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marți, 13 decembrie 2011

Childhood Cancer Survivors' Exposure To Chemotherapy, Radiation Does Not Increase Risk Of Birth Defects In Their Children

Main Category: Pediatrics / Children's Health
Also Included In: Cancer / Oncology
Article Date: 13 Dec 2011 - 1:00 PST

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A large, retrospective study shows that children of childhood cancer survivors who received prior treatment involving radiation to testes or ovaries and/or chemotherapy with alkylating agents do not have an increased risk for birth defects compared to children of survivors who did not have such cancer treatment. The findings provide reassurance that increased risks of birth defects are unlikely for cancer survivors who are concerned about the potential effects of their treatment on their children, and can help guide family planning choices.

"We hope this study will become part of the arsenal of information used by the physicians of childhood cancer survivors if reproductive worries arise," said lead author Lisa Signorello, Sc.D., associate professor of medicine at Vanderbilt University in Nashville, TN, and senior epidemiologist at the International Epidemiology Institute in Rockville, MD.

"Childhood cancer survivors face real reproductive concerns, including unknowns related to the effects of therapy. But, hopefully this study will provide some reassurance that their children are unlikely to be at increased risk for genetic defects stemming from their earlier treatment."

According to Signorello, childhood cancer patients frequently receive aggressive, though life-saving, radiation and chemotherapy treatments that can affect their ability to have children. For girls, radiation to the pelvis and the resulting damage to the uterus has been associated with a risk for pregnancy outcomes such as miscarriage and preterm birth, and effects on the ovaries can lead to infertility. Radiotherapy and chemotherapy with alkylating agents (e.g., busulphan, cyclophosphamide and dacarbazine) are DNA-damaging treatments, affecting both cancer and healthy cells. Studies to date have not adequately addressed the question of whether genetic damage from a parent's treatment could be passed down to their offspring. Genetic-based birth defects are rare in the general population (about 3 percent), and while previous research results indicated little or no increased risk for birth defects among the offspring of cancer survivors, such studies were relatively small in size and lacked detailed information about radiation and chemotherapy treatments, such as specific radiation doses to the testes and ovaries.

In the current study, investigators used information from the Childhood Cancer Survivor Study, a large retrospective study of treatment and outcomes in more than 20,000 childhood cancer survivors diagnosed between 1970 and 1986. Signorello and her colleagues examined data from 4,699 children of 1,128 men and 1,627 women who were 5-year childhood cancer survivors. The survivors reported their children's health problems through questionnaires, and investigators also examined medical records from survivors and their children, focusing on survivors' history of radiation to the testes or ovaries and chemotherapy with alkylating agents.

Of the survivors, 63 percent (1,736) had received radiation for their cancer as children, and 44 percent of men (496) and 50 percent of women (810) had received chemotherapy with alkylating agents. Overall, 2.7 percent (129) of the survivors' children had at least one birth defect, such as Down syndrome, achondroplasia or cleft lip. Researchers found that 3 percent of children of mothers exposed to radiation or treated with alkylating chemotherapy agents had a genetic birth defect, compared to 3.5 percent of children of mothers who were cancer survivors but did not have such exposures. Only 1.9 percent of children of male cancer survivors who received these DNA-damaging treatments had such birth defects, compared to 1.7 percent of children of male survivors who did not have this type of chemotherapy or radiation. The researchers concluded that children of cancer survivors were not at higher risk for birth defects stemming from parents' exposure to chemotherapy and/or radiation.

The researchers also noted that a strength of their study is the comparison they made to the children of other cancer survivors and not to the children of people randomly sampled from the general population. Signorello said that comparing cancer survivors to individuals in the general population can be difficult because the latter may not be as thorough in reporting health problems of their children, and the children of cancer survivors may be under heightened clinical surveillance and may appear to have higher rates of birth defects as a result. The investigators did, however, find that the overall prevalence of birth defects among the cancer survivors' children was very similar to what has been reported in the general population.

The study is among the largest to examine birth defects in children of childhood cancer survivors, and among the first to evaluate birth defects using medical records to validate both the children's health problems and the parents' radiation and chemotherapy exposures.

"The possibility of birth defects in offspring has been a lingering concern among cancer survivors because it's hard to address," Signorello said. "We know these are rare outcomes, and a large study group was needed to address these questions. It took years to validate the parents' self-reported outcomes, and to assemble and use the medical records of radiation and chemotherapy treatment exposures to allow us to quantify their exposure doses. These are the strongest results to date, adding greater certainty to other studies examining this common concern among survivors of childhood cancer."

The researchers would like to continue to sequence the DNA of families of childhood cancer survivors (survivors and their children) to see if there is any evidence of radiation- or chemical-induced genetic damage, even if the children did not have birth defects. They would also like to combine data from all U.S. and international studies on this topic in order to provide even larger, more definitive results.

"As the proportion of childhood cancer survivors within our population grows, it is clear that a very large number of former patients will be impacted by the results of this study. Cancer survivors and newly diagnosed patients worry about the effect that chemotherapy and radiation therapy may have on their future children. While we as oncologists have felt the risk of congenital abnormalities to be low, we now have concrete data from a very large number of children to support us in our conversations with survivors and newly diagnosed patients. These results will reassure survivors that their previous cancer therapy does not appear to result in an increased risk of birth defects in their future offspring."

Article adapted by Medical News Today from original press release. Source: American Society of Clinical Oncology
Visit our pediatrics / children's health section for the latest news on this subject. American Society of Clinical Oncology Please use one of the following formats to cite this article in your essay, paper or report:

MLA

American Society of Clinical Oncology. "Childhood Cancer Survivors' Exposure To Chemotherapy, Radiation Does Not Increase Risk Of Birth Defects In Their Children." Medical News Today. MediLexicon, Intl., 13 Dec. 2011. Web.
13 Dec. 2011. APA
American Society of Clinical Oncology. (2011, December 13). "Childhood Cancer Survivors' Exposure To Chemotherapy, Radiation Does Not Increase Risk Of Birth Defects In Their Children." Medical News Today. Retrieved from
http://www.medicalnewstoday.com/releases/239068.php.

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Brain Tumor Chemotherapy Resistance Prediction

Main Category: Cancer / Oncology
Also Included In: Neurology / Neuroscience;  Radiology / Nuclear Medicine
Article Date: 13 Dec 2011 - 1:00 PST

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Glioblastoma multiforme (GBM) is the most common and lethal of all human brain tumors that originate in the brain.

For most patients, treatment involves surgery followed by both radiation therapy and chemotherapy with temozolomide. However, many GBMs are resistant to the effects of temozolomide.

A team of researchers led by Sameer Agnihotri, at the University of Toronto, Toronto, has now determined that the protein APNG can contribute to GBM resistance to the effects of temozolomide. Importantly, high levels of expression of APNG in the nucleus of ressected tumor cells correlated with poorer overall survival compared with patients lacking APNG expression. Agnihotri, and colleagues therefore suggest that monitoring APNG levels could provide insight into whether or not a patient with GBM will respond to temozolomide, although this awaits confirmation in predictive and prospective studies.

TITLE: Alkylpurine-DNA-N-glycosylase confers resistance to temozolomide in xenograft models of glioblastoma multiforme and is associated with poor survival in patients

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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Journal of Clinical Investigation. "Brain Tumor Chemotherapy Resistance Prediction." Medical News Today. MediLexicon, Intl., 13 Dec. 2011. Web.
13 Dec. 2011. APA

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Immune System Repaired In Leukemia Patients Following Chemotherapy

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Immune System / Vaccines
Article Date: 13 Dec 2011 - 0:00 PST

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A new treatment using leukemia patients' own infection-fighting cells appears to protect them from infections and cancer recurrence following treatment with fludarabine-based chemotherapy, according to new research from the Perelman School of Medicine at the University of Pennsylvania. The new process is a step toward eliminating the harsh side effects that result from the commonly prescribed drug, which improves progression-free survival in patients with chronic lymphocytic leukemia (CLL) but destroys patients' healthy immune cells in the process, leaving them vulnerable to serious viral and bacterial infections. The drug's effects on the immune system tend to be so violent that it has been dubbed "AIDS in a bottle."

At the 53rd American Society of Hematology Annual Meeting, the research team presented results showing how they use a patient's own T cells to repair his or her immune system after fludarabine treatment. With a restored immune system, patients can stop taking prophylactic antibiotics and may have prolonged progression-free survival.

"Fludarabine is a double-edged sword," says Stephen J. Schuster, MD, an associate professor in the division of Hematology-Oncology and director of the Lymphoma Program at Penn's Abramson Cancer Center. "Although it is very active at killing CLL cells, it is also very active at killing normal cells in the immune system, particularly T lymphocytes, which are the master regulators of the immune system. So you rid the patient of their disease, but you also rid them of a normal immune system."

Thirty-four patients enrolled in the multicenter study. Prior to chemotherapy treatment, the researchers isolated healthy T lymphocytes from each patient's blood. When the patient finished chemotherapy, the team grew the T cells in Penn's Clinical Cell and Vaccine Production Facility using a technique that induces them to proliferate rapidly. The researchers then infused the expanded T cells back into the patient. "What we showed was that by giving them back their own T cells after treatment, we can restore patients' immune systems," Schuster said.

"Within four weeks of the T cell infusion, their T cell counts were within the normal range."

After chemotherapy and prior to T cell infusion, the median CD4 T cell count for fludarabine-treated patients was 119 cells/ml blood and the median CD8 T cell count was 80 cells/ml. Thirty days after the patients received the infusion of their own T cells, the median cell counts were in the normal range, at 373 cells/ml and 208 cells/ml for CD4 and CD8 cells, respectively. The T cell numbers remained in the normal range beyond 90 days, leading Schuster and colleagues to conclude that the autologous T cell transfer repaired the immune system of patients.

Although all of the patients' T cell counts returned to the normal range after treatment, not all patients responded equally well to the T cell therapy. Patients who had a complete response to chemotherapy had a more robust T cell recovery than did patients who had only a partial response. "We believe that having a complete remission of CLL seems to create a larger space for the normal immune cells to expand into," Schuster says. "Somehow, the cancer seems to interfere with recovery of the immune system."

In addition to quashing the complications ordinarily associated with treatment, the team hopes that the restored immune system will help keep the cancer in check. At a median follow-up of 14 months after T cell infusion, two-thirds of the patients remain progression-free. Longer follow up will be needed to compare treatment results for patients receiving T cells with published results for patients receiving similar chemotherapy without T cell support.

What is clear from the small trial is that patients can safely stop prophylactic antibiotic therapy after their T cell numbers rebound. Physicians regularly keep CLL patients on extended prophylactic antibiotic therapy to help stave off infections. In this study, though, patients stopped taking antibiotics about a month after receiving T cells without developing significant infections.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our lymphoma / leukemia / myeloma section for the latest news on this subject. In addition to the Penn researchers, investigators from the MD Anderson Cancer Center, the Baylor College of Medicine, Texas Children's Hospital, and the Methodist Hospital in Houston also participated in the study.
The study was funded by the CLL Global Research Foundation.
This research was presented Sunday, December 11, 2011 between 6 PM and 8 PM in Hall GH of the San Diego Convention Center.
University of Pennsylvania School of Medicine Please use one of the following formats to cite this article in your essay, paper or report:

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University of Pennsylvania School of Medicine. "Immune System Repaired In Leukemia Patients Following Chemotherapy." Medical News Today. MediLexicon, Intl., 13 Dec. 2011. Web.
13 Dec. 2011. APA

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