri, A, De Franceschi, L, Gaulard, P, Gottgens, B, Greinacher, A, Gresele, P, Gribben, J, de Haan, G, Hansen, JB, Hochhaus, A, Kadir, R, Kaveri, S, Kouskoff, V, Kuhne, T, Kyrle, P, Ljungman, P, Maschmeyer, G, Mendez-Ferrer, S, Milsom, M, Mummery, C, Ossenkoppele, G, Pecci, A, Peyvandi, F, Philipsen, Sjaak, Reitsma, P, Ribera, JM, Risitano, A, Rivella, S, Ruf, W, Schroeder, T, Scully, M, Socie, G, Staal, F, Stanworth, S, Stauder, R, Stilgenbauer, S, Tamary, H, Theilgaard-Monch, K, Thein, SL, Tilly, H, Trneny, M, Vainchenker, W, Vannucchi, AM, Viscoli, C, Vrielink, H, Zaaijer, H, Zanella, A, Zolla, L, Zwaginga, JJ, Martinez, PA, van den Akker, E, Allard, S, Anagnou, N, Andrau, JC, Angelucci, E, Anstee, D, Aurer, I, Avet-Loiseau, H, Aydinok, Y, Bakchoul, T, Balduini, A, Barcellini, W, Baruch, D, Baruchel, A, Bayry, J, Bento, C, van den Berg, A (Andrea), Bernardi, R, Bianchi, P, Bigas, A, Biondi, A, Bohonek, M, Bonnet, D, Borchmann, P, Borregaard, N, Braekkan, S, ten Brink, M (Mirian), Brodin, E, Bullinger, L, Buske, C, Butzeck, B, Cammenga, J, Campo, E, Carbone, A, Cervantes, F, Cesaro, S, Charbord, P, Claas, F, Cohen, H, Conard, J, Coppo, P, Corrons, JLV, da Costa, L, Davi, F, Delwel, Ruud, Dianzani, I, Domanovic, D, Donnelly, P, Drnovsek, TD, Dreyling, M, Du, MQ, Durand, CML (Charles), Efremov, D, Eleftheriou, A, Elion, J, Emonts, Marieke, Engelhardt, M, Ezine, S, Falkenburg, F, Favier, R, Federico, M, Fenaux, P, Fitzgibbon, J, Flygare, J, Foa, R, Forrester, L, Galacteros, F, Garagiola, I, Gardiner, C, Garraud, O, van Geet, C, Geiger, H, Geissler, J, Germing, U, Ghevaert, C, Girelli, D, Godeau, B, Gokbuget, N, Goldschmidt, H, Goodeve, A, Graf, T, Graziadei, G, Griesshammer, M, Gruel, Y, Guilhot, F, von Gunten, S, Gyssens, I, Halter, J, Harrison, C, Harteveld, C, Hellstrom-Lindberg, E, Hermine, O, Higgs, D, Hillmen, P, Hirsch, H, Hoskin, P, Huls, G, Inati, A, Johnson, P, Kattamis, A, Kiefel, V, Kleanthous, M, Klump, H, Krause, D, Hovinga, JK, Lacaud, G, Lacroix-Desmazes, S, Landman-Parker, J, LeGouill, S, Lenz, G, von Lilienfeld-Toal, M, Lindern, Marieke, Lopez-Guillermo, A, Lopriore, E, Lozano, M, Macintyre, E, Makris, M, Martens, John, Mathas, S, Matzdorff, A, Medvinsky, A, Menendez, P, Migliaccio, AR, Miharada, K, Mikulska, M, Minard, V, Montalban, C, de Montalembert, M, Montserrat, E, Morange, PE, Mountford, J, Muckenthaler, M, Muller-Tidow, C, Mumford, A, Nadel, B, Navarro, JT, el Nemer, W, Noizat-Pirenne, F, O'Mahony, B, Oldenburg, J, Olsson, M, Oostendorp, R, Palumbo, A, Passamonti, F, Patient, R, de Latour, RP, Pflumio, F, Pierelli, L, Piga, A, Pollard, D, Raaijmakers, M, Radford, J, Rambach, R, Rao, AK, Raslova, H, Rebulla, P, Rees, D, Ribrag, V, Rijneveld, Anita, Rinalducci, S, Robak, T, Roberts, I, Rodrigues, C, Rosendaal, F, Rosenwald, A, Rule, S, Russo, R, Saglio, G, Sanchez, M, Scharf, RE, Schlenke, P, Semple, J, Sierra, J, So-Osman, C, Soria, JM, Stamatopoulos, K, Stegmayr, B, Stunnenberg, H, Swinkels, D, Barata, JPT, Taghon, T, Taher, A, Terpos, E, Thachil, J, Tissot, JD, Touw, Ivo, Toye, A, Trappe, R, Traverse-Glehen, A, Unal, S, Vaulont, S, Viprakasit, V, Vitolo, U, van Wijk, R, Wojtowicz, A, Zeerleder, S, and Zieger, B

Abstract

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.

Published
2016

28. Molecular Cytogenetic Characterization of a Critical Region in Bands 7q35-q36 Commonly Deleted in Malignant Myeloid Disorders

Author

Dohner, K., Brown, J., Hehmann, U., Hetzel, C., Stewart, J., Lowther, G., Scholl, C., Frohling, S., Cuneo, A., Tsui, Lc, Lichter, P., Stephen W. Scherer, and Dohner, H.

Subjects
Genetic Markers, Leukemia, Myeloid, hemic and lymphatic diseases, Immunology, Chromosome Mapping, Humans, Genes, Tumor Suppressor, Cell Biology, Hematology, Biochemistry, Chromosomes, Human, Pair 7, Sequence Deletion
Abstract

Loss of chromosome 7 (−7) or deletion of the long arm (7q−) are recurring chromosome abnormalities in myeloid leukemias. The association of −7/7q− with myeloid leukemia suggests that these regions contain novel tumor suppressor gene(s), whose loss of function contribute to leukemic transformation or tumor progression. Based on chromosome banding analysis, two critical regions have been identified, one in band q22 and another in bands q32-q35. Presently there are no data available on the molecular delineation of the distal critical region. In this study we analyzed bone marrow and blood samples from 13 patients with myeloid leukemia (de novo myelodysplastic syndrome [MDS] , n = 3; de novo acute myeloid leukemia [AML], n = 9; therapy-related (t-) AML, n = 1) which, on chromosome banding analysis, exhibited deletions (n = 12) or in one case a balanced translocation involving bands 7q31-qter using fluorescence in situ hybridization (FISH). As probes we used representative clones from a contig map of yeast artificial chromosome (YAC) clones that spans chromosome bands 7q31.1-qter. In the 12 cases with loss of 7q material, we identified a commonly deleted region of approximately 4 to 5 megabasepairs in size encompassing the distal part of 7q35 and the proximal part of 7q36. Furthermore, the breakpoint of the reciprocal translocation from the patient with t-AML was localized to a 1,300-kb sized YAC clone that maps to the proximal boundary of the commonly deleted region. Interestingly, in this case both homologs of chromosome 7 were affected: one was lost (−7) and the second exhibited the t(7q35). The identification and delineation of translocation and deletion breakpoints provides the first step toward the identification of the gene(s) involved in the pathogenesis of 7q35-q36 aberrations in myeloid disorders.

Published
1998

29. Kruppel-like factor 4 (KLF4) inactivation in chronic lymphocytic leukemia correlates with promoter DNA-methylation and can be reversed by inhibition of NOTCH signaling

Author

Filarsky, K., primary, Garding, A., additional, Becker, N., additional, Wolf, C., additional, Zucknick, M., additional, Claus, R., additional, Weichenhan, D., additional, Plass, C., additional, Dohner, H., additional, Stilgenbauer, S., additional, Lichter, P., additional, and Mertens, D., additional

Published
2016
Full Text
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30. Salvage therapy with high-dose cytarabine and mitoxantrone in combination with all-trans retinoic acid and gemtuzumab ozogamicin in acute myeloid leukemia refractory to first induction therapy

Author

Hutter-Kronke, M.-L., primary, Benner, A., additional, Dohner, K., additional, Krauter, J., additional, Weber, D., additional, Moessner, M., additional, Kohne, C.-H., additional, Horst, H. A., additional, Schmidt-Wolf, I. G. H., additional, Rummel, M., additional, Gotze, K., additional, Koller, E., additional, Petzer, A. L., additional, Salwender, H., additional, Fiedler, W., additional, Kirchen, H., additional, Haase, D., additional, Kremers, S., additional, Theobald, M., additional, Matzdorff, A. C., additional, Ganser, A., additional, Dohner, H., additional, and Schlenk, R. F., additional

Published
2016
Full Text
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31. Obinutuzumab (GA101) plus chlorambucil (Clb) versus rituximab plus Clb in patients with chronic lymphocytic leukaemia (CLL) and comorbidities: Recently published results of the CLL11 trial.

Author

Humphrey K., Dohner H., Asikanius E., Wenger M.K., Goede V., Hallek M., Fischer K., Busch R., Engelke A., Eichhorst B., Wendtner C.M., Chagorova T., Dela Serna J., Dilhuydy M.S., Opat S., Owen C.J., Samoylova O., Kreuzer K.A., Langerak A.W., Ritgen M., Stilgenbauer S., Humphrey K., Dohner H., Asikanius E., Wenger M.K., Goede V., Hallek M., Fischer K., Busch R., Engelke A., Eichhorst B., Wendtner C.M., Chagorova T., Dela Serna J., Dilhuydy M.S., Opat S., Owen C.J., Samoylova O., Kreuzer K.A., Langerak A.W., Ritgen M., and Stilgenbauer S.

Abstract

CLL11 is a phase 3 trial investigating first-line chemoimmunotherapy in CLL patients with comorbidities. Here, we present published results of the head-to-head comparison between GA101 plus Clb (G-Clb) and rituximab plus Clb (R-Clb), and of the G-Clb versus Clb and R-Clb versus Clb comparisons. Treatment-naive CLL patients with a CIRS score >6 and/or a CrCl <70 ml/min were eligible. Patients received Clb alone (0.5 mg/kg po d1, d15 q28 days, 6 cycles), G-Clb (100 mg iv d1, 900 mg d2, 1000 mg d8, d15 of cycle 1, 1000 mg d1 cycles 2-6), or R-Clb (375 mg/m2 iv d1 cycle 1, 500 mg/m2 d1 cycles 2-6). The G-Clb and R-Clb treatment arms were well balanced for baseline characteristics. Median age, CIRS score, and CrCl at baseline were 73 years, 8, and 62 ml/min respectively. Key results of the G-Clb versus R-Clb comparison are shown in the table. The number of patients with MRD negative blood samples at end-of-treatment was significantly higher with G-Clb compared with R-Clb. OS analysis demonstrated a benefit of G-Clb over Clb alone. In conclusion, GA101, a novel, glycoengineered, type II CD20 antibody, in combination with Clb improved outcomes compared with R-Clb in previously untreated CLL patients with comorbidities. (Table presented) .

Published
2015

32. A randomized phase II study on the effects of 5-Aza-2'-deoxycytidine combined with either amsacrine or idarubicin in patients with relapsed acute leukemia: an EORTC Leukemia Cooperative Group phase II study (06893)

Author

Willemze, R., Suciu, S., Archimbaud, E., Muus, P., Stryckmans, P., Louwagie, E.A., Berneman, Z., Tjean, M., Wijermans, P., Dohner, H., Jehn, U., Labar, Boris, Jakšić, Branimir, Dardenne, M., and Zittoun, R.

Subjects
azacytidine, randomized trial, relapsed leukemia, The activity of Idarubicin in relation to multidrug resistance expression and proliferation in subpopulations of hematopoietic progenitor cells in normal and leukemic bone marrow, De activiteit van Idarubicine in relatie tot "multiple drug resistance" (MDR)-expressie en proliferatie in subpopulaties van hematopoietische progenitorcellen in normaal en leukemisch beenme
Abstract

5-Aza-2"-deoxycytidine combined with either amsacrine or idarubicin has been applied in a treatment protocol for patients with a relapse of acute myeloid or lymphocytic leukemia. Sixty-three patients received 5-Aza-2"-deoxycytidine 125 mg/m2 as a 6 h infusion every 12 h for 6 days in combination with either amsacrine 120 mg/m2 as a 1 h infusion on days 6 and 7 (n=30) or idarubicin 12 mg/m2 as a 15 min infusion on days 5, 6 and 7 (n = 33). Twenty-three patients (36.5%) obtained a complete remission (CR) ; eight of 30 patients treated with amsacrine and 15 of 33 treated with idarubicin. Patients with an interval of more than 1 year between initial diagnosis and start of the protocol achieved CR in 51.4%, compared to 15.4% for patients with an interval of less than 1 year. Patients with normal cytogenetics had a higher CR rate (61%) than those with abnormal cytogenetic findings (15.8%). Digestive tract and hematologic toxicity was prolonged, compared to standard induction schedules. Median disease-free survival was approximately 8 months, with only 20% of patients staying in remission for more than 1 year. 5-Aza-2"-deoxycytidine is a good antileukemic agent with considerable toxicity. Current results merit further investigations in previously untreated leukemia.

Published
1997

33. Aml1-eto collaborates with the homeobox genes meis1 and meis2 in inducing aml

Author

Vegi, N.M., Klappacher, J., Oswald, F., Claus, R., Mulaw, M.A., Mandoli, A., Thiel, V., Martens, J.H.A., Rawat, V.P.S., Quintanilla-Fend, L., Plass, C., Dohner, K., Dohner, H., Hiddemann, W., Stunnenberg, H.G., Feuring-Buske, M., and Buske, C.

Subjects
Molecular Biology
Abstract

Item does not contain fulltext

Published
2013

34. The European LeukemiaNet: achievements and perspectives

Author

Hehlmann, R., Grimwade, D., Simonsson, B., Apperley, J., Baccarani, M., Barbui, T., Barosi, G., Bassan, R., Bene, M. C., Berger, U., Buchner, T., Burnett, A., Cross, N. C. P., De Witte, T. J. M., Dohner, H., Dombret, H., Einsele, H., Engelich, G., Foa, Roberto, Fonatsch, C., Gokbuget, N., Gluckman, E., Gratwohl, A., Guilhot, F., Haferlach, C., Haferlach, T., Hallek, M., Hasford, J., Hochhaus, A., Hoelzer, D., Kiladjian, J. J., Labar, B., Ljungman, P., Mansmann, U., Niederwieser, D., Ossenkoppele, G., Ribera, J. M., Rieder, H., Serve, H., Schrotz King, P., Sanz, M. A., Sauele, S., European Leukemianet For The, Hematology, and CCA - Innovative therapy

Subjects
Gerontology, Economic growth, Biomedical Research, Cooperative research, International Cooperation, Chronic lymphocytic leukemia, Medical Oncology, cooperative leukemia research, cure of leukemia, european leukemianet, leukemia management guidelines, transnational and interdisciplinary cooperation on leukemia, Special Article, European LeukemiaNet, hemic and lymphatic diseases, medicine, Humans, Competence (human resources), Societies, Medical, Leukemia, business.industry, Myelodysplastic syndromes, Translational research Immune Regulation [ONCOL 3], Myeloid leukemia, Hematology, medicine.disease, Minimal residual disease, Europe, european leukemia net, perspectives, business
Abstract

Contains fulltext : 96402.pdf (Publisher’s version ) (Open Access) The only way to cure leukemia is by cooperative research. To optimize research, the European LeukemiaNet integrates 105 national leukemia trial groups and networks, 105 interdisciplinary partner groups and about 1,000 leukemia specialists from 175 institutions. They care for tens of thousands of leukemia patients in 33 countries across Europe. Their ultimate goal is to cure leukemia. Since its inception in 2002, the European LeukemiaNet has steadily expanded and has unified leukemia research across Europe. The European LeukemiaNet grew from two major roots: 1) the German Competence Network on Acute and Chronic Leukemias; and 2) the collaboration of European Investigators on Chronic Myeloid Leukemia. The European LeukemiaNet has improved leukemia research and management across Europe. Its concept has led to funding by the European Commission as a network of excellence. Other sources (European Science Foundation; European LeukemiaNet-Foundation) will take over when the support of the European Commission ends.

Published
2011

35. Outcome of advanced chronic lymphocytic leukemia following different first-line and relapse therapies: a meta-analysis of five prospective trials by the German CLL Study Group (GCLLSG)

Author

Cramer, P., primary, Isfort, S., additional, Bahlo, J., additional, Stilgenbauer, S., additional, Dohner, H., additional, Bergmann, M., additional, Stauch, M., additional, Kneba, M., additional, Lange, E., additional, Langerbeins, P., additional, Pflug, N., additional, Kovacs, G., additional, Goede, V., additional, Fink, A.-M., additional, Elter, T., additional, Fischer, K., additional, Wendtner, C.-M., additional, Hallek, M., additional, and Eichhorst, B., additional

Published
2015
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36. ASXL1 mutations in younger adult patients with acute myeloid leukemia: a study by the German-Austrian Acute Myeloid Leukemia Study Group

Author

Paschka, P., primary, Schlenk, R. F., additional, Gaidzik, V. I., additional, Herzig, J. K., additional, Aulitzky, T., additional, Bullinger, L., additional, Spath, D., additional, Teleanu, V., additional, Kundgen, A., additional, Kohne, C.-H., additional, Brossart, P., additional, Held, G., additional, Horst, H.-A., additional, Ringhoffer, M., additional, Gotze, K., additional, Nachbaur, D., additional, Kindler, T., additional, Heuser, M., additional, Thol, F., additional, Ganser, A., additional, Dohner, H., additional, and Dohner, K., additional

Published
2015
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37. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet

Author

Dohner, H, Estey, EH, Amadori, S, Appelbaum, FR, Buchner, T, Burnett, AK, Dombret, H, Fenaux, P, Grimwade, D, Larson, RA, Lo-Coco, F, Naoe, T, Niederwieser, D, Ossenkoppele, GJ, Sanz, MA, Sierra, J, Tallman, MS, Lowenberg, B, and Bloomfield, CD

Abstract

In 2003, an international working group last reported on recommendations for diagnosis, response assessment, and treatment outcomes in acute myeloid leukemia (AML). Since that time, considerable progress has been made in elucidating the molecular pathogenesis of the disease that has resulted in the identification of new diagnostic and prognostic markers. Furthermore, therapies are now being developed that target disease-associated molecular defects. Recent developments prompted an international expert panel to provide updated evidence- and expert opinion-based recommendations for the diagnosis and management of AML, that contain both minimal requirements for general practice as well as standards for clinical trials. A new standardized reporting system for correlation of cytogenetic and molecular genetic data with clinical data is proposed. (Blood. 2010; 115: 453-474)

Published
2010

38. Clinical, molecular, and prognostic significance of WHO type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and various other 3q abnormalities in acute myeloid leukemia: A study of 6,515 cases of AML

Author

Groschel, S., Lugthart, S., Beverloo, B.H., Kayser, S., Valk, P.J., Van Zelderen-Bhola, S.L., Ossenkoppele, G.J., Vellenga, E., van den Berg-de Ruiter, E., Schanz, U., Verhoef, G., Ferrant, A, Kohne, C.H., Pfreundschuh, M., Horst, H.A., Koller, E., von Lilienfeld-Toal, M., Bentz, M., Ganser, A., Schlegelberger, B., Jotterand, M., Krauter, J., Pabst, T., Theobald, M, Schlenk, R.F., Delwel, R., Dohner, K., Lowenberg, B., Dohner, H., Hematology, and CCA - Innovative therapy

Published
2010

39. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions.

Author

Hallek M., Dohner H., Langerak A.W., Ritgen M., Kneba M., Asikanius E., Humphrey K., Wenger M., Goede V., Fischer K., Busch R., Engelke A., Eichhorst B., Wendtner C.M., Chagorova T., De La Serna J., Dilhuydy M.-S., Illmer T., Opat S., Owen C.J., Samoylova O., Kreuzer K.-A., Stilgenbauer S., Hallek M., Dohner H., Langerak A.W., Ritgen M., Kneba M., Asikanius E., Humphrey K., Wenger M., Goede V., Fischer K., Busch R., Engelke A., Eichhorst B., Wendtner C.M., Chagorova T., De La Serna J., Dilhuydy M.-S., Illmer T., Opat S., Owen C.J., Samoylova O., Kreuzer K.-A., and Stilgenbauer S.

Abstract

BACKGROUND: The monoclonal anti-CD20 antibody rituximab, combined with chemotherapeutic agents, has been shown to prolong overall survival in physically fit patients with previously untreated chronic lymphocytic leukemia (CLL) but not in those with coexisting conditions. We investigated the benefit of the type 2, glycoengineered antibody obinutuzumab (also known as GA101) as compared with that of rituximab, each combined with chlorambucil, in patients with previously untreated CLL and coexisting conditions. METHOD(S): We randomly assigned 781 patients with previously untreated CLL and a score higher than 6 on the Cumulative Illness Rating Scale (CIRS) (range, 0 to 56, with higher scores indicating worse health status) or an estimated creatinine clearance of 30 to 69 ml per minute to receive chlorambucil, obinutuzumab plus chlorambucil, or rituximab plus chlorambucil. The primary end point was investigator-assessed progression-free survival. RESULT(S): The patients had a median age of 73 years, creatinine clearance of 62 ml per minute, and CIRS score of 8 at baseline. Treatment with obinutuzumab-chlorambucil or rituximab-chlorambucil, as compared with chlorambucil monotherapy, increased response rates and prolonged progression-free survival (median progression-free survival, 26.7 months with obinutuzumab-chlorambucil vs. 11.1 months with chlorambucil alone; hazard ratio for progression or death, 0.18; 95% confidence interval [CI], 0.13 to 0.24; P<0.001; and 16.3 months with rituximab-chlorambucil vs. 11.1 months with chlorambucil alone; hazard ratio, 0.44; 95% CI, 0.34 to 0.57; P<0.001). Treatment with obinutuzumab-chlorambucil, as compared with chlorambucil alone, prolonged overall survival (hazard ratio for death, 0.41; 95% CI, 0.23 to 0.74; P = 0.002). Treatment with obinutuzumab-chlorambucil, as compared with rituximab-chlorambucil, resulted in prolongation of progression-free survival (hazard ratio, 0.39; 95% CI, 0.31 to 0.49; P<0.001) and higher rates of comple

Published
2014

40. Clinical and functional implications of microRNA mutations in a cohort of 935 patients with myelodysplastic syndromes and acute myeloid leukemia

Author

Thol, F., primary, Scherr, M., additional, Kirchner, A., additional, Shahswar, R., additional, Battmer, K., additional, Kade, S., additional, Chaturvedi, A., additional, Koenecke, C., additional, Stadler, M., additional, Platzbecker, U., additional, Thiede, C., additional, Schroeder, T., additional, Kobbe, G., additional, Bug, G., additional, Ottmann, O., additional, Hofmann, W.-K., additional, Kroger, N., additional, Fiedler, W., additional, Schlenk, R., additional, Dohner, K., additional, Dohner, H., additional, Krauter, J., additional, Eder, M., additional, Ganser, A., additional, and Heuser, M., additional

Published
2014
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41. Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in First Complete Remission Systematic Review and Meta-analysis of Prospective Clinical Trials

Author

Koreth, J, Schlenk, R, Kopecky, KJ, Honda, S, Sierra, J, Djulbegovic, BJ, Wadleigh, M, DeAngelo, DJ, Stone, RM, Sakamaki, H, Appelbaum, FR, Dohner, H, Antin, JH, Soiffer, RJ, and Cutler, C

Abstract

Context The optimal treatment of acute myeloid leukemia (AML) in first complete remission (CR1) is uncertain. Current consensus, based on cytogenetic risk, recommends myeloablative allogeneic stem cell transplantation (SCT) for poor-risk but not for good-risk AML. Allogeneic SCT, autologous transplantation, and consolidation chemotherapy are considered of equivalent benefit for intermediate-risk AML. Objective To quantify relapse-free survival (RFS) and overall survival benefit of allogeneic SCT for AML in CR1 overall and also for good-, intermediate-, and poor-risk AML. Methods Systematic review and meta-analysis of prospective trials evaluating allogeneic SCT vs nonallogeneic SCT therapies for AML in CR1. The search used the combined search terms allogeneic; acut* and leukem*/leukaem*/leucem*/leucaem*/aml; myelo* or nonlympho* in the PubMed, Embase, and Cochrane Registry of Controlled Trials databases in March 2009. The search identified 1712 articles. Study Selection Prospective trials assigning adult patients with AML in CR1 to undergo allogeneic SCT vs nonallogeneic SCT treatment(s) based on donor availability and trials reporting RFS and/or overall survival outcomes on an intention-to-treat, donor vs no-donor basis were identified. Data Extraction Two reviewers independently extracted study characteristics, interventions, and outcomes. Hazard ratios (HRs) with 95% confidence intervals (CIs) were determined. Data Synthesis Overall, 24 trials and 6007 patients were analyzed (5951 patients in RFS analyses and 5606 patients in overall survival analyses); 3638 patients were analyzed by cytogenetic risk (547, 2499, and 592 with good-, intermediate-, and poor-risk AML, respectively). Interstudy heterogeneity was not significant. Fixed-effects meta-analysis was performed. Compared with nonallogeneic SCT, the HR of relapse or death with allogeneic SCT for AML in CR1 was 0.80 (95% CI, 0.74-0.86). Significant RFS benefit of allogeneic SCT was documented for poor- risk (HR, 0.69; 95% CI, 0.57-0.84) and intermediate- risk AML (HR, 0.76; 95% CI, 0.68-0.85) but not for good- risk AML (HR, 1.06; 95% CI, 0.80-1.42). The HR of death with allogeneic SCT for AML in CR1 was 0.90 ( 95% CI, 0.82-0.97). Significant overall survival benefit with allogeneic SCT was documented for poor- risk (HR, 0.73; 95% CI, 0.59-0.90) and intermediate- risk AML (HR, 0.83; 95% CI, 0.74-0.93) but not for good- risk AML (HR, 1.07; 95% CI, 0.83-1.38). Conclusion Compared with nonallogeneic SCT therapies, allogeneic SCT has significant RFS and overall survival benefit for intermediate- and poor- risk AML but not for good- risk AML in first complete remission. JAMA. 2009;301(22):2349-2361 www.jama.com

Published
2009

42. Genome-wide genotyping of acute myeloid leukemia with translocation t(9;11)(p22;q23) reveals novel recurrent genomic alterations

Author

Kuhn, M. W. M., primary, Bullinger, L., additional, Groschel, S., additional, Kronke, J., additional, Edelmann, J., additional, Rucker, F. G., additional, Eiwen, K., additional, Paschka, P., additional, Gaidzik, V. I., additional, Holzmann, K., additional, Schlenk, R. F., additional, Dohner, H., additional, and Dohner, K., additional

Published
2014
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43. Head-to-head comparison of obinutuzumab (GA101) plus chlorambucil (CLB) versus rituximab plus CLB in patients with chronic lymphocytic leukemia (CLL) and co-existing medical conditions (comorbidities): Final stage 2 results of the CLL11 trial.

Author

Humphrey K., Dohner H., Asikanius E., Wenger M.K., Goede V., Fischer K., Busch R., Engelke A., Eichhorst B., Wendtner C.M., Hallek M., Chagorova T., De La Serna J., Dilhuydy M.-S., Opat S., Owen C.J., Samoylova O., Kreuzer K.-A., Langerak A.W., Ritgen M., Stilgenbauer S., Humphrey K., Dohner H., Asikanius E., Wenger M.K., Goede V., Fischer K., Busch R., Engelke A., Eichhorst B., Wendtner C.M., Hallek M., Chagorova T., De La Serna J., Dilhuydy M.-S., Opat S., Owen C.J., Samoylova O., Kreuzer K.-A., Langerak A.W., Ritgen M., and Stilgenbauer S.

Abstract

Introduction CLL11 is a large randomized phase 3 trial investigating first-line chemoimmunotherapy in CLL patients with comorbidities, i.e. patients typically treated in daily practice. Here, we present: (i) The final stage 2 analysis with efficacy and safety results of the head-to-head comparison between GA101 plus Clb (GClb) and rituximab plus Clb (RClb); at the pre-planned interim analysis, the primary endpoint was met early and the results were released by the independent data monitoring board. (ii) An update on the stage I analysis (GClb vs. Clb and RClb vs. Clb comparisons) with longer observation time; the final stage 1 analysis recently showed that GClb or RClb has superior efficacy to chemotherapy with Clb alone. Methods Treatment-naive CLL patients with a Cumulative Illness Rating Scale (CIRS) total score >6 and/or an estimated creatinine clearance (CrCl) <70 mL/min were eligible. Patients received Clb alone (0.5 mg/kg po d1, d15 q28 days, 6 cycles), GClb (100 mg iv d1, 900 mg d2, 1000 mg d8, d15 of cycle 1, 1000 mg d1 cycles 2-6), or RClb (375 mg/m2 iv d1 cycle 1, 500 mg/m2 d1 cycles 2-6). Primary endpoint was investigator-assessed progression-free survival (PFS). Response rates, minimal residual disease (MRD), and overall survival (OS) were key secondary efficacy endpoints. Results Final results of the stage 2 analysis: Median observation time was 19 months. The GClb and RClb treatment arms were well balanced for baseline characteristics. Median age, CIRS score, and CrCl at baseline were 73 years, 8, and 63 mL/min respectively. Key efficacy and safety results are shown in the table. (Table Presented) Updated results of the stage 1 analysis: Median observation time was 23 months. Confirming the primary stage 1 results, GClb or RClb compared with Clb alone was associated with statistically significant and clinically meaningful improvement in PFS (GClb vs. Clb: HR 0.18, CI 0.13-0.24, p<.0001, RClb vs. Clb: HR 0.44, CI 0.34-0.57, p<.0001). The updated median

Published
2013

44. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet

Author

Sanz, MA, Grimwade, D, Tallman, MS, Löwenberg, Bob, Fenaux, P, Estey, EH, Naoe, T, Lengfelder, E, Buchner, T, Dohner, H, Burnett, AK, Lo-Coco, F, Sanz, MA, Grimwade, D, Tallman, MS, Löwenberg, Bob, Fenaux, P, Estey, EH, Naoe, T, Lengfelder, E, Buchner, T, Dohner, H, Burnett, AK, and Lo-Coco, F

Abstract

The introduction of all-trans retinoic acid (ATRA) and, more recently, arsenic trioxide (ATO) into the therapy of acute promyelocytic leukemia (APL) has revolutionized the management and outcome of this disease. Several treatment strategies using these agents, usually in combination with chemotherapy, but also without or with minimal use of cytotoxic agents, have provided excellent therapeutic results. Cure of APL patients, however, is also dependent on peculiar aspects related to the management and supportive measures that are crucial to counteract life-threatening complications associated with the disease biology and molecularly targeted treatment. The European LeukemiaNet recently appointed an international panel of experts to develop evidence-and expert opinion-based guidelines on the diagnosis and management of APL. Together with providing current indications on genetic diagnosis, modern risk-adapted front-line therapy and salvage treatment, the review contains specific recommendations for the identification and management of most important complications such as the bleeding disorder, APL differentiation syndrome, QT prolongation and other ATRA- and ATO-related toxicities, as well as for molecular assessment of response to treatment. Finally, the approach to special situations is also discussed, including management of APL in children, elderly patients, and pregnant women. (Blood. 2009; 113: 1875-1891)

Published
2009

45. A one-mutation mathematical model can explain the age incidence of acute myeloid leukemia with mutated nucleophosmin (NPM1)

Author

Liso, A, Castiglione, F, Cappuccio, A, Stracci, F, Schlenk, RF, Amadori, S, Thiede, C, Schnittger, S, Valk, Peter, Dohner, K, Martelli, MF, Schaich, M, Krauter, J, Ganser, A, Martelli, MP, Bolli, N, Löwenberg, Bob, Haferlach, T, Ehninger, G, Mandelli, F, Dohner, H, Michor, F, Falini, B, Liso, A, Castiglione, F, Cappuccio, A, Stracci, F, Schlenk, RF, Amadori, S, Thiede, C, Schnittger, S, Valk, Peter, Dohner, K, Martelli, MF, Schaich, M, Krauter, J, Ganser, A, Martelli, MP, Bolli, N, Löwenberg, Bob, Haferlach, T, Ehninger, G, Mandelli, F, Dohner, H, Michor, F, and Falini, B

Abstract

Acute myeloid leukemia with mutated NPM1 gene and aberrant cytoplasmic expression of nucleophosmin (NPMc(+) acute myeloid leukemia) shows distinctive biological and clinical features. Experimental evidence of the oncogenic potential of the nucleophosmin mutant is, however, still lacking, and it is unclear whether other genetic lesion(s), e.g. FLT3 internal tandem duplication, cooperate with NPM1 mutations in acute myeloid leukemia development. An analysis of age-specific incidence, together with mathematical modeling of acute myeloid leukemia epidemiology, can help to uncover the number of genetic events needed to cause leukemia. We collected data on age at diagnosis of acute myeloid leukemia patients from five European Centers in Germany, The Netherlands and Italy, and determined the age-specific incidence of AML with mutated NPM1 (a total of 1,444 cases) for each country. Linear regression of the curves representing age-specific rates of diagnosis per year showed similar slopes of about 4 on a double logarithmic scale. We then adapted a previously designed mathematical model of hematopoietic tumorigenesis to analyze the age incidence of acute myeloid leukemia with mutated NPM1 and found that a one-mutation model can explain the incidence curve of this leukemia entity. This model fits with the hypothesis that NPMc(+) acute myeloid leukemia arises from an NPM1 mutation with haploinsufficiency of the wild-type NPM1 allele.

Published
2008

46. Intensive induction is effective in selected octogenarian acute myeloid leukemia patients: prognostic significance of karyotype and selected molecular markers used in the European LeukemiaNet classification

Author

Wetzler, M., primary, Mrozek, K., additional, Kohlschmidt, J., additional, Dombret, H., additional, Dohner, H., additional, Pilorge, S., additional, Krug, U., additional, Carroll, A. J., additional, Larson, R. A., additional, Marcucci, G., additional, Hiddemann, W., additional, Buchner, T., additional, and Bloomfield, C. D., additional

Published
2013
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50. The experience of family carers of older people in the use of support services in Europe : Selected findings from the EUROFAMCARE project [Erfahrungen von pflegenden angehörigen älterer menschen in Europa bei der inanspruchnahme von unterstützungsleistungen

Author

Lamura, G., Mnich, E., Wojszel, B., Nolan, M., Krevers, Barbro, Mestheneos, L., Dohner, H., Lamura, G., Mnich, E., Wojszel, B., Nolan, M., Krevers, Barbro, Mestheneos, L., and Dohner, H.

Abstract

This article presents selected findings of the EUROFAMCARE research project, reporting up-to-date information on the use and accessibility of support services for family carers of older people in six European countries representing different typologies of welfare systems (Germany, Greece, Italy, Poland, Sweden and the UK). Data were collected by means of face-to-face interviews to national samples of about 1000 family carers per country (i.e. 6000 in total), based on a common recruitment and data collection protocol. The reported findings reveal the crossnational usage of different support services - subdivided for comparative reasons in the categories of socio-emotional support, information, respite care, training and assessment services - as well as of available care allowances. The analysis includes the perceived experience of carers in using them, in terms of costs sustained, factors affecting service accessibility - i.e. main obstacles and greatest helps in accessing them - as well as reasons for not using (needed) services or for stopping using (still needed) services. Cross-national differences are relevant, showing a greater availability in Northern European countries, where however higher refusal rates by potential users of available services are recorded, possibly in connection to their lack of flexibility and low customisation. © 2006 Steinkopff-Verlag.

Published
2006
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