Response to Cuneo et al

Moorman, Anthony V.; Martineau, Mary; Harrison, Christine J.

doi:10.1038/sj.leu.2402802

Cited by 8 publications

(13 citation statements)

References 6 publications

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“…For hyperdiploidy, we assessed on SNP arrays trisomies of the chromosomes 3,5,7,9,11,15,17,18,19, and 21. Because it has been shown in childhood acute lymphoblastic leukemia 10 and myeloma 11 that the number of trisomies is important for outcome (hyperdiploidy .50 was associated with a better outcome than hyperdiploidy 47 to 50), we also counted the number of chromosomes on the SNP arrays for each patient and defined hypodiploidy (,46 chromosomes), pseudodiploidy (46 chromosomes), mild hyperdiploidy (47 to 50 chromosomes), and large hyperdiploidy (.50 chromosomes)…”

Section: Methodsmentioning

confidence: 99%

Understanding the role of hyperdiploidy in myeloma prognosis: which trisomies really matter?

Chrétien

Corre

Lauwers‐Cancès

et al. 2015

Blood

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Key Points• In myeloma patients, trisomy 3 improved time to progression and trisomies 3 and/or 5 improved overall survival. • In contrast, trisomy 21 significantly worsened overall survival.The prognosis of multiple myeloma is mainly dependent upon chromosomal changes. The 2 major abnormalities driving poor outcome are del(17p) and t(4;14). However, the outcome of these high-risk patients is not absolutely uniform, with some patients presenting long survival. We hypothesized that these better outcomes might be related to concomitant "good-risk" chromosomal changes exploring hyperdiploidy. We analyzed a large series of 965 myeloma patients, including 168 patients with t(4;14) and 126 patients with del(17p), using high-throughput single-nucleotide polymorphism arrays after plasma cell sorting. As expected, trisomic chromosomes were highly associated. Using the LASSO model, we found that only chromosome 3, when trisomic, was associated with a longer progression-free survival and that 3 trisomies modulated overall survival (OS) in myeloma patients: trisomies 3 and 5 significantly improved OS, whereas trisomy 21 worsened OS. In patients with t(4;14), trisomies 3 and/or 5 seemed to overcome the poor prognosis. For the first time, using a specific modeling approach, we show that not all trisomies display the same prognostic impact. This finding could be important for routine assessment of prognosis in myeloma, and some highrisk patients with a traditional evaluation could in fact be standard-risk patients. (Blood. 2015;126(25):2713-2719

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Section: Methodsmentioning

confidence: 99%

Understanding the role of hyperdiploidy in myeloma prognosis: which trisomies really matter?

Chrétien

Corre

Lauwers‐Cancès

et al. 2015

Blood

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“…17,18 However, the prognostic value of these combinations has not been validated by other protocols. 4,5,13 Few studies have focused on the prognostic impact of structural abnormalities observed in HD.50. The poorer outcome initially reported by Pui et al 19 has not been corroborated by other large series with long follow-ups, 4,5,13 except for 2 reports relying on small series of patients.…”

Section: Introductionmentioning

confidence: 99%

“…4,5,13 Few studies have focused on the prognostic impact of structural abnormalities observed in HD.50. The poorer outcome initially reported by Pui et al 19 has not been corroborated by other large series with long follow-ups, 4,5,13 except for 2 reports relying on small series of patients. 20,21 Given this absence of consensus, the current trials use different criteria for identifying patients with best prognosis.…”

Section: Introductionmentioning

confidence: 99%

“…5 The outcome of HD.50 has improved over years and the overall survival of patients with DI > 1.16 treated with current therapies now ranges around 95% to 96%. [9][10][11][12] Other studies have focused on the favorable prognostic impact of specific trisomies or association of trisomies: 118 for the Medical Research Council group, 4,13 14,110 for the Pediatric Oncology Group, 14 110,117 for the Children's Cancer Group, 15 and 14,110,117 on a meta-analysis of the Children's Cancer Group and Pediatric Oncology Group, 16 leading the Children's Oncology Group group to use 14,110,117 and 14,110 in conjunction with other features for stratifying patients in low risk arms. 17,18 However, the prognostic value of these combinations has not been validated by other protocols.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] In HD.50, the modal number of chromosomes (MNC) ranges from 51 to 66 or 67 chromosomes, peaks at 55 or 56, and the chromosome gains occur nonrandomly: gains of chromosomes X, 4,6,10,14,17,18, and 21 are common within the range MNC 51-54, trisomies of chromosomes 8, 5, 11, 12 appear as of MNC 57-60 in addition to the former series, whereas gains of chromosomes 2, 3, 9, 16, and 22 are observed among the highest MNC 63-67 as evidenced in Heerema's study. [4][5][6] Hyperdiploidies can also be detected by flow cytometry (FCM), which measures the cellular DNA content and allows determination of the DNA index (DI). 7 In HD.50, DIs range from 1.10 to 1.45, and the cutoff 1.16 corresponds to MNC 53 or 54.…”

Section: Introductionmentioning

confidence: 99%

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Hyperdiploidy with 58-66 chromosomes in childhood B-acute lymphoblastic leukemia is highly curable: 58951 CLG-EORTC results

Dastugue

Suciu

Plat³

et al. 2013

Blood

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Key Points• Patients with 58-66 chromosomes have 99% event-free survival and 100% overall survival in the 58951 EORTC-CLG study.• The higher the ploidy, the better the prognosis in the 58951 EORTC-CLG study.The aim of our study was to analyze the factors contributing to heterogeneity of prognosis in patients with hyperdiploidy>50 chromosomes (HD>50), a group of B-cell precursor acute lymphoblastic leukemia with favorable outcome. The 541 HD>50 patients registered prospectively in the 58951 European Organisation for Research and Treatment of Cancer (EORTC) Children's Leukemia Group (CLG) trial, identified by karyotype (446 patients) and by DNA index (DI) (490 patients), had a 6-year event-free survival (EFS) of 89.0% (standard error [SE] 5 1.5%) and a 6-year overall survival (OS) of 95.9% (SE 5 0.9%). The strongest prognostic factor was the modal number of chromosomes (MNC): the 6-year EFS of 51-53, 54-57, and 58-66 MNC groups were 80%, 89%, and 99%, respectively (P < .0001). Ploidy assessed by DI was also a favorable factor: the higher the DI, the better the outcome. The 6-year EFS of the 3 subgroups of DI < 1.16/ ‡ 1.16-<1.24/ ‡1.24 were 83%, 90%, and 95%, respectively (P 5 .009). All usual combinations of trisomies (chromosomes 4, 10, 17, 18) were significant favorable factors but had lower EFS when MNC was lower than 58. In multivariate analysis, MNC remained the strongest factor. Consequently, the best indicator for excellent outcome was ploidy assessed by karyotype because patients with 58-66 chromosomes stood every chance of being cured (OS of 100% at 6-year followup) with less-intensive therapy. This trial was registered at www.clinicaltrials.gov as #NCT00003728. Registered: http://www.eortc. org/, http://clinicaltrials.gov/show/NCT00003728. (Blood. 2013;121(13):2415-2423

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Using Big Data to Reveal Chronic Respiratory Disease Mortality Patterns and Identify Potential Public Health Interventions

Mannino

Sanderson

2017

JAMA

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the cost-effectiveness of this strategy. 15 Based on the GIFT trial composite primary outcome, 26 patients would need to be genotyped to prevent 1 "event" (most commonly an INR ≥4). Although the cost of genotyping continues to decline, health insurers and publically funded health systems have not yet been convinced that genotype-guided warfarin prescribing is a cost-effective strategy worthy of investment. This is despite modeling from EU-PACT trial data suggesting that from a Swedish or UK health system perspective, pharmacogenomic testing would be cost-effective for patients with atrial fibrillation initiating warfarin therapy. 16 Ideally an up-dated meta-analysis of trial data should be applied to costeffectiveness modeling to inform new policy.However, exploring the value of genotyping from the perspective of a single prescribing decision is the wrong question. A single pharmacogenomic test covering many common variants relevant to multiple different prescribing decisions over time is far more likely to be cost-effective; however, the evidence for this proposition is lacking. In the meantime, genotype-guided warfarin dosing probably has some clinical utility but it might be simpler and less expensive to implement wider use of clinical dosing algorithms to reduce the harms of anticoagulation.

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Response to Cuneo et al

Cited by 8 publications

References 6 publications

Understanding the role of hyperdiploidy in myeloma prognosis: which trisomies really matter?

Understanding the role of hyperdiploidy in myeloma prognosis: which trisomies really matter?

Hyperdiploidy with 58-66 chromosomes in childhood B-acute lymphoblastic leukemia is highly curable: 58951 CLG-EORTC results

Using Big Data to Reveal Chronic Respiratory Disease Mortality Patterns and Identify Potential Public Health Interventions

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