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Lianna Marks, MD

Specialties

Hematology-Oncology

Work and Education

Professional Education

Indiana University School of Medicine, Indianapolis, IN, 05/15/2011

Residency

Children's Hospital of Philadelphia Pediatric Residency, Philadelphia, PA, 06/30/2014

Fellowship

NY Presbyterian Hospital Columbia Pediatric Hematology and Oncology Fellowship, New York, NY, 06/30/2017

Board Certifications

Pediatric Hematology-Oncology, American Board of Pediatrics

Pediatrics, American Board of Pediatrics

All Publications

Distinct Hodgkin lymphoma subtypes defined by noninvasive genomic profiling. Nature Alig, S. K., Esfahani, M. S., Garofalo, A., Li, M. Y., Rossi, C., Flerlage, T., Flerlage, J. E., Adams, R., Binkley, M. S., Shukla, N., Jin, M. C., Olsen, M., Telenius, A., Mutter, J. A., Schroers-Martin, J. G., Sworder, B. J., Rai, S., King, D. A., Schultz, A., Bgeholz, J., Su, S., Kathuria, K. R., Liu, C. L., Kang, X., Strohband, M. J., Langfitt, D., Pobre-Piza, K. F., Surman, S., Tian, F., Spina, V., Tousseyn, T., Buedts, L., Hoppe, R., Natkunam, Y., Fornecker, L. M., Castellino, S. M., Advani, R., Rossi, D., Lynch, R., Ghesquires, H., Casasnovas, O., Kurtz, D. M., Marks, L. J., Link, M. P., Andr, M., Vandenberghe, P., Steidl, C., Diehn, M., Alizadeh, A. A. 2023

Abstract

The scarcity of malignant Hodgkin and Reed-Sternberg (HRS) cells hamper tissue-based comprehensive genomic profiling of classic Hodgkin lymphoma (cHL). Liquid biopsies, in contrast, show promise for molecular profiling of cHL due to relatively high circulating tumor DNA (ctDNA) levels1-4. Here, we show that the plasma representation of mutations exceeds the bulk tumor representation in most cases, making cHL particularly amenable to noninvasive profiling. Leveraging single-cell transcriptional profiles of cHL tumors, we demonstrate HRS ctDNA shedding to be shaped by DNASE1L3, whose increased tumor microenvironment-derived expression drives high ctDNA concentrations. Using this insight, we comprehensively profile 366 patients, revealing two distinct cHL genomic subtypes with characteristic clinical and prognostic correlates, as well as distinct transcriptional and immunological profiles. Furthermore, we identify a novel class of truncating IL4R-mutations that are dependent on IL13 signaling and therapeutically targetable with IL4R blocking antibodies. Finally, using PhasED-Seq5 we demonstrate the clinical value of pre- and on-treatment ctDNA levels for longitudinally refining cHL risk prediction, and for detection of radiographically occult minimal residual disease. Collectively, these results support the utility of noninvasive strategies for genotyping and dynamic monitoring of cHL as well as capturing molecularly distinct subtypes with diagnostic, prognostic, and therapeutic potential.

View details for DOI 10.1038/s41586-023-06903-x

View details for PubMedID 38081297

Disease site number was not prognostic in a low-risk Hodgkin lymphoma combined modality trial: revisiting PHC HOD90. Blood advances Feraco, A. M., Zhou, Y., Zheng, Y., Marks, L. J., Friedmann, A. M., Weinstein, H. J., Link, M. P., Flerlage, J. E. 2023

View details for DOI 10.1182/bloodadvances.2023010944

View details for PubMedID 37647596

Outcomes in pediatric relapsed/refractory anaplastic large cell lymphoma: A multi-institutional retrospective analysis Marks, L., Ritter, V., Schultz, L. M., Lowe, E. J., Aftandilian, C., Relapsed ALCL Real Consortium LIPPINCOTT WILLIAMS & WILKINS. 2023
POST-TRANSPLANT LYMPHOPROLIFERATIVE DISEASE IN A PATIENT WITH SCHIMKE IMMUNO-OSSEOUS DYSPLASIA Rao, R., Grimm, P., Lewis, D., Spunt, S., Marks, L. WILEY. 2023: S75-S76
Brentuximab Vedotin Following Autologous Transplantation in Pediatric Patients with Relapsed/Refractory Hodgkin Lymphoma. Blood advances Forlenza, C. J., Rosenzweig, J., Mauguen, A., Buhtoiarov, I. N., Cuglievan, B., Dave, H., Deyell, R., Flerlage, J. E., Franklin, A. R., Krajewski, J., Leger, K. J., Marks, L. J., Norris, R. E., Pacheco, M., Willen, F. K., Yan, A. P., Harker-Murray, P., Giulino-Roth, L. 2023

Abstract

Outcomes for children and adolescents with relapsed and refractory Hodgkin lymphoma (HL) are poor, with approximately 50% of patients experiencing a subsequent relapse. The anti-CD30 antibody-drug conjugate brentuximab vedotin improved progression-free survival (PFS) when used as consolidation after autologous stem cell transplant (ASCT) in adults with high-risk relapsed/refractory HL. Data on brentuximab vedotin as consolidative therapy after ASCT in pediatric patients with HL are extremely limited, with only 11 patients reported in the literature. We performed a retrospective analysis of 67 pediatric patients who received brentuximab vedotin as consolidation therapy following ASCT for the treatment of relapsed/refractory HL to describe the experience of this regimen in the pediatric population. This is the largest cohort reported to date. We found that brentuximab vedotin was well tolerated with a safety profile similar to adult patients. With a median follow up of 37 months, the 3-year PFS was 85%. These data suggest a potential role for the use of brentuximab vedotin as consolidation therapy after ASCT for children with relapsed/refractory Hodgkin lymphoma.

View details for DOI 10.1182/bloodadvances.2022009323

View details for PubMedID 36897253

Cellular and humoral immunotherapy in children, adolescents and young adults with non-Hodgkin lymphoma. Best practice & research. Clinical haematology Chu, Y., Gardenswartz, A., Diorio, C., Marks, L. J., Lowe, E., Teachey, D. T., Cairo, M. S. 2023; 36 (1): 101442

Abstract

The prognosis is dismal (2-year overall survival less than 25%) for childhood, adolescent, and young adult (CAYA) with relapsed and/or refractory (R/R) non-Hodgkin lymphoma (NHL). Novel targeted therapies are desperately needed for this poor-risk population. CD19, CD20, CD22, CD79a, CD38, CD30, LMP1 and LMP2 are attractive targets for immunotherapy in CAYA patients with R/R NHL. Novel anti-CD20 monoclonal antibodies, anti-CD38 monoclonal antibody, antibody drug conjugates and T and natural killer (NK)-cell bispecific and trispecific engagers are being investigated in the R/R setting and are changing the landscape of NHL therapy. A variety of cellular immunotherapies such as viral activated cytotoxic T-lymphocyte, chimeric antigen receptor (CAR) T-cells, NK and CAR NK-cells have been investigated and provide alternative options for CAYA patients with R/R NHL. Here, we provide an update and clinical practice guidance of utilizing these cellular and humoral immunotherapies in CAYA patients with R/R NHL.

View details for DOI 10.1016/j.beha.2023.101442

View details for PubMedID 36907635

Multicenter study of pediatric Epstein-Barr virus-negative monomorphic post solid organ transplant lymphoproliferative disorders. Cancer Afify, Z. A., Taj, M. M., Orjuela-Grimm, M., Srivatsa, K., Miller, T. P., Edington, H. J., Dalal, M., Robles, J., Ford, J. B., Ehrhardt, M. J., Ureda, T. J., Rubinstein, J. D., McCormack, S., Rivers, J. M., Chisholm, K. M., Kavanaugh, M. K., Bukowinski, A. J., Friehling, E. D., Ford, M. C., Reddy, S. N., Marks, L. J., Smith, C. M., Mason, C. C. 2022

Abstract

BACKGROUND: Pediatric Epstein-Barr virus-negative monomorphic post solid organ transplant lymphoproliferative disorder [EBV(-)M-PTLD] comprises approximately 10% of M-PTLD. No large multi-institutional pediatric-specific reports on treatment and outcome are available.METHODS: A multi-institutional retrospective review of solid organ recipients diagnosed with EBV(-)M-PTLD aged 21years between 2001 and 2020 in 12 centers in the United States and United Kingdom was performed, including demographics, staging, treatment, and outcomes data.RESULTS: Thirty-six patients were identified with EBV(-)M-PTLD. Twenty-three (63.9%) were male. Median age (range) at transplantation, diagnosis of EBV(-)M-PTLD, and interval from transplant to PTLD were 2.2 years (0.1-17), 14 years (3.0-20), and 8.5 years (0.6-18.3), respectively. Kidney (n=17 [47.2%]) and heart (n=13 [36.1%]) were the most commonly transplanted organs. Most were Murphy stage III (n=25 [69.4%]). Lactate dehydrogenase was elevated in 22/34 (64.7%) and 2 times upper limit of normal in 11/34 (32.4%). Pathological diagnoses included diffuse large B-cell lymphoma (n=31 [86.1%]) and B-non-Hodgkin lymphoma (B-NHL) not otherwise specified (NOS) (n=5 [13.9%]). Of nine different regimens used, the most common were: pediatric mature B-NHL-specific regimen (n=13 [36.1%]) and low-dose cyclophosphamide, prednisone, and rituximab (n=9 [25%]). Median follow-up from diagnosis was 3.0 years (0.3-11.0 years). Three-year event-free survival (EFS) and overall survival (OS) were 64.8% and 79.9%, respectively. Of the seven deaths, six were from progressive disease.CONCLUSIONS: EFS and OS were comparable to pediatric EBV(+) PTLD, but inferior to mature B-NHL in immunocompetent pediatric patients. The wide range of therapeutic regimens used directs our work toward developing an active multi-institutional registry to design prospective studies.PLAIN LANGUAGE SUMMARY: Pediatric Epstein-Barr virus-negative monomorphic post solid organ transplant lymphoproliferative disorders (EBV(-)M-PTLD) have comparable outcomes to EBV(+) PTLD, but are inferior to diffuse large B-cell lymphoma in immunocompetent pediatric patients. The variety of treatment regimens used highlights the need to develop a pediatric PTLD registry to prospectively evaluate outcomes. The impact of treatment regimen on relapse risk could not be assessed because of small numbers. In the intensive pediatric B-non-Hodgkin lymphoma chemoimmunotherapy group, 11 of 13 patients remain alive in complete remission after 0.6 to 11years.

View details for DOI 10.1002/cncr.34600

View details for PubMedID 36571557

Burkitt lymphoma after solid-organ transplant: Treatment and outcomes in the paediatric PTLD collaborative. British journal of haematology Afify, Z., Orjuela-Grimm, M., Smith, C. M., Dalal, M., Ford, J. B., Pillai, P., Robles, J. M., Reddy, S., McCormack, S., Ehrhardt, M. J., Ureda, T., Alperstein, W., Edington, H., Miller, T. P., Rubinstein, J. D., Kavanaugh, M., Bukowinski, A. J., Friehling, E., Rivers, J. M., Chisholm, K. M., Marks, L. J., Mason, C. C. 2022

Abstract

Burkitt lymphoma arising in paediatric post-solid-organ transplantation-Burkitt lymphoma (PSOT-BL) is a clinically aggressive malignancy and a rare form of post-transplant lymphoproliferative disorder (PTLD). We evaluated 35 patients diagnosed with PSOT-BL at 14 paediatric medical centres in the United States. Median age at organ transplantation was 2.0years (range: 0.1-14) and age at PSOT-BL diagnosis was 8.0years (range: 1-17). All but one patient had late onset of PSOT-BL (2years post-transplant), with a median interval from transplant to PSOT-BL diagnosis of 4.0years (range: 0.4-12). Heart (n=18 [51.4%]) and liver (n=13 [37.1%]) were the most frequently transplanted organs. No patients had loss of graft or treatment-related mortality. A variety of treatment regimens were used, led by intensive Burkitt lymphoma-specific French-American-British/Lymphomes Malins B (FAB/LMB), n=13 (37.1%), and a low-intensity regimen consisting of cyclophosphamide, prednisone and rituximab (CPR) n=12 (34.3%). Median follow-up was 6.7years (range: 0.5-17). Three-year event-free and overall survival were 66.2% and 88.0%, respectively. Outcomes of PSOT-BL patients receiving BL-specific intensive regimens are comparable to reported BL outcomes in immunocompetent children. Multi-institutional collaboration is feasible and provides the basis of prospective data collection to determine the optimal treatment regimen for PSOT-BL.

View details for DOI 10.1111/bjh.18498

View details for PubMedID 36454546

Development of clinical pathways to improve multidisciplinary care of high-risk pediatric oncology patients. Frontiers in oncology Reschke, A., Richards, R. M., Smith, S. M., Long, A. H., Marks, L. J., Schultz, L., Kamens, J. L., Aftandilian, C., Davis, K. L., Gruber, T., Sakamoto, K. M. 2022; 12: 1033993

Abstract

Clinical pathways are evidence-based tools that have been integrated into many aspects of pediatric hospital medicine and have proven effective at reducing in-hospital complications from a variety of diseases. Adaptation of similar tools for specific, high-risk patient populations in pediatric oncology has been slower, in part due to patient complexities and variations in management strategies. There are few published studies of clinical pathways for pediatric oncology patients. Pediatric patients with a new diagnosis of leukemia or lymphoma often present with one or more "oncologic emergencies" that require urgent intervention and deliberate multidisciplinary care to prevent significant consequences. Here, we present two clinical pathways that have recently been developed using a multidisciplinary approach at a single institution, intended for the care of patients who present with hyperleukocytosis or an anterior mediastinal mass. These clinical care pathways have provided a critical framework for the immediate care of these patients who are often admitted to the pediatric intensive care unit for initial management. The goal of the pathways is to facilitate multidisciplinary collaborations, expedite diagnosis, and streamline timely treatment initiation. Standardizing the care of high-risk pediatric oncology patients will ultimately decrease morbidity and mortality associated with these diseases to increase the potential for excellent outcomes.

View details for DOI 10.3389/fonc.2022.1033993

View details for PubMedID 36523979

View details for PubMedCentralID PMC9744920

Viral cfDNA Profiling Reveals Distinct EBV Subtypes and Stratifies Risk in Hodgkin Lymphomas Garofalo, A., Alig, S. K., Schroers-Martin, J., Shyam, R., Olsen, M., Kurtz, D. M., Rossi, C., Schultz, A., Kathuria, K. R., Liu, C., Spina, V., Flerlage, J. E., Castellino, S. M., Advani, R. H., Rossi, D., Lynch, R. C., Casasnovas, O., Marks, L. J., Link, M. P., Andre, M., Vandenberghe, P., Steidl, C., Diehn, M., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2022: 1318-1319
End of Treatment Positron Emission Tomography Response and Outcomes in Post-Transplant Lymphoproliferative Disorder Marks, L. J., Green, M., Agarwal, M., Goss, C., Storch, G., Gratzinger, D., Dharnidharka, V. AMER SOC HEMATOLOGY. 2022: 9559-9560
Distinct Molecular Subtypes of Classic Hodgkin Lymphoma Identified By Comprehensive Noninvasive Profiling Alig, S. K., Esfahani, M., Li, M. Y., Adams, R., Garofalo, A., Jin, M. C., Olsen, M., Telenius, A., Sworder, B., Schroers-Martin, J., King, D. A., Rossi, C., Schultz, A., Kathuria, K. R., Liu, C., Spina, V., Buedts, L., Flerlage, J. E., Castellino, S. M., Advani, R. H., Rossi, D., Lynch, R. C., Casasnovas, O., Kurtz, D. M., Marks, L. J., Link, M. P., Andre, M., Vandenberghe, P., Steidl, C., Diehn, M., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2022: 1295-1296
TREATMENT OF POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER (PTLD): A MULTI-CENTER PEDIATRIC SERIES Marks, L., Green, M., Storch, G., Gratzinger, D., Gu, H., Goss, C., Dharnidharka, V. WILEY. 2022
Validation of a non-oncogene encoded vulnerability to exportin 1 inhibition in pediatric renal tumors. Med (New York, N.Y.) Coutinho, D. F., Mundi, P. S., Marks, L. J., Burke, C., Ortiz, M. V., Diolaiti, D., Bird, L., Vallance, K. L., Ibez, G., You, D., Long, M., Rosales, N., Grunn, A., Ndengu, A., Siddiquee, A., Gaviria, E. S., Rainey, A. R., Fazlollahi, L., Hosoi, H., Califano, A., Kung, A. L., Dela Cruz, F. S. 2022

Abstract

Malignant rhabdoid tumors (MRTs) and Wilms' tumors (WTs) are rare and aggressive renal tumors of infants and young children comprising 5% of all pediatric cancers. MRTs are among the most genomically stable cancers, and although WTs are genomically heterogeneous, both generally lack therapeutically targetable genetic mutations.Comparative protein activity analysis of MRTs (n= 68) and WTs (n= 132) across TCGA and TARGET cohorts, using metaVIPER, revealed elevated exportin 1 (XPO1) inferred activity. Invitro studies were performed on a panel of MRT and WT cell lines to evaluate effects on proliferation and cell-cycle progression following treatment with the selective XPO1 inhibitor selinexor. Invivo anti-tumor activity was assessed in patient-derived xenograft (PDX) models of MRTs and WTs.metaVIPER analysis identified markedly aberrant activation of XPO1 in MRTs and WTs compared with other tumor types. All MRT and most WT cell lines demonstrated baseline, aberrant XPO1 activity with invitro sensitivity to selinexor via cell-cycle arrest and induction of apoptosis. Invivo, XPO1 inhibitors significantly abrogated tumor growth in PDX models, inducing effective disease control with sustained treatment. Corroborating human relevance, we present a case report of a child with multiply relapsed WTs with prolonged disease control on selinexor.We report on a novel systems-biology-based comparative framework to identify non-genetically encoded vulnerabilities in genomically quiescent pediatric cancers. These results have provided preclinical rationale for investigation of XPO1 inhibitors in an upcoming investigator-initiated clinical trial of selinexor in children with MRTs and WTs and offer opportunities for exploration of inferred XPO1 activity as a potential predictive biomarker for response.This work was funded by CureSearch for Children's Cancer, Alan B. Slifka Foundation, NIH (U01 CA217858, S10 OD012351, and S10 OD021764), Michael's Miracle Cure, Hyundai Hope on Wheels, Cannonball Kids Cancer, Conquer Cancer the ASCO Foundation, Cycle for Survival, Paulie Strong Foundation, and the Grayson Fund.

View details for DOI 10.1016/j.medj.2022.09.002

View details for PubMedID 36195086

Targeting of the nuclear export protein XPO1 represents a non-genetically encoded vulnerability in malignant rhabdoid and Wilms tumors Coutinho, D. F., Burke, C., Mundi, P., Ortiz, M. V., Vallance, K. L., Long, M., Rosales, N., Ibanez, G., Marks, L. J., Diolaiti, D., Ndengu, A., You, D., Siddiquee, A., Gaviria, E. S., Rainey, A. R., Califano, A., Kung, A. L., Dela Cruz, F. S. AMER ASSOC CANCER RESEARCH. 2022
Pediatric EBV-negative monomorphic post-solid organ transplant lymphoproliferative disorders [EBV(-)M-PTLD]: Characteristics, treatment, and outcome from 11 pediatric academic centers. Afify, Z. M., Taj, M., Srivatsa, K., Miller, T. P., Edington, H., Dalal, M., Robles, J., Ford, J., Ehrhardt, M. J., Ureda, T., Rubinstein, J., McCormack, S., Rivers, J. M., Chisholm, K. M., Kavanaugh, M., Bukowinski, A. J., Friehling, E., Marks, L., Smith, C., Mason, C. LIPPINCOTT WILLIAMS & WILKINS. 2022
Early presentation of post-transplant lymphoproliferative disorders (PTLD) or tumor positivity for epstein-barr virus does not confer better patient survival: A multicenter pediatric series Green, M., Marks, L., Storch, G. A., Dharnidharka, V. R., PTLD MSMS Grp WILEY. 2022
Practice patterns for the management of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL): an international survey by the Global NLPHL One Working Group (GLOW). Leukemia & lymphoma Lo, A. C., Major, A., Super, L., Appel, B., Shankar, A., Constine, L. S., Marks, L. J., Kelly, K. M., Metzger, M. L., Buhtoiarov, I. N., Mauz-Korholz, C., Costa, A. R., Binkley, M. S., Flerlage, J. 2022: 1-4

View details for DOI 10.1080/10428194.2022.2053533

View details for PubMedID 35357263

Pediatric Aggressive Mature B-Cell Lymphomas, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN Barth, M., Xavier, A. C., Armenian, S., Audino, A. N., Blazin, L., Bloom, D., Chung, J., Davies, K., Ding, H., Ford, J. B., Galardy, P. J., Hanna, R., Hayashi, R., Lee-Miller, C., Machnitz, A. J., Maloney, K. W., Marks, L., Martin, P. L., McCall, D., Pacheco, M., Reilly, A. F., Roshal, M., Song, S., Weinstein, J., Zarnegar-Lumley, S., McMillian, N., Schonfeld, R., Sundar, H. 2022; 20 (11): 1267-1275

Abstract

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Aggressive Mature B-Cell Lymphomas include recommendations for the diagnosis and management of pediatric patients with primary mediastinal large B-cell lymphoma (PMBL) and sporadic variants of Burkitt lymphoma and diffuse large B-cell lymphoma. PMBL is now considered as a distinct entity arising from mature thymic B-cells accounting for 2% of mature B-cell lymphomas in children and adolescents. This discussion section includes the recommendations outlined in the NCCN Guidelines for the diagnosis and management of pediatric patients with PMBL.

View details for DOI 10.6004/jnccn.2022.0057

View details for PubMedID 36351334

Brentuximab Vedotin As Consolidation Therapy Following Autologous Stem Cell Transplantation in Children and Adolescents with Relapsed/Refractory Hodgkin Lymphoma: A Multi-Center Retrospective Analysis Forlenza, C. J., Rosenzweig, J., Mauguen, A., Buhtoiarov, I., Cuglievan, B., Dave, H., Deyell, R. J., Flerlage, J., Franklin, A., Krajewski, J., Leger, K. J., Marks, L., Norris, R., Pacheco, M., Willen, F., Yan, A., Harker-Murray, P., Roth, L. AMER SOC HEMATOLOGY. 2021
Outcome of Post Solid Organ Transplant Burkitt Lymphoma (PSOT-BL): A Report from the Pediatric PTLD Collaborative (PPC) Afify, Z., Orjuela, M., Smith, C., Dalal, M., Ford, J. B., Pillai, P., Robles, J., Reddy, S., McCormack, S., Ehrhardt, M. J., Ureda, T., Edington, H., Miller, T. P., Rubinstein, J., Marks, L., Mason, C. C. AMER SOC HEMATOLOGY. 2021
Improving Risk Stratification to Guide Treatment Decisions for Children, Adolescents, and Young Adults With Hodgkin Lymphoma JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Marks, L. J. 2021; 19 (6): 666-668

View details for DOI 10.6004/jnccn.2021.7041

View details for Web of Science ID 000672859700004

View details for PubMedID 34214966

Expert consensus statements for Waldeyer's ring involvement in pediatric Hodgkin lymphoma: The staging, evaluation, and response criteria harmonization (SEARCH) for childhood, adolescent, and young adult Hodgkin lymphoma (CAYAHL) group. Pediatric blood & cancer Seelisch, J. n., De Alarcon, P. A., Flerlage, J. E., Hoppe, B. S., Kaste, S. C., Kelly, K. M., Kurch, L. n., Marks, L. J., Mauz-Koerholz, C. n., McCarten, K. n., Metzger, M. L., Stroevesandt, D. n., Voss, S. D., Punnett, A. n. 2020: e28361

Abstract

Waldeyer's ring (WR) involvement in pediatric Hodgkin lymphoma (HL) is extremely rare and criteria for determining involvement and response to treatment are unclear. The international Staging, Evaluation, and Response Criteria Harmonization for Childhood, Adolescent and Young Adult Hodgkin Lymphoma (SEARCH for CAYAHL) Group performed a systematic review of the literature in search of involvement or response criteria, or evidence to support specific criteria. Only 166 cases of HL with WR involvement were reported in the literature, 7 of which were pediatric. To date no standardized diagnostic or response assessment criteria are available. Given the paucity of evidence, using a modified Delphi survey technique, expert consensus statements were developed by the SEARCH group to allow for a more consistent definition of disease and response evaluation related to this rare site of involvement among pediatric oncologists. The available evidence and expert consensus statements are summarized.

View details for DOI 10.1002/pbc.28361

View details for PubMedID 32672879

Pediatric Aggressive Mature B-Cell Lymphomas, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN Davies, K., Barth, M., Armenian, S., Audino, A. N., Barnette, P., Cuglievan, B., Ding, H., Ford, J. B., Galardy, P. J., Gardner, R., Hanna, R., Hayashi, R., Kovach, A. E., Machnitz, A. J., Maloney, K. W., Marks, L., Page, K., Reilly, A. F., Weinstein, J. L., Xavier, A. C., McMillian, N. R., Freedman-Cass, D. A. 2020; 18 (8): 110523

Abstract

Pediatric aggressive mature B-cell lymphomas are the most common types of non-Hodgkin lymphoma in children, and they include Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). These diseases are highly aggressive but curable, the treatment is complex, and patients may have many complicated supportive care issues. The NCCN Guidelines for Pediatric Aggressive Mature B-Cell Lymphomas provide guidance regarding pathology and diagnosis, staging, initial treatment, disease reassessment, surveillance, therapy for relapsed/refractory disease, and supportive care for clinicians who treat sporadic pediatric BL and DLBCL.

View details for DOI 10.6004/jnccn.2020.0036

View details for PubMedID 32755986

Brentuximab Vedotin as Consolidation Therapy After Autologous Stem Cell Transplantation in Children and Adolescents (<18y) With Early Relapse Hodgkin Lymphoma. Journal of pediatric hematology/oncology Fernandez, K. S., Mavers, M., Marks, L. J., Agarwal, R. 2019

Abstract

We describe 6 pediatric patients (12 to 18y) with relapsed or refractory Hodgkin lymphoma treated with consolidative Brentuximab vedotin (Bv) following reinduction chemotherapy and autologous stem cell transplantation. The progression-free survival after autologous stem cell transplantation was 12, 18, 22, 24, 30, and 30 months. Most patients tolerated Bv well although 2 patients developed grade 3 neuropathy that prevent them from completing the scheduled 16 doses of Bv. Consolidative Bv in children and adolescents, as currently recommended for adult patients with early relapsed or refractory Hodgkin lymphoma, is feasible but with some significant toxicities.

View details for DOI 10.1097/MPH.0000000000001703

View details for PubMedID 31876780

Outcomes in intermediate-risk pediatric lymphocyte-predominant Hodgkin lymphoma: A report from the Children's Oncology Group. Pediatric blood & cancer Marks, L. J., Pei, Q., Bush, R., Buxton, A., Appel, B., Kelly, K. M., Schwartz, C. L., Friedman, D. L. 2018; 65 (12): e27375

Abstract

Optimal management of patients with intermediate-risk lymphocyte-predominant Hodgkin lymphoma (LPHL) is unclear due to their small numbers in most clinical trials. Children's Oncology Group AHOD0031, a randomized phase III trial of pediatric patients with intermediate-risk Hodgkin lymphoma (HL), included patients with LPHL. We report the outcomes of these patients and present directions for future therapeutic strategies.Patients received two cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC) followed by response evaluation. Slow early responders were randomized to two additional ABVE-PC cycles two dexamethasone, etoposide, cisplatin, and cytarabine cycles and all received involved field radiotherapy(IFRT). Rapid early responders (RERs) received two additional ABVE-PC cycles. RERs with complete response (CR) were randomized to IFRT or no further therapy. RERs without CR received IFRT.Ninety-six (5.6%) of 1711 patients on AHOD0031 had LPHL. Patients with LPHL were more likely to achieve RER (93.6% vs. 81.0%; P=0.002) and CR (74.2% vs. 49.3%; P=0.000005) following chemotherapy compared with patients with classical HL. Five-year event-free survival (EFS) was superior in patients with LPHL (92.2%) versus classical HL (83.5%) (P=0.04), without difference in overall survival (OS). Among RERs with CR following chemotherapy (n=33), there was no difference in EFS or OS between those randomized to receive or not receive IFRT.Children and adolescents with intermediate-risk LPHL represent ideal candidates for response-adapted therapy based on their favorable outcomes. The majority of patients treated with the ABVE-PC backbone achieve RER with CR status and can be treated successfully without IFRT.

View details for DOI 10.1002/pbc.27375

View details for PubMedID 30277639

View details for PubMedCentralID PMC6192844

Pericardial effusion in Hodgkin lymphoma: a report from the Children's Oncology Group AHOD0031 protocol BLOOD Marks, L. J., McCarten, K. M., Pei, Q., Friedman, D. L., Schwartz, C. L., Kelly, K. M. 2018; 132 (11): 120811

View details for DOI 10.1182/blood-2018-02-834465

View details for Web of Science ID 000444425900016

View details for PubMedID 30061157

View details for PubMedCentralID PMC6137557

Stroke Prevalence in Children With Sickle Cell Disease in Sub-Saharan Africa: A Systematic Review and Meta-Analysis. Global pediatric health Marks, L. J., Munube, D., Kasirye, P., Mupere, E., Jin, Z., LaRussa, P., Idro, R., Green, N. S. 2018; 5: 2333794X18774970

Abstract

Objectives. The prevalence of stroke among children with sickle cell disease (SCD) in sub-Saharan Africa was systematically reviewed. Methods. Comprehensive searches of PubMed, Embase, and Web of Science were performed for articles published between 1980 and 2016 (English or French) reporting stroke prevalence. Using preselected inclusion criteria, titles and abstracts were screened and full-text articles were reviewed. Results. Ten full-text articles met selection criteria. Cross-sectional clinic-based data reported 2.9% to 16.9% stroke prevalence among children with SCD. Using available sickle gene frequencies by country, estimated pediatric mortality, and fixed- and random-effects model, the number of affected individuals is projected as 29 800 (95% confidence interval = 25 571-34 027) and 59 732 (37 004-82 460), respectively. Conclusion. Systematic review enabled the estimation of the number of children with SCD stroke in sub-Saharan Africa. High disease mortality, inaccurate diagnosis, and regional variability of risk hamper more precise estimates. Adopting standardized stroke assessments may provide more accurate determination of numbers affected to inform preventive interventions.

View details for DOI 10.1177/2333794X18774970

View details for PubMedID 29785408

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Precision Medicine in Children and Young Adults with Hematologic Malignancies and Blood Disorders: The Columbia University Experience FRONTIERS IN PEDIATRICS Marks, L. J., Oberg, J. A., Pendrick, D., Sireci, A. N., Glasser, C., Coval, C., Zylber, R. J., Chung, W. K., Pang, J., Turk, A. T., Hsiao, S. J., Mansukhani, M. M., Bender, J., Kung, A. L., Sulis, M. 2017; 5: 265

Abstract

The advent of comprehensive genomic profiling has markedly advanced the understanding of the biology of pediatric hematological malignancies, however, its application to clinical care is still unclear. We present our experience integrating genomic data into the clinical management of children with high-risk hematologic malignancies and blood disorders and describe the broad impact that genomic profiling has in multiple aspects of patient care.The Precision in Pediatric Sequencing Program at Columbia University Medical Center instituted prospective clinical next-generation sequencing (NGS) for high-risk malignancies and blood disorders. Testing included cancer whole exome sequencing (WES) of matched tumor-normal samples or targeted sequencing of 467 cancer-associated genes, when sample adequacy was a concern, and tumor transcriptome (RNA-seq). A multidisciplinary molecular tumor board conducted interpretation of results and final tiered reports were transmitted to the electronic medical record according to patient preferences.Sixty-nine samples from 56 patients with high-risk hematologic malignancies and blood disorders were sequenced. Patients carried diagnoses of myeloid malignancy (n=25), lymphoid malignancy (n=25), or histiocytic disorder (n=6). Six patients had only constitutional WES, performed for a suspicion of an inherited predisposition for their disease. For the remaining 50 patients, tumor was sequenced with matched normal tissue when available. The mean number of somatic variants per sample was low across the different disease categories (2.85 variants/sample). Interestingly, a gene fusion was identified by RNA-seq in 58% of samples who had adequate RNA available for testing. Molecular profiling of tumor tissue led to clinically impactful findings in 90% of patients. Forty patients (80%) had at least one targetable gene variant or fusion identified in their tumor tissue; however, only seven received targeted therapy. Importantly, NGS findings contributed to the refinement of diagnosis and prognosis for 34% of patients. Known or likely pathogenic germline alterations were discovered in 24% of patients involving cancer predisposition genes in 12% of cases.Incorporating whole exome and transcriptome profiling of tumor and normal tissue into clinical practice is feasible, and the value that comprehensive testing provides extends beyond the ability to target-specific mutations.

View details for DOI 10.3389/fped.2017.00265

View details for Web of Science ID 000417730800001

View details for PubMedID 29312904

View details for PubMedCentralID PMC5732960