Infections with certain viruses, bacteria, and parasites have been identified as strong risk factors for specific cancers. To examine the link between infections and cancer, researchers performed a systematic analysis of the proportion of cancer cases attributable to infection in 2008. They used data on cancer incidence from the GLOBOCAN project along with epidemiological data regarding the causal effects of infection on cancer. The data included information on 27 types of cancer from 182 countries.

They found that of the 12.7 million new cancer cases that occurred worldwide in 2008, 16 percent—or roughly two million—were attributable to infections. The rate of infection-related cancer was about three times higher in developing countries. For example, 3.3 percent of cancers in Australia and New Zealand were infection related, whereas 32.7 percent of cancers in sub-Saharan Africa were attributable to infections. The four main infections associated with cancer were human papillomavirus, hepatitis C, hepatitis B, and Helicobacter pylori. These infections were responsible for approximately 1.9 million cancer cases in 2008, mainly gastric, liver, and cervical cancers.

Cervical cancer accounted for about half of the infection-related cancers in women. Liver and gastric cancers accounted for more than 80 percent of the infection-related cancers in men.  About 30 percent of infection-related cancers occurred in people younger than 50 years. It’s important to note that it takes decades of chronic infection before an infection progresses to cancer.

Based on the statistics, the researchers noted that approximately two million cancer cases each year might be preventable with better public health methods for preventing infection. In an accompanying editorial, Dr. Goodarz Danaei, an assistant professor of global health at Harvard School of Public Medicine in Boston, noted that vaccines for HPV and hepatitis B are effective and that increasing their availability should be a priority for higher risk countries.[2] He suggests that increasing vaccine coverage could reduce the global burden of cancer.

References:

How does cancer treatment affect fertility in men?

Chemotherapy: Chemotherapy can temporarily—and in some cases, permanently—stop sperm production by the testes.[1] The extent to which chemotherapy affects sperm production depends on several factors, including the type and dose of chemotherapy.

Radiation: Radiation to the abdomen or pelvis can also reduce or eliminate sperm production by the testes.

Surgery: Surgery that involves the removal of both testicles (an option for some men with prostate cancer) eliminates sperm production, but other types of surgery can also affect a man’s fertility. Some types of pelvic surgery, for example, can change or eliminate ejaculation.

Options for preserving fertility in men

Although many men are able to conceive naturally after cancer treatment, others are not.

If possible, men should talk with their doctor about their future fertility before beginning cancer treatment. Some options for preserving fertility require that steps be taken before cancer treatment begins.

Sperm banking is the most well-established method of preserving fertility in men.[2] It involves the collection and storage of sperm, ideally before cancer treatment begins. The samples are kept frozen at a lab or sperm bank until they are needed. Sperm can be stored in this way for many years. After being thawed, the sperm can be used for intrauterine insemination (IUI) or in vitro fertilization (IVF). During IUI, sperm are placed directly into a woman’s uterus. During IVF, mature eggs are removed from a woman’s ovary and mixed with the sperm in the lab. Embryos that result from IVF can then be placed in a woman’s uterus or frozen for later use.

If a sample contains very few viable sperm (or if a man has already undergone cancer treatment and has a low sperm count), another approach may be used to fertilize an egg. Intracytoplasmic sperm injection (ICSI) requires only a small number of healthy sperm, along with mature eggs that have been collected from a woman’s ovary. A single sperm is injected directly into each egg. The embryos that develop can then be placed in a woman’s uterus or frozen for later use.

If it is not possible to collect sperm from ejaculate, it may in some cases be possible to collect sperm directly from the testicles. This approach is still investigational.

Finally, it may also be possible to modify some cancer treatments to minimize their effects on subsequent fertility. During radiation therapy, for example, it may be possible to shield the testes in order to preserve sperm production.

Pregnancy after cancer

In the event that your fertility is not affected by cancer treatment (or recovers quickly or unexpectedly), you and your partner should use birth control if you do not wish to have a child. If you are trying to conceive a child naturally, your doctor may advise you to wait for several months after treatment; this allows for the elimination of sperm that may have been damaged during treatment.

In general, the risk of birth defects in children born to cancer survivors appears to be similar to the risk in the general population.[3] If your cancer was due to a hereditary cancer syndrome, such as Lynch syndrome (hereditary nonpolyposis colorectal cancer), your children may inherit the gene mutation responsible for your family’s increased risk of cancer. Talking with a genetic counselor may be helpful.

Other options for parenthood

Not all men have the luxury of being able to explore their reproductive options before beginning cancer treatment, and not all men will find a fertility preservation option that meets their needs. But there are still ways to become a parent. Discussion of other routes to parenthood may be a painful topic for men who want to father a child but cannot. But as cancer survivors consider how best to build their families, methods such as adoption are important options.

Adoption: Couples and individuals who wish to adopt have a range of options, including different types of domestic and international adoptions. You may wish to start by learning about the adoption laws in your state and by talking with other adoptive parents about the professionals and agencies they worked with. Before selecting an adoption agency, you may wish to talk with them about their attitudes toward placing a child with a cancer survivor. Many agencies will be receptive toward this, but it’s important to know before making a final decision.

Donor Sperm: Donor sperm is readily available from sperm banks and can be used for either intrauterine insemination or in vitro fertilization.

Individual decisions within a larger community

The decisions that you make about building a family (or about coming to terms with not building a family) will be intensely personal, but know that you are part of a larger community of patients and healthcare providers who are grappling with these issues.  To think about future parenthood is to think about life after cancer. For many people with cancer, planning for the future may provide the motivation needed to get through treatment.

More information?

Discuss with others…. http://cancerconnect.com/groups/young-adults/topics/fertility-after-cancer-treatment

Fertile Hope (www.fertilehope.org) provides a range of fertility resources for people with cancer.

References:

How does cancer treatment affect fertility in women?

Chemotherapy: Many chemotherapy drugs are toxic to the egg cells (oocytes) in the ovaries. If the number of remaining oocytes in the ovaries reaches a critically low point during treatment, women experience “acute ovarian failure.” This means that the ovaries stop functioning during or shortly after cancer treatment. If oocytes are lost during treatment but do not reach this critically low point, women are at risk for early menopause but may still be able to get pregnant for some time after treatment.

Radiation: Radiation to the pelvis can also destroy oocytes. Radiation to the pelvis can also affect uterine growth and blood flow, particularly if received before puberty.[1] A poorly developed uterus may make a woman more likely to have a miscarriage, or more likely to have a preterm or low-birthweight infant.

Surgery: Some cancers require surgical removal of the uterus, the ovaries, or both.

The effects of cancer treatment on fertility can vary substantially by age. Younger women, who have a larger pool of oocytes when they start cancer treatment, are more likely than older women to be able to get pregnant after treatment.[2]

Options for preserving fertility in women

If possible, women should talk with their doctor about their future fertility before beginning cancer treatment. Some options for preserving fertility require that steps be taken before cancer treatment begins.

One of the most established approaches for preserving fertility among female cancer patients is embryo freezing.[3] Before starting cancer treatment, a woman would be given hormones to stimulate the development of eggs in her ovaries. Mature eggs would be removed and fertilized with the sperm of her husband, partner or a sperm donor. The embryos that result from these fertilized eggs would be frozen for later use.

Although embryo freezing is an established approach to helping women become pregnant after cancer, there are downsides. A woman may not currently have a male partner and may be unwilling to use an anonymous sperm donor. It’s also important to be aware that embryo freezing takes approximately two weeks after the start of a woman’s period. If a woman needs to begin cancer treatment immediately, she may not be able to go through this process. Finally, this approach is only an option for women of childbearing age; stimulating the ovaries to produce mature eggs is not an option for girls who develop cancer during childhood.

Several other options are still in the experimental phase. One approach being explored is the freezing of unfertilized eggs.3 Once again, the ovaries would be stimulated to produce mature eggs before cancer treatment begins. The eggs would then be frozen without being fertilized by sperm. Currently, freezing unfertilized eggs is less likely to result in pregnancy than freezing embryos, largely because unfertilized eggs are less likely than embryos to survive the process of freezing and thawing. Nevertheless, it may be an option for women who do not have a male partner at the time of their cancer diagnosis, and it avoids the difficult issue of what to do with unused embryos.

Another promising but still experimental approach is to freeze all or a part of an ovary before cancer treatment.[4] After treatment, the ovarian tissue is implanted either back in the woman’s pelvis or in another location (such as under her skin). If this process is successful, the ovarian tissue will begin producing eggs. A safety concern with this approach is the possibility of reintroducing cancer cells along with the ovarian tissue, and the tissue will need to be carefully screened for cancer before it is transplanted.4

Finally, it may also be possible to modify some cancer treatments to minimize their effects on subsequent fertility. For example, shielding the ovaries during radiation, or moving the ovaries out of the radiation field, may protect them from the effects of radiation. Scientists are also exploring whether using drugs to suppress the activity of the ovaries during chemotherapy will make the ovaries less susceptible to damage by chemotherapy.[5] For women with certain types of cervical or ovarian cancer, fertility-preserving surgery may also be an option.[6] It’s important to understand that only specific subsets of patients will be candidates for these approaches, and that some of the methods are still in the early stages of evaluation.

Pregnancy after cancer

In addition to having concerns about their ability to get pregnant, women may have concerns about whether pregnancy after cancer treatment will be safe for themselves and their children. While there is a limited amount of information about these topics, the news is generally good.

The risk of cancer recurrence during or after pregnancy has been most studied in women with breast cancer, and these studies generally have reported that pregnancy does not increase the risk of breast cancer recurrence. [7] Many doctors, however, suggest waiting for a period of time after treatment before becoming pregnant. [8]

If chemotherapy or radiation therapy has damaged her heart or lungs, a woman may also have concerns about the strain that pregnancy will put on her body. Studies of breast cancer survivors suggest that long-term heart problems are uncommon after chemotherapy or radiation therapy, [9] but a woman may wish to talk with her doctor about her current health status and the likely effects of pregnancy.

Children born after their mother’s cancer treatment do not appear to be more likely than other children to have birth defects or cancer.[10] If a woman’s cancer was due to a hereditary cancer syndrome, such as Lynch syndrome (hereditary nonpolyposis colorectal cancer), her child may inherit the gene mutation responsible for her family’s increased risk of cancer. Talking with a genetic counselor may help clarify the child’s risk.

When planning for pregnancy, be aware that some cancer treatments may cause you to have an early menopause even if your periods resume after treatment. Also be aware that you may be capable of conceiving even if your periods do not resume; continue to use birth control if you do not wish to become pregnant.

Other Options for Parenthood

Not all women have the luxury of being able to explore their reproductive options before beginning cancer treatment, and not all women will find a fertility preservation option that meets their needs. But there are still ways to become a parent. Discussion of other routes to parenthood may be a painful topic for women who want to become pregnant and cannot. But as cancer survivors consider how best to build their families, methods such as adoption are important options.

Adoption: Couples and individuals who wish to adopt have a range of options, including different types of domestic and international adoptions. You may wish to start by learning about the adoption laws in your state and by talking with other adoptive parents about the professionals and agencies they worked with. Before selecting an adoption agency, women may wish to talk with them about their attitudes toward placing a child with a cancer survivor. Many agencies will be receptive toward this, but it’s important to know before making a final decision.

Egg Donation: Women who still have a uterus may be able to become pregnant using an egg donated by another woman. Through in vitro fertilization, the donated egg would be fertilized by the cancer survivor’s male partner or a sperm donor, and implanted in her uterus. Alternatively, another couple may donate a frozen embryo that could be implanted in her uterus.

Gestational Carrier or Surrogate: Women who do not have a uterus, or who are otherwise unable to sustain a pregnancy, may be able to have another woman carry a pregnancy for them. If the cancer survivor has functioning ovaries, her own egg can be fertilized by her male partner’s sperm and transferred to the uterus of another woman. In this case, the woman who carries the pregnancy is known as a gestational carrier. If the cancer survivor does not have functioning ovaries, another woman can both donate an egg and carry the pregnancy. This is the arrangement traditionally known as surrogacy.

Individual Decisions Within a Larger Community

The decisions that you make about building a family (or about coming to terms with not building a family) will be intensely personal, but know that you are part of a larger community of patients and healthcare providers who are grappling with these issues.

To think about future parenthood is to think about life after cancer. For many people with cancer, planning for the future may provide the motivation needed to get through treatment.

More Information?

Discuss with others….. http://cancerconnect.com/groups/young-adults/topics/fertility-after-cancer-treatment

Fertile Hope (www.fertilehope.org) provides a range of fertility resources for people with cancer.

References:

Acute myeloid leukemia (AML) is a cancer of the bone marrow (spongy portion found in the middle of bones) and blood characterized by the rapid, uncontrolled growth of immature white blood cells known as myelocytes. The disease is more common in adults than in children; the average age at diagnosis is over 65.

There have been relatively large improvements in survival of younger patients with AML over the past two decades due to increased dose-intensity of therapy and stem cell transplants. However, there has been little, if any, improvement in the treatment of elderly patients with AML, often because elderly patients are not able to tolerate the more aggressive treatments used for younger patients. Treatment of elderly patients with AML remains unsatisfactory, and most patients die within a few months of diagnosis. One of the reasons for the dismal prognosis is the association with adverse cytogenetic and molecular abnormalities.

Mylotarg is a targeted agent that was originally approved in 2000 under the U.S. Food and Drug Administration’s (FDA) accelerate approval program; however, the confirmatory clinical trial required for full approval indicated that the drug did not improve survival and increased toxicity, including treatment-related death. Although the manufacturer (Pfizer, Inc.) voluntarily withdrew the drug from the market in 2010, clinical trials have continued.

The current trial involved 280 patients aged 50-70 years with previously untreated AML. The patients were randomized to receive either standard chemotherapy (with daunorubicin and cytrabine) or standard chemotherapy plus Mylotarg. In order to reduce side effects, the researchers used a low, fractionated dose of Mylotarg delivered over 3 days during chemotherapy (instead of a higher dose given over 2 days).

The researches found that adding a low, fractionated dose of Mylotarg to standard chemotherapy improved overall survival and event-free survival. After 2 years of follow-up, event-free survival was 41% for the patients in the Mylotarg/chemotherapy group compared to 17% for those in the chemotherapy group. Furthermore, the overall survival 2 years following treatment was 53% for patients who received Mylotarg compared to 42% for those who did not.

Patients in the Mylotarg group were more likely to experience side effects, including persistent reductions in white blood cells and platelets; however, the number of treatment-related deaths did not differ significantly between the two groups.

The researchers concluded that low fractionated-dose Mylotarg improves outcomes in patients with AML. As this runs directly counter to earlier studies that indicated that the drug was ineffective and too toxic, research will likely be ongoing.

Reference:

Castaigne S, Pautas C, Terre C, et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. The Lancet. 2012; 379(9825): 1508-16.

ALL—a fast-growing cancer of the white blood cells—is the most commonly diagnosed type of leukemia in children. Each year, there are approximately 6,000 new cases of ALL diagnosed in the United States.

The treatment of childhood ALL is carried out in two phases. The initial treatment phase is called remission induction and its goal is to achieve a complete remission or disappearance of all detectable leukemia cells in the peripheral blood and bone marrow. After a complete remission is achieved, the second phase of treatment, called post-remission therapy, begins. Post-remission therapy is necessary because despite achieving a complete remission of leukemia with induction treatment, hidden undetectable leukemia cells still exist and the leukemia will return without additional post-remission therapy.

Induction failure is rare, but children who do fail induction are at a very high risk for poor outcomes. The overall long-term survival rate for childhood ALL patients is 80 percent, but that rate plummets to 32 percent for patients who fail induction. They are sometimes treated with bone marrow transplants, but this may not always be the best course of action according to the new data.

This international study included a total of 14 cooperative study groups in the U.S., Europe, and Asia. It was the largest study ever of pediatric ALL patients, involving 44,017 patients ages 0 to 18 with newly diagnosed ALL who were treated between 1985 and 2000. The researchers identified 1,041 patients (2.4%) whose cancer did not go into remission after four to six weeks of induction therapy and then analyzed the relationships among disease characteristics and outcomes in these patients.

They identified a subset of young patients who achieved 10-year survival rates of 72 percent after additional chemotherapy rather than bone marrow transplantation. These patients had B-cell leukemia, were between the ages of 1 and 5 when their cancer was diagnosed, and many had more than 50 chromosomes in their leukemia cells, rather than the normal number of 46 chromosomes. They also had no other markers of high risk, including high white blood cell counts or chromosomal rearrangements involving the MLL gene.

In contrast, the researchers found that transplants are still the best hope for some other young ALL patients who fail induction therapy—namely those with T-cell leukemia, which accounts for 12 to 15 percent of childhood ALL.

The bottom line—one size does not fit all when it comes to treating childhood ALL. The researchers concluded that patients with T-cell leukemia appear to have better outcomes with allogeneic stem cell transplantation than with chemotherapy, whereas patients with B-cell leukemia without other adverse features appear to have better outcomes with chemotherapy.

The researchers concluded that bone marrow transplantation should not be an automatic response to induction failure—instead, physicians should be aware that some patients will benefit from additional chemotherapy.

Reference:

Acute myeloid leukemia is a cancer of the bone marrow and blood characterized by the rapid uncontrolled growth of immature white blood cells known as myelocytes. The disease is more common in adults than in children, with the average age at diagnosis being more than 65 years.

For several types of cancer—including AML—researchers are attempting to develop more individualized approaches to treatment by using specific characteristics of the cancer to guide treatment choices.

One factor that can affect response to treatment is the cancer’s genetic makeup. To explore how a broad range of genetic alternations affect AML’s prognosis and response to treatment, researchers examined 18 genes in 398 patients under the age of 60. The patients were participants in a clinical trial that compared high-dose and standard-dose daunorubicin.

• The researchers identified several genetic alterations that affected AML prognosis. Information about the presence or absence of each of these may allow doctors to more accurately classify AML as favorable-risk, intermediate-risk, or unfavorable-risk.
• Genetic changes were also linked with response to high-dose chemotherapy: patients with certain changes in the DNMT3A, NPM1, or MLL genes had better outcomes with high-dose chemotherapy than with standard-dose chemotherapy. In contrast, patients without changes in these genes did not benefit from high-dose chemotherapy.

These results suggest that more extensive genetic profiling of AML may influence treatment decisions and provide better information about a patient’s prognosis. The goal of this type of research is more individualized and more effective cancer treatment.

Reference: Patel JP, Gonen M, Figueroa ME et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. New England Journal of Medicine. 2012;366:1079-89.

A growing body of evidence suggests that aspirin may reduce the risk of several types of cancer, with particularly strong evidence for colorectal cancer. Not all studies have found a benefit, however, and any potential benefits of aspirin must be weighed against risks such as bleeding.

To further explore the relationships between daily aspirin and cancer, researchers conducted a combined analysis of 51 previous randomized trials.[1] The trials were originally designed to evaluate the effect of daily aspirin on outcomes such as heart disease, but information about cancer was also available.

• Daily aspirin reduced cancer deaths. After five years, aspirin users had a 37 percent reduction in risk of cancer death.
• Aspirin also reduced the likelihood of developing cancer. From three years onward, aspirin users had a 24 percent reduction in the risk of being diagnosed with cancer.
• As expected, aspirin carried a risk of major bleeding, but this risk appeared to diminish over time.

Another study published in the same issue of The Lancet evaluated the effect of daily aspirin on cancer metastasis (the spread of cancer from its original site to other parts of the body). The study focused on 987 people who were diagnosed with cancer while participating in one of five trials of aspirin use. Those who were taking aspirin were less likely to have metastatic cancer than those who were not taking aspirin.[2]

These results suggest that regular aspirin use may reduce cancer incidence and mortality, but concerns remain about the risks of regular aspirin use in healthy individuals. People who are considering using aspirin on a regular basis are advised to discuss the risks and benefits with their physician.

References:

ALL—a fast-growing cancer of the white blood cells—is the most commonly diagnosed type of leukemia in children. Each year, there are approximately 6,000 new cases of ALL diagnosed in theUnited States.

In recent decades, progress made in clinical trials has led to substantial improvements in survival for children diagnosed with ALL. In the 1960s, five-year survival for children with ALL was less than 10 percent. By the late 1980s and early 1990s, this figure had increased to 77 percent.

To explore more-recent trends in ALL outcomes, researchers collected information about more than 21,000 children and adolescents who had participated in clinical trials conducted by the Children’s Oncology Group (COG). The study participants had been diagnosed with ALL between 1990 and 2005, and were between the ages of 0 and 22 years at the time of diagnosis.

The Children’s Oncology Group involves more than 200 institutions in theUnited States,Canada,Australia, andNew Zealand.

• Five-year survival increased from 83.7 percent during 1990-1994 to 90.4 percent during 2000-2005.
• Survival increased for all groups of patients except those under the age of 1 year. Five-year survival in infants remained fairly steady at slightly over 50 percent.

This study highlights the ongoing improvement in outcomes for children and adolescents with ALL. Maintaining high levels of participation in clinical trials will be important for further progress. Areas in which progress is needed include the treatment of infants with ALL.

Reference: Hunger SP, Lu X, Devidas M et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the Children’s Oncology Group. Journal of Clinical Oncology. Early online March 12, 2012.

Myelofibrosis is a chronic disease characterized by abnormal blood cell development and the formation of scar tissue in the bone marrow. Symptoms of myelofibrosis can include fatigue, shortness of breath, abdominal discomfort, pain under the ribs, feeling full, muscle and bone pain, itching, and night sweats. Most patients with myelofibrosis have an enlarged spleen, and many have an enlarged liver.

For people who are experiencing symptoms from myelofibrosis, previous approaches to treatment have included blood transfusions, drug therapy, radiation therapy, surgery to remove the spleen, or stem cell transplantation.

Jakafi was the first drug approved specifically for myelofibrosis. It is taken orally and inhibits two enzymes—JAK1 and JAK2—that contribute to myelofibrosis.

The current study enrolled 309 patients from 89 centers in theUnited States. The patients had intermediate-2 or high-risk myelofibrosis. Half received Jakafi and half received a placebo.

• A substantial reduction in the size of the spleen (a 35 percent or greater reduction in volume) occurred in 42 percent of patients in the Jakafi group and less than 1 percent of patients in the placebo group.
• A 50 percent or greater reduction in total symptom score was experienced by 46 percent of patients in the Jakafi group and 5 percent of patients in the placebo group.
• After roughly one-year, 8 percent of patients in the Jakafi group and 16 percent of patients in the placebo group had died.
• Anemia and low platelet counts were more common in the Jakafi group than in the placebo group, but could generally be managed.
• Jakafi did not reverse the damage that had been done to the bone marrow by myelofibrosis.

These results demonstrate that Jakafi improves both quality and duration of life among patients with intermediate- or high-risk myelofibrosis. This is an important new treatment option for patients with this condition.

Reference: Verstovsek S, MesaRA, Gotlib J et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. New England Journal of Medicine. 2012;366:799-807.

Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia. The American Cancer Society estimates that approximately 16,000 people will be diagnosed with CLL this year. Currently, there are approximately 95,000 people in theUnited Statesliving with CLL.

CLL is characterized by the production of atypical lymphocytes. Lymphocytes are specialized immune cells that exist in two forms: B- and T-cells. These cells are produced in the bone marrow and each serves a specific function in aiding the body fight infection.

The large majority of CLL cases involve mature B-lymphocytes that tend to live much longer than normal. B-lymphocytes accumulate in the blood, bone marrow, lymph nodes, and spleen. This results in overcrowding of these areas and suppression of the formation and function of blood and immune cells. Additionally, the cancerous lymphocytes themselves do not function normally, leading to a further reduction in the body’s ability to fight infection.

Campath is a monoclonal antibody that is targeted against B-cells. It has been designed to bind to specific sites on B-cells and cause the immune system to attack the cells to which it is bound.

To evaluate the combination of Campath and fludarabine in patients with previously treated CLL, researchers conducted a Phase III clinical trial among 335 patients. All study participants had CLL that had relapsed after prior treatment or that was resistant to prior treatment. Half the patients were treated with fludarabine alone and half were treated with fludarabine plus Campath.

• Survival without cancer progression was 23.7 months among patients treated with fludarabine and Campath, versus 16.5 months among patients treated with fludarabine alone.
• Overall survival was also better among patients treated with fludarabine and Campath.
• Serious side effects were more common among patients given the combination treatment (33 percent versus 25 percent among patients treated with fludarabine alone).

These results suggest that the combination of Campath and fludarabine is more effective than fludarabine alone for patients with relapsed or refractory CLL.

Reference: Elter T, Gercheva-Kyuchukova L, Pylylpenko H et al. Fludarabine plus alemtuzumab versus fludarabine alone in patients with previously treated chronic lymphocytic leukaemia: a ramdomised phase 3 trial. Lancet Oncology. 2011;12:1204-13.