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Alert Number 205

Women Donors for Stem Cell Transplants

Did you have a good turkey day?

We have reported in several articles on our website that the survival statistics are constantly improving for stem cell transplants, using stem cells from sibling donors, unrelated donors and even cord blood from babies. The improvements come from using “kinder and gentler” pre-conditioning regimens (the so called mini-transplants), better matching of donors to recipients, far better techniques in managing opportunistic infections during the period of immune reconstitution, and controlling graft-versus-host-disease while encouraging graft-versus-leukemia effects. Here is the link to our review of mini-allo transplants: Chances of Success: The Only Real Cure.

But there is no question that stem cell transplants carry a significant risk of death due to the process itself, as well as failure of the graft down the road and a relapse of the original cancer, for a subset of patients. A risk factor that is not often captured in the statistics is the risk of secondary cancers several years down the road, sometimes as much a decade or more later. There is no question that even the procedures used in mini-transplants carry risk of some toxicity and mutagenicity. I have also read several articles suggesting that the risk of secondary cancers is higher when the donor of the stem cells is female, as opposed to male.

While the details of why this is so are not yet fully understood, it may have to do with the fact that most women donors are likely to have had one of more children. This may come as a surprise to most of us girls, but we carry small but lasting colonies of fetal cells in our bodies, a life-long memory of our pregnancies and a link to our children that survives the passage of time. When women who have been through childbirth become donors of stem cells, the theory is that the recipient of the stem cells gets not only the woman’s cells, but also a certain amount of DNA and cells from all the children she ever had. And this may contribute to the complexities associated with women donors.

I would like to put this in perspective, however. If you are a poor prognostic CLL patient, and you have arrived at the conclusion that you need a stem cell transplant to save your life, and the only fully matched donor happens to be of the female persuasion, please be smart and don’t turn your nose up at the generous gift. As always, it is a question of weighing the risks and rewards. Any day of the week, I will bet on a chance to live today and fight another day, rather than give up on the option because of a potential (and small) risk down the road.

This Alert just reiterates a point I have tried to make several times: getting your ducks in a row for a stem cell transplant is no easy business, it takes a lot of organization and getting all your options sorted out. If you are likely to be a candidate for a transplant, it really makes sense to get things squared away ahead of time, keep the transplant option as a get-out-of-jail-free card in your back pocket, as it were, for if and when you need to use it.

Be well,


Journal Article:

New Scientist Article

Stem cell transplants from women raise cancer risk

05:00 27 November 2006 news service

Roxanne Khamsi

People who receive stem cell transplants for diseases such as leukaemia appear to face a higher risk of developing secondary cancers, especially if the cells come from a female donor, according to a preliminary study.

The scientists behind the new report caution that future stem cell treatments for ailments such as spinal cord injury and heart failure might also carry a cancer risk. However, experts point out that the study is far from conclusive and more work needs to be done to confirm a link between stem cell transplants and tumours.

Donna Forrest of the British Columbia Cancer Agency in Canada, and colleagues, reviewed the medical records of more than 900 adult patients who had received haematopoietic stem cell transplants, also known as bone marrow transplants, in the past two decades. The vast majority of these transplant recipients were suffering from leukaemia.

Of the patients included in the study, 28 developed secondary tumours – such as skin, lung or breast cancer – within 10 years of receiving the stem cell transplant. After Forrest and her colleagues had excluded some of these cancers from their analysis due to incomplete reporting, they found that the remaining patients faced a 2.3% risk of cancer over the course of 10 years – nearly twice the risk in the general population.

Female donors

The analysis also revealed that patients who received stem cell transplants from female donors had an even higher risk of developing a secondary tumour. Their risk of developing cancer over the course of 10 years was 4.6%, while patients given stem cells from a male donor had a 1.8% risk.

Men who received stem cells from female donors had more than twice the risk of developing cancer compared with women who received the same.

This is the first study to demonstrate that stem cells from women carry a greater cancer risk than those from men, Forrest says. She suggests that the cells from female donors – many of whom have had children – might differ somehow. Their pregnancies might have made their cells more likely to be disruptive when transplanted into recipients. This in turn might have caused chronic inflammation in the patients, putting them at greater risk for cancer, she speculates.

Forrest adds that the findings are preliminary and that the analysis did not control for confounding factors, such as whether a patient smoked or maintained a healthy body weight. It therefore remains unclear exactly how much the stem cell transplants contributed to the risk of second cancers, she says.

Unsurprising risk

Experts also caution that the drugs given following such transplants are known to put patients at greater risk of these secondary tumours. "The findings from this study are not surprising,” explains Ed Yong at the London-based organisation Cancer Research UK. “Cancer patients who undergo stem cell transplants are given very intensive treatments and immunosuppressive drugs, which make them more vulnerable to developing other cancers later on in life.”

He stresses that the transplants helped save the leukaemia patients’ lives: "These treatments are only offered to patients with very poor long-term prognoses, or who have failed to respond to more conventional treatments. While this study indicates that stem cell transplants may carry an additional risk, they are only given to patients who have limited options.”

Given the hope that stem cell transplants might one day help patients recover from numerous ailments – ranging from spinal cord injury to heart failure – more studies are necessary to find out whether such treatments might influence cancer risk, says Forrest.

There is a growing need to understand what happens to transplanted stem cells, says Simon Cherry, a researcher at the University of California, Davis, US, “because they can develop into many different cell types and there’s always the danger that something can go wrong”. He says that researchers should actively investigate the possible cancer risk to avoid any unexpected negative outcomes of future trials involving stem cells.

Journal: Cancer (DOI: 10.1002/cncr.22375)

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