Forlenza, Christopher J., Rosenzweig, Jaclyn, Mauguen, Audrey, Buhtoiarov, Ilia, Cuglievan, Branko, Dave, Hema, Deyell, Rebecca J., Flerlage, Jamie E., Franklin, Anna K., Krajewski, Jennifer, Leger, Kasey J., Marks, Lianna J., Norris, Robin E., Pacheco, Martha, Willen, Faye, Yan, Adam Paul, Harker-Murray, Paul D., and Giulino-Roth, Lisa
Gordon, Oren M., primary, Terpilowski, Madeline, additional, Dulman, Robin, additional, Keller, Michael D., additional, Burbelo, Peter D., additional, Cohen, Jeffrey I., additional, Bollard, Catherine M., additional, and Dave, Hema, additional
Holland, Elizabeth M., primary, Gonzalez, Corina, additional, Levy, Elliot, additional, Valera, Vladimir A., additional, Chalfin, Heather, additional, Klicka-Skeels, Jacquelyn, additional, Yates, Bonnie, additional, Kleiner, David E., additional, Hadigan, Colleen, additional, Dave, Hema, additional, Shalabi, Haneen, additional, Hickstein, Dennis D., additional, Su, Helen C., additional, Grimley, Michael, additional, Freeman, Alexandra F., additional, and Shah, Nirali N., additional
Hall, Anurekha G., primary, Winestone, Lena E., additional, Sullivan, Erin M., additional, Wu, Qian Vicky, additional, Lamble, Adam J., additional, Walters, Mark C., additional, Aguayo-Hiraldo, Paibel, additional, Baez Conde, Lourdes, additional, Coker, Tumaini R., additional, Dave, Hema, additional, Dornsife, Dana, additional, Keating, Amy K., additional, Merino, Diana M., additional, Ramsey, Bonnie, additional, Park, Julie R., additional, and Agrawal, Anurag K., additional
Toner, Keri, Dave, Hema, Pezzella, Gloria, Pei, Qinglin, Horton, Terzah M., Kelly, Kara M., Roth, Lisa Giulino, Castellino, Sharon M., and Bollard, Catherine M.
CAR-T cells were not detectable in the blood sample for Patient 1, but for Patients 2 and 3, they were present at 30 days post-infusion, after treatment which included anakinra as well as corticosteroids. Chimeric antigen receptor-T (CAR-T) therapy has demonstrated impressive efficacy in B-cell malignancies, but its therapeutic index has been impaired by unique immune-mediated toxicities not seen with traditional cytotoxic chemotherapy.[1],[2] These toxicities include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hemophagocytic lymphohistiocytosis (HLH)-like syndrome.[2] Although IL-6 blockade with tocilizumab has become standard treatment for CRS, patients refractory to tocilizumab or those with ICANS often require corticosteroids. She was treated with bridging chemotherapy including cyclophosphamide, etoposide, vincristine, and dexamethasone, and then lymphodepleting therapy with fludarabine (30 mg/m SP 2 sp , 4 doses) and cyclophosphamide (500 mg/m SP 2 sp , 2 doses) prior to the CAR-T cell infusion. HT
Abraham, Allistair A., primary, John, Tami D., primary, Keller, Michael D., primary, Cruz, C. Russell Y., primary, Salem, Baheyeldin, primary, Roesch, Lauren, primary, Liu, Hao, primary, Hoq, Fahmida, primary, Grilley, Bambi J., primary, Gee, Adrian P., primary, Dave, Hema, primary, Jacobsohn, David A., primary, Krance, Robert A., primary, Shpall, Elizabeth. J., primary, Martinez, Caridad A., primary, Hanley, Patrick J., primary, and Bollard, Catherine M., primary
Dave, Hema, primary, Hanisch, Benjamin, additional, Mukherjee, Rithu, additional, Jacobsohn, David A., additional, Williams, Devona, additional, Bollard, Catherine M., additional, and Williams, Kirsten M., additional
Zamora, Carlos A., primary, Oppenheimer, Avi G., additional, Dave, Hema, additional, Symons, Heather, additional, Huisman, Thierry A. G. M., additional, and Izbudak, Izlem, additional
Medulloblastoma, the most common malignant brain tumor in children, occurs with increased frequency in individuals with Fanconi anemia who have biallelic germline mutations in BRCA2. We describe an 8-year-old child who had disseminated anaplastic medulloblastoma and a deleterious heterozygous BRCA2 6174delT germline mutation. Molecular profiling was consistent with Group 4 medulloblastoma. The posterior fossa mass was resected and the patient received intensive chemotherapy and craniospinal irradiation. Despite this, the patient succumbed to a second recurrence of his medulloblastoma, which presented 8 months after diagnosis as malignant pleural and peritoneal effusions. Continuous medulloblastoma cell lines were isolated from the original tumor (CHLA-01-MED) and the malignant pleural effusion (CHLA-01R-MED). Here, we provide their analyses, including in vitro and in vivo growth, drug sensitivity, comparative genomic hybridization, and next generation sequencing analysis. In addition to the BRCA2 6174delT, the medulloblastoma cells had amplification of MYC, deletion at Xp11.2, and isochromosome 17, but no structural variations or overexpression of GFI1 or GFI1B. To our knowledge, this is the first pair of diagnosis/recurrence medulloblastoma cell lines, the only medulloblastoma cell lines with BRCA2 6174delT described to date, and the first reported case of a child with medulloblastoma associated with a germline BRCA2 6174delT who did not also have Fanconi anemia. [ABSTRACT FROM AUTHOR]
Dave H, Luo M, Blaney JW, Patel S, Barese C, Cruz CR, Shpall EJ, Bollard CM, and Hanley PJ
Abstract
Umbilical cord blood (CB) has emerged as an effective alternative donor source for hematopoietic stem cell transplantation. Despite this success, the prolonged duration of immune suppression following CB transplantation and the naiveté of CB T cells leave patients susceptible to viral infections. Adoptive transfer of ex vivo-expanded virus-specific T cells from CB is both feasible and safe. However, the manufacturing process of these cells is complicated, lengthy, and labor-intensive. We have now developed a simplified method to manufacture a single culture of polyclonal multivirus-specific cytotoxic T cells in less than 30 days. It eliminates the need for a live virus or transduction with a viral vector, thus making this approach widely available and GMP-applicable to target multiple viruses. The use of overlapping PepMixes as a source of antigen stimulation enable expansion of the repertoire of the T cell product to any virus of interest and make it available as a third party "off the shelf" treatment for viral infections following transplantation.