Blood 2003 May 22
Nash RA, Bowen JD, McSweeney PA, Pavletic SZ, Maravilla KR, Park MS, Storek J, Sullivan KM, Al-Omaishi J, Corboy JR, DiPersio J, Georges GE, Gooley TA, Holmberg LA, LeMaistre CF, Openshaw H, Sunderhaus J, Storb R, Zunt J, Kraft GH.
Fred Hutchinson Cancer Research Center, Seattle, WA, USA; University of Washington, Seattle, WA, USA.
Twenty-six patients were enrolled in a pilot study of high-dose immunosuppressive therapy (HDIT) for severe multiple sclerosis (MS).
Median baseline Expanded Disability Status Scale (EDSS) was 7.0 (5.0-8.0).
HDIT consisted of total body irradiation, cyclophosphamide and antithymocyte globulin (ATG) and was followed by transplantation of autologous, G-CSF-mobilized CD34-selected stem cells.
Regimen-related toxicities were mild.
Because of bladder dysfunction, there were eight infectious events of the lower urinary tract.
One patient died from EBV-PTLD associated with a change from horse-derived to rabbit-derived ATG in the HDIT regimen.
An engraftment syndrome characterized by noninfectious fever +/- rash developed in 13 of the first 18 patients and was associated in some cases with transient worsening of neurological symptoms.
Two significant adverse neurologic events occurred, including a flare of MS during mobilization and an episode of irreversible neurological deterioration after HDIT associated with fever.
With a median follow-up of 24 (3-36) months, the Kaplan-Meier estimate of progression (>/=1.0 points EDSS) at 3 years was 27%.
Of 12 patients who had oligoclonal bands in the cerebrospinal fluid at baseline, 9 had persistence after HDIT.
Four patients developed new enhancing lesions on magnetic resonance imaging of the brain after HDIT.
The estimate of survival at 3 years was 91%.
Important clinical issues in the use of HDIT and stem cell transplantation for MS were identified; however, modifications of the initial approaches appear to reduce treatment risks.
This was a heterogeneous high-risk group, and a phase III study is planned to fully assess efficacy.