Treatment-Related Myelodysplastic Sydromes (t-MDS) after Autotransplants (AT) for Multiple Myeloma (MM)

Reviewer: Tracy d'Entremont, MD
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Last Modified: December 9, 2002

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Presenter: Guido J. Tricot
Presenter's Affiliation: University of Arkansas for Medical Sciences; Little Rock, AR
Type of Session: Scientific

Background

    Overall Survival (OS) in Multiple Myeloma (MM) has increased with the recent onset of tandem transplants. With the increase use of these double transplants, attention must be paid to the late complications of high dose therapy such as transplant related MDS (t-MDS) and AML. The diagnosis of t-MDS is based mainly on the presence of cytopenias and cytogenetic abnormalities.

Materials and Methods

  • 1000 consecutive patients with MM treated with AT from 9/89 to 6/98 were evaluated.
  • All patients got hi dose melphalan as the preparative regimen.
  • The median duration of prior treatments was 10 months.
  • The median follow-up was 5.6 years.

Results

  • The risk of t-MDS at 10 years post- AT was 6%.
  • None of those patients had the karyotypic abnormality prior to AT.
  • The cumulative risk of t-MDS at 10 years based on length of prior therapy was as follows:
    <6 months 3%
    6-12 months 5%
    > 12 months 9%
  • THe median time after AT before development of t-MDS was 21 months.
  • The median survival after diagnosis of t-MDS was 25 months.
  • THe most common cytogenetic abnormalities were 20q-, t(1;7), -7, 7q-, 5q-, and +8.
  • Multivariate analysis showed that age >49 and having collected < 20x10^6/kg CD34+ cells were significant predictors of developing t-MDS.
  • The cumulative risk of developing t-MDS with 0, 1, or 2 of these risk factors was 2%, 5%, and 10.2% respectively.
  • FISH analysis was then performed on the stem cells of the patients who developed t-MDS and all patients had the cytogenetic abnormality present prior to transplantation.

Author's Conclusions

  • The 10 year risk of t-MDS is 6% in this poplulation of patients.
  • The major predictors of t-MDS were age >49 and collection of < 20x 10^6 CD34+ stem cells.
  • The cytogenetic abnormalities seen in t-MDS in retrospect were already present in the stem cells collected prior to transplantation.

Clinical/Scientific Implications

    AT and tandem transplants are more and more frequently used in the treatment of MM. With patients living longer after transplant, the long term effects of AT become more relavent. This study gives us an idea of the risk of t-MDS after AT for MM. The risk is a real and calculable one at 6% at 10years time. The question remains is there a way to predict who those patients may be. There is an indication that those who develop t-MDS already had cytogenetic abnormalities going into the transplant. Whether it is reasonable to FISH all patients before transplant and to deny transplantation to those patients with cytogenetic abnormalities remains to be seen.

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