Lisa M Kopp

Interests

Research

Sarcoma

Courses

Scholarly Contributions

Journals/Publications

• Davis, L. E., Janeway, K. A., Weiss, A. R., Chen, Y. E., Scharschmidt, T. J., Krailo, M., Glade Bender, J. L., Kopp, L. M., Patel, S. R., Schwartz, G. K., Horvath, L. E., Hawkins, D. S., Chuk, M. K., Reinke, D. K., Gorlick, R. G., & Randall, R. L. (2017). Clinical trial enrollment of adolescents and young adults with sarcoma. Cancer.
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  More than half of all sarcomas occur in adolescents and young adults (AYAs) aged 15 to 39 years. After the publication of the AYA series in the April 1, 2016 issue of Cancer, several leaders in the field of sarcoma across disciplines gathered to discuss the status of sarcoma clinical research in AYAs. They determined that a focused effort to include the underrepresented and understudied AYA population in current and future sarcoma clinical trials is overdue. Trial enrichment for AYA-aged sarcoma patients will produce more meaningful results that better represent the disease's biology, epidemiology, and treatment environment. To address the current deficit, this commentary outlines changes believed to be necessary to expediently achieve an increase in the enrollment of AYAs in sarcoma clinical trials. Cancer 2017. © 2017 American Cancer Society.
• Katsanis, E., Sapp, L. N., Pelayo-Katsanis, L., Whitney, K., Zeng, Y., & Kopp, L. M. (2016). Alternative Donor Hematopoietic Cell Transplantation Conditioned With Myeloablative Busulfan, Fludarabine, and Melphalan is Well Tolerated and Effective Against High-risk Myeloid Malignancies. Journal of pediatric hematology/oncology, 38(8), e315-e318.
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  Busulfan, fludarabine, and melphalan as hematopoietic cell transplant conditioning, was used in 6 patients aged 1 to 19 years with very high-risk myeloid malignancies. This dose regimen had an acceptable toxicity profile resulting in complete donor engraftment even following transplantation of small 2/6 antigen disparate umbilical cord blood grafts. It provided excellent disease control as all patients had high-risk features in terms of cytogenetics, therapy-related leukemia, and/or significant measurable disease before transplant. All patients remain in remission, without acute or chronic graft-versus-host disease with a median follow-up of 24 months. A larger study is indicated to confirm the efficacy and safety of this regimen.
• Liu, J., Cranmer, L., Larsen, B. T., Kuo, P. H., & Kopp, L. M. (2016). Recurrent Osteosarcoma Presenting as an Isolated Bone Marrow Relapse. Journal of pediatric hematology/oncology.
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  Osteosarcoma (OS) is a malignant bone tumor which is found primarily in adolescents, with the distal femur as the most common location. OS with a jaw primary is present in only about 10% of cases and the risk of recurrence is considered to be decreased in the jaw versus other primary locations. We present a unique case of a patient with localized OS of the jaw with an isolated recurrence in her bone marrow almost 5 years after completion of initial treatment.
• Houghtelin, A. B., Kopp, L. M., Pelayo-Katsanis, L., Kuo, P. H., Yeager, A. M., & Katsanis, E. (2015). Extramedullary Breast Relapse of Acute Lymphoblastic Leukemia Controlled with a Second Allogeneic/Autologous Hematopoietic Cell Transplant. Journal of adolescent and young adult oncology, 4(1), 50-3.
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  Relapse of acute lymphoblastic leukemia (ALL) in the breast is uncommon and often precedes systemic relapse, resulting in poor survival. We report the development of breast involvement of ALL in a 20-year-old woman 32 months after a related allogeneic peripheral blood hematopoietic cell transplantation (PBHCT) in first remission. This extramedullary relapse occurred in the continuous presence of complete donor chimerism. After systemic re-induction chemotherapy and a second PBHCT using donor cells that had been cryopreserved at first transplant, our patient has remained in second complete remission for more than 44 months.
• Kopp, L. M., Hu, C., Rozo, B., White-Collins, A., Huh, W. W., Yarborough, A., Herzog, C. E., & Hingorani, P. (2015). Utility of bone marrow aspiration and biopsy in initial staging of Ewing sarcoma. Pediatric blood & cancer, 62(1), 12-5.
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  The current standard of care for initial staging of pediatric Ewing sarcoma (EWS) patients is to obtain a bilateral bone marrow aspiration and biopsy (BMAB). The incidence of bone marrow (BM) disease in patients deemed non-metastatic by conventional and metabolic imaging and the concordance of BM positivity with other clinical characteristics are not well established.
• Combs, D., Rice, S. A., & Kopp, L. M. (2014). Incidence of delirium in children with cancer. Pediatric blood & cancer, 61(11), 2094-5.
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  There are limited data on the incidence of delirium in children with cancer. We performed a retrospective chart review of all pediatric oncology admissions over a 1 year period to determine the incidence of delirium in this population. We identified seven patients with delirium (10% incidence). Delirium is associated with significant morbidity and mortality, and is likely under-recognized in this population. Improved diagnosis and treatment of delirium may improve outcomes in children with cancer.
• Kopp, L. M., Desoky, S., Pugh, J., & Herzog, C. E. (2013). Small cell carcinoma of the ovary of the hypercalcemic type presenting in a 5-year-old girl. Journal of pediatric hematology/oncology, 35(5), e217-8.
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  Small cell carcinoma of the ovary, hypercalcemic type is a very rare, highly aggressive tumor associated with a poor prognosis. Diagnosis is typically challenging secondary to undifferentiated cells and the rarity of the tumor. We report our experience with a 5-year-old girl who presented with stage IV disease.
• Kopp, L. M., Ray, A., Denman, C. J., Senyukov, V. S., Somanchi, S. S., Zhu, S., & Lee, D. A. (2013). Decitabine has a biphasic effect on natural killer cell viability, phenotype, and function under proliferative conditions. Molecular immunology, 54(3-4), 296-301.
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  DNA hypermethylation resulting in aberrant epigenetic silencing plays an important role in the oncogenesis of many cancer types, including acute myelogenous leukemia (AML).(4) The modulation of NK cell receptors and their cognate ligands is a known mechanism of immune escape in AML, and some membrane proteins, such as killer immunoglobulin-like receptors (KIR), are known to be transcriptionally regulated by DNA methylation of their promoter regions. Thus, restoring proper expression of immunoreceptors or their ligands with immunosensitizing drugs is an attractive approach to improving cancer immunotherapy. The cytidine analog 5-aza-2'-deoxycytidine (decitabine, DAC) has both a hypomethylating effect at low doses when incorporated into DNA and a cytotoxic effect at higher doses as a result of interfering with translation when incorporated into RNA. Thus, decitabine has been used at higher doses for its direct anti-leukemic effect, and is being tested at low doses for its ability to correct the malignant gene expression phenotype. A known benefit of hypomethylating agents is their ability to sensitize AML blasts to lysis by NK cells. However, there is little information on the direct effect of hypomethylating agents on NK cell phenotype, proliferation, survival, or function. We recently described a method for inducing robust proliferation of NK cells, enabling us to study the hypomethylating effects of decitabine. To distinguish direct toxicity of the decitabine from its hypomethylating effect, and promote hypomethylation during proliferation, decitabine was added to human peripheral blood NK cells at concentrations from 0.02 to 5μM under either static or proliferation-inducing culture conditions. After 5 days, NK cells were assessed for viability, proliferation, cytotoxicity, expression of major activating and inhibitory receptors, and global DNA methylation. Increasing concentrations of decitabine not only causes increased expression of KIR and the activating receptor NKp44, but also causes decreased viability, proliferation, and expression of the activating receptor NKG2D. Decitabine treatment results in a biphasic effect in overall NK cell lytic function, which correlates with a biphasic pattern of global hypomethylation. Decitabine affects the expression of activating and inhibitory receptors in NK cells at low concentrations when exposed during cell proliferation. High doses of decitabine decrease NK cell proliferation and viability, likely through direct inhibition of mRNA transcription. The results of these combined effects leads to a biphasic response in hypomethylation and cytotoxicity. This suggests that optimal immunomodulation with decitabine occurs at low dose ranges and that high doses abrogate this effect through inhibition of proliferation and direct toxicity to NK cells.
• Denman, C. J., Senyukov, V. V., Somanchi, S. S., Phatarpekar, P. V., Kopp, L. M., Johnson, J. L., Singh, H., Hurton, L., Maiti, S. N., Huls, M. H., Champlin, R. E., Cooper, L. J., & Lee, D. A. (2012). Membrane-bound IL-21 promotes sustained ex vivo proliferation of human natural killer cells. PloS one, 7(1), e30264.
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  NK cells have therapeutic potential for a wide variety of human malignancies. However, because NK cells expand poorly in vitro, have limited life spans in vivo, and represent a small fraction of peripheral white blood cells, obtaining sufficient cell numbers is the major obstacle for NK-cell immunotherapy. Genetically-engineered artificial antigen-presenting cells (aAPCs) expressing membrane-bound IL-15 (mbIL15) have been used to propagate clinical-grade NK cells for human trials of adoptive immunotherapy, but ex vivo proliferation has been limited by telomere shortening. We developed K562-based aAPCs with membrane-bound IL-21 (mbIL21) and assessed their ability to support human NK-cell proliferation. In contrast to mbIL15, mbIL21-expressing aAPCs promoted log-phase NK cell expansion without evidence of senescence for up to 6 weeks of culture. By day 21, parallel expansion of NK cells from 22 donors demonstrated a mean 47,967-fold expansion (median 31,747) when co-cultured with aAPCs expressing mbIL21 compared to 825-fold expansion (median 325) with mbIL15. Despite the significant increase in proliferation, mbIL21-expanded NK cells also showed a significant increase in telomere length compared to freshly obtained NK cells, suggesting a possible mechanism for their sustained proliferation. NK cells expanded with mbIL21 were similar in phenotype and cytotoxicity to those expanded with mbIL15, with retained donor KIR repertoires and high expression of NCRs, CD16, and NKG2D, but had superior cytokine secretion. The mbIL21-expanded NK cells showed increased transcription of the activating receptor CD160, but otherwise had remarkably similar mRNA expression profiles of the 96 genes assessed. mbIL21-expanded NK cells had significant cytotoxicity against all tumor cell lines tested, retained responsiveness to inhibitory KIR ligands, and demonstrated enhanced killing via antibody-dependent cell cytotoxicity. Thus, aAPCs expressing mbIL21 promote improved proliferation of human NK cells with longer telomeres and less senescence, supporting their clinical use in propagating NK cells for adoptive immunotherapy.
• Kopp, L. M., Gupta, P., Pelayo-Katsanis, L., Wittman, B., & Katsanis, E. (2012). Late effects in adult survivors of pediatric cancer: a guide for the primary care physician. The American journal of medicine, 125(7), 636-41.
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  Because of significant medical advances in the past 50 years, the number of adult survivors of childhood/adolescent cancer has increased dramatically. Unfortunately, more than 60% of these survivors will have at least 1 long-term side effect from treatment. This growing population requires dedicated care by their primary physicians because they have specific risk factors depending on their initial cancer diagnosis and the treatment modalities they received. Internists and family physicians play an integral role in providing appropriate screening, treatment, and counseling to prevent morbidity and mortality in these patients.
• Anderson, P., Kopp, L., Anderson, N., Cornelius, K., Herzog, C., Hughes, D., & Huh, W. (2008). Novel bone cancer drugs: investigational agents and control paradigms for primary bone sarcomas (Ewing's sarcoma and osteosarcoma). Expert opinion on investigational drugs, 17(11), 1703-15.
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  New investigational agents and chemotherapy regimens including cyclophosphamide + topotecan, temozolomide + irinotecan, and anti-IGF-1R antibodies in Ewing's sarcoma (ES) and liposomal muramyltripeptide phosphatidylethanolamine (L-MTP-PE), aerosol therapy, and bone-specific agents in osteosarcoma (OS) may improve survival and/or quality of life on 'continuation' therapy.
• Quezada, G., Kopp, L., Estey, E., & Wells, R. J. (2008). All-trans-retinoic acid and arsenic trioxide as initial therapy for acute promyelocytic leukemia. Pediatric blood & cancer, 51(1), 133-5.
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  Acute promyelocytic leukemia (APL) is a rare subtype of acute myeloid leukemia (AML). Treatment of pediatric APL is based on the combination of all-trans-retinoic acid (ATRA), an anthracycline and cytosine arabinoside. Arsenic trioxide (ATO) has been studied in adults with newly diagnosed or relapsed APL with excellent response rates both when used as a single agent or in combination with ATRA or ATRA plus chemotherapy. There is little data on combination therapy with ATRA and ATO in pediatric APL. We present a case of an adolescent male with APL who was treated using ATRA and ATO without conventional chemotherapy agents.

Presentations

• Kopp, L. M., Malempati, S., Krailo, M., Weigel, B., Teot, L. A., Cates, J., Neuman, A. R., Villalobos, V., Randall, R. L., Reid, J., Lin, G., Eicher, A., Davis, J., Stahlman, M., Gao, Y., Gorlick, R., & Janeway, K. (2017, November). Phase 2 Trial of the GPNMB-Targeted Antibody Drug Conjugate, CDX-011 (Glembatumumab Vedotin) In Recurrent/Refractory Osteosarcoma (OS): A Report From the Children’s Oncology Group (COG). Connective Tissue Oncology Society (CTOS). Maui.

Poster Presentations

• Kopp, L., Bernstein, M., Schwartz, C., Ebb, D., Franco, V., Hall, D., Barkauskas, D., Krailo, M., Grier, H., Meyers, P., Wexler, L., Marina, N., Womer, R., Janeway, K., Gorlick, R., & Lipshultz, S. (2017, June). Complete Dexrazoxane Cardioprotection for Cardiac Function but Incomplete Female Cardioprotection for Cardiac Structure in Doxorubicin-treated Osteosarcoma Survivors: Hearts Too Small for The Body.. 2017 ASCO Annual Meeting. Chicago: American Society of Clinical Oncology.
• Kopp, L. (2016, December 2016). Effect of Dexrazoxane on Heart Function Among Long-Term Survivors of Childhood Leukemia and lymphoma: A Report from the Children’s Oncology Group (COG). American Society of Hematology.
• Kopp, L. (2016, September). A report of two clinically unsuspected cases, including a unique case arising within the globe. College of American Pathologists – CAP16 Annual Meeting.

Reviews

• Kopp, L. M., & Katsanis, E. (2016. Targeted immunotherapy for pediatric solid tumors(pp e1087637).
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  Metastatic and refractory pediatric solid tumor malignancies continue to have a poor outcome despite the > 80% cure rates appreciated in many pediatric cancers. Targeted immunotherapy is impacting treatment and survival in these aggressive tumors. We review current promising immunotherapeutic approaches in the pediatric oncology solid tumor setting.
• Kopp, L. M., Gastelum, Z., Guerrero, C. H., Howe, C. L., Hingorani, P., & Hingle, M. (2017. Lifestyle behavior interventions delivered using technology in childhood, adolescent, and young adult cancer survivors: A systematic review(pp 13-17).
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  Childhood, adolescent, and young adult cancer survivors demonstrate increased cardio-metabolic risk factors, which are amenable to lifestyle changes. The use of technology to impact lifestyle change expands previously limited intervention access, yet little is known about its use. We summarized lifestyle interventions for survivors delivered using technology, finding six studies, primarily targeting physical activity. Study samples were small and durations ranged from 5 to 16 weeks and outcomes modest. Participants were older, white, survivors of leukemia or brain tumors, and the majority received Web-based interventions. Study quality was moderate. Few technology-based interventions have been developed, suggesting an area of opportunity for survivors.