Autologous Hematopoietic Stem Cell Transplantation in Autoimmune Diseases

Claudio Annaloro; Francesco Onida; Giorgio Lambertenghi Deliliers


Expert Rev Hematol. 2009;2(6):699-715. 

In This Article

Expert Commentary

The results of autologous HSCT in ADs are frequently compared with a half-full glass[169] and authors generally try to show why the glass is full, overshadowing the reasons why it is also empty. Table 3 summarizes the expected results of autologous HSCT in the most common ADs.

In many reviews dealing with autologous HSCT in ADs, a common incipit is to state that the term AD encompasses heterogeneous diseases.[5,7,8] According to this assumption, the results of autologous HSCT in ADs are also heterogeneous. In diseases such as SLE and CD, clinical improvement or even complete remission may be the result of autologous HSCT, with many responders experiencing long-term DFS. Conversely, less striking improvements or disease stabilization are the most common outcomes in MS. Moreover, only a cutaneous response may be awaited in SS not influencing life-threatening progression of visceral involvement; even the claimed stabilization of organ compromise may be partially the result of time censoring effect. In other settings, results may be even worse. On the other hand, autologous HSCT bears the potential of offering a treatment-free survival to patients otherwise be candidates for continuous poorly effective long-term immunosuppression. In a half-full glass perspective, the choice of referring a patient to autologous HSCT should be weighed against the lack of alternatives.

Worthy of mention, a feared complication of autologous HSCT as secondary acute myeloid leukemia does not seem to constitute a major problem in autoimmune disease both after myeloablative and immunoablative conditioning regimens. This observation recalls the complex pathogenesis of secondary post-transplant acute myeloid leukemia, where baseline disease and previous conventional therapy are likely to play primary roles.[170] On the other hand, the strength of immunosuppression (immunoablative regimen, CD34 selection and ATG) makes these patients prone to the development of complications characteristic of allogeneic HSCT, as PTLD, recurrent CMV reactivation and BK virus hemorrhagic cystitis.[69,70,112]

At the opposite corner, invoking larger, prospective and controlled clinical trials is a favorite conclusion.[10,49,69,72,171,172] Referral to autografting, is commonly justified by the assumption that patients with intractable AD have a short life expectancy. Nevertheless, the evolving concepts in patient selection have progressively led to perform autologous HSCT in patients who were not dramatically ill as in the most outdated series. This resulted in a striking reduction in TRM but, at the same time, hinders the possibility of demonstrating a clear-cut advantage in survival over a reference population, taking also into account the limited availability of epidemiological studies. Moreover, an additional somewhat overlooked item is represented by the developing conventional therapy, that, over the last decade, has unevenly concerned the different varieties of AD and can be expected to have changed perspectives in some but not all of them.

On the other hand, the term autologous HSCT by itself encompasses a host of possible variables, including patient selection, mobilization strategy, harvest manipulation, in vivo purging and conditioning regimens; the complex of these variables may deeply influence the outcome of autologous HSCT, as presented in the RA section. It is hard to believe that the ongoing clinical trials will have the potential of addressing all of these points for each AD. Therefore, any future conclusions about autografting in ADs should be judged taking into account the above considerations.

In the meantime, it can be assumed that autologous HSCT is an interesting therapeutic option for some ADs, but cannot be considered as indicated in all ADs. In some varieties, referral to autografting is more than a promising choice only awaiting to be refined and to be supported by the ongoing randomized clinical trials. In others, autografting is performed because of a lack of alternatives rather than of intrinsic activity; in these patients, a thorough rethinking is warranted to better define indication criteria, objectives and strategy of autologous HSCT. Lastly, in some other AD diseases, autografting should be discouraged or reserved to single highly selected cases.

Optimizing patient selection and HSCT strategy (conditioning and cell selection) can be expected to improve results in ADs where the benefit of autologous HSCT remains controversial.[173]

Exploration of alternative cell therapy modalities, such as mesenchymal stem cell transplantation, may be a promising resource for ADs where autologous HSCT seems to give rise to doubt results.[174]

At the same time, progress in conventional treatment of ADs should be encouraged.[175]


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