Myelodysplastic Syndromes (MDS) is considered a disease of the hematopoietic (blood-forming) stem cells (HSCs) that are housed in the bone marrow. Replacing diseased HSCs with healthy HSCs from healthy donors (through a procedure called allogeneic (i.e., not genetically related) bone marrow transplantation (aBMT)) is the only cure for MDS. In order to kill the diseased cells and to make space in the bone marrow so that transplanted healthy HSCs can be received, patients are “conditioned” prior to the actual transplant. This so-called “conditioning regimen” is unfortunately associated with a toxicity to normal cells (in the bone marrow and outside). Potentially life-threatening complications from the conditioning regimen or from the transplant itself seem to be less well tolerated as the age of the patient increases. Therefore, old age (over 60 years) has been traditionally considered a contraindication for aBMT. However, recent advances have been made in that less intensive conditioning regimens have been developed as well as treatments to deal with complications. As a result, there has been a steady increase in the number of older MDS patients that have received an aBMT. This study evaluates the outcomes of aBMTs in older MDS patients as reported in other studies. The goal is to determine if old age should still be considered a reason for not performing an aBMT (i.e, a contraindication for aBMT), or whether other parameters should be taken into account instead.
In a study conducted by Nicolaus Kroger at University Medical Center Hamberg-Eppendorf, Germany, he found that chronological age alone is not a contraindication for aBMT; other parameters and considerations may be more important. These include the presence of comorbidities (i.e, existence of other diseases, in addition to MDS), increased serum ferritin levels (≥ 1000mg/l) (an indicator of the body’s failing ability to deal with the excess of iron, often seen after repetitive red blood cell transfusions), status of the disease (i.e., advanced status, high blast cell count, the presence of chromosomal abnormalities indicative of high-risk MDS). Although these parameters were related to a worse BMT outcome in most patient studies evaluated, unbiased, prospective patient studies are required to determine its value as a predictor of aBMT outcome. (Only parameters that can accurately predict success vs. failure of a procedure have true value in the decision making whether to perform it or not.)
This study also evaluated the aBMT outcome in relation to the conditioning regimen that was received, i.e., a less intense (less toxic) vs a traditional (more toxic) regimen.The less intensive conditioning regimen was indeed associated with a lower therapy-related mortality, however, it was also associated with an higher risk for relapse, resulting in similar survival rates in both groups. It was also concluded that biological age should not be the deciding factor in choosing the type of condition regimen; the presence of co-morbidities and disease status seems to be more appropriate. Timing of the transplant and donor age need to be taken into consideration when evaluating BMT outcomes. In regards to timing the results of two studies evaluated were contradictive and only one study looked at donor age and it was suggested that for elderly MDS patients, an unrelated donor was only preferable if the donor was ≤ 30 years old. Otherwise an HLA-identical donor was preferred. No prospective studies were available yet for evaluation.
In conclusion: chronological age per se should not be a determinant factor in deciding whether an MDS patient should receive an aBMT or not. Other factors may, such as co-morbidity and disease status, but randomized, prospective studies are required to determine this. Moreover, a better understanding of the conditioning regimen choices and the timing of the transplant is important. Lastly, to fully understand the place of aBMT as a treatment choice for elderly MDS patients, outcomes of transplant procedures need to be directly compared to those of non-transplant procedures.