The role of growth factor administration and T-cell recovery after peripheral blood progenitor cell transplantation in the treatment of solid tumors: results from a randomized comparison of G–CSF and GM–CSF

BACKGROUND: Peripheral blood progenitor cell (PBPC) transplantation (PBPCT) combined with post-PBPCT administration of myelopoietic growth factors is a valid therapeutic intervention to rapidly restore hematopoiesis after the delivery of intensive, myeloablative cancer chemotherapy. On the other hand, the best growth factor regimen to potentiate PBPC-mediated immunohematopoietic recovery has yet to be determined. STUDY DESIGN AND METHODS: In a randomized evaluation, the effects produced by post-PBPCT G-CSF and GM-CSF on myeloid/lymphoid recovery and transplant outcome in women with chemosensitive cancer were compared. Thirty-seven ovarian cancer patients and 34 breast cancer patients ranging in age from 24 to 60 years were treated with carboplatin, etoposide, and melphalan (CEM) high-dose chemotherapy and then randomly assigned to receive G-CSF (5 microg/kg subcutaneously) or GM-CSF (5 microg/kg subcutaneously) until Day 13 after PBPCT. Patients were compared in regard to hematopoietic recovery, posttransplant clinical management, and immune recovery. Finally, clinical outcome was estimated as time to progression and overall survival. RESULTS: Hematopoietic recovery and posttransplant clinical management were comparable in both the G-CSF and GM-CSF series. Conversely, significantly higher T-cell counts were observed in G-CSF-treated patients during the early and late posttransplant follow-up. Patients who received G-CSF showed a significantly longer median time to progression. A parallel analysis revealed that patients in whom a higher CD3+ count was recovered had a significantly longer overall survival and time to progression. CONCLUSION: The enhancement of post-PBPCT T-cell recovery observed in G-CSF-treated patients encourages the use of G-CSF to ameliorate immune recovery, which seems to play a role in post-PBPCT control of disease in cancer patients. GM-CSF might be administered to prolong immunosuppression after autologous PBPCT for autoimmune diseases or allogeneic PBPCT.     

Are Infertile Men Less Healthy than Fertile Men? Results of a Prospective Case-Control Survey

Background

An association between either subfertility or infertility and an elevated risk of certain male cancers has been previously reported. Nothing is known about abnormalities in infertility and general health conditions.

Objective

To assess whether men with male factor infertility (MFI) are overall less healthy than fertile men, regardless of the reasons for infertility.

Design, setting, and participants

From September 2006 to September 2007, 344 consecutive European Caucasian men with MFI were enrolled in this prospective case-controlled study. Patients were compared with a control group of 293 consecutive age-comparable fertile men. Infertile men were consecutively attending the outpatient male reproductive clinic at a tertiary academic center. Fertile controls were consecutively recruited by use of advertisements posted within our hospital.

Measurements

Comorbidities of patients and fertile men were objectively scored with the Charlson Comorbidity Index (CCI) according to the International Classification of Diseases modified ninth version (ICD-9-CM) codes. Multivariate linear regression models tested the association between predictors and CCI score, as a proxy of general health status.

Results

According to the CCI scores, infertile men had a significantly higher rate of comorbidities compared with the fertile controls (CCI: 0.33 [0.8] vs 0.14 [0.5]; p < 0.001; 95% CI: 0.08–0.29). Linear regression analyses showed that although educational status did not have an impact on CCI (β: 0.035; p = 0.365), while CCI linearly increased with age (β: 0.196; p < 0.001) and body mass index (BMI; β: 0.161; p < 0.001). After adjusting for age, BMI, and educational status, a significantly lower CCI was calculated for fertile men and compared with MFI patients (β: −0.199; p < 0.001).

Conclusions

These results show that MFI accounts for a higher CCI, which may be considered a reliable proxy of a lower general health status.     

Identification and Management of Women at High Risk for Hereditary Breast/Ovarian Cancer Syndrome

Abstract:  Despite advances in identifying genetic markers of high risk patients and the availability of genetic testing, it remains challenging to efficiently identify women who are at hereditary risk and to manage their care appropriately. HughesRiskApps, an open-source family history collection, risk assessment, and Clinical Decision Support (CDS) software package, was developed to address the shortcomings in our ability to identify and treat the high risk population. This system is designed for use in primary care clinics, breast centers, and cancer risk clinics to collect family history and risk information and provide the necessary CDS to increase quality of care and efficiency. This paper reports on the first implementation of HughesRiskApps in the community hospital setting. HughesRiskApps was implemented at the Newton-Wellesley Hospital. Between April 1, 2007 and March 31, 2008, 32,966 analyses were performed on 25,763 individuals. Within this population, 915 (3.6%) individuals were found to be eligible for risk assessment and possible genetic testing based on the 10% risk of mutation threshold. During the first year of implementation, physicians and patients have fully accepted the system, and 3.6% of patients assessed have been referred to risk assessment and consideration of genetic testing. These early results indicate that the number of patients identified for risk assessment has increased dramatically and that the care of these patients is more efficient and likely more effective.     

Ventricular Septal Crypts: Remnants of Spontaneous Interventricular Defect Closure?

Background: Ventricular crypts are quite a common finding during cardiac imaging, but their etiology is unclear. A possible final result of a spontaneous ventricular septal defect closure has been supposed but never investigated in earlier studies. Method: From January 1997 to December 2020, all newborns diagnosed to have a ventricular septal defect were prospectively entered in our database and those with an isolated defect were included in the study. Ventricular septal defects were classified into four types: perimembranous, trabecular muscular, inlet and outlet. A long-term follow up was performed in order to visualize the possible residual formation of a septal myocardial crypt. Results: A total of 376 isolated ventricular septal defects (314 muscular and 54 perimembranous, 4 inlet, 4 outlet) were detected. Follow up ranged from 1 to 23 years and showed that, among muscular type, a spontaneous closure occurred in 284 (91%), 26 did not close (8,28%), 2 required surgical intervention (0,63%), 3 were lost at follow up (0,95%). During this period, after spontaneous defect closure closure, 20 crypts were found (6,4%). Conclusion: This study shows that a muscular ventricular septal defect may evolve in the 6.4% of cases in a residual septal crypt. Although septal crypts occur more frequently in patients affected by hypertrophic and hypertensive cardiomyopathy, they may also represent the evolution of a spontaneous closure of a muscular interventricular defect.