Laura Pardo

Hospital Pedro de Elizalde

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Soheil Meshinchi

Fred Hutch Cancer Center

Michael R. Loken

Applied Biomathematics (United States)

Todd A. Alonzo

University of Southern California

Robert B. Gerbing

Children's Oncology Group

Rhonda E. Ries

Fred Hutch Cancer Center

Alan S. Gamis

Children's Mercy Hospital

Richard Aplenc

Children's Hospital of Philadelphia

Tiffany Hylkema

Fred Hutch Cancer Center

Lisa Eidenschink Brodersen

Children's Hospital of Philadelphia

Katherine Tarlock

Seattle Children's Hospital

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Fred Hutch Cancer Center

University of Washington

Children's Oncology Group

Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa

Cancer Research Center

Seattle Children's Hospital

Hospital Universitari de Girona Doctor Josep Trueta

St. Jude Children's Research Hospital

Seattle University

University of British Columbia

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Table S4 from Functional Properties of KIT Mutations Are Associated with Differential Clinical Outcomes and Response to Targeted Therapeutics in CBF Acute Myeloid Leukemia

Katherine Tarlock Todd A. Alonzo Yi‐Cheng Wang Robert B. Gerbing Rhonda E. Ries

Supplementary Table 4. Clinical outcomes for patients with CBF AML according to E8+ vs KIT- mutational status

Table (database)

10.1158/1078-0432.22473627.v1

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Data from Functional Properties of KIT Mutations Are Associated with Differential Clinical Outcomes and Response to Targeted Therapeutics in CBF Acute Myeloid Leukemia

Katherine Tarlock Todd A. Alonzo Yi‐Cheng Wang Robert B. Gerbing Rhonda E. Ries

<div>AbstractPurpose:KIT mutations (KIT+) are common in core binding factor (CBF) AML and have been associated with varying prognostic significance. We sought to define the functional and clinical significance of distinct KIT mutations in CBF pediatric AML.Experimental Design:Following transfection of exon 17 (E17) and exon 8 (E8) mutations into HEK293 and Ba/F3 cells, KIT phosphorylation, cytokine-independent growth, and response to tyrosine kinase inhibitors (TKI) were evaluated. Clinical outcomes of patients treated on COG AAML0531 (NCT01407757), a phase III study of gemtuzumab ozogamicin (GO), were analyzed according to mutation status [KIT+ vs. wild-type KIT (KIT−)] and mutation location (E8 vs. E17).Results:KIT mutations were detected in 63 of 205 patients (31%); 22 (35%) involved only E8, 32 (51%) only E17, 6 (10%) both exons, and 3 (5%) alternative exons. Functional studies demonstrated that E17, but not E8, mutations result in aberrant KIT phosphorylation and growth. TKI exposure significantly affected growth of E17, but not E8, transfected cells. Patients with KIT+ CBF AML had overall survival similar to those with KIT− (78% vs. 81%, P = 0.905) but higher relapse rates (RR = 43% vs. 21%; P = 0.005). E17 KIT+ outcomes were inferior to KIT− patients [disease-free survival (DFS), 51% vs. 73%, P = 0.027; RR = 21% vs. 46%, P = 0.007)], although gemtuzumab ozogamicin abrogated this negative prognostic impact. E8 mutations lacked significant prognostic effect, and GO failed to significantly improve outcome.Conclusions:E17 mutations affect prognosis in CBF AML, as well as response to GO and TKIs; thus, clinical trials using both agents should be considered for KIT+ patients.</div>

10.1158/1078-0432.c.6528567

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Functional Properties of KIT Mutations Are Associated with Differential Clinical Outcomes and Response to Targeted Therapeutics in CBF Acute Myeloid Leukemia

Clinical Cancer Research (2019)

Katherine Tarlock Todd A. Alonzo Yi-Cheng Wang Robert B. Gerbing Rhonda E. Ries

KIT mutations (KIT+) are common in core binding factor (CBF) AML and have been associated with varying prognostic significance. We sought to define the functional and clinical significance of distinct KIT mutations in CBF pediatric AML.Following transfection of exon 17 (E17) and exon 8 (E8) mutations into HEK293 and Ba/F3 cells, KIT phosphorylation, cytokine-independent growth, and response to tyrosine kinase inhibitors (TKI) were evaluated. Clinical outcomes of patients treated on COG AAML0531 (NCT01407757), a phase III study of gemtuzumab ozogamicin (GO), were analyzed according to mutation status [KIT+ vs. wild-type KIT (KIT-)] and mutation location (E8 vs. E17).KIT mutations were detected in 63 of 205 patients (31%); 22 (35%) involved only E8, 32 (51%) only E17, 6 (10%) both exons, and 3 (5%) alternative exons. Functional studies demonstrated that E17, but not E8, mutations result in aberrant KIT phosphorylation and growth. TKI exposure significantly affected growth of E17, but not E8, transfected cells. Patients with KIT+ CBF AML had overall survival similar to those with KIT- (78% vs. 81%, P = 0.905) but higher relapse rates (RR = 43% vs. 21%; P = 0.005). E17 KIT+ outcomes were inferior to KIT- patients [disease-free survival (DFS), 51% vs. 73%, P = 0.027; RR = 21% vs. 46%, P = 0.007)], although gemtuzumab ozogamicin abrogated this negative prognostic impact. E8 mutations lacked significant prognostic effect, and GO failed to significantly improve outcome.E17 mutations affect prognosis in CBF AML, as well as response to GO and TKIs; thus, clinical trials using both agents should be considered for KIT+ patients.

Gemtuzumab ozogamicin

Core binding factor

Targeted Therapy

10.1158/1078-0432.ccr-18-1897

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Supplementary Tables from Comprehensive Transcriptome Profiling of Cryptic CBFA2T3–GLIS2 Fusion–Positive AML Defines Novel Therapeutic Options: A COG and TARGET Pediatric AML Study

Jenny L. Smith Rhonda E. Ries Tiffany Hylkema Todd A. Alonzo Robert B. Gerbing

Supplemental tables including clinical characteristics and differentially expressed gene lists.

Cog

10.1158/1078-0432.22473323

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Factores pronósticos en el cáncer colorrectal: Análisis multivariado de 224 pacientes

Revista médica de Chile (2001)

Guillermo Bannura Miguel A. Cumsille Juan Pablo Contreras Carlos Melo ALEJANDRO BARRERA E

Staging of colorectal carcinoma has prognostic value and allows to take decisions about adjuvant therapy and follow up. Prognostic factors are not universally accepted and there are different staging classifications.To assess the prognostic value of clinical and pathological variables in 224 patients subjected to a curative resection of a colorectal carcinoma.A retrospective analysis of 99 men and 125 women, aged 23 to 91 years old subjected to a curative resection of a colorectal carcinoma and followed up for a mean of 72 months.Global survival at 60 months was 72%. Univariate analysis showed that tumor localization, vascular permeation, wall infiltration and number of involved lymph nodes had an influence on survival. A Cox regression model disclosed tumor localization (colon versus rectum), a carcino-embryonic antigen over 30 ng/ml, vascular permeation, presence of 1 to 4 involved lymph nodes, or 5 or more lymph nodes and the presence of an apical lymph node as variables with significant prognostic value.Our series confirms the prognostic importance of lymph node involvement. This parameter is incorporated in Jass, GITSG (both modifications of Dukes classIfication) and TNM staging scores.

Univariate analysis

Adjuvant Therapy

10.4067/s0034-98872001000300001

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Down Syndrome AML Is Unique in Phenotype Both at Diagnosis and in Post Chemotherapy Regeneration

Blood (2016)

Elisabeth R. Wilson Lisa Eidenschink Brodersen Barbara K. Zehentner Andrew J. Menssen Andrew P. Voigt

Immunophenotyping

Minimal Residual Disease

10.1182/blood.v128.22.1687.1687

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Prognostic Significance of Albumin Levels Prior to Treatment in Patients With Head and Neck Squamous Cell Carcinoma

Acta Otorrinolaringologica (English Edition) (2020)

Xavier León Laura Pardo Aina Sansa Rocío Puig Cristina Serrano

Serum Albumin

10.1016/j.otoeng.2019.06.004

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Comparing survival of patients with single or multiple primary melanoma in The Netherlands: 1994- 2009

Dermatology Online Journal (2016)

Laura Pardo R.J.T. ven der Leest Elisabeth G.E. de Vries Isabelle Soerjomataram Tamar Nijsten

There is conflicting literature as to whether the survival of patients with multiple melanoma is worse that this of single melanoma cases. We used extended Cox-proportional hazard models to estimate hazard-ratios (HR) of patients with multiple melanomas against single melanomas. Data from the nationwide Dutch Cancer Registry was used to retrieve cutaneous melanoma cases between 1994 and 2009 and linked with municipal records to assess the vital status. To account for the longer survival in the multiple melanoma cases we modelled multiple melanoma as time-varying variable, as well as Breslow thickness, histological subtype and nodal/distant metastasis. In total, 42,733 melanoma cases were identified, of which 1210 (3%) developed a new primary melanoma during a total follow-up of 11 years. The adjusted HR for multiple melanoma was 1.32 (95 %CI: 1.17-1.50) adjusting for age, sex, Breslow thickness, histological subtype and presence of nodal and distant metastasis . Our study showed that patients with multiple melanomas have an increased risk of dying when compared with single melanoma cases, and suggests that the improved survival of patients with multiple melanoma shown in previous studies was an artefact due to survival bias. Based on our findings we advise, within the guideline of five years of follow-up, to focus on high-quality patient-education about skin self-examination and the risks of subsequent melanomas.

Breslow Thickness

Guideline

10.5070/d3229032530

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Discovery and Validation of Cell-Surface Protein Mesothelin (MSLN) As a Novel Therapeutic Target in AML: Results from the COG/NCI Target AML Initiative

Blood (2016)

Katherine Tarlock Allison Kaeding Todd A. Alonzo Michael R. Loken Rhonda E. Ries

Mesothelin

10.1182/blood.v128.22.2873.2873

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Citations (5)