Discussion
Treatment of immune-mediated TTP with PEX aims to eliminate ADAMT13
inhibitors from circulation, and to provide ADAMTS13 in amounts
sufficient for cleaving ULVWF, while immunosuppression aims to stop
further production of inhibitors by B-lymphocytes and plasma cells. It
has been shown that treatment with rituximab in addition to PEX and
glucocorticoids increases the probability of achieving remission,
reduces the probability of relapse, and shortens the interval to
remission.6 Relapses of TTP are common and are due to
the continued production of anti-ADAMTS13 antibodies. Hematologic
remission are not equivalent to immunologic remission, as levels of
ADAMTS13 activity exceeding 5-10% are sufficient in a steady state to
maintain the appropriate cleavage of ULVWF.9 Thus, the
ultimate goal of TTP treatment is to restore ADAMTS13 activity to normal
by eliminating anti-ADAMTS13 antibodies. Historically, many
immunosuppressive interventions, such as vincristine, cyclophosphamide,
or splenectomy, have been used in patients with TTP with varying degrees
of success.
The proteasome inhibitor bortezomib , have proven to be an effective
therapy of multiple myeloma, resulting in the long-term suppression of
malignant plasma cells. Bortezomib has been used successfully in the
treatment of a variety of autoimmune conditions, including TTP, but only
one publication has reported its use in
adolescents.10-14 In line with published cases, our
two patients with short-lived responses to PEX, rituximab, and high-dose
glucocorticoids subsequently went into long-term remission with the
elimination of inhibitors and normalisation of ADAMTS13 activity after
just one course of bortezomib. No side effects of bortezomib were seen,
indicating that this treatment is safe and thus suitable for use in
children. Monitoring the level of ADAMTS13 activity and inhibitor
activity after the achievement of clinical and hematological remission
is appropriate for determining the timing of this intervention.
Acknowledgements: Authors wish to thank Vitali Demkin for
designing high quality images.
Conflicts of interest : All authors declare no conflict of
interest.