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Stem Cell Transplants: Are You a Good Candidate?

Date: April 4, 2024

We have discussed mini-allo stem cell transplants in previous articles on this site (see links provided below). In fact, the only therapy that has demonstrated an ability to cure CLL (that’s right, CURE, as in the English word you and I understand) right now is a stem cell transplant from a healthy donor. “Mini-allo” transplants have taken a big bite out of the danger associated with the more aggressive full myeloablative transplant procedures used just a few years ago. As donor banks grow, more and more patients are likely to find a matched, unrelated donor (“MUD”), even if he or she does not have a well matched sibling donor. And if you strike out on both counts, it is worth exploring cord-blood transplants.

Not every one is a good candidate for a stem cell transplant. There is still a substantial risk of dying from the process itself, and it makes sense to consider whether you are a good candidate before you make the decision. This is particularly true if you have other therapy options. So, what makes a good candidate for mini-allo transplants? Here are some points worth remembering:

1. It helps a lot if you have a well matched and healthy adult donor, whether he or she is a sibling or a stranger. Cord blood transplants are still coming up the learning curve.

2. People with other “baggage” going in do not do as well as otherwise healthy patients. It is logical that if you are in good fighting trim, you are more likely to sail through the heavy-duty preconditioning and post transplant graft-versus-host-disease (GVHD) and related therapy. If you are an obese couch potato with tendencies towards heart disease, diabetes, pulmonary issues, etc, you may want to take a hard look at yourself and consider some lifestyle changes before you consider a mini-allo transplant. And if you still smoke, you should hurry up and have your head examined!

3. Age restrictions have become a lot less stringent with the advent of mini-allo transplants. Your general state of health is a lot more important than your chronological age.

4. Mini-allo transplants depend on the GVL (“Graft versus Leukemia”) effect to clean out the remaining CLL cells in your body. Patients who go into a transplant with no more than the bare minimum of residual disease are much more likely not to relapse. If you make the job too hard for the newly grafted immune system, with way too many cancer cells to fight, you may not be so lucky. Since it is a lot easier to get clean responses in early stage CLL, it may not be a good idea to wait too long if your game plan is to go in for a transplant eventually. This is particularly true of younger patients, and those with high-risk prognostics. You may have only a couple of years and a couple of rounds of therapy before you run into diminishing options. The first really deep CR you get may be the best one you are going to get, and it may be a good idea not to “waste” the window of opportunity while you dither.

5. Last but not least, the abstract below points out one of the long-term risk factors associated with stem cell transplants. You may be cured of CLL at the end of it, but the immune suppressive drugs necessary to control graft rejection and GVHD may leave you vulnerable to secondary cancers. Skin cancer is a huge risk factor. If you are already prone to skin cancer (when was the last time you had a good dermatological examination for basal cell carcinoma or squamous cell carcinoma?) this is an important issue to consider. T-cell depletion, whether it be due to routine therapy with immune suppressive agents such as steroids, fludarabine, Campath or more complex regimens to control GVHD, will lead to a lack of T-cell surveillance which may be a lot riskier for patients who are already prone to skin cancer.

Only Real Cure, for Now
Matching Made Simple
GVHD
Primer on Bone Marrow SCTs
Dying to Get a Tan?

Be well,

Chaya
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Abstract

Blood. 2024 May 15;105(10):3802-11.

Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study.

Curtis RE, Metayer C, Rizzo JD, Socie G, Sobocinski KA, Flowers ME, Travis WD, Travis LB, Horowitz MM, Deeg HJ.

Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Executive Plaza South, Suite 7042, 6120 Executive Blvd, Bethesda, MD 20242, USA.

Previous studies of recipients of hematopoietic stem-cell transplants suggest that graft-versus-host disease (GVHD) and its therapy may increase the risk for solid cancers, particularly squamous-cell carcinomas (SCCs) of the buccal cavity and skin. However, the importance and magnitude of these associations are not well characterized. We conducted a case-control study of 183 patients with posttransplantation solid cancers (58 SCCs, 125 non-SCCs) and 501 matched control patients within a cohort of 24,011 patients who underwent hematopoietic stem-cell transplantation (HSCT) at 215 centers worldwide. Our results showed that chronic GVHD and its therapy were strongly related to the risk for SCC, whereas no increase in risk was found for non-SCCs. Major risk factors for the development of SCC were long duration of chronic GVHD therapy (P < .001); use of azathioprine, particularly when combined with cyclosporine and steroids (P < .001); and severe chronic GVHD (P = .004). Given that most patients who received prolonged immunosuppressive therapy and those with severe chronic GVHD were also treated with azathioprine, the independent effects of these factors could not be evaluated. Additional analyses determined that prolonged immunosuppressive therapy and azathioprine use were also significant risk factors for SCC of the skin and of the oral mucosa. These data provide further encouragement for strategies to prevent chronic GVHD and for the development of more effective and less carcinogenic treatment regimens for patients with moderate or severe chronic GVHD. Our results also suggest that clinical screening for SCC is appropriate among patients exposed to persistent chronic GVHD, prolonged immunosuppressive therapy, or both.

PMID: 15687239
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