Michelina De La Maza

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Journals/Publications

• Goldsmith, R. M., Xing, J. L., Heal, C. W., De La Maza, M. C., & Stea, B. (2024). Stereotactic Body Radiation Therapy and Concurrent Targeted Therapy for Lung Metastases in Pediatric Sarcoma. Advances in radiation oncology, 9(7), 101517.
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  The purpose of this investigation was to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) for pulmonary metastases from pediatric sarcomas.
• Nwosu, I. E., Zhang, J., Elliott, A. S., De La Maza, M., & Sun, B. L. (2024). Large cell neuroendocrine carcinoma in pancreatoblastoma with TP53 and SMAD4 mutations: a clinicopathologic study of a rare entity. Journal of surgical case reports, 2024(11), rjae654.
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  Pancreatoblastoma, a rare pancreatic tumor, exhibits diverse differentiation pathways, including acinar, ductal, and neuroendocrine lineages, often with distinct squamoid nests [3]. We present a notable case of pancreatoblastoma coexisting with large cell neuroendocrine carcinoma in a 10-year-old boy, presenting with abdominal discomfort, weight loss, and lesions in the pancreas, spleen, and liver visible on imaging. A liver biopsy revealed a poorly differentiated carcinoma with neuroendocrine features, while a splenic biopsy showed acinar cell differentiation, raising possible diagnoses of pancreatoblastoma or acinar cell carcinoma. Subsequent surgical resection after chemotherapy revealed diverse components within the pancreatoblastoma, including well-differentiated acinar and neuroendocrine cells, squamoid nests, and a high-grade neuroendocrine carcinoma. Genetic analysis detected pathogenic variants in TP53 and SMAD4, rarely found in pancreatoblastomas. This juxtaposition of large cell neuroendocrine carcinoma and pancreatoblastoma suggests a potential evolution from well-differentiated neuroendocrine tumors to poorly-differentiated carcinomas within pancreatoblastomas.
• Strah, D., Stanley, K., Oatmen, K., Kylat, R. I., Dishop, M., & de la Maza, M. (2023). An unusual presentation of neonatal rhabdomyosarcoma: a case report. Frontiers in pediatrics, 11, 1233334.
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  A full-term infant with an unremarkable prenatal course presented at birth with a large midline facial mass and smaller masses in the head and neck. In addition, multiple diffuse flesh-colored nodules spread along all the upper and lower limbs. An extensive evaluation to cover a broad differential diagnosis of infectious, lymphatic/vascular, and oncologic etiology was undertaken. The initial suspicion was confirmed by biopsy of the skin lesion as congenital alveolar rhabdomyosarcoma (RMS). RMS is the most common soft tissue sarcoma that occurs in childhood. However, neonatal RMS is exceedingly rare. The infant's initial treatment included vincristine, dactinomycin, and cyclophosphamide in addition to salvage ifosfamide and etoposide, which were dose-adjusted for age. Herein, we present a case of an infant with RMS who showed initial improvement before relapsing and succumbing to her disease at 5 months of age. A review of the limited literature available on this rare condition and newer treatment regimens with improved mortality rates is performed.
• Truscott, L., Pariury, H., Hanmod, S., Davini, M., de la Maza, M., Sapp, L. N., Staples, K., Proytcheva, M., & Katsanis, E. (2023). Busulfan, fludarabine, and melphalan are effective conditioning for pediatric and young adult patients with myeloid malignancies underdoing matched sibling or alternative donor transplantation. Pediatric blood & cancer, 70(2), e30102.
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  Allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative option for patients with high-risk myeloid malignancies.
• Davini, M., Hanmod, S., Katsanis, E., Maza, M. d., Pariury, H., Proytcheva, M., Sapp, L., Staples, K., & Truscott, L. (2022). Busulfan Fludarabine and Melphalan is effective conditioning for pediatric and young adult patients with myeloid malignancies underdoing matched sibling or alternative donor transplantation. Pediatric Blood & Cancer. doi:10.21203/rs.3.rs-1717185/v1
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  Abstract Background: Allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative option for patients with high-risk myeloid malignancies. Objectives : We reviewed our ten-year experience (October 2012 thru October 2021) of allo-HCT in patients with myeloid malignancies treated on the pediatric HCT service and conditioned with myeloablative targeted dose-busulfan (BU), fludarabine (FLU) and melphalan (MEL). Study Design: Twenty-three children, adolescents, and young adult patients (CAYA) (median age 15.4 years, range 0.6 to 27.2) with acute myeloid leukemia (AML) (n=17), myelodysplastic syndrome (MDS) (n=4), or chronic myeloid leukemia (CML) (n=2) underwent allo-HCT conditioned with BU-FLU-MEL. Four patients had treatment-related AML/MDS, following osteogenic and Ewing sarcoma (t-AML, n=2) and acute lymphoblastic leukemia (t-MDS, n=2). Donor/stem cell source was matched sibling donor (MSD) peripheral blood stem cells (PBSC) (n=7), matched unrelated donor (MUD) PBSC (n=2), unrelated single (n=1) or double umbilical cord blood (UCB) (n=2) or haploidentical donor bone marrow (haplo-BMT) (n=11). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine-methotrexate (CSA-MTX) for MSD and MUD, and CSA-mycophenolate mofetil (MMF) for unrelated UCB transplants. Patients undergoing T-cell replete haplo-BMT received post-transplant cyclophosphamide (PT-CY) (n=7) or cyclophosphamide and bendamustine PT-CY/BEN (n=4) with tacrolimus and MMF. Thirteen patients with of AML were in first remission (CR1) with seven being minimal residual disease negative (MRD - ), three patients in second remission (CR2) with two MRD - , and five patients had received no treatment prior to allo-HCT (MDS, n=4 and AML evolved from del(7q) MDS). Risk stratification based on remission/MRD status, cytogenetics and age was low (n=2), intermediate (n=15), high (=3) and very high risk (n=1). The two patients with CML had failed tyrosine kinase inhibitor therapies. Results: With a median follow-up of 37.2 months the relapse rate is only 4.5% with a remarkable overall survival (OS) of 100%, progression-free survival (PFS) of 95.5% and graft-versus-host-free relapse-free survival (GRFS) of 67.8%. The donor source and the graft-versus-host-disease (GvHD) prophylaxis regimen significantly impacted the cumulative incidence of grades II-IV acute GvHD (aGvHD) 66.7% versus 18.2% ( P=0.03 ) and chronic GvHD (cGvHD) 66.7% versus 0% ( P=0.001 ) in the patients receiving MSD or MUD PBSC compared to haplo-BMT respectively. This resulted in significantly improved GRFS in haplo-BMT recipients of 83.3% compared to 40% in patients receiving related or unrelated matched donor PBSC transplantation ( P=0.025 ). Conclusions: Our results demonstrate that BU-FLU-MEL is an efficacious conditioning regimen for disease control in young patients with myeloid malignancies undergoing matched sibling or alternative donor hematopoietic cell transplantation but in the setting of PBSC grafts with CSA-MTX GvHD prophylaxis it results in an unacceptably high incidence of GvHD.
• de la Maza, M., Katsanis, E., Davini, M., Proytcheva, M., Truscott, L., de la Maza, M., Pariury, H., Davini, M., Hanmod, S., Hanmod, S., Sapp, L. N., Pariury, H., Staples, K., Truscott, L., Proytcheva, M., Sapp, L. N., Staples, K., & Katsanis, E. (2022). Busulfan, fludarabine, and melphalan are effective conditioning for pediatric and young adult patients with myeloid malignancies underdoing matched sibling or alternative donor transplantation. Pediatric Blood & Cancer, 70(2). doi:10.1002/pbc.30102
• Markus, H., Zhao, J., Contente-Cuomo, T., Stephens, M. D., Raupach, E., Odenheimer-Bergman, A., Connor, S., McDonald, B. R., Moore, B., Hutchins, E., McGilvrey, M., de la Maza, M. C., Van Keuren-Jensen, K., Pirrotte, P., Goel, A., Becerra, C., Von Hoff, D. D., Celinski, S. A., Hingorani, P., & Murtaza, M. (2021). Analysis of recurrently protected genomic regions in cell-free DNA found in urine. Science translational medicine, 13(581).
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  Cell-free DNA (cfDNA) in urine is a promising analyte for noninvasive diagnostics. However, urine cfDNA is highly fragmented. Whether characteristics of these fragments reflect underlying genomic architecture is unknown. Here, we characterized fragmentation patterns in urine cfDNA using whole-genome sequencing. Size distribution of urine cfDNA fragments showed multiple strong peaks between 40 and 120 base pairs (bp) with a modal size of 81- and sharp 10-bp periodicity, suggesting transient protection from complete degradation. These properties were robust to preanalytical perturbations, such as at-home collection and delay in processing. Genome-wide sequencing coverage of urine cfDNA fragments revealed recurrently protected regions (RPRs) conserved across individuals, with partial overlap with nucleosome positioning maps inferred from plasma cfDNA. The ends of cfDNA fragments clustered upstream and downstream of RPRs, and nucleotide frequencies of fragment ends indicated enzymatic digestion of urine cfDNA. Compared to plasma, fragmentation patterns in urine cfDNA showed greater correlation with gene expression and chromatin accessibility in epithelial cells of the urinary tract. We determined that tumor-derived urine cfDNA exhibits a higher frequency of aberrant fragments that end within RPRs. By comparing the fraction of aberrant fragments and nucleotide frequencies of fragment ends, we identified urine samples from cancer patients with an area under the curve of 0.89. Our results revealed nonrandom genomic positioning of urine cfDNA fragments and suggested that analysis of fragmentation patterns across recurrently protected genomic loci may serve as a cancer diagnostic.
• Boklan, J. L., Walsh, A. M., de la Maza, M. C., Su, L. L., Nizzi, F. A., & Schafernak, K. T. (2018). Pediatric Chronic Myeloid Leukemia Presenting With Extreme Thrombocytosis Simulating Essential Thrombocythemia. Journal of pediatric hematology/oncology, 40(6), 456-457.
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  A 10-year-old boy presented with spontaneous bruising and was found to have extreme thrombocytosis without neutrophilia/shift to immaturity, basophilia or eosinophilia. While the peripheral blood and bone marrow findings initially suggested essential thrombocythemia, BCR-ABL1 translocation was detected and chronic myeloid leukemia, chronic phase, was diagnosed. Apheresis for platelet depletion was performed as a bridge given the delayed effects of medical therapy.

Proceedings Publications

• Maza, M. d., Davini, M., Katsanis, E., Truscott, L., Pariury, H., Hanmod, S., CPNP, L. S., Staples, K., & Proytcheva, M. (2022). Busulfan Fludarabine and Melphalan is effective conditioning for pediatric and young adult patients with myeloid malignancies underdoing matched sibling or alternative donor transplantation. In Pediatric Blood and Cancer.
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  Abstract Background: Allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative option for patients with high-risk myeloid malignancies. Objectives : We reviewed our ten-year experience (October 2012 thru October 2021) of allo-HCT in patients with myeloid malignancies treated on the pediatric HCT service and conditioned with myeloablative targeted dose-busulfan (BU), fludarabine (FLU) and melphalan (MEL). Study Design: Twenty-three children, adolescents, and young adult patients (CAYA) (median age 15.4 years, range 0.6 to 27.2) with acute myeloid leukemia (AML) (n=17), myelodysplastic syndrome (MDS) (n=4), or chronic myeloid leukemia (CML) (n=2) underwent allo-HCT conditioned with BU-FLU-MEL. Four patients had treatment-related AML/MDS, following osteogenic and Ewing sarcoma (t-AML, n=2) and acute lymphoblastic leukemia (t-MDS, n=2). Donor/stem cell source was matched sibling donor (MSD) peripheral blood stem cells (PBSC) (n=7), matched unrelated donor (MUD) PBSC (n=2), unrelated single (n=1) or double umbilical cord blood (UCB) (n=2) or haploidentical donor bone marrow (haplo-BMT) (n=11). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine-methotrexate (CSA-MTX) for MSD and MUD, and CSA-mycophenolate mofetil (MMF) for unrelated UCB transplants. Patients undergoing T-cell replete haplo-BMT received post-transplant cyclophosphamide (PT-CY) (n=7) or cyclophosphamide and bendamustine PT-CY/BEN (n=4) with tacrolimus and MMF. Thirteen patients with of AML were in first remission (CR1) with seven being minimal residual disease negative (MRD - ), three patients in second remission (CR2) with two MRD - , and five patients had received no treatment prior to allo-HCT (MDS, n=4 and AML evolved from del(7q) MDS). Risk stratification based on remission/MRD status, cytogenetics and age was low (n=2), intermediate (n=15), high (=3) and very high risk (n=1). The two patients with CML had failed tyrosine kinase inhibitor therapies. Results: With a median follow-up of 37.2 months the relapse rate is only 4.5% with a remarkable overall survival (OS) of 100%, progression-free survival (PFS) of 95.5% and graft-versus-host-free relapse-free survival (GRFS) of 67.8%. The donor source and the graft-versus-host-disease (GvHD) prophylaxis regimen significantly impacted the cumulative incidence of grades II-IV acute GvHD (aGvHD) 66.7% versus 18.2% ( P=0.03 ) and chronic GvHD (cGvHD) 66.7% versus 0% ( P=0.001 ) in the patients receiving MSD or MUD PBSC compared to haplo-BMT respectively. This resulted in significantly improved GRFS in haplo-BMT recipients of 83.3% compared to 40% in patients receiving related or unrelated matched donor PBSC transplantation ( P=0.025 ). Conclusions: Our results demonstrate that BU-FLU-MEL is an efficacious conditioning regimen for disease control in young patients with myeloid malignancies undergoing matched sibling or alternative donor hematopoietic cell transplantation but in the setting of PBSC grafts with CSA-MTX GvHD prophylaxis it results in an unacceptably high incidence of GvHD.
• McGilvrey, M., Murtaza, M., Hingorani, P., Celinski, S., Hoff, D. D., Becerra, C., Goel, A., Pirrotte, P., Jensen, K. V., Maza, M. C., Hutchins, E., McDonald, B. R., Connor, S., Odenheimer-Bergman, A., Raupach, E. A., Contente-Cuomo, T., Zhao, J., & Markus, H. (2020). Abstract PR14: Sub-nucleosomal fragmentation in urine cell-free DNA. In NA.

Poster Presentations

• De La Maza, M., Stea, B., Riley, G., Jessica, X., & Cory, H. (2022, November). Stereotactic Ablative Body Radiotherapy for Pediatric Osteosarcoma Pulmonary Metastases. CTOS. Vancouver, BC.
• Stephens, L., & De La Maza, M. (2022, November). Seeing Red: Iatrogenic Transfusion Reaction in a Pediatric Oncology Patient. AABB.