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3.
Blood Adv ; 7(13): 3225-3231, 2023 07 11.
Article in English | MEDLINE | ID: mdl-36897253

ABSTRACT

Outcomes for children and adolescents with relapsed and refractory Hodgkin lymphoma (HL) are poor, with ∼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 transplantation (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 data of only 11 patients reported in the literature. We performed a retrospective analysis of 67 pediatric patients who received brentuximab vedotin as consolidation therapy after 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 that of 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 HL.


Subject(s)
Hematopoietic Stem Cell Transplantation , Hodgkin Disease , Adult , Adolescent , Humans , Child , Brentuximab Vedotin/therapeutic use , Hodgkin Disease/drug therapy , Hodgkin Disease/pathology , Transplantation, Autologous , Retrospective Studies
4.
Cancer Genet ; 262-263: 43-46, 2022 04.
Article in English | MEDLINE | ID: mdl-34995897

ABSTRACT

The KMT2A::AFF3 fusion, t(2;11)(q11.2;q23.2), is a very rare fusion occurring in pediatric B-cell acute lymphoblastic leukemia (B-ALL). Our patient is a 2-year-old male who presented with three weeks of intermittent fever. Bone marrow biopsy showed 82% blasts and cytogenetic analysis demonstrated a complex 3-way chromosomal rearrangement involving KMT2A and an unknown fusion partner. Molecular testing identified the fusion partner as AFF3, a FLT3-TKD non-D835 mutation, and an NF1 mutation. This case demonstrates a highly complex three-way variant translocation resulting in the rare KMT2A::AFF3 fusion with only a few cases previously described in the literature.


Subject(s)
Lymphoma, Non-Hodgkin , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Child, Preschool , Chromosome Aberrations , Gene Fusion , Humans , Lymphoma, Non-Hodgkin/genetics , Male , Myeloid-Lymphoid Leukemia Protein/genetics , Nuclear Proteins/genetics , Oncogene Proteins, Fusion/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Translocation, Genetic
5.
J Natl Compr Canc Netw ; 18(8): 1125-1134, 2020 08.
Article in English | MEDLINE | ID: mdl-32755987

ABSTRACT

Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), and primary mediastinal B-cell lymphoma are the most common aggressive pediatric mature B-cell non-Hodgkin lymphomas (B-NHLs). Despite excellent survival with current chemotherapy regimens, therapy for Burkitt lymphoma and DLBCL has a high incidence of short- and long-term toxicities. Patients who experience relapse generally have a very poor prognosis. Therefore, novel approaches using targeted therapies to reduce toxicities and improve outcomes in the relapse setting are needed. The addition of rituximab, a monoclonal antibody against CD20, to upfront therapy has improved survival outcomes for high-risk patients and may allow decreased total chemotherapy in those with low-risk disease. Antibody-drug conjugates have been combined with chemotherapy in relapsed/refractory (R/R) NHL, and multiple antibody-drug conjugates are in development. Additionally, bispecific T-cell-engaging antibody constructs and autologous CAR T-cells have been successful in the treatment of R/R acute leukemias and are now being applied to R/R B-NHL with some successes. PD-L1 and PD-L2 on tumor cells can be targeted with checkpoint inhibitors, which restore T-cell-mediated immunity and antitumor responses and can be added to conventional chemotherapy and immune-directed therapies to augment responses. Lastly, trials of small molecule inhibitors targeting cell signaling pathways in NHL subtypes are underway. This article reviews many of the targeted therapies under development that could be considered for future trials in R/R pediatric mature B-NHL.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Lymphoma, Non-Hodgkin , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Non-Hodgkin/drug therapy , Rituximab/therapeutic use
6.
Pediatr Blood Cancer ; 61(4): 579-86, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24504790

ABSTRACT

Risk-adapted, response-based therapies for pediatric Hodgkin lymphoma have resulted in 5-year survival exceeding 90%. Although high-dose chemotherapy and autologous hematopoietic stem cell transplantation (AHSCT) are considered standard for most patients with relapsed or refractory Hodgkin lymphoma, a subset of children with low risk relapse do not require AHSCT for cure. Currently there are no widely accepted criteria defining who should receive standard dose chemotherapy and/or radiotherapy, nor is there a standardized treatment regimen. We propose a risk-stratified, response-based algorithm for children with relapsed or refractory Hodgkin lymphoma that is based on a critical appraisal of published outcomes and prognostic factors.


Subject(s)
Hodgkin Disease/therapy , Neoplasm Recurrence, Local/therapy , Combined Modality Therapy , Humans
7.
Biol Blood Marrow Transplant ; 14(6): 685-92, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18489994

ABSTRACT

Allogeneic hematopoietic cell transplantation (HCT) is the standard of care for pediatric patients with early medullary relapse of acute lymphoblastic leukemia (ALL). Most patients with isolated central nervous system (CNS) relapse have good outcomes when treated with intrathecal and systemic chemotherapy followed by irradiation to the neuroaxis. However, the role of HCT remains unclear for those patients with early isolated CNS relapse (<18 months) or who had high risk disease at diagnosis. We therefore compared the HCT outcomes of 116 children treated at the University of Minnesota from 1991 to 2006 with relapsed ALL involving the CNS alone (CNS, n = 14), the bone marrow alone (BM, n = 85), or both bone marrow and CNS (BM + CNS, n = 17). There were no significant differences among groups in age at diagnosis or transplant, length of first complete remission (CR1), remission status (CR2 versus >or=CR3), graft source, or preparative regimen. The incidence of acute GVHD was similar between groups. Patients with isolated CNS relapse had the lowest cumulative incidence of mortality following transplant (CNS: 0%, BM: 19%, BM + CNS: 29%, P = .03) and relapse (CNS: 0% BM: 30%, BM + CNS: 12%, at 2 years, P = .01) and highest leukemia-free survival (CNS: 91%, BM: 35%, BM + CNS: 46%, P < .01) at 5 years. Risk factors for poor survival were: T cell leukemia or BCR-ABL gene rearrangement, history of marrow relapse, and receipt of HLA-mismatched marrow. These data support the use of allogeneic HCT in the treatment of children with poor prognosis isolated CNS relapse.


Subject(s)
Central Nervous System/pathology , Hematopoietic Stem Cell Transplantation/statistics & numerical data , Leukemic Infiltration/surgery , Precursor Cell Lymphoblastic Leukemia-Lymphoma/surgery , Adolescent , Age Factors , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow Transplantation/statistics & numerical data , Child , Child, Preschool , Combined Modality Therapy , Cord Blood Stem Cell Transplantation/statistics & numerical data , Cranial Irradiation , Female , Humans , Infant , Leukemic Infiltration/radiotherapy , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/radiotherapy , Prognosis , Radiotherapy, Adjuvant , Recurrence , Remission Induction , Retrospective Studies , Risk Factors , Survival Analysis , Transplantation Conditioning , Transplantation, Homologous , Treatment Outcome
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