I have always been a bit apprehensive about my low levels of ferritin (= a protein that binds to and stores iron, which the body can use when needed). At times, my ferritin has even fallen below the normal reference range…this happened in last May, in fact. Well, I am happy to say that my ferritin is now within the normal range, albeit on the low end. And that is where I hope it will stay…

You see, day before yesterday, after reading a study (full study: http://tinyurl.com/yco8rsq) on the ferritin-myeloma connection, I threw all of my ferritin worries out the window…Incidentally, I would like to express my gratitude to the blog reader who sent me the link to this study, which apparently is the first to examine the possible impact of serum ferritin on the survival of myeloma patients.

The authors measured the serum ferritin levels in newly diagnosed MM patients to determine whether the level is correlated with outcome and is an independent predictor of survival in patients with MM. They examined 89 myeloma patients, all of whom had been following different chemotherapy regimens (see the study for details). The average follow-up was two years (up to six years).

Of these patients, 39 had high ferritin levels, 50 had normal levels. Compared to the normal ferritin group, the high ferritin patients had lower albumin and higher B2M (=Beta-2 microglobulin) and CRP (=C-reactive protein) = not good news, as we know by now. Calcium, creatinine and haemoglobin were the same in both groups, though. Longer survival was associated with higher albumin and haemoglobin levels, and with normal B2M, LDH (=lactate dehydrogenase…an increase of this marker may signal myeloma progression) and CRP. Check out Figure 2, in particular. Impressive.

The authors state that high ferritin was an independent predictor of mortality in patients with multiple myeloma…in this particular study, of course…

Okay, let’s have a look at the Discussion part: The serum ferritin level reflects acute phase reactions and is usually associated with iron storage. Iron overload increases the susceptibility to organ damage and the risk for infection. Recent studies have shown that serum ferritin is a surrogate of iron overload and is an important predictor of survival in transplantation patients. A quick search of PubMed led me to this 2010 study on an ALL patient who suffered from iron overload and liver toxicity after an allogeneic transplant: http://tinyurl.com/yfnl9n5 See also this 2007 Dana Farber study: http://tinyurl.com/yj7fsrx And this 2006 study shows that myeloma patients undergoing autologous stem cell transplants are more likely to suffer from severe infections if their pre-transplant bone marrow iron stores or BMIS are high(serum ferritin is a reliable marker of BMIS, I read): http://tinyurl.com/yhhrukh Iron overload is a problem also for patients requiring chronic transfusions, see for example this 2010 study: http://tinyurl.com/yg2npcz

Well, after reading all these abstracts, the fact that the high ferritin patients had a worse outcome than the normal ferritin ones should not come as a shock: the patients in the elevated ferritin level group had more adverse prognostic factors at baseline and a poorer clinical outcome compared with patients in the normal ferritin group. Furthermore, the serum ferritin levels at the time of diagnosis were correlated with survival in newly diagnosed MM patients. So, the lower, the better…

The authors themselves point out that the ferritin-myeloma study has some limitations, namely the small number of myeloma patients, the lack of FISH testing and the fact that the patients followed different chemotherapy regimens. That is why their conclusion uses the conditional tense: the serum ferritin level may be associated with OS in patients with newly diagnosed MM. Further investigation is warranted to determine whether serum ferritin is an independent prognostic marker and a measure of disease activity. (“OS” means “overall survival.”)

My own conclusion. Yes, the study was a very small one and yes, the patients involved were taking different types of chemo (etc.)…but we know enough now about the iron overload link to cancer (take another look also at my July 19 2008 post titled “Double-edged sword”) for this study to make sense on a variety of levels. And that is why I have decided not to worry about my low ferritin levels anymore…