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  1. Article ; Online: Comparison of karyotype scoring guidelines for evaluating karyotype complexity in chronic lymphocytic leukemia.

    Avenarius, Matthew R / Huang, Ying / Kittai, Adam S / Bhat, Seema A / Rogers, Kerry A / Grever, Michael R / Woyach, Jennifer A / Miller, Cecelia R

    Leukemia

    2024  Volume 38, Issue 3, Page(s) 676–678

    MeSH term(s) Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Karyotyping ; Karyotype
    Language English
    Publishing date 2024-02-19
    Publishing country England
    Document type Letter
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/s41375-024-02177-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Culture and Harvest of CpG-Stimulated Peripheral Blood or Bone Marrow in Chronic Lymphocytic Leukemia.

    Miller, Cecelia R / Heerema, Nyla A

    Methods in molecular biology (Clifton, N.J.)

    2018  Volume 1881, Page(s) 27–34

    Abstract: Chromosome analysis of chronic lymphocytic leukemia (CLL) is an important clinical tool for evaluating prognosis and disease progression. Visualizing chromosomes microscopically using traditional cytogenetic techniques requires dividing cells to be ... ...

    Abstract Chromosome analysis of chronic lymphocytic leukemia (CLL) is an important clinical tool for evaluating prognosis and disease progression. Visualizing chromosomes microscopically using traditional cytogenetic techniques requires dividing cells to be arrested during metaphase. The major challenge for performing this analysis on CLL samples is stimulating the cells to divide in culture. Stimulation of CLL cells with CpG oligodeoxynucleotides has improved our ability to perform chromosome analysis for this leukemia. This protocol should help the reader successfully culture CLL samples for clinical chromosome analysis.
    MeSH term(s) B-Lymphocytes/drug effects ; Bone Marrow Cells/drug effects ; Humans ; Karyotyping/instrumentation ; Karyotyping/methods ; Leukemia, Lymphocytic, Chronic, B-Cell/blood ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Metaphase/drug effects ; Mitogens/pharmacology ; Oligodeoxyribonucleotides/pharmacology ; Primary Cell Culture/instrumentation ; Primary Cell Culture/methods ; Specimen Handling/instrumentation ; Specimen Handling/methods ; Tumor Cells, Cultured
    Chemical Substances CPG-oligonucleotide ; GNKG168 ; Mitogens ; Oligodeoxyribonucleotides
    Language English
    Publishing date 2018-10-22
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-8876-1_3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Characteristics and outcomes of patients with CLL and CDKN2A/B deletion by fluorescence in situ hybridization.

    Teierle, Samantha M / Huang, Ying / Kittai, Adam S / Bhat, Seema A / Grever, Michael / Rogers, Kerry A / Zhao, Weiqiang / Jones, Daniel / Byrd, John C / Avenarius, Matthew R / Heerema, Nyla A / Woyach, Jennifer A / Miller, Cecelia R

    Blood advances

    2023  Volume 7, Issue 23, Page(s) 7239–7242

    MeSH term(s) Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Chromosome Deletion ; Gene Deletion ; Cyclin-Dependent Kinase Inhibitor p16/genetics
    Chemical Substances CDKN2A protein, human ; Cyclin-Dependent Kinase Inhibitor p16
    Language English
    Publishing date 2023-10-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2023010753
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  4. Article ; Online: Combined BCL2 and BTK inhibition in CLL demonstrates efficacy after monotherapy with both classes.

    Hyak, Jonathan M / Huang, Ying / Rogers, Kerry A / Bhat, Seema A / Grever, Michael R / Byrd, John C / Kittai, Adam S / Jones, Dan / Miller, Cecelia R / Woyach, Jennifer A

    Blood advances

    2022  Volume 6, Issue 17, Page(s) 5124–5127

    MeSH term(s) Agammaglobulinaemia Tyrosine Kinase ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Proto-Oncogene Proteins c-bcl-2 ; Pyrimidines/pharmacology ; Pyrimidines/therapeutic use
    Chemical Substances BCL2 protein, human ; Proto-Oncogene Proteins c-bcl-2 ; Pyrimidines ; Agammaglobulinaemia Tyrosine Kinase (EC 2.7.10.2)
    Language English
    Publishing date 2022-07-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2022007708
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Refining prognosis in chronic lymphocytic leukemia with normal Fluorescence in situ hybridization results.

    Avenarius, Matthew R / Huang, Ying / Hyak, Jonathan / Byrd, John C / Bhat, Seema A / Grever, Michael / Kittai, Adam S / Rogers, Kerry A / Jones, Dan / Zhao, Weiqiang / Heerema, Nyla A / Abruzzo, Lynne V / Woyach, Jennifer / Miller, Cecelia R

    Hematological oncology

    2023  Volume 41, Issue 4, Page(s) 771–775

    Abstract: Fluorescence in situ hybridization (FISH) to detect the recurrent cytogenetics abnormalities deletion 13q, trisomy 12, deletion 11q, and deletion 17p is important for prognostication in chronic lymphocytic leukemia (CLL). A subset of patients are ... ...

    Abstract Fluorescence in situ hybridization (FISH) to detect the recurrent cytogenetics abnormalities deletion 13q, trisomy 12, deletion 11q, and deletion 17p is important for prognostication in chronic lymphocytic leukemia (CLL). A subset of patients are negative for each of these abnormalities (normal 12/13/11/17 FISH), and outcomes are heterogenous within this group. To elucidate variables important for prognostication in this subgroup we conducted a retrospective analysis of 280 treatment-naïve CLL patients with normal standard CLL FISH results. In a multivariable model, advanced Rai stage (p = 0.04, hazard ratio [HR] 1.24 (95% confidence interval [CI] 1.01-1.53)), unmutated immunoglobulin heavy chain gene (IGHV) (p < 0.0001, HR 5.59 (95% CI 3.63-8.62)) and IGH rearrangement by FISH (p = 0.02, HR 2.56 (95% CI 1.20-5.48)) were significantly associated with shorter time to first treatment. In a multivariable model for overall survival, increasing age at 5-year increments (p < 0.0001, HR 1.55 (95% CI 1.25-1.93)), unmutated IGHV (p = 0.01, HR 5.28 (95% CI 1.52-18.35)) and gain of REL (p = 0.01, HR 4.08 (5% CI 1.45-11.49)) were significantly associated with shorter survival. Our study identifies variables important for refining prognosis for CLL patients with normal standard CLL FISH results.
    MeSH term(s) Humans ; Child, Preschool ; In Situ Hybridization, Fluorescence/methods ; Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Retrospective Studies ; Chromosome Aberrations ; Prognosis
    Language English
    Publishing date 2023-04-03
    Publishing country England
    Document type Letter
    ZDB-ID 604884-5
    ISSN 1099-1069 ; 0278-0232
    ISSN (online) 1099-1069
    ISSN 0278-0232
    DOI 10.1002/hon.3134
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Patient characteristics that predict Richter's transformation in patients with chronic lymphocytic leukemia treated with ibrutinib.

    Kittai, Adam S / Huang, Ying / Beckwith, Kyle A / Bhat, Seema A / Bond, David A / Byrd, John C / Goldstein, Daniel / Grever, Michael R / Miller, Cecelia / Rogers, Kerry A / Yano, Max / Woyach, Jennifer A

    American journal of hematology

    2022  Volume 98, Issue 1, Page(s) 56–65

    Abstract: Chronic lymphocytic leukemia (CLL) transformation to aggressive lymphoma, known as Richter's Transformation (RT), has a dismal prognosis. There are limited data evaluating risk of RT in patients treated with ibrutinib. We performed a retrospective ... ...

    Abstract Chronic lymphocytic leukemia (CLL) transformation to aggressive lymphoma, known as Richter's Transformation (RT), has a dismal prognosis. There are limited data evaluating risk of RT in patients treated with ibrutinib. We performed a retrospective analysis to determine prognostic variables associated with development of RT and overall survival (OS) at progression after treatment with ibrutinib. We identified 559 patients with CLL treated with ibrutinib from 2010-2019. After a median follow-up of 44.5 months from ibrutinib start, 179 patients progressed and were included in our analysis. After a median follow-up of 20.8 months from progression, 54 out of 179 patients developed RT. Progression on treatment (hazard ratio [HR] 4.01 [1.60-10.00], p = .003), higher LDH (HR 1.80 for 2-fold increase [1.33-2.43], p = .0001), and lymphadenopathy without lymphocytosis (HR 2.88 [1.15-7.20], p = .02) were independent prognostic variables for the development of RT at progression. Progression with lymphadenopathy without lymphocytosis continued to be an independent prognostic variable of worse OS post-progression. In a subset analysis of 50 patients who obtained a PET-CT at progression, the median SUV
    MeSH term(s) Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; Positron Emission Tomography Computed Tomography ; Retrospective Studies ; Lymphocytosis ; Lymphoma, Large B-Cell, Diffuse ; Lymphadenopathy
    Chemical Substances ibrutinib (1X70OSD4VX)
    Language English
    Publishing date 2022-10-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 196767-8
    ISSN 1096-8652 ; 0361-8609
    ISSN (online) 1096-8652
    ISSN 0361-8609
    DOI 10.1002/ajh.26755
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy for Richter Transformation: An International, Multicenter, Retrospective Study.

    Kittai, Adam S / Bond, David / Huang, Ying / Bhat, Seema A / Blyth, Emily / Byrd, John C / Chavez, Julio C / Davids, Matthew S / Dela Cruz, Jamie P / Dowling, Mark R / Duffy, Caitlyn / Ho, Carrie / Jacobson, Caron / Jaglowski, Samantha / Jain, Nitin / Lin, Kevin H / Miller, Cecelia / McCarthy, Christine / Omer, Zulfa /
    Parry, Erin / Rai, Manoj / Rogers, Kerry A / Saha, Aditi / Schachter, Levanto / Scott, Hamish / Senapati, Jayastu / Shadman, Mazyar / Siddiqi, Tanya / Stephens, Deborah M / Vanguru, Vinay / Wierda, William / Woyach, Jennifer A / Thompson, Philip A

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2024  , Page(s) JCO2400033

    Abstract: Purpose: Outcomes for Richter transformation (RT) are poor with current therapies. The efficacy and safety of anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T) for RT are not established.: Methods: We performed an international multicenter ... ...

    Abstract Purpose: Outcomes for Richter transformation (RT) are poor with current therapies. The efficacy and safety of anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T) for RT are not established.
    Methods: We performed an international multicenter retrospective study of patients with RT who received CAR-T. Patient, disease, and treatment characteristics were summarized using descriptive statistics, and modeling analyses were used to determine association with progression-free survival (PFS) and overall survival (OS). PFS and OS were estimated from the date of CAR-T infusion.
    Results: Sixty-nine patients were identified. The median age at CAR-T infusion was 64 years (range, 27-80). Patients had a median of four (range, 1-15) previous lines of therapy for CLL and/or RT, including previous Bruton tyrosine kinase inhibitor and/or BCL2 inhibitor therapy in 58 (84%) patients. The CAR-T product administered was axicabtagene ciloleucel in 44 patients (64%), tisagenlecleucel in 17 patients (25%), lisocabtagene maraleucel in seven patients (10%), and brexucabtagene autoleucel in one patient (1%). Eleven patients (16%) and 25 patients (37%) experienced grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, respectively. The overall response rate was 63%, with 46% attaining a complete response (CR). After a median follow-up of 24 months, the median PFS was 4.7 months (95% CI, 2.0 to 6.9); the 2-year PFS was 29% (95% CI, 18 to 41). The median OS was 8.5 months (95% CI, 5.1 to 25.4); the 2-year OS was 38% (95% CI, 26 to 50). The median duration of response was 27.6 months (95% CI, 14.5 to not reached) for patients achieving CR.
    Conclusion: CAR-T demonstrates clinical efficacy for patients with RT.
    Language English
    Publishing date 2024-03-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.24.00033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Follow-up from the A041202 study shows continued efficacy of ibrutinib regimens for older adults with CLL.

    Woyach, Jennifer A / Perez Burbano, Gabriela / Ruppert, Amy S / Miller, Cecelia / Heerema, Nyla A / Zhao, Weiqiang / Wall, Anna / Ding, Wei / Bartlett, Nancy L / Brander, Danielle M / Barr, Paul M / Rogers, Kerry A / Parikh, Sameer A / Stephens, Deborah M / Brown, Jennifer R / Lozanski, Gerard / Blachly, James / Nattam, Sreenivasa / Larson, Richard A /
    Erba, Harry / Litzow, Mark / Luger, Selina / Owen, Carolyn / Kuzma, Charles / Abramson, Jeremy S / Little, Richard F / Dinner, Shira / Stone, Richard M / Uy, Geoffrey / Stock, Wendy / Mandrekar, Sumithra J / Byrd, John C

    Blood

    2024  Volume 143, Issue 16, Page(s) 1616–1627

    Abstract: Abstract: A041202 (NCT01886872) is a phase 3 study comparing bendamustine plus rituximab (BR) with ibrutinib and the combination of ibrutinib plus rituximab (IR) in previously untreated older patients with chronic lymphocytic leukemia (CLL). The initial ...

    Abstract Abstract: A041202 (NCT01886872) is a phase 3 study comparing bendamustine plus rituximab (BR) with ibrutinib and the combination of ibrutinib plus rituximab (IR) in previously untreated older patients with chronic lymphocytic leukemia (CLL). The initial results showed that ibrutinib-containing regimens had superior progression-free survival (PFS) and rituximab did not add additional benefits. Here we present an updated analysis. With a median follow-up of 55 months, the median PFS was 44 months (95% confidence interval [CI], 38-54) for BR and not yet reached in either ibrutinib-containing arm. The 48-month PFS estimates were 47%, 76%, and 76% for BR, ibrutinib, and IR, respectively. The benefit of ibrutinib regimens over chemoimmunotherapy was consistent across subgroups of patients defined by TP53 abnormalities, del(11q), complex karyotype, and immunoglobulin heavy chain variable region (IGHV). No significant interaction effects were observed between the treatment arm and del(11q), the complex karyotype, or IGHV. However, a greater difference in PFS was observed among the patients with TP53 abnormalities. There was no difference in the overall survival. Notable adverse events with ibrutinib included atrial fibrillation (afib) and hypertension. Afib was observed in 11 patients (pts) on BR (3%) and 67 pts on ibrutinib (18%). All-grade hypertension was observed in 95 pts on BR (27%) and 263 pts on ibrutinib (55%). These data show that ibrutinib regimens prolong PFS compared with BR for older patients with treatment-naïve CLL. These benefits were observed across subgroups, including high-risk groups. Strikingly, within the ibrutinib arms, there was no inferior PFS for patients with abnormalities in TP53, the highest risk feature observed in CLL. These data continue to demonstrate the efficacy of ibrutinib in treatment-naïve CLL.
    MeSH term(s) Humans ; Aged ; Rituximab/therapeutic use ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Follow-Up Studies ; Atrial Fibrillation/etiology ; Bendamustine Hydrochloride/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Hypertension/etiology ; Adenine/analogs & derivatives ; Piperidines
    Chemical Substances Rituximab (4F4X42SYQ6) ; ibrutinib (1X70OSD4VX) ; Bendamustine Hydrochloride (981Y8SX18M) ; Adenine (JAC85A2161) ; Piperidines
    Language English
    Publishing date 2024-01-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2023021959
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  9. Article ; Online: Significance of chromosome 2p gain in ibrutinib-treated chronic lymphocytic leukemia patients.

    Miller, Cecelia R / Huang, Ying / Ruppert, Amy S / Labanowska, Jadwiga / Jaglowski, Samantha M / Maddocks, Kami J / Rogers, Kerry A / Bhat, Seema / Kittai, Adam S / Grever, Michael / Lapalombella, Rosa / Abruzzo, Lynne V / Heerema, Nyla A / Byrd, John C / Hertlein, Erin K / Woyach, Jennifer A

    Leukemia

    2021  Volume 35, Issue 11, Page(s) 3287–3290

    MeSH term(s) Adenine/analogs & derivatives ; Adenine/therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Chromosome Aberrations ; Chromosomes, Human, Pair 2/genetics ; Cohort Studies ; Female ; Follow-Up Studies ; Gene Dosage ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Male ; Middle Aged ; Piperidines/therapeutic use ; Prognosis ; Survival Rate
    Chemical Substances Piperidines ; ibrutinib (1X70OSD4VX) ; Adenine (JAC85A2161)
    Language English
    Publishing date 2021-04-05
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/s41375-021-01237-x
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  10. Article ; Online: Genetic Characterization of Pediatric Sarcomas by Targeted RNA Sequencing.

    Avenarius, Matthew R / Miller, Cecelia R / Arnold, Michael A / Koo, Selene / Roberts, Ryan / Hobby, Martin / Grossman, Thomas / Moyer, Yvonne / Wilson, Richard K / Mardis, Elaine R / Gastier-Foster, Julie M / Pfau, Ruthann B

    The Journal of molecular diagnostics : JMD

    2020  Volume 22, Issue 10, Page(s) 1238–1245

    Abstract: Somatic variants, primarily fusion genes and single-nucleotide variants (SNVs) or insertions/deletions (indels), are prevalent among sarcomas. In many cases, accurate diagnosis of these tumors incorporates genetic findings that may also carry prognostic ... ...

    Abstract Somatic variants, primarily fusion genes and single-nucleotide variants (SNVs) or insertions/deletions (indels), are prevalent among sarcomas. In many cases, accurate diagnosis of these tumors incorporates genetic findings that may also carry prognostic or therapeutic significance. Using the anchored multiplex PCR-based FusionPlex system, a custom RNA sequencing panel was developed that simultaneously detects fusion genes, SNVs, and indels in 112 genes found to be recurrently mutated in solid tumors. Using this assay, a retrospective analysis was conducted to identify somatic variants that may have assisted with classifying a cohort of 90 previously uncharacterized primarily pediatric sarcoma specimens. In total, somatic variants were identified in 45.5% (41/90) of the samples tested, including 22 cases with fusion genes and 19 cases with SNVs or indels. In addition, two of these findings represent novel alterations: a WHSC1L1/NCOA2 fusion and a novel in-frame deletion in the NRAS gene (NM_002524: c.174_176delAGC p.Ala59del). These sequencing results, taken in context with the available clinical data, indicate a potential change in the initial diagnosis, prognosis, or management in 27 of the 90 cases. This study presents a custom RNA sequencing assay that detects fusion genes and SNVs in tandem and has the ability to identify novel fusion partners. These features highlight the advantages associated with utilizing anchored multiplex PCR technology for the rapid and highly sensitive detection of somatic variants.
    MeSH term(s) Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Sarcoma/genetics ; Sequence Analysis, RNA
    Language English
    Publishing date 2020-08-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2000060-1
    ISSN 1943-7811 ; 1525-1578
    ISSN (online) 1943-7811
    ISSN 1525-1578
    DOI 10.1016/j.jmoldx.2020.07.004
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