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1.
JAMA Oncol ; 6(5): 696-705, 2020 05 01.
Article in English | MEDLINE | ID: mdl-32105293

ABSTRACT

Importance: Human papillomavirus (HPV) infection is found in about 40% of women who survive allogeneic hematopoietic stem cell transplant and can induce subsequent neoplasms. Objective: To determine the safety and immunogenicity of the quadrivalent HPV vaccine (HPV-6, -11, -16, and -18) in clinically stable women post-allogeneic transplant compared with female healthy volunteers. Interventions: Participants received the quadrivalent HPV vaccine in intramuscular injections on days 1 and 2 and then 6 months later. Design, Setting, and Participants: This prospective, open-label phase-1 study was conducted in a government clinical research hospital and included clinically stable women posttransplant who were or were not receiving immunosuppressive therapy compared with healthy female volunteers age 18 to 50 years who were followed up or a year after first receiving quadrivalent HPV vaccination. The study was conducted from June 2, 2010, until July 19, 2016. After all of the results of the study assays were completed and available in early 2018, the analysis took place from February 2018 to May 2019. Main Outcomes and Measures: Anti-HPV-6, -11, -16, and -18-specific antibody responses using L1 virus-like particle enzyme-linked immunosorbent assay were measured in serum before (day 1) and at months 7 and 12 postvaccination. Anti-HPV-16 and -18 neutralization titers were determined using a pseudovirion-based neutralization assay. Results: Of 64 vaccinated women, 23 (35.9%) were receiving immunosuppressive therapy (median age, 34 years [range, 18-48 years]; median 1.2 years posttransplant), 21 (32.8%) were not receiving immunosuppression (median age, 32 years [range, 18-49 years]; median 2.5 years posttransplant), and 20 (31.3%) were healthy volunteers (median age, 32 years [range, 23-45 years]). After vaccine series completion, 18 of 23 patients receiving immunosuppression (78.3%), 20 of 21 not receiving immunosuppression (95.2%), and all 20 volunteers developed antibody responses to all quadrivalent HPV vaccine types (P = .04, comparing the 3 groups). Geometric mean antibody levels for each HPV type were higher at months 7 and 12 than at baseline in each group (all geometric mean ratios >1; P < .001) but not significantly different across groups. Antibody and neutralization titers for anti-HPV-16 and anti-HPV-18 correlated at month 7 (Spearman ρ = 0.92; P < .001 for both). Adverse events were mild and not different across groups. Conclusions and Relevance: Treatment with the HPV vaccination was followed by strong, functionally active antibody responses against vaccine-related HPV types and no serious adverse events. These findings suggest that HPV vaccination may be safely administered to women posttransplant to potentially reduce HPV infection and related neoplasia. Trial Registration: ClinicalTrials.gov Identifier: NCT01092195.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines/immunology , Transplantation Conditioning/methods , Transplantation, Homologous/methods , Adolescent , Adult , Female , Healthy Volunteers , Humans , Middle Aged , Prospective Studies , Young Adult
2.
Obstet Gynecol ; 121(2 Pt 2 Suppl 1): 424-7, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23344397

ABSTRACT

BACKGROUND: Hematopoietic stem cell transplant is an effective treatment strategy for a variety of hematologic disorders, but patients are at risk for dysfunctional coagulation and abnormal bleeding. Gynecologists are often consulted before transplant for management of abnormal uterine bleeding, which may be particularly challenging in this context. CASE: A premenopausal woman with MonoMAC (a rare adult-onset immunodeficiency syndrome characterized by monocytopenia and Mycobacterium avium complex infections resulting from mutations in GATA2, a crucial gene in early hematopoiesis) presented with pancytopenia, evolving leukemia, and recent strokes, necessitating anticoagulation. During preparation for hematopoietic stem cell transplant, she experienced prolonged menorrhagia requiring transfusions. Surgical therapy was contraindicated, and medical management was successful only when combined with balloon tamponade. CONCLUSION: Balloon tamponade may be a potentially life-saving adjunct to medical therapy for control of uterine hemorrhage before hematopoietic stem cell transplant.


Subject(s)
Estrogens/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Induction Chemotherapy/adverse effects , Leuprolide/therapeutic use , Medroxyprogesterone/therapeutic use , Menorrhagia/therapy , Uterine Balloon Tamponade , Adult , Antineoplastic Agents, Hormonal/therapeutic use , Contraceptives, Oral, Synthetic/therapeutic use , Female , GATA2 Transcription Factor/genetics , Humans , Immunologic Deficiency Syndromes/complications , Immunologic Deficiency Syndromes/therapy , Leiomyoma/complications , Menorrhagia/chemically induced , Stroke/complications , Uterine Neoplasms/complications
3.
Semin Hematol ; 49(1): 83-93, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22221788

ABSTRACT

Female long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) incur a significant burden of late effects. Genital graft-versus-host disease (GVHD), human papillomavirus (HPV) reactivation, ovarian failure and infertility, sexual dysfunction, and osteoporosis are concerns that can significantly impact quality of life. This review examines the risk, pathogenesis, clinical presentation, and implications of these common complications. Recommendations are provided for evaluation and management of these late effects and other obstetric and gynecologic issues that may arise in this patient population.


Subject(s)
Graft vs Host Disease/etiology , Graft vs Host Disease/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Infertility, Female/complications , Osteoporosis/complications , Papillomavirus Infections/complications , Survivors , Female , Graft vs Host Disease/complications , Humans , Infertility, Female/therapy , Osteoporosis/therapy , Papillomavirus Infections/therapy , Papillomavirus Infections/virology , Time Factors , Transplantation, Homologous
4.
J Clin Endocrinol Metab ; 89(10): 4999-5002, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15472197

ABSTRACT

Hypothalamic/chiasmatic gliomas (H/CG) in children are commonly accompanied by endocrine dysfunction due to mass effects of the tumor itself or as a consequence of tumor therapy, with GH deficiency (GHD) being the most common disorder. We report the height outcomes of GH-treated H/CG patients with GHD. We reviewed the records of 14 GHD patients with H/CG who were treated with human GH. A comparison group of non-GH-treated H/CG patients was also identified. Heights were expressed as sd scores (SDS). For GH-treated patients, the mean initial height was -0.7 +/- 0.3 (+/-se). Their mean final height was -0.3 +/- 0.3. The mean change in height SDS for the GH-treated group was +0.4. The mean initial and final height SDS for the non-GHD patients were 0.6 (se = 0.4) and 0.0 (se = 0.4), respectively. The mean change in height SDS was -0.6. The GHD patients had significantly lower initial height SDS compared with the non-GHD patients (P = 0.01) and had a significantly greater change in their height SDS (P = 0.04). GH treatment for H/CG patients restores much of their growth potential and improves adult height to within normal limits.


Subject(s)
Body Height/drug effects , Glioma/drug therapy , Human Growth Hormone/therapeutic use , Hypothalamic Neoplasms/drug therapy , Adolescent , Adult , Databases, Factual , Female , Humans , Male , Optic Chiasm
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