September 2012

Editor:
Deborah Sesok-Pizzini, MD, MBA

• Should the qualitative serum pregnancy test be considered obsolete?
• Autologous mesenchymal stem cells for treating multiple sclerosis
• Followup with CA125 after primary therapy for advanced ovarian cancer

Should the qualitative serum pregnancy test be considered obsolete?

Rapid testing for the qualitative detection of human chorionic gonadotropin in urine or serum using point-of-care testing devices is frequently performed as a pregnancy test. The urine samples require no special processing and are considered waived testing under the Clinical Laboratory Improvement Amendments. However, serum samples are considered moderately complex testing due to the need to collect a whole blood specimen and centrifuge the sample to recover just the serum. Therefore, serum samples cannot be readily performed as a point-of-care test. Because of this, some members of the medical community have questioned the value of this qualitative test for pregnancy, especially with the availability of a more sensitive quantitative test with comparable turnaround times. The authors conducted a survey to assess physicians’ perceptions of human chorionic gonadotropin (hCG) tests and compared the turnaround times and diagnostic performance of qualitative versus quantitative pregnancy tests. The investigators surveyed 1,058 physicians about their perceptions of hCG tests and collected seven months of data on turnaround times. They also repeated quantitative hCG testing on 740 samples and reviewed the medical charts for 52 patients with a positive qualitative result or an hCG concentration of more than 5 IU/L. Results showed that the diagnostic sensitivity and negative predictive value of the qualitative test were lowest (78 percent and 98.4 percent, respectively) when using a cutoff of 5 IU/L. By comparison, when using age-specific hCG cutoffs for the quantitative serum hCG test, the performance was identical to the qualitative test, with 96.8 percent sensitivity and 99.9 percent negative predictive value. Therefore, a negative test using either the qualitative or quantitative method could confidently exclude a pregnancy. Interestingly, of the 183 physicians who completed the survey, 49 percent indicated that they preferred to order a qualitative serum hCG test compared to 31 percent who preferred a quantitative hCG test. The physicians perceived that a quantitative hCG test took longer. However, this study found that turnaround time was about the same when the time to transport the sample to the lab was included in the analysis. The authors concluded that the qualitative serum hCG test continues to be a less expensive test, with good performance characteristics and turnaround times that are similar to the quantitative serum hCG test. Eliminating the qualitative serum hCG testing platform based on this study and survey results would not be widely supported.

Furtado LV, Lehman CM, Thompson C, et al. Should the qualitative serum pregnancy test be considered obsolete? Am J Clin Pathol. 2012;137:194–202.

Correspondence: Dr. David Grenache, ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108

Autologous mesenchymal stem cells for treating multiple sclerosis

Multiple sclerosis is a progressive disease that affects more than 2 million children and adults worldwide. Recent interest in cellular-based therapeutic treatments for multiple sclerosis (MS) is based on promising results observed in acute and chronic animal models. Mesenchymal stem cells are stromal cells derived from bone marrow that can be expanded ex vivo and will readily differentiate into mesodermal cell derivatives. The cells are thought to offer neuroprotection through paracrine effects on the central nervous system microenvironment, augmentation of endogenous axonal and myelin repair processes, and immune regulatory activity. The authors conducted an open-label study in which they infused patients who had secondary progressive multiple sclerosis involving the visual pathways with autologous bone marrow–derived mesenchymal stem cells. They compared adverse events from up to 20 months before treatment until up to 10 months after infusion. A secondary outcome was efficacy to assess the anterior visual pathway. The authors isolated, expanded, characterized, and administered mesenchymal stem cells in 10 MS patients using a mean dose of 1.6 10⁶ cells/kg of body weight. The authors reported no serious adverse reactions, although one patient had a self-limiting rash and two had bacterial infections three to four weeks after treatment. The study showed improvement after treatment in visual acuity and visual evoked response latency and an increase in optic nerve area. The authors did not identify any significant effects on color vision, visual fields, macular volume, retinal nerve fiber layer thickness, or optic nerve magnetization transfer ratio. The authors concluded that their proof-of-concept study showed that mesenchymal stem cells may be safely administered to patients with secondary progressive MS and that the intervention may improve outcomes, including visual function. The authors noted the limited size of the study and that changes may not be exclusively attributed to mesenchymal stem cell treatment. Therefore, they recommend a larger trial design for feasibility and safety analysis.

Connick P, Kolappan M, Crawley C, et al. Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study. Lancet Neurol. 2012;11:150–156.

Correspondence: Siddharthan Chandran at siddharthan.chandran@ed.ac.uk

Followup with CA125 after primary therapy for advanced ovarian cancer

The CA125 antigen is expressed by a large number of epithelial ovarian cancers. Ovarian cancer is the fourth leading cause of cancer-related death in women, and a high percentage of women with advanced stage disease will experience recurrence after treatment. The CA125 antigen is detected by the OC125 monoclonal antibody, which is obtained after immunization with the OVCA 433 cell line. CA125 is well accepted as a tumor marker for epithelial ovarian cancer and may be used as a surrogate marker of clinical response during followup. This raises the question of whether CA125 should be used routinely in patients with asymptomatic recurrence. The authors noted that a recent Medical Research Council (U.K.)/European Organisation for Research and Treatment of Cancer trial demonstrated that early chemotherapy in asymptomatic patients undergoing CA125 monitoring does not prolong survival. Despite these findings, the authors maintained that CA125 monitoring should be performed as part of routine followup in asymptomatic patients to help identify patients who should undergo additional radiological studies. This will help in selecting patients who may benefit from early surgery or treatment before symptoms occur. The authors also noted that studies have shown that rising CA125 levels are associated with relapse in 56 percent to 94 percent of cases. However, there is a percentage of patients with normal CA125 levels for whom residual disease is noted at second-look surgery. So although CA125 may not be highly sensitive for detecting relapse in all patients, there appears to be a continued role for CA125 monitoring in some patients with ovarian cancer. This may also help in selecting patients who are appropriate for clinical drug trials to identify more efficacious treatments for this type of cancer.

Pignata S, Cannella L, Leopardo D, et al. Follow-up with CA125 after primary therapy of advanced ovarian cancer in favor of continuing to prescribe CA125 during follow-up. Ann Oncol. 2011;22 (suppl 8):viii40–viii44.

Correspondence: Dr. S. Pignata at s.pignata@istitutotumori.na.it