Lack of efficacy (repeat course of HSCT): HSCT is a not a typical IRT, in that is usually given as a single one-off treatment. Therefore breakthrough MS disease activity after HSCT usually triggers the introduction of another licensed DMT. However, there are case reports of patients with MS and other autoimmune diseases having repeat HSCT.
DMTs: Provided the baseline screening tests are okay and there are no specific contraindications in an individual MSer I see no reason why HSCT can't be used after any of the licensed DMTs. However, there are some specific caveats highlighted below.
Interferon-beta and glatiramer acetate: No contraindications or specific issues.
Non-selective cell depleting DMTs (alemtuzumab or mitoxantrone): a persistently low peripheral white cell count post alemtuzumab or mitoxantrone, i.e. a neutrophil count < 1000/mm³ or a total lymphocyte count <800/mm³ is a relative contraindication to HSCT. Another hit on the bone marrow and the primary and secondary lymphoid organs may worsen your leukopaenia and render you more immunosuppressed. The decision to use HSCT in this situation has to be based on the potential benefits of HSCT versus the risks of HSCT and the risks of untreated active MS.
Selective cell depleting DMTs (cladribine): a persistently low peripheral lymphocyte cell count post cladribine, i.e. a total lymphocyte count <800/mm³ is a relative contraindication to HSCT. The effect of HSCT on primary and secondary lymphoid organs may worsen the lymphopaenia. However, the decision to use HSCT after cladribine has to be based on the potential benefits of HSCT versus the risks of lymphopaenia and the risks of untreated active MS.
Selective cell depleting DMTs (ocrelizumab): as ocrelizumab is a selective B-cell depleting agent, HSCT is theoretically much safer than the other less selective and non-selective agents. In my opinion an anti-CD20 is the safest depleting DMT to use before HSCT.
Fingolimod: Chemotherapy used for mobilising stem cells will require them to become mobile. Therefore it will be necessary to have an adequate wash-out period after stopping fingolimod before starting the HSCT procedure. It is important to make sure that the peripheral lymphocyte counts return towards normal (>800) or are normal (>1,000) before giving HSCT. This is to prevent persistent lymphopaenia post-HSCT.
Natalizumab: As HSCT is a non-selective IRT that can't be rapidly reversed, it is critical to make sure that there is no asymptomatic PML. Carry-over PML from natalizumab to HSCT would potentially be fatal. It is therefore essential that a baseline MRI scan and possibly a CSF examination is done prior to starting HSCT, to exclude the possibility of PML.
Dimethyl fumarate: DMF reduces the lymphocyte count by approximately 30% and in some MSers by more than this. Therefore, MSers who have lymphopaenia on DMF may be more susceptible to developing clinically significant prolonged lymphopaenia post-HSCT.
Teriflunomide: Because teriflunomide is an antiproliferative agent it may delay or prevent the recovery of the peripheral white cell count post-HSCT. One option is to do an accelerated teriflunomide washout to prevent this potential problem. Interestingly, rheumatologists who use leflunomide, a prodrug that is converted to teriflunomide, don't use an accelerated washout when using antiproliferative agents post-leflunomide.
Special circumstances: Specific comorbidities and adverse events may make it difficult to start HSCT after certain DMTs, for example the development of chemotherapy-related cardiomyopathy post mitoxantrone.