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 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 PARTICIPANTSThis 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 MEASURESAnti-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.
Optimum care of female transplant recipients requires gynecologic care at several stages through the allogeneic hematopoietic stem cell transplantation (HCT) process. Sex-based considerations in women post-HCT span gynecologic sequelae of transplant along with assessment and maintenance of optimal sexual and gynecologic health. Pre-HCT, managing menstruation and abnormal uterine or genital bleeding, considering fertility preservation, and assessing for sexually transmitted infections, including human papillomavirus (HPV)-related disease and cervical cancer, enhance women's health. While inpatient during transplant when women are thrombocytopenic, menstrual bleeding requires suppression. Whenever graft-versus-host disease (GVHD) is assessed, screening for genital GVHD merits consideration. After the first 100 days, periodic assessments include obtaining a menstrual history, assessing ovarian function, and reviewing current hormonal use and contraindications to hormonal methods. Regular assessment for primary ovarian insufficiency, dyspareunia, and intimacy guides provision of contraception and hormone replacement options. As part of ongoing screening for genital GVHD and HPV-related disease, including sexually transmitted infections, periodic pelvic examinations are performed. Once successful long-term survival is achieved, planning for fertility may be considered. This article offers a comprehensive approach to these aspects of gynecologic care of patients throughout the trajectory of HCT and beyond into survivorship. We review the effects of HCT treatment on sexual health, ovarian function, and resulting menstrual changes and fertility challenges. Identification, treatment, and prevention of subsequent malignancies, including breast cancer, are discussed, with a focus on regular assessment of genital HPV disease and GVHD in long-term follow-up.
We studied the outcome significance of pre-HCT colonization with intrinsics by reviewing the medical records of all allo-HCT recipients with available pre-HCT rectal swab or stool culture results at our institution (2011)(2012)(2013)(2014)(2015)(2016)(2017). Cases with ≥1 positive pre-HCT result for E. gallinarum or E. casseliflavus and no positive test for VRE were defined as intrinsics. Patients with no positive pre-HCT test for intrinsics or VRE, and with at least 2 negative tests for these, were defined as controls. Due to the rare occurrence of colonization with intrinsics and the preponderance of pediatric patients with this condition, each intrinsic was matched to a control using the following hierarchical criteria: (i) Disease (malignant vs. nonmalignant), (ii) disease risk (standard vs. high vs. nonmalignant), (iii) donor (sibling vs. unrelated vs. cord), (iv) conditioning (ablative vs. reduced-intensity), and (v) age (±10 years). The groups were similar in all studied variables (Table 1). The intrinsic group had a higher 2-year overall survival (OS) of 86 [52-96]% vs. controls with OS of 35 [8-65]% (P < .01, Figure 1). This remarkable difference was due to a significantly lower non-relapse mortality (NRM) in the intrinsic group (0% vs. 36 [8-65]%, P = .01). Both deaths in the intrinsic group were due to relapse. In contrast, deaths in the control group were due to organ failure in 45%, relapse in 33%, infection in 11%, and GVHD in 11%. Other transplant outcomes (GVHD and relapse) were similar between the groups.
Background: Approval to pertuzumab as part of a complete treatment regimen for patients with early stage breast cancer (EBC) before surgery (neoadjuvant setting) was granted by the FDA in September 2013. Since then, the relevance of neoadjuvant treatment in Her2 overexpressing breast cancer has increased considerably. This for instance has been emphasized by the results of the Neosphere Study, in which dual blockade of Her2 was combined with docetaxel as chemotherapy backbone and resulted in favorable pCR rates. But it is likely, that anthracyclines could play an important role in enhancing the effectiveness of the above mentioned treatment. However, there is only little data about the cardiac safety of this combination. The use of liposomal doxorubicin might be a valuable alternative with low cardiotoxicity, as it has been shown in comparable publications without the use of pertuzumab. Therefore we report pCR-rate and cardiac safety of a single arm, retrospective, multicenter analysis of neoadjuvant treatment for Her2 positive EBC with liposomal doxorubicin, docetaxel, trastuzumab and pertuzumab. Methods: In this study 42 women with Her2 positive EBC were investigated in 4 oncological departments in Austria. 41 patients were treated with liposomal doxorubicin (50 mg/m2), docetaxel (75 mg/m2) concurrent with trastuzumab and pertuzumab in standard dosage for 6 cycles as neoadjuvant therapy. One patient refused to receive a chemotherapy but agreed to be treated with combined antibody therapy alone. All patients were free of cardiovascular disease and had a left ventricular ejection fraction (LVEF) of ≥ 50%. Cardiac function was measured by LVEF and was examined at regular intervals (cycles 0-3, cycle 6, FU). Clinical response was evaluated by diagnostic breast imaging after cycles 3 and 6. All patients underwent surgery after neoadjuvant chemotherapy. The absence of any residual invasive cancer in the breast and axilla was defined as pathological complete response (pCR). Median follow up was 1.3 years. Results: Median age of the patients was 49 years. After 6 cycles of treatment the pCR rate was 76.2%. In this cohort a negative estrogen-and/or progesteron receptor was predictive for pCR (p<0.001). These patients achieved pCR in 95.2%. The antibody only treatment in one case also resulted in a pCR. No patient progressed during treatment. Only one of the patients (2,4%) suffered symptomatic heart failure after surgery. The patient initially presented with an LVEF of 16%. Conclusions: In this multicenter analysis we observed a considerably high rate of pCR in HER2-positive EBC treated with liposomal doxorubicin, docetaxel, trastuzumab and pertuzumab. Especially the group of hormone receptor negative patients showed a remarkable response rate. The addition of liposomal doxorubicin entails a very favorable cardiotoxicity profile. This regimen is a safe treatment option in patients with HER-2 positive breast cancer. Citation Format: Egle D, Hubalek M, Hager C, Poyßl C, Lang A, Jäger T, Volgger B, Abdel-Azim S, Tiechl J, Angerer J, Marth C. Efficacy and cardiac safety in neoadjuvant treatment of Her2 positive breast cancer with concomitant nonpegylated liposomal doxorubicin, docetaxel and dual blockade with trastuzumab and pertuzumab: A retrospective analysis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-14-11.
Background: About 25%-35% of breast cancers are non-palpable at the time of diagnosis. Wire guided localization (WGL) had been considered as the standard technique for many years for excision of theses breast lesions. The aim of this study is to assess the efficacy of WGL biopsy in the management of non-palpable suspicious breast masses. Patients & Methods: This retrospective study concerned thirty female patients who were presented by non-palpable breast lesions as proved by mammography and complimentary ultrasonography between February 2013 and September 2014. According to BIRADS classification system, all the lesions were BIRADS III, IV and V. However, BIRADS I and II lesions proved to be benign were excluded from this study. The patients were submitted to WGL under local anesthesia. Then, they were shifted to the operating theatre, where they underwent WGL biopsy. The removed specimens were sent for radiological confirmation of complete excision. Then, it was sent for histopathological examination. Results: The mean age was 52.63 years. Eighteen patients (60%) were asymptomatic, 7 (23.3%) patients were with breast pain, and 5 patients (16.7%) had nipple discharge. Ten lesions (33.3%) were BIRADS III, 17 lesions (56.7%) were BIRADS IV, and 3 lesions (10%) were BIRADS V. The WGL was done by mammography in 19 patients (63.3%) and under ultrasonographic guidance in 11 patients (36.7%). No post-operative complications were reported. The mean tumor size was 11.23 mm and the mean safety margin of excision was 6.7 mm. IDC was found in 56.7% or cases, DCIS in 30%, and ILC in 13.3% of cases. 40% of the lesions were of grade I, 30% were of grade II, and 30% were of grade III. There were positive resection margins in 11 patients (36.7%). Conclusion: WGL biopsy is a safe and reliable surgical technique for management of non-palpable suspicious breast lesions. Special care should be paid for proper margin excision. However, WGL biopsy is technically demanding and needs learning curve for both the surgeon and the radiologist.
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