Kooperativer Bibliotheksverbund

In: Blood, American Society of Hematology, Vol. 122, No. 9 ( 2013-08-29), p. 1576-1582

Abstract: In AML with bialleleic CEBPA-mut relapse-free survival was improved by allogeneic and autologous hematopoietic stem cell transplantation. In relapsed patients second complete remission rate was high and survival was favorable after an allogeneic transplantation.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2013-05-503847

Language: English

Publisher: American Society of Hematology

Publication Date: 2013

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 449-449

Abstract: Background: Internal tandem duplications (ITD) in the receptor tyrosine kinase FLT3 occur in roughly 25% of younger adult patients (pts) with acute myeloid leukemia (AML). The multi-targeted kinase inhibitor midostaurin combined with intensive chemotherapy has shown activity against AML with FLT3 mutations. However, toxicity and potential drug-drug interactions with strong CYP3A4 inhibitors such as posaconazole may necessitate dose reduction. Aims: To evaluate the impact of age and midostaurin dose-adaptation after intensive induction chemotherapy on response and outcome in AML with FLT3-ITD within the AMLSG 16-10 trial (NCT01477606). Methods: The study included adult pts (age 18-70 years (yrs)) with newly diagnosed FLT3-ITD positive AML enrolled in the ongoing single-arm phase-II AMLSG 16-10 trial. Pts with acute promyelocytic leukemia were not eligible. The presence of FLT3-ITD was analyzed within our diagnostic study AMLSG-BiO (NCT01252485) by Genescan-based DNA fragment-length analysis. Induction therapy consisted of daunorubicin (60 mg/m², d1-3) and cytarabine (200 mg/m², continuously, d1-7); midostaurin 50 mg bid was applied from day 8 until 48h before start of the next treatment cycle. A second cycle was allowed in case of partial remission (PR). For consolidation therapy, pts proceeded to allogeneic hematopoietic-cell transplantation (HCT) as first priority; if alloHCT was not feasible, pts received three cycles of age-adapted high-dose cytarabine (HDAC) in combination with midostaurin starting on day 6. In all pts one-year maintenance therapy with midostaurin was intended. The first patient entered the study in June 2012 and in April 2014, after recruitment of n=147 pts, the study was amended including a sample size increase to 284 pts and a dose reduction to 12.5% of the initial dose of midostaurin in case of co-medication with strong CYP3A4 inhibitors (e.g. posaconazole). This report focuses on age and the comparison between the first (n=147) and the second cohort (n=137) of the study in terms midostaurin dose-adaptation. Results: Patient characteristics were as follows: median age 54 yrs (range, 18-70; younger, 68% 〈 60 yrs; older, 32% ≥ 60 yrs); median white cell count 44.7G/l (range 1.1-1543 G/l); karyotype, n=161 normal, n=16 high-risk according to ELN recommendations; mutated NPM1 n=174 (59%). Data on response to first induction therapy were available in 277 pts; complete remission (CR) including CR with incomplete hematological recovery (CRi) 60%, PR 20%, refractory disease (RD) 15%, and death 5%. A second induction cycle was given in 54 pts. Overall response (CR/CRi) after induction therapy was 76% (76%, younger; 76%, older) and death 6% (4%, younger; 10% older). The dose of midostaurin during first induction therapy was reduced in 53% and 71% of patients in cohort-1 and cohort-2, respectively. Reasons for dose reduction were in 58% and 49% toxicity, and in 9% and 23% co-medication in cohort-1 and cohort-2, respectively. No difference in response to induction therapy was noted between cohorts (p=0.81). Median follow-up was 18 months. Overall 146 pts received an alloHCT, 128 in first CR (n=94 younger, n=34 older; n=92 from a matched unrelated and n=36 from a matched related donor). In pts receiving an alloHCT within the protocol in median two chemotherapy cycles were applied before transplant (range 1-4). The cumulative incidence of relapse (CIR) and death after transplant were 13% (SE 3.2%) and 16% (SE 3.5%) without differences (p=0.97, p=0.41, respectively) between younger and older patients. So far maintenance therapy was started in 86 pts, 61 pts after alloHCT and 25 pts after HDAC. Fifty-five adverse events 3°/4° were reported being attributed to midostaurin; cytopenias after alloHCT were the most frequent (29%). CIR in patients starting maintenance therapy was 20% one year after start of maintenance without difference between alloHCT and HiDAC (p=0.99). In addition, no difference in CIR was identified in patients after consolidation with alloHCT or HDAC according to dose reduction of midostaurin during first induction therapy (p=0.43, p=0.98, respectively). Median overall survival was 25 months (younger, 26 months; older 23 months; p=0.15). Conclusions: The addition of midostaurin to intensive induction therapy and as maintenance after alloHCT or HDAC is feasible and effective without an impact of age and dose adaptation on outcome. Disclosures Schlenk: Amgen: Research Funding; Pfizer: Honoraria, Research Funding. Fiedler:GSO: Other: Travel; Pfizer: Research Funding; Kolltan: Research Funding; Amgen: Consultancy, Other: Travel, Patents & Royalties, Research Funding; Gilead: Other: Travel; Ariad/Incyte: Consultancy; Novartis: Consultancy; Teva: Other: Travel. Lübbert:Celgene: Other: Travel Funding; Janssen-Cilag: Other: Travel Funding, Research Funding; Ratiopharm: Other: Study drug valproic acid. Greil:Janssen-Cilag: Honoraria; Genentech: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; Merck: Honoraria; AstraZeneca: Honoraria; Boehringer-Ingelheim: Honoraria; GSK: Research Funding; Ratiopharm: Research Funding; Cephalon: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; Bristol-Myers-Squibb: Consultancy, Honoraria; Pfizer: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Sanofi Aventis: Honoraria; Eisai: Honoraria; Amgen: Honoraria, Research Funding. Greiner:BMS: Research Funding. Paschka:ASTEX Pharmaceuticals: Consultancy; Novartis: Consultancy; Medupdate GmbH: Honoraria; Bristol-Myers Squibb: Honoraria; Pfizer Pharma GmbH: Honoraria; Celgene: Honoraria. Heuser:Bayer Pharma AG: Research Funding; Karyopharm Therapeutics Inc: Research Funding; Novartis: Consultancy, Research Funding; Celgene: Honoraria; Pfizer: Research Funding; BerGenBio: Research Funding; Tetralogic: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.449.449

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

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In: Annals of Hematology, Springer Science and Business Media LLC, Vol. 95, No. 12 ( 2016-12), p. 1931-1942

Type of Medium: Online Resource

ISSN: 0939-5555 , 1432-0584

URL: Article

DOI: 10.1007/s00277-016-2810-z

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2016

detail.hit.zdb_id: 1458429-3

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 8569-8569

Abstract: 8569 Background: Vitamin D deficiency was shown to be is associated with a worse outcome in patients with non-Hodgkin's lymphoma (Drake et al., 2010) To study whether this observation could be confirmed in patients with aggressive B-cell lymphomas treated uniformly within a prospective trial, we analyzed 25-OH vitamin D serum levels in patients treated within the RICOVER-60 trial of the DSHNHL. Methods: 25-OH Vitamin D serum levels were determined with a commercial chemoluminescence immunoassay in the serum from elderly patients of the RICOVER-60 trial which compared 6 or 8 cycles of CHOP, both with and without rituximab. Results: 193 of 359 pts (53.8%) had vitamin D deficiency ( 〈 10 ng/ml) and 165/359 patients (46.0%) had vitamin D insufficiency (10-30 ng/ml) according to current definitions. When treated with R-CHOP, patients with vitamin D levels ≤8 ng/ml had a 3-year EFS of 59% compared to 79% of patients with vitamin D serum levels 〉 8 ng/ml; the respective figures for 3-year overall survival were 70% and 82%, respectively. In R-CHOP pts these differences were significant in a multivariable analysis adjusting for IPI risk factors with a hazard ratio (HR) of 2.1 (p=0.008) for EFS and a HR of 1.9 (p=0.040) for OS. In pts treated without R effects of vitamin D deficiency were significant only for OS (HR 1.8; p=0.025), but not with respect to EFS (HR 1.2; p=0.388). These results were confirmed in an independent validation set of 63 patients treated within the prospective RICOVER-noRx study. Conclusions: Vitamin D deficiency is a significant risk factor for patients with aggressive B-cell lymphomas treated with R-CHOP. The stronger adverse effect of vitamin D deficiency in patients receiving rituximab suggests that vitamin D deficiency interferes with the R mechanisms of this antibody. A prospective study evaluating the effects of vitamin D substitution on outcome of patients receiving R-CHOP is warranted. Supported by Deutsche Krebshilfe.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/jco.2013.31.15_suppl.8569

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2013

detail.hit.zdb_id: 2005181-5

In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 1819-1819

Abstract: To investigate the impact and underlying mechanisms of vitamin-D-deficiency (VDD) on outcome of elderly (61 to 80 year-old) DLBCL patients. Methods Pretreatment 25-OH-vitamin-D serum levels from 359 patients treated in the prospective multicenter RICOVER-60 trial with 6 or 8 cycles of CHOP-14 with and without 8 cycles rituximab and 63 patients in the RICOVER-noRT study treated with 6xCHOP-14 + 8xR were determined determined by LIASION®, a commercially available chemoluminescent immunoassay. Results RICOVER-60 patients with VDD (defined as serum levels ≤8 ng/m l) and treated with rituximab had a 3-year event-free survival of 59% compared to 79% in patients with 〉 8 ng/ml; 3-year overall survival was 70% and 82%, respectively. These differences were significant in a multivariable analysis adjusting for IPI risk factors with a hazard ratio of 2.1 [p=0.008] for event-free survival and 1.9 [p=0.040] for overall survival. In patients treated without rituximab 3-year EFS was not significantly different in patients with vitamin-D levels ≤8 and 〉 8 ng/ml (HR 1.2; p=0.388). These results were confirmed in an independent validation set of 63 patients treated within the RICOVER-noRT study. Rituximab-mediated cellular toxicity (RMCC) against the CD20+ cell line Daudi as determined by LDH release assay increased significantly (p 〈 0.005) in 5/5 vitamin-D-deficient individuals after vitamin-D substitution and normalization of their vitamin-D levels. Conclusions VDD is a significant risk factor for elderly DLBCL patients treated with rituximab. Our results show that VDD impairs RMCC and that RMCC can be improved by vitamin-D substitution. This together with the differential effect of VDD in patients treated with and without rituximab suggests that vitamin-D substitution might result in a better outcome of these patients when treated with CHOP plus rituximab. Supported by a grant from Deutsche Krebshilfe. Disclosures: No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V122.21.1819.1819

Language: English

Publisher: American Society of Hematology

Publication Date: 2013

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In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3818-3818

Abstract: Background: The ASXL2 (Additional Sex comb-like 2) gene on chromosome 2p23.3 encodes an epigenetic regulator that is thought to act through histone modification and thereby regulating gene transcription in a context-dependent manner. Recently, ASXL2 mutations (ASXL2mut) were found with a high incidence (~23%) in a cohort of 110 pediatric or adult AML patients (pts) with t(8;21)(q22;q22) (Micol et al., Blood 2014). Aim: We assessed the frequency and prognostic impact of ASXL2mut in the context of other clinical and genetic factors in a large clinically well-defined cohort of intensively treated adults with t(8;21) AML. In addition, the stability of ASXL2 mutation status was analysed in a subset of pts at the time of relapse. Methods: Diagnostic samples from 204 adults with t(8;21);RUNX1/RUNX1T1 -positive AML [median age: 49 years, range: 18-82] were analysed for ASXL2mut in exon 11 and 12 using a combination of PCR-based amplification and subsequent direct DNA-sequencing. Paired samples at diagnosis and relapse were evaluated for the ASXL2 mutation status in a subset of 22 pts. Additional mutation analyses were performed for KIT, FLT3 (ITD and TKD), NRAS, and ASXL1 genes. All pts received intensive treatment either within AMLSG trials (n=155) or according to standard chemotherapy regimens. Results: Thirty four ASXL2mut were identified in 33 (16.2%) of the 204 pts. All mutations (frame-shifts, n=32; non-sense, n=2) created stop codons leading to premature protein truncation with loss of the terminal PHD domain; 27% of the mutations affected codon T740 in exon 12. At diagnosis, there was no significant difference between pts with ASXL2mut and ASXL2 wildtype (ASXL2wt) with respect to sex, WBC, haemoglobin, platelets, LDH serum levels, and circulating or bone marrow blasts. Of note, ASXL2mut were not associated with increasing age, a finding which is commonly observed for ASXL1 mutations in AML. In terms of secondary chromosome aberrations ASXL2mut were frequently associated with del(9q) (P=.006), whereas they never co-occurred with trisomy 8. There was no significant association between ASXL2mut and all other gene mutations analysed. Analysis for ASXL2 mutation status in 22 paired samples obtained at diagnosis and relapse showed a high stability since the mutation was still present in two pts at relapse whereas none of the remaining 20 ASXL2 wildtype cases acquired ASXL2mut. There was no difference in complete remission (CR) rate after double induction between pts with ASXL2mut (88%) and those with ASXL2wt (92%); the same was true when comparing pts with ASXL1 or ASXL2 mutations (ASXL1/2mut) as one group (93%) versus those with ASXL1/2 wildtype. Neither ASXL2mut nor ASXL1/2mut did impact the endpoints event-free-survival, cumulative incidence of relapse, relapse-free and overall survival. Conclusions: Beside KIT and NRAS, ASXL2 is among the most frequently mutated genes in t(8;21) AML. ASXL2mut did not impact achievement of CR or any survival endpoint. Nevertheless, the high incidence (16.2%) of ASXL2mut in t(8;21) AML and the exclusivity to this subgroup of core-binding factor AML implies a peculiar role of ASXL2 in the leukemogenesis of t(8;21) AML providing a basis for further studies. Disclosures Horst: MSD: Research Funding; Pfizer: Research Funding; Amgen: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Boehringer Ingleheim: Research Funding. Schlenk:Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim: Honoraria; Arog: Honoraria, Research Funding; Teva: Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.3818.3818

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

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In: Blood, American Society of Hematology, Vol. 119, No. 2 ( 2012-01-12), p. 551-558

Abstract: We aimed to determine the prognostic impact of monosomal karyotype (MK) in acute myeloid leukemia (AML) in the context of the current World Health Organization (WHO) classification and to evaluate the outcome of MK+ patients after allogeneic HSCT. Of 1058 patients with abnormal cytogenetics, 319 (30%) were MK MK+. MK+ patients were significantly older (P = .0001), had lower white blood counts (P = .0006), and lower percentages of BM blasts (P = .0004); MK was associated with the presence of −5/5q−, −7, 7q−, abnl(12p), abnl(17p), −18/18q−, −20/20q−, inv(3)/t(3;3), complex karyotype (CK), and myelodysplasia (MDS)–related cytogenetic abnormalities (P 〈 .0001, each); and NPM1 mutations (P 〈 .0001), FLT3 internal tandem duplications (P 〈 .0001), and tyrosine kinase domain mutations (P = .02) were less frequent in MK+. Response to induction therapy and overall survival in MK+ patients were dismal with a complete remission rate of 32.5% and a 4-year survival of 9%. MK retained its prognostic impact in AML with CK, AML with MDS-related cytogenetic abnormalities, and in a revised definition (MK-R) excluding cases with recurrent genetic abnormalities according to WHO classification and those with derivative chromosomes not leading to true monosomies. In younger patients, allogeneic HSCT from matched related and unrelated donors resulted in a limited improvement of overall survival.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2011-07-367508

Language: English

Publisher: American Society of Hematology

Publication Date: 2012

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In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 1332-1332

Abstract: Based on their association with certain biological and clinical features as well as their prognostic significance, mutations in the CCAAT/enhancer-binding protein-alpha (CEBPA) gene have been included as a provisional entity into the 2008 World Health Organization (WHO) classification of myeloid neoplasms. CEBPA mutations (CEBPAmut) are mainly found in acute myeloid leukemia (AML) with normal cytogenetics, and approximately 60% of the mutated patients (pts) carry biallelic mutations. Several studies showed that in particular pts with double mutant CEBPA (CEBPAdm) have a favorable outcome compared to all others. Recently, mutations in the transcription factor GATA2 were identified as genetic lesions potentially cooperating with CEBPAdm. Both, CEBPA and GATA2 are involved in the control of proliferation and differentiation of myeloid progenitors, and mutations in both genes are discussed as pre-disposing events in myeloid leukemia. Based on functional studies there is an important interplay between the two genes, e.g. through the formation of direct protein complexes. Finally, preliminary data suggest that the genotype CEBPAdm/GATA2 mutated (GATA2mut) is associated with a favorable outcome in AML pts. Aims To evaluate the frequency and the clinical impact of GATA2mut within a large cohort of CEBPAmut AML pts and to further analyze the CEBPAmut/GATA2mutgenotype within the context of other genetic alterations. Methods In total 202 AML pts (age 18 to 78 years) with CEBPA single mutations (n=89) or CEBPAdm (n=113) were analyzed for the presence of GATA2mut. All pts were enrolled on one of 6 AMLSG treatment trials applying intensive therapy [AMLHD93 n=15; AMLHD98A (NCT00146120) n=53; AMLHD98B n=13; AMLSG 07-04 (NCT00151242) n=74; AMLSG 06-04 (NCT00151255) n=25 and AMLSG 12-09 (NCT01180322) n=22]. GATA2 mutation screening was performed using a DNA-based PCR-assay covering exons 2 to 6 followed by Sanger sequencing. Results GATA2 mut were restricted to the cytogenetic intermediate-risk group; in total we detected 42 GATA2mut in 40 of the 202 pts (20.7%); 36 pts had CEBPAdm (36/113, 31.8%), 4 were CEBPA single mutated (4/89, 4.4%). All mutations were heterozygous, with 2 pts having two mutations (in exon 4 and 5, respectively). 31 (73.8%) of the 42 mutations were located in zinc-finger 1 (ZF1, exon 4) and 11 (26.1%) in ZF2 (exon 5). GATA2 sequence alterations included 39 missense and 3 frameshift mutations. The median follow-up of the 202 pts was 64.2 months (95%-CI: 60.1 – 75.1). First, we evaluated the clinical impact of GATA2mut in the whole cohort. Here, we found no differences in overall (OS), event-free (EFS), and relapse-free (RFS) survival as well as for the cumulative incidence of relapse (CIR) between GATA2mut and GATA2 wildtype pts. Next, the effects of GATA2mut in CEBPAdm pts (n=113) were analyzed without seeing any differences for the clinical endpoints OS, EFS, RFS and CIR. The same was also true when we investigated the impact of GATA2mut with respect to their location in the ZF domains; there were no differences between pts with ZF1 (n=29) and ZF2 (n=9) mutations, respectively. Finally, we evaluated the possible relevance of GATA2mut in the subgroup of CEBPAdm pts 〈 60 years with intermediate-risk cytogenetics (n=94); but again GATA2mut did not impact the endpoints OS, EFS, RFS and CIR. In contrast to recently published data, we also detected GATA2mut in a small number of pts with CEBPA single mutations (n=4); however the low pt number did not allow a meaningful analysis. In addition, in our study GATA2mut occurred in rare cases with NPM1mut, FLT3-ITD or FLT3-TKD mutations. Conclusions In our study on a large cohort of CEBPA mutated AML pts we could confirm the high coincidence of GATA2 mutations, in particular in the subgroup of pts with CEBPA double mutations. However, GATA2 mutations had no impact on clinical outcome neither in the whole cohort nor in distinct pt subgroups. Disclosures: Schlegelberger: Celgene: Consultancy. Germing:Celgene: Honoraria, Research Funding. Kindler:Novartis: Membership on an entity’s Board of Directors or advisory committees. Schlenk:Novartis: Research Funding; Amgen: Research Funding; Chugai: Research Funding; Pfizer: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Ambit: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V122.21.1332.1332

Language: English

Publisher: American Society of Hematology

Publication Date: 2013

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In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 29, No. 19 ( 2011-07-01), p. 2709-2716

Abstract: To evaluate the prognostic value of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) with NPM1 mutation (NPM1 mut ). Patients and Method RNA-based real-time quantitative polymerase chain reaction (RQ-PCR) specific for the detection of six different NPM1 mut types was applied to 1,682 samples (bone marrow, n = 1,272; blood, n = 410) serially obtained from 245 intensively treated younger adult patients who were 16 to 60 years old. Results NPM1 mut transcript levels as a continuous variable were significantly associated with prognosis after each treatment cycle. Achievement of RQ-PCR negativity after double induction therapy identified patients with a low cumulative incidence of relapse (CIR; 6.5% after 4 years) compared with RQ-PCR–positive patients (53.0%; P 〈 .001); this translated into significant differences in overall survival (90% v 51%, respectively; P = .001). After completion of therapy, CIR was 15.7% in RQ-PCR–negative patients compared with 66.5% in RQ-PCR–positive patients (P 〈 .001). Multivariable analyses after double induction and after completion of consolidation therapy revealed higher NPM1 mut transcript levels as a significant factor for a higher risk of relapse and death. Serial post-treatment assessment of MRD allowed early detection of relapse in patients exceeding more than 200 NPM1 mut /10 4 ABL copies. Conclusion We defined clinically relevant time points for NPM1 mut MRD assessment that allow for the identification of patients with AML who are at high risk of relapse. Monitoring of NPM1 mut transcript levels should be incorporated in future clinical trials to guide therapeutic decisions.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2011.35.0371

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2011

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In: Blood, American Society of Hematology, Vol. 117, No. 7 ( 2011-02-17), p. 2137-2145

Abstract: To study the characteristics and clinical impact of therapy-related acute myeloid leukemia (t-AML). 200 patients (7.0%) had t-AML and 2653 de novo AML (93%). Patients with t-AML were older (P 〈 .0001) and they had lower white blood counts (P = .003) compared with de novo AML patients; t-AML patients had abnormal cytogenetics more frequently, with overrepresentation of 11q23 translocations as well as adverse cytogenetics, including complex and monosomal karyotypes, and with underrepresentation of intermediate-risk karyotypes (P 〈 .0001); t-AML patients had NPM1 mutations (P 〈 .0001) and FLT3 internal tandem duplications (P = .0005) less frequently. Younger age at diagnosis of primary malignancy and treatment with intercalating agents as well as topoisomerase II inhibitors were associated with shorter latency periods to the occurrence of t-AML. In multivariable analyses, t-AML was an adverse prognostic factor for death in complete remission but not relapse in younger intensively treated patients (P 〈 .0001 and P = .39, respectively), relapse but not death in complete remission in older, less intensively treated patients (P = .02 and P = .22, respectively) and overall survival in younger intensively treated patients (P = .01). In more intensively treated younger adults, treatment-related toxicity had a major negative impact on outcome, possibly reflecting cumulative toxicity of cancer treatment.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2010-08-301713

Language: English

Publisher: American Society of Hematology

Publication Date: 2011

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