ABSTRACT
Vanishing bile duct syndrome is a rare paraneoplastic syndrome occasionally seen in pediatric Hodgkin lymphoma. It is usually regarded as a fatal disorder. Here, we present a case of vanishing bile duct syndrome cholestasis related to Hodgkin lymphoma that resolved after chemotherapy and radiation.
Subject(s)
Cholestasis , Hodgkin Disease , Paraneoplastic Syndromes , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bile Ducts/pathology , Child , Cholestasis/etiology , Hodgkin Disease/complications , Hodgkin Disease/drug therapy , Hodgkin Disease/pathology , Humans , Paraneoplastic Syndromes/drug therapy , Paraneoplastic Syndromes/etiologyABSTRACT
We describe 6 pediatric patients (12 to 18 y) 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.
Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Brentuximab Vedotin/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Hodgkin Disease/therapy , Neoplasm Recurrence, Local/therapy , Adolescent , Child , Combined Modality Therapy , Consolidation Chemotherapy , Female , Follow-Up Studies , Hodgkin Disease/pathology , Humans , Male , Neoplasm Recurrence, Local/pathology , PrognosisABSTRACT
Juvenile nasopharyngeal angiofibroma (JNA) is a pathologically benign yet locally aggressive and destructive tumor that develops in the choana and nasopharynx. Historical treatment of JNA has included embolization, surgical resection, and radiation. Here, we describe three patients who received therapy with the mTOR inhibitor sirolimus with improvement in clinical symptoms, imaging, and overall well-being.
Subject(s)
Angiofibroma/drug therapy , Antibiotics, Antineoplastic/therapeutic use , Nasopharyngeal Neoplasms/drug therapy , Sirolimus/therapeutic use , Adolescent , Angiofibroma/pathology , Child , Humans , Male , Nasopharyngeal Neoplasms/pathology , Treatment OutcomeABSTRACT
BACKGROUND: In previous clinical trials involving children with X-linked severe combined immunodeficiency (SCID-X1), a Moloney murine leukemia virus-based γ-retrovirus vector expressing interleukin-2 receptor γ-chain (γc) complementary DNA successfully restored immunity in most patients but resulted in vector-induced leukemia through enhancer-mediated mutagenesis in 25% of patients. We assessed the efficacy and safety of a self-inactivating retrovirus for the treatment of SCID-X1. METHODS: We enrolled nine boys with SCID-X1 in parallel trials in Europe and the United States to evaluate treatment with a self-inactivating (SIN) γ-retrovirus vector containing deletions in viral enhancer sequences expressing γc (SIN-γc). RESULTS: All patients received bone marrow-derived CD34+ cells transduced with the SIN-γc vector, without preparative conditioning. After 12.1 to 38.7 months of follow-up, eight of the nine children were still alive. One patient died from an overwhelming adenoviral infection before reconstitution with genetically modified T cells. Of the remaining eight patients, seven had recovery of peripheral-blood T cells that were functional and led to resolution of infections. The patients remained healthy thereafter. The kinetics of CD3+ T-cell recovery was not significantly different from that observed in previous trials. Assessment of insertion sites in peripheral blood from patients in the current trial as compared with those in previous trials revealed significantly less clustering of insertion sites within LMO2, MECOM, and other lymphoid proto-oncogenes in our patients. CONCLUSIONS: This modified γ-retrovirus vector was found to retain efficacy in the treatment of SCID-X1. The long-term effect of this therapy on leukemogenesis remains unknown. (Funded by the National Institutes of Health and others; ClinicalTrials.gov numbers, NCT01410019, NCT01175239, and NCT01129544.).
Subject(s)
Gammaretrovirus/genetics , Genetic Therapy , Genetic Vectors , X-Linked Combined Immunodeficiency Diseases/therapy , Animals , Antigens, CD34 , DNA, Complementary/therapeutic use , Gene Expression , Gene Silencing , Genetic Therapy/adverse effects , Humans , Infant , Interleukin Receptor Common gamma Subunit/genetics , Male , Mice , Mutation , T-Lymphocytes/immunology , Transduction, Genetic , Transgenes/physiology , X-Linked Combined Immunodeficiency Diseases/genetics , X-Linked Combined Immunodeficiency Diseases/immunologySubject(s)
Antineoplastic Agents , Gilbert Disease , Immunoconjugates , Brentuximab Vedotin , Humans , Ki-1 Antigen , MutationSubject(s)
Acne Vulgaris , Darier Disease , Hair Diseases , Lymphoma , Polyomavirus Infections , Polyomavirus , Abnormalities, Multiple , Acne Vulgaris/complications , Child , Darier Disease/complications , Eyebrows/abnormalities , Hair Diseases/etiology , Hair Diseases/pathology , Humans , Lymphoma/complications , Polyomavirus Infections/complications , Polyomavirus Infections/pathologyABSTRACT
PURPOSE: We evaluated the outcome of children (<15 years) versus that of adolescents and young adults (AYA; 15-≤ 21 years) treated for Hodgkin lymphoma (HL) in two Pediatric Oncology Group/Children's Oncology Group clinical trials, P9425 and P9426, that used dose-dense, response-based chemotherapy and reduced dose radiotherapy. PATIENTS AND METHODS: Subjects 21 years or younger with HL were eligible for these studies. Subjects with low-risk (stages IA, IIA, and IIIA1) without large mediastinal adenopathy biopsy-proven HL, eligible for P9426, were treated with two to four 28-day cycles of doxorubicin, bleomycin, vincristine, and etoposide (ABVE) chemotherapy and 25.5 Gy of involved field radiotherapy. Subjects with intermediate-risk (stages IB, IIA, IIIA1 with large mediastinal adenopathy, and IIIA2) and high-risk (stages IIB, IIIB, and IV) biopsy-proven HL, eligible for P9425, were treated with three to five 21-day cycles of ABVE plus prednisone and cyclophosphamide (ABVE-PC) chemotherapy and 21 Gy of involved region radiotherapy. We compared the 5-year event-free survival (EFS), based on Kaplan-Meier product-limit method, of children versus that of AYA. RESULTS: Four hundred seventy-one subjects were enrolled on P9425 and P9426 combined. Of these subjects, 203 were AYA, 104 with intermediate and high-risk HL, and 99 with low-risk HL. The 5-year EFS of children did not significantly differ from that of AYA (85.9 vs. 87.1%) with a median follow up of 7.7 years (P = 0.51). CONCLUSION: Given the equivalent and excellent results of therapy, HL represents an opportunity for adult and pediatric cancer treatment collaborative groups to jointly design clinical trials targeted to AYA. These trials should focus on both treatment efficacy and the quality of life of AYA while receiving chemotherapy and in reduction of long-term side effects in the survivorship years.
Subject(s)
Hodgkin Disease/drug therapy , Adolescent , Child , Clinical Protocols , Female , Hodgkin Disease/mortality , Humans , Male , Young AdultABSTRACT
BACKGROUND: Children of Hispanic ancestry have a higher incidence of acute lymphoblastic leukemia (ALL) compared with other ethnic groups, but to the authors' knowledge, the genetic basis for these racial disparities remain incompletely understood. Genome-wide association studies of childhood ALL to date have focused on inherited genetic effects; however, maternal genetic effects (the role of the maternal genotype on phenotype development in the offspring) also may play a role in ALL susceptibility. METHODS: The authors conducted a family-based exome-wide association study of maternal genetic effects among Hispanics with childhood B-cell ALL using the Illumina Infinium HumanExome BeadChip. A discovery cohort of 312 Guatemalan and Hispanic American families and an independent replication cohort of 152 Hispanic American families were used. RESULTS: Three maternal single-nucleotide polymorphisms (SNPs) approached the study threshold for significance after correction for multiple testing (P<1.0 × 10-6 ): MTL5 rs12365708 (testis expressed metallothionein-like protein [tesmin]) (relative risk [RR], 2.62; 95% confidence interval [95% CI], 1.61-4.27 [P = 1.8 × 10-5 ]); ALKBH1 rs6494 (AlkB homolog 1, histone H2A dioxygenase) (RR, 3.77; 95% CI, 1.84-7.74 [P = 3.7 × 10-5 ]); and NEUROG3 rs4536103 (neurogenin 3) (RR, 1.75; 95% CI, 1.30-2.37 [P = 1.2 × 10-4 ]). Although effect sizes were similar, these SNPs were not nominally significant in the replication cohort in the current study. In a meta-analysis comprised of the discovery cohort and the replication cohort, these SNPs were still not found to be statistically significant after correction for multiple comparisons (rs12365708: pooled RR, 2.27 [95% CI, 1.48-3.50], P = 1.99 × 10-4 ; rs6494: pooled RR, 2.31 [95% CI, 1.38-3.85], P = .001; and rs4536103: pooled RR, 1.67 [95% CI, 1.29-2.16] P = 9.23 × 10-5 ). CONCLUSIONS: In what to the authors' knowledge is the first family-based based exome-wide association study to investigate maternal genotype effects associated with childhood ALL, the results did not implicate a strong role of maternal genotype on disease risk among Hispanics; however, 3 maternal SNPs were identified that may play a modest role in susceptibility. Cancer 2016;122:3697-704. © 2016 American Cancer Society.
Subject(s)
B-Lymphocytes/pathology , Exome/genetics , Genetic Predisposition to Disease/genetics , Hispanic or Latino/genetics , Polymorphism, Single Nucleotide/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Adolescent , Adult , Child , Child, Preschool , Female , Genome-Wide Association Study/methods , Genotype , Humans , Incidence , Infant , Infant, Newborn , Male , Phenotype , Young AdultSubject(s)
Encephalitis , Ovarian Neoplasms , Teratoma , Adolescent , Encephalitis/diagnosis , Female , Humans , Ovarian Neoplasms/diagnosis , Teratoma/diagnosisSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Burkitt Lymphoma/drug therapy , Hair/abnormalities , Hirschsprung Disease/drug therapy , Immunity, Cellular/drug effects , Immunocompromised Host/drug effects , Osteochondrodysplasias/congenital , Primary Immunodeficiency Diseases/drug therapy , Adolescent , Burkitt Lymphoma/complications , Burkitt Lymphoma/immunology , Burkitt Lymphoma/pathology , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Hair/immunology , Hair/pathology , Hirschsprung Disease/complications , Hirschsprung Disease/immunology , Hirschsprung Disease/pathology , Humans , Methotrexate/administration & dosage , Osteochondrodysplasias/complications , Osteochondrodysplasias/drug therapy , Osteochondrodysplasias/immunology , Osteochondrodysplasias/pathology , Prednisone/administration & dosage , Primary Immunodeficiency Diseases/complications , Primary Immunodeficiency Diseases/immunology , Primary Immunodeficiency Diseases/pathology , Prognosis , Rituximab/administration & dosage , Vincristine/administration & dosageABSTRACT
BACKGROUND: Carcinoid tumors (CTs) are rare in the pediatric population and are generally noted as an incidental finding on histopathologic examination. Cure is usually achieved with wide surgical excision. Second primary malignancies (SPM) of the gastrointestinal tract after CTs have been reported in 13% to 33% of affected adults. The risk of SPM appears highest after small bowel or appendiceal CTs and usually presents within 7 years from diagnosis. PURPOSE: The purpose of this study was to investigate the natural history of CTs in pediatric patients treated at a major children's hospital and to determine whether children and adolescents with primary CTs developed SPM during routine long-term follow-up. METHODS: We conducted a retrospective review of the medical records of children and adolescents with CTs diagnosed at Nationwide Children's Hospital, Columbus, Ohio between 1945 and 2012. RESULTS: Thirty-two patients with CT were identified, representing 0.48% of all malignancies diagnosed at Nationwide Children's Hospital. Mean age at presentation was 13 years (range, 8 to 20 y). The majority were appendiceal (87.5%) followed by bronchial (9.4%). Most of the appendiceal tumors presented with clinical appendicitis (25/28). Three had incidental appendectomies at the time of a planned abdominal surgery for other reasons. Four patients with appendiceal CTs had invasive features. All patients with appendiceal and bronchial CTs were successfully treated by complete surgical excision and were free of disease at an average of 7 years from diagnosis. None of our patients developed SPM during the period of observation (median 84 mo; range, 12 to 156 mo). CONCLUSIONS: In this single-institution retrospective review, survival of children with CT was excellent. No SPMs were observed over the period of follow-up differing from previously reported adult CT series.