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Competing Interests: Elias K. Mai reports consulting or advisory role with Amgen, BMS/Celgene, GlaxoSmithKline, Janssen‐Cilag, Pfizer, Sanofi, Stemline, and Takeda; honoraria from Amgen, BMS/Celgene, GlaxoSmithKline, Janssen‐Cilag, Pfizer, Sanofi, Stemline, and Takeda; research funding from BMS/Celgene, GlaxoSmithKline, Janssen‐Cilag, Sanofi, and Takeda; and travel accommodations and expenses from BMS/Celgene, GlaxoSmithKline, Janssen‐Cilag, Sanofi, Stemline, and Takeda. Axel Nogai reports consulting or advisory role with Celgene, Roche, Takeda, Alexion, Janssen, BMS, Sanofi and GSK; honoraria from Celgene, Roche, Takeda, Alexion, Janssen, BMS, Sanofi, and GSK; research support from BMS, Janssen, and Celgene; and travel accommodations and expenses from Takeda, Janssen, Alexion, and Amgen. Bronno van der Holt reports honoraria for data safety monitoring board membership from IFM. Sonja Zweegman reports consulting or advisory role with Janssen, BMS, Sanofi, Oncopeptides, and GSK; and research funding from Takeda and Janssen. Katja C. Weisel reports consulting or advisory role with Abbvie, Amgen, Adaptive Biotech, Bristol Myers Squibb/Celgene, BeiGene, Janssen, GlaxoSmithKline, Karyopharm, Oncopeptides, Pfizer, Regeneron, Roche Pharma, Sanofi, Takeda, and Menarini; honoraria from Abbvie, Amgen, Adaptive Biotech, Astra Zeneca, Bristol Myers Squibb/Celgene, BeiGene, Janssen, GlaxoSmithKline, Karyopharm, Novartis, Oncopeptides, Pfizer, Roche Pharma, Sanofi, Stemline, Takeda, and Menarini; and research funding from Abbvie, Amgen, Bristol Myers Squibb/Celgene, Janssen, GlaxoSmithKline, Pfizer, Sanofi, and Takeda. Jens Hillengass reports advisory role with Prothena, Sebia, and Regeneron; honoraria from Targeted Oncology; and member of data safety monitoring boards with Janssen. Marc S. Raab reports consulting or advisory role with BMS, Amgen, GSK, Janssen, Sanofi, Pfizer, AbbVie, and Takeda; research funding from BMS, Janssen, Sanofi, and Heidelberg Pharma; travel accommodation and expenses from BMS, Amgen, and Janssen; and honoraria from BMS, Janssen, AbbVie, and Sanofi. Annemiek Broijl reports honoraria from Amgen, Sanofi, Janssen, and BMS. Peter Brossart reports consulting or advisory role from Astra‐Zeneca, BMS, MSD, BeiGene, and Gilead; research funding from BMS; and honoraria from Gilead, MSD, BMS, and Astra‐Zeneca. Christoph Scheid reports consulting or advisory role from Bristol Myers Squibb, GlaxoSmithKline, Janssen, Pfizer, Roche, and Takeda; honoraria from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, MSD, Novartis, Roche, Sanofi, and Takeda; research funding from Janssen, and Takeda; and travel accommodation and expenses from Bristol Myers Squibb, Janssen, Sanofi Aventis, and Takeda. Hans J. Salwender reports consulting or advisory role with Amgen, AstraZeneca, Bristol Myers Squibb/Celgene, Genzyme, GSK, Janssen Cilag, Oncopeptides, Pfizer, Sanofi, and Stemline; honoraria from Abbvie, Amgen, AstraZeneca, Bristol Myers SquibbMS/Celgene, Genzyme, GSK, Janssen Cilag, Oncopeptides, Pfizer, Roche, Sanofi, Stemline, and Takeda; and travel accommodation and expenses from Amgen, Bristol Myers Squibb/Celgene, Janssen Cilag, and Sanofi. Hartmut Goldschmidt reports consulting or advisory role with Amgen, BMS, Janssen, Sanofi, and Adaptive Biotechnology; honoraria from Amgen, BMS, Chugai, GlaxoSmithKline, Janssen, Novartis, Sanofi, and Pfizer; research funding from Amgen, BMS, Celgene, GlycoMimetics Inc., GlaxoSmithKline, Heidelberg Pharma, Hoffmann‐La Roche, Karyopharm, Janssen, Incyte Corporation, Millenium Pharmaceuticals Inc., Molecular Partners, Merck Sharp and Dohme, MorphoSys AG, Pfizer, Sanofi, Takeda, and Novartis; travel accommodations and expenses from Amgen, BMS, GlaxoSmithKline, Janssen, Novartis, Sanofi, and Pfizer; grants from Amgen, Array Biopharma/Pfizer, BMS/Celgene, Chugai, Dietmar‐Hopp‐Foundation, Janssen, Johns Hopkins University, Mundipharma GmbH, and Sanofi. Pieter Sonneveld reports advisory role with Amgen, BMS, Celgene, Janssen, Karyopharm, and Pfizer; research funding from Amgen, BMS, Janssen, and Karyopharm. All other authors declare no competing interests.

Optical Genome Mapping (OGM) is rapidly emerging as an exciting cytogenomic technology both for research and clinical purposes. In the last 2 years alone, multiple studies have demonstrated that OGM not only matches the diagnostic scope of conventional standard of care cytogenomic clinical testing but it also adds significant new information in certain cases. Since OGM consolidates the diagnostic benefits of multiple costly and laborious tests (e.g., karyotyping, fluorescence in situ hybridization, and chromosomal microarrays) in a single cost-effective assay, many clinical laboratories have started to consider utilizing OGM. In 2021, an international working group of early adopters of OGM who are experienced with routine clinical cytogenomic testing in patients with hematological neoplasms formed a consortium (International Consortium for OGM in Hematologic Malignancies, henceforth "the Consortium") to create a consensus framework for implementation of OGM in a clinical setting. The focus of the Consortium is to provide guidance for laboratories implementing OGM in three specific areas: validation, quality control and analysis and interpretation of variants. Since OGM is a complex technology with many variables, we felt that by consolidating our collective experience, we could provide a practical and useful tool for uniform implementation of OGM in hematologic malignancies with the ultimate goal of achieving globally accepted standards., (© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Background: Many older patients with acute myeloid leukaemia die or cannot undergo allogeneic haematopoietic stem-cell transplantation (HSCT) due to toxicity caused by intensive chemotherapy. We hypothesised that replacing intensive chemotherapy with decitabine monotherapy could improve outcomes., Methods: This open-label, randomised, controlled, phase 3 trial was conducted at 54 hospitals in nine European countries. Patients aged 60 years and older who were newly diagnosed with acute myeloid leukaemia and had not yet been treated were enrolled if they had an Eastern Cooperative Oncology Group performance status of 2 or less and were eligible for intensive chemotherapy. Patients were randomly assigned (1:1) to receive decitabine or standard chemotherapy (known as 3 + 7). For the decitabine group, decitabine (20 mg/m 2 ) was administered for the first 10 days in the first 28-day cycle, followed by 28-day cycles consisting of 5 days or 10 days of decitabine. For the 3 + 7 group, daunorubicin (60 mg/m 2 ) was administered over the first 3 days and cytarabine (200 mg/m 2 ) over the first 7 days, followed by 1-3 additional chemotherapy cycles. Allogeneic HSCT was strongly encouraged. Overall survival in the intention-to-treat population was the primary endpoint. Safety was assessed in all patients who received the allocated treatment. This trial is registered at ClinicalTrials.gov, NCT02172872, and is closed to new participants., Findings: Between Dec 1, 2014, and Aug 20, 2019, 606 patients were randomly assigned to the decitabine (n=303) or 3 + 7 (n=303) group. Following an interim analysis which showed futility, the IDMC recommended on May 22, 2019, that the study continued as planned considering the risks and benefits for the patients participating in the study. The cutoff date for the final analysis presented here was June 30, 2021. At a median follow-up of 4·0 years (IQR 2·9-4·8), 4-year overall survival was 26% (95% CI 21-32) in the decitabine group versus 30% (24-35) in the 3 + 7 group (hazard ratio for death 1·04 [95% CI 0·86-1·26]; p=0·68). Rates of on-protocol allogeneic HSCT were similar between groups (122 [40%] of 303 patients for decitabine and 118 [39%] of 303 patients for 3+7). Rates of grade 3-5 adverse events were 254 (84%) of 302 patients in the decitabine group and 279 (94%) of 298 patients in the 3 + 7 group. The rates of grade 3-5 infections (41% [125 of 302] vs 53% [158 of 298]), oral mucositis (2% [seven of 302] vs 10% [31 of 298]) and diarrhoea (1% [three of 302] vs 8% [24 of 298]) were lower in the decitabine group than in the 3 + 7 group. Treatment-related deaths were reported for 12% (35 of 302) of patients in the decitabine group and 14% (41 of 298) in the 3 + 7 group., Interpretation: 10-day decitabine did not improve overall survival but showed a better safety profile compared with 3 + 7 chemotherapy in older patients with acute myeloid leukaemia eligible for intensive chemotherapy. Decitabine could be considered a better-tolerated and sufficiently efficacious alternative to 3 + 7 induction in fit older patients with acute myeloid leukaemia without favourable genetics., Funding: Janssen Pharmaceuticals., Competing Interests: Declaration of interests MLü received research support to his institution from Janssen and European Organisation for Research and Treatment of Cancer (EORTC); is on the advisory boards for AbbVie, Astex, Janssen-Cilag, Otsuka, and Syros; and is currently working in an ongoing trial with a study drug provided by Cheplapharm. MK received research funding from Merck, Bristol Myers Squibb (BMS), Pierre Fabre, Janssen, and Immunocore. SF received personal funding by BMS and Celgene. AG received a grant for study conduct, and drug supply for Dacogen from Janssen Pharma Educational. JHJ received support for molecular analysis from Janssen and EORTC. FE received personal funding from AbbVie, Incyte, Janssen, Novartis, and Syros. RW received consulting fees from Amgen, BMS, Celgene, Janssen, Kite, Gilead, Novartis, Pfizer, and Sanofi; payment from AbbVie, Amgen, BMS, Celgene, Janssen, Kite, Gilead, Pfizer, and Sanofi; and support for attending meetings or travel from Janssen. HB is secretary of EORTC Leukemia Group; received research funding by the German Jose Carreras Leukemia Foundation and German Research Foundation; and honoraria from AbbVie, BMS, Celgene, Merck, Novartis, and Servier. UD received personal honoraria for participation in a data safety monitoring board from Avencell Europe and data safety monitoring board for an acute myeloid leukaemia CAR-T cell trial from Avencell Europe. FB received payments to his institution from Incyte Biosciences, Takeda, ExCellThera, and MaaT Pharma. SS received funding to his institution from Janssen Pharmaceuticals. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Genome Mapping Technologies (optical and electronic) use ultra-high molecular weight DNA to detect structural variation and have application in constitutional genetic disorders, hematological neoplasms, and solid tumors. Genome mapping can detect balanced and unbalanced structural variation, copy number changes, and haplotypes. The technique is analogous to chromosomal microarray analysis, although genome mapping has the added benefit of being able to detect and ascertain the nature of more abnormalities in a single assay than array, karyotyping, or FISH alone., Key Messages: This paper describes a specific nomenclature for genome mapping that can be used by diagnostic and research centers to report their findings accurately. An international nomenclature is essential for patient results to be understood by different healthcare providers as well as for clear communication in publications and consistency in databases., Summary: Genome mapping can detect aneuploidy, balanced and unbalanced structural variation, as well as copy number changes. The Standing Committee for the International System for Human Cytogenomic Nomenclature (ISCN) recognised there was a need for a specific nomenclature for genome mapping that encompasses the range of abnormalities detected by this technique. This paper explains the general principles of the nomenclature as well as giving specific ISCN examples for the different types of numerical and structural rearrangements., (© 2024 S. Karger AG, Basel.)

Chromosomal aberrations including structural variations (SVs) are a major cause of human genetic diseases. Their detection in clinical routine still relies on standard cytogenetics. Drawbacks of these tests are a very low resolution (karyotyping) and the inability to detect balanced SVs or indicate the genomic localization and orientation of duplicated segments or insertions (copy number variant [CNV] microarrays). Here, we investigated the ability of optical genome mapping (OGM) to detect known constitutional chromosomal aberrations. Ultra-high-molecular-weight DNA was isolated from 85 blood or cultured cells and processed via OGM. A de novo genome assembly was performed followed by structural variant and CNV calling and annotation, and results were compared to known aberrations from standard-of-care tests (karyotype, FISH, and/or CNV microarray). In total, we analyzed 99 chromosomal aberrations, including seven aneuploidies, 19 deletions, 20 duplications, 34 translocations, six inversions, two insertions, six isochromosomes, one ring chromosome, and four complex rearrangements. Several of these variants encompass complex regions of the human genome involved in repeat-mediated microdeletion/microduplication syndromes. High-resolution OGM reached 100% concordance compared to standard assays for all aberrations with non-centromeric breakpoints. This proof-of-principle study demonstrates the ability of OGM to detect nearly all types of chromosomal aberrations. We also suggest suited filtering strategies to prioritize clinically relevant aberrations and discuss future improvements. These results highlight the potential for OGM to provide a cost-effective and easy-to-use alternative that would allow comprehensive detection of chromosomal aberrations and structural variants, which could give rise to an era of "next-generation cytogenetics.", (Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Complex karyotype (CK) identified by chromosome-banding analysis (CBA) has shown prognostic value in chronic lymphocytic leukemia (CLL). Genomic arrays offer high-resolution genome-wide detection of copy-number alterations (CNAs) and could therefore be well equipped to detect the presence of a CK. Current knowledge on genomic arrays in CLL is based on outcomes of single center studies, in which different cutoffs for CNA calling were used. To further determine the clinical utility of genomic arrays for CNA assessment in CLL diagnostics, we retrospectively analyzed 2293 arrays from 13 diagnostic laboratories according to established standards. CNAs were found outside regions captured by CLL FISH probes in 34% of patients, and several of them including gains of 8q, deletions of 9p and 18p (p<0.01) were linked to poor outcome after correction for multiple testing. Patients (n=972) could be divided in three distinct prognostic subgroups based on the number of CNAs. Only high genomic complexity (high-GC), defined as ≥5 CNAs emerged as an independent adverse prognosticator on multivariable analysis for time to first treatment (Hazard ratio: 2.15, 95% CI: 1.36-3.41; p=0.001) and overall survival (Hazard ratio: 2.54, 95% CI: 1.54-4.17; p<0.001; n=528). Lowering the size cutoff to 1 Mb in 647 patients did not significantly improve risk assessment. Genomic arrays detected more chromosomal abnormalities and performed at least as well in terms of risk stratification compared to simultaneous chromosome banding analysis as determined in 122 patients. Our findings highlight genomic array as an accurate tool for CLL risk stratification.

The standard prognostic marker for multiple myeloma (MM) patients is the revised International Staging System (R-ISS). However, there is room for improvement in guiding treatment. This applies particularly to older patients, in whom the benefit/risk ratio is reduced because of comorbidities and subsequent side effects. We hypothesized that adding gene-expression data to R-ISS would generate a stronger marker. This was tested by combining R-ISS with the SKY92 classifier (SKY-RISS). The HOVON-87/NMSG-18 trial (EudraCT: 2007-004007-34) compared melphalan-prednisone-thalidomide followed by thalidomide maintenance (MPT-T) with melphalan-prednisone-lenalidomide followed by lenalidomide maintenance (MPR-R). From this trial, 168 patients with available R-ISS status and gene-expression profiles were analyzed. R-ISS stages I, II, and III were assigned to 8%, 75%, and 7% of patients, respectively (3-year overall survival [OS] rates: 80%, 65%, 33%, P = 8 × 10-3). Using the SKY92 classifier, 13% of patients were high risk (HR) (3-year OS rates: standard risk [SR], 70%; HR, 28%; P < .001). Combining SKY92 with R-ISS resulted in 3 risk groups: SKY-RISS I (SKY-SR + R-ISS-I; 15%), SKY-RISS III (SKY-HR + R-ISS-II/III; 11%), and SKY-RISS II (all other patients; 74%). The 3-year OS rates for SKY-RISS I, II, and III are 88%, 66%, and 26%, respectively (P = 6 × 10-7). The SKY-RISS model was validated in older patients from the CoMMpass dataset. Moreover, SKY-RISS demonstrated predictive potential: HR patients appeared to benefit from MPR-R over MPT-T (median OS, 55 and 14 months, respectively). Combined, SKY92 and R-ISS classify patients more accurately. Additionally, benefit was observed for MPR-R over MPT-T in SKY92-RISS HR patients only., (© 2020 by The American Society of Hematology.)

We provide a long-term evaluation of patients enrolled in the EORTC/GIMEMA AML-10 trial which included a total of 2157 patients, 15-60 years old, randomized to receive either daunorubicin (DNR, 50 mg/m 2 ), mitoxantrone (MXR, 12 mg/m 2 ), or idarubicin (IDA, 10 mg/m 2 ) in addition to standard-dose cytarabine and etoposide for induction chemotherapy and intermediate dose cytarabine for consolidation. Younger patients who reached complete remission with complete (CR) or incomplete (CRi) recovery were then scheduled to receive an allogeneic hematopoietic stem cell transplantation (HSCT). That was if they had a HLA-identical sibling donor; in all other cases, an autologous HSCT had to be administered. At an 11-year median follow-up, the 5-year, 10-year and 15-year overall survival (OS) rates were 33.2%, 30.1% and 28.0%, respectively. No significant difference between the three randomized groups regarding OS was observed (P = .38). In young patients, 15-45 years old, no treatment difference (P = .89) regarding OS was observed, while in patients 46-60 years old, MXR and IDA groups had a trend for a longer OS as compared to the DNR group (P = .029). Among younger patients without a favorable MRC cytogenetic risk subgroup who achieved a CR/CRi after induction chemotherapy, those with a HLA-identical sibling donor had higher 10-year and 15-year OS rates than those without. In older patients who reached CR/CRi, the long-term outcomes of those with or without a donor was similar. In conclusion, long-term outcomes of the study confirmed similar OS in the three randomized groups in the whole cohort of patients., (© 2020 Wiley Periodicals, Inc.)

Ring sideroblasts (RS) emerge as result of aberrant erythroid differentiation leading to excessive mitochondrial iron accumulation, a characteristic feature for myelodysplastic syndromes (MDS) with mutations in the spliceosome gene SF3B1. However, RS can also be observed in patients diagnosed with acute myeloid leukemia (AML). The objective of this study was to characterize RS in patients with AML. Clinically, RS-AML is enriched for ELN adverse risk (55%). In line with this finding, 35% of all cases had complex cytogenetic aberrancies, and TP53 was most recurrently mutated in this cohort (37%), followed by DNMT3A (26%), RUNX1 (25%), TET2 (20%), and ASXL1 (19%). In contrast to RS-MDS, the incidence of SF3B1 mutations was low (8%). Whole-exome sequencing and SNP array analysis on a subset of patients did not uncover a single genetic defect underlying the RS phenotype. Shared genetic defects between erythroblasts and total mononuclear cell fraction indicate common ancestry for the erythroid lineage and the myeloid blast cells in patients with RS-AML. RNA sequencing analysis on CD34+ AML cells revealed differential gene expression between RS-AML and non RS-AML cases, including genes involved in megakaryocyte and erythroid differentiation. Furthermore, several heme metabolism-related genes were found to be upregulated in RS- CD34+ AML cells, as was observed in SF3B1mut MDS. These results demonstrate that although the genetic background of RS-AML differs from that of RS-MDS, they have certain downstream effector pathways in common., (© 2019 by The American Society of Hematology.)

Monosomal karyotype confers a poor prognosis in patients with acute myeloid leukemia. Here, we determined the impact of the type of remission-induction chemotherapy and the impact of having a donor in younger acute myeloid leukemia patients with a monosomal karyotype included in two phase III trials. In the first trial patients were randomized to receive either daunorubicin, mitoxantrone, or idarubicin in addition to standard-dose cytarabine and etoposide for induction chemotherapy. In the second trial patients were randomized to standard-dose cytarabine or high-dose cytarabine induction, both with daunorubicin and etoposide. In both trials, patients who achieved a complete remission with or without complete hematologic recovery underwent allogeneic hematopoietic stem cell transplantation if they had a donor; otherwise, they underwent autologous transplantation. In comparison to patients with intermediate-risk cytogenetics without a monosomal karyotype (n=1,584) and with adverse cytogenetics without a monosomal karyotype (n=218), patients with a monosomal karyotype (n=188) were more likely not to achieve a complete remission with or without count recovery [odds ratio=2.85, 95% confidence interval (95%, CI): 2.10-3.88] and had shorter overall survival [hazard ratio, (HR)=2.44, 95% CI: 2.08-2.88]. There was no impact of the type of anthracycline or of the dose of cytarabine on outcomes in patients with a monosomal karyotype. Among monosomal karyo type patients who achieved a complete remission with or without count recovery, HLA-identical related donor availability was associated with longer survival from complete remission with or without count recovery (HR=0.59, 95% CI: 0.37-0.95). ClinicalTrials.gov identifiers: AML-10: NCT00002549; AML-12: NCT00004128., (Copyright© 2019 Ferrata Storti Foundation.)

The presence of cytogenetic clonal heterogeneity has been associated with poor prognosis in patients with acute myeloid leukemia (AML). Here, we reassessed this association. The study cohort consisted of all patients with an abnormal karyotype randomized in the EORTC/GIMEMA AML-10 and AML-12 trials. Abnormal karyotypes were classified as no subclones present (cytogenetic abnormality in a single clone), defined subclones present (presence of one to three subclones), and composite karyotypes (CP) (clonal heterogeneity not allowing enumeration of individual subclones). The main endpoints were overall survival (OS) and disease-free survival (DFS). Among 1291 patients with an abnormal karyotype, 1026 had no subclones, 226 at least 1 subclone, and 39 a CP. Patients with defined subclones had an OS similar to those with no subclones (hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.88-1.26), but CP patients had a shorter OS (HR = 1.58, 95% CI 1.11-2.26). However, in a multivariate Cox model stratified by protocol and adjusted for age, cytogenetic risk group, secondary versus primary AML, and performance status, clonal heterogeneity lost its prognostic importance (HR = 1.10, 95% CI 0.91-1.32 for defined subclones versus no subclones; HR = 0.96, 95% CI 0.67-1.38 for CP versus no subclones). Also, the impact of having a donor on DFS was similar in the three clonal subgroups. In summary, in patients with cytogenetic abnormality, presence of subclones had no impact on OS. The dismal outcome in patients with a CP was explained by the known predictors of poor prognosis., Trial Registration: AML-10: ClinicalTrials.gov identifier: NCT00002549, retrospectively registered July 19, 2004; AML12: ClinicalTrials.gov identifier: NCT00004128, registered January 27, 2003.

The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR)=0.76, 95% confidence interval (95% CI) of 0.65-0.89, P=0.001). Overall survival (OS) was similar in the PAD versus VAD arm (HR=0.89, 95% CI: 0.74-1.08, P=0.24). The incidence of SPM were similar between the two arms (7% each, P=0.73). The negative prognostic effects of the cytogenetic aberration deletion 17p13 (clone size ⩾10%) and renal impairment at baseline (serum creatinine >2 mg dl -1 ) on PFS and OS remained abrogated in the PAD but not VAD arm. OS from first relapse/progression was similar between the study arms (HR=1.02, P=0.85). In conclusion, the survival benefit with BTZ induction/maintenance compared with classical cytotoxic agents and thalidomide maintenance is maintained without an increased risk of SPM.

A standardized nomenclature is critical for the accurate and consistent description of genomic changes as identified by karyotyping, fluorescence in situ hybridization and microarray. The International System for Human Cytogenomic Nomenclature (ISCN) is the central reference for the description of karyotyping, FISH, and microarray results, and provides rules for describing cytogenetic and molecular cytogenetic findings in laboratory reports. These laboratory reports are documents to the referring clinician, and should be clear, accurate and contain all information relevant for good interpretation of the cytogenetic findings. Here, we describe guidelines for cytogenetic nomenclature and laboratory reports for cytogenetic testing applied to tumor samples.

Genetic profiling is important for disease evaluation and prediction of prognosis or responsiveness to therapy in neoplasia. Microarray technologies, including array comparative genomic hybridization and single-nucleotide polymorphism-detecting arrays, have in recent years been introduced into the diagnostic setting for specific types of haematological malignancies and solid tumours. It can be used as a complementary test or depending on the neoplasia investigated, also as a standalone test. However, comprehensive and readable presentation of frequently identified complex genomic profiles remains challenging. To assist diagnostic laboratories, standardization and minimum criteria for clinical interpretation and reporting of acquired genomic abnormalities detected through arrays in neoplastic disorders are presented., (© 2016 Wiley Periodicals, Inc.)

Multiple myeloma is a heterogeneous disease, which is characterized by the occurrence of specific genomic abnormalities that are both of diagnostic and prognostic relevance. Since the detection of these abnormalities through molecular-genetic techniques is hampered by the overall low percentage of plasma cells present in primary bone marrow aspirates, we assessed the efficacy of these techniques in enriched plasma cell fractions from 61 multiple myeloma patients. Using interphase FISH, genomic abnormalities could be detected in 96% of the enriched samples as compared to 61% in the cultured whole bone marrow samples. We also found that microarray-based genomic profiling of enriched plasma samples facilitates the detection of additional, possibly clinically relevant, genomic abnormalities. We conclude that the genomic delineation of enriched plasma cells from multiple myeloma patients results in a significantly increased detection rate of clinically relevant genomic abnormalities. In order to facilitate molecular-genetic data interpretation, we recommend morphological assessment of plasma cell purity after enrichment., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: We investigated whether bortezomib during induction and maintenance improves survival in newly diagnosed multiple myeloma (MM)., Patients and Methods: In all, 827 eligible patients with newly diagnosed symptomatic MM were randomly assigned to receive induction therapy with vincristine, doxorubicin, and dexamethasone (VAD) or bortezomib, doxorubicin, and dexamethasone (PAD) followed by high-dose melphalan and autologous stem-cell transplantation. Maintenance consisted of thalidomide 50 mg (VAD) once per day or bortezomib 1.3 mg/m(2) (PAD) once every 2 weeks for 2 years. The primary analysis was progression-free survival (PFS) adjusted for International Staging System (ISS) stage., Results: Complete response (CR), including near CR, was superior after PAD induction (15% v 31%; P < .001) and bortezomib maintenance (34% v 49%; P < .001). After a median follow-up of 41 months, PFS was superior in the PAD arm (median of 28 months v 35 months; hazard ratio [HR], 0.75; 95% CI, 0.62 to 0.90; P = .002). In multivariate analysis, overall survival (OS) was better in the PAD arm (HR, 0.77; 95% CI, 0.60 to 1.00; P = .049). In high-risk patients presenting with increased creatinine more than 2 mg/dL, bortezomib significantly improved PFS from a median of 13 months to 30 months (HR, 0.45; 95% CI, 0.26 to 0.78; P = .004) and OS from a median of 21 months to 54 months (HR, 0.33; 95% CI, 0.16 to 0.65; P < .001). A benefit was also observed in patients with deletion 17p13 (median PFS, 12 v 22 months; HR, 0.47; 95% CI, 0.26 to 0.86; P = .01; median OS, 24 months v not reached at 54 months; HR, 0.36; 95% CI, 0.18 to 0.74; P = .003)., Conclusion: Bortezomib during induction and maintenance improves CR and achieves superior PFS and OS.