Safety of stem cell mobilization – long-term follow-up studies

by Alexey Bersenev on August 26, 2009 · 0 comments

in clinical trials and cases

 
I was very concerned about reports which showed possible development of leukemia in healthy donors of hematopoietic stem cell induced by drug-mobilizer G-CSF.

If you look at statistics for hematopoietic stem cell transplants in adults by cell source, you can see that value of peripheral mobilized blood (light green) consistently increased with years:


(credit: MNDP)

So, because number of reports give us a caution about severe long-term complications of mobilization, such as development of malignancies, we have to make sure that procedure is safe for healthy donors and probability of these events is the same as in general population.

A year ago I wrote:

So, right now, while data is insufficient, if any of my relatives will get leukemia I’d agree to mobilize and donate my HSC to save a life. But we definitely need more independent clinical studies that evaluate a potential risk of leukemogenesis – the sooner the better! Also because of huge interest in other areas of regenerative medicine and active advertisement of companies selling G-CSF generics. So it’s a billion dollar question.

Since that, a few more cases were reported with caution for G-CSF future use, including one of anaphylactic reaction.

Now a couple of new studies, published in Blood journal, gave us some reasons for optimism.

The first study is analysis of 12-years period of mobilization outcome in almost 4000 (!) healthy donors in one center:

We present the results of PBSC mobilization, collection and follow-up from 3928 consecutive unrelated stem cell donors in a single collection centre between Jan 1996 and Jan 2008. Assessments were performed prospectively at baseline, leukapheresis, 1, 6 months and annually after PBSC donation. During follow-up side-effects were recorded by return post questionnaires.

Malignancies occurred in 12 donors (0.3%), among whom were 1 case of acute myeloid leukaemia, 1 case of chronic lymphatic leukaemia and 2 cases of Hodgkin’s disease. Only the incidence of Hodgkin’s lymphoma differed significantly from an age-adjusted population. In conclusion, 7.5 µg/kg/d lenograstim proved to be safe and effective for mobilizing hematopoietic stem cells for allogeneic transplantation. Long-term monitoring of healthy PBSC donors remains important to guarantee the safety standards of PBSC mobilization and collection.

The second study evaluated adverse events in 2408 of unrelated healthy donors under National Marrow Donor Program (NMDP) prospectevily in 10-years period:

PBSC collection in unrelated donors is generally safe, but nearly all donors will experience bone pain, 1 in 4 will have significant headache, nausea, or citrate toxicity, and a small percentage will experience serious short-term adverse events. In addition, women and larger donors are at higher risk for donation-related AEs.

We reviewed NMDP follow-up data regarding the incidence of development of malignancies in this cohort of 2408 donors. Annual attempts at follow-up were made for all donors (median follow-up, 49 months; range, 2 days to 99 months). No cases of acute myelogenous leukemia or myelodysplasia were reported. Twenty-five nonhematologic cancers of various types occurred along with one case of chronic lymphocytic leukemia. Comparison of the incidence of these cancers to expected rates according to the SEER database showed no evidence of increased cancer risk in the donor cohort.

So, studies with large cohort of healthy volunteers showed that mobilization procedure is safe in long-term and doesn’t increase incidence of cancer risk.

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