High-dose immunosuppressive therapy and autologous HCT for relapsing-remitting MS.
OBJECTIVE
To evaluate the safety, efficacy, and durability of multiple sclerosis (MS) disease stabilization after high-dose immunosuppressive therapy (HDIT) and autologous hematopoietic cell transplantation (HCT).


METHODS
High-Dose Immunosuppression and Autologous Transplantation for Multiple Sclerosis (HALT-MS) is a phase II clinical trial of HDIT/HCT for patients with relapsing-remitting (RR) MS who experienced relapses with disability progression (Expanded Disability Status Scale [EDSS] 3.0-5.5) while on MS disease-modifying therapy. The primary endpoint was event-free survival (EFS), defined as survival without death or disease activity from any one of: disability progression, relapse, or new lesions on MRI. Participants were evaluated through 5 years posttransplant. Toxicities were reported using the National Cancer Institute Common Terminology Criteria for Adverse Events (AE).


RESULTS
Twenty-five participants were evaluated for transplant and 24 participants underwent HDIT/HCT. Median follow-up was 62 months (range 12-72). EFS was 69.2% (90% confidence interval [CI] 50.2-82.1). Progression-free survival, clinical relapse-free survival, and MRI activity-free survival were 91.3% (90% CI 74.7%-97.2%), 86.9% (90% CI 69.5%-94.7%), and 86.3% (90% CI 68.1%-94.5%), respectively. AE due to HDIT/HCT were consistent with expected toxicities and there were no significant late neurologic adverse effects noted. Improvements were noted in neurologic disability with a median change in EDSS of -0.5 (interquartile range -1.5 to 0.0;p= 0.001) among participants who survived and completed the study.


CONCLUSIONS
HDIT/HCT without maintenance therapy was effective for inducing long-term sustained remissions of active RRMS at 5 years.


BACKGROUND
NCT00288626.


METHODS
This study provides Class IV evidence that participants with RRMS experienced sustained remissions with toxicities as expected from HDIT/HCT.
From the Colorado Blood Cancer Institute (R.A.N.), Denver; Baylor College of Medicine (G.J.H.), Houston, TX; Ohio State University (M.K.R., S.M.D.), Columbus; MD Anderson Cancer Research Center (U.P.), Houston, TX; Rho, Inc. (K.C.S.), Chapel Hill, NC; National Institute of Allergy and Infectious Diseases (L.M.G.), National Institutes of Health, Bethesda, MD; Division of Brain Sciences (P.A.M.), Imperial College London, UK; City of Hope National Medical Center (H.O.), Duarte, CA; Immune Tolerance Network (P.H.S.), University of California San Francisco; University of Texas Southwestern (O.S.), Dallas; NeuroRx (D.L.A.), McGill University, Montreal, Canada; Fred Hutchinson Cancer Research Center (G.E.G.), University of Washington (M.H.W., A.W., G.H.K.); and Swedish Hospital Medical Center (J.D.B.), Seattle, WA. richard.nash@healthonecares.com.
Richard A
RA
Nash
From the Colorado Blood Cancer Institute (R.A.N.), Denver; Baylor College of Medicine (G.J.H.), Houston, TX; Ohio State University (M.K.R., S.M.D.), Columbus; MD Anderson Cancer Research Center (U.P.), Houston, TX; Rho, Inc. (K.C.S.), Chapel Hill, NC; National Institute of Allergy and Infectious Diseases (L.M.G.), National Institutes of Health, Bethesda, MD; Division of Brain Sciences (P.A.M.), Imperial College London, UK; City of Hope National Medical Center (H.O.), Duarte, CA; Immune Tolerance Network (P.H.S.), University of California San Francisco; University of Texas Southwestern (O.S.), Dallas; NeuroRx (D.L.A.), McGill University, Montreal, Canada; Fred Hutchinson Cancer Research Center (G.E.G.), University of Washington (M.H.W., A.W., G.H.K.); and Swedish Hospital Medical Center (J.D.B.), Seattle, WA.
George J
GJ
Hutton
From the Colorado Blood Cancer Institute (R.A.N.), Denver; Baylor College of Medicine (G.J.H.), Houston, TX; Ohio State University (M.K.R., S.M.D.), Columbus; MD Anderson Cancer Research Center (U.P.), Houston, TX; Rho, Inc. (K.C.S.), Chapel Hill, NC; National Institute of Allergy and Infectious Diseases (L.M.G.), National Institutes of Health, Bethesda, MD; Division of Brain Sciences (P.A.M.), Imperial College London, UK; City of Hope National Medical Center (H.O.), Duarte, CA; Immune Tolerance Network (P.H.S.), University of California San Francisco; University of Texas Southwestern (O.S.), Dallas; NeuroRx (D.L.A.), McGill University, Montreal, Canada; Fred Hutchinson Cancer Research Center (G.E.G.), University of Washington (M.H.W., A.W., G.H.K.); and Swedish Hospital Medical Center (J.D.B.), Seattle, WA.
Michael K
MK
Racke
From the Colorado Blood Cancer Institute (R.A.N.), Denver; Baylor College of Medicine (G.J.H.), Houston, TX; Ohio State University (M.K.R., S.M.D.), Columbus; MD Anderson Cancer Research Center (U.P.), Houston, TX; Rho, Inc. (K.C.S.), Chapel Hill, NC; National Institute of Allergy and Infectious Diseases (L.M.G.), National Institutes of Health, Bethesda, MD; Division of Brain Sciences (P.A.M.), Imperial College London, UK; City of Hope National Medical Center (H.O.), Duarte, CA; Immune Tolerance Network (P.H.S.), University of California San Francisco; University of Texas Southwestern (O.S.), Dallas; NeuroRx (D.L.A.), McGill University, Montreal, Canada; Fred Hutchinson Cancer Research Center (G.E.G.), University of Washington (M.H.W., A.W., G.H.K.); and Swedish Hospital Medical Center (J.D.B.), Seattle, WA.
Uday
U
Popat
From the Colorado Blood Cancer Institute (R.A.N.), Denver; Baylor College of Medicine (G.J.H.), Houston, TX; Ohio State University (M.K.R., S.M.D.), Columbus; MD Anderson Cancer Research Center (U.P.), Houston, TX; Rho, Inc. (K.C.S.), Chapel Hill, NC; National Institute of Allergy and Infectious Diseases (L.M.G.), National Institutes of Health, Bethesda, MD; Division of Brain Sciences (P.A.M.), Imperial College London, UK; City of Hope National Medical Center (H.O.), Duarte, CA; Immune Tolerance Network (P.H.S.), University of California San Francisco; University of Texas Southwestern (O.S.), Dallas; NeuroRx (D.L.A.), McGill University, Montreal, Canada; Fred Hutchinson Cancer Research Center (G.E.G.), University of Washington (M.H.W., A.W., G.H.K.); and Swedish Hospital Medical Center (J.D.B.), Seattle, WA.
Steven M
SM
Devine
From the Colorado Blood Cancer Institute (R.A.N.), Denver; Baylor College of Medicine (G.J.H.), Houston, TX; Ohio State University (M.K.R., S.M.D.), Columbus; MD Anderson Cancer Research Center (U.P.), Houston, TX; Rho, Inc. (K.C.S.), Chapel Hill, NC; National Institute of Allergy and Infectious Diseases (L.M.G.), National Institutes of Health, Bethesda, MD; Division of Brain Sciences (P.A.M.), Imperial College London, UK; City of Hope National Medical Center (H.O.), Duarte, CA; Immune Tolerance Network (P.H.S.), University of California San Francisco; University of Texas Southwestern (O.S.), Dallas; NeuroRx (D.L.A.), McGill University, Montreal, Canada; Fred Hutchinson Cancer Research Center (G.E.G.), University of Washington (M.H.W., A.W., G.H.K.); and Swedish Hospital Medical Center (J.D.B.), Seattle, WA.
Kaitlyn C
KC
Steinmiller
From the Colorado Blood Cancer Institute (R.A.N.), Denver; Baylor College of Medicine (G.J.H.), Houston, TX; Ohio State University (M.K.R., S.M.D.), Columbus; MD Anderson Cancer Research Center (U.P.), Houston, TX; Rho, Inc. (K.C.S.), Chapel Hill, NC; National Institute of Allergy and Infectious Diseases (L.M.G.), National Institutes of Health, Bethesda, MD; Division of Brain Sciences (P.A.M.), Imperial College London, UK; City of Hope National Medical Center (H.O.), Duarte, CA; Immune Tolerance Network (P.H.S.), University of California San Francisco; University of Texas Southwestern (O.S.), Dallas; NeuroRx (D.L.A.), McGill University, Montreal, Canada; Fred Hutchinson Cancer Research Center (G.E.G.), University of Washington (M.H.W., A.W., G.H.K.); and Swedish Hospital Medical Center (J.D.B.), Seattle, WA.
Linda M
LM
Griffith
From the Colorado Blood Cancer Institute (R.A.N.), Denver; Baylor College of Medicine (G.J.H.), Houston, TX; Ohio State University (M.K.R., S.M.D.), Columbus; MD Anderson Cancer Research Center (U.P.), Houston, TX; Rho, Inc. (K.C.S.), Chapel Hill, NC; National Institute of Allergy and Infectious Diseases (L.M.G.), National Institutes of Health, Bethesda, MD; Division of Brain Sciences (P.A.M.), Imperial College London, UK; City of Hope National Medical Center (H.O.), Duarte, CA; Immune Tolerance Network (P.H.S.), University of California San Francisco; University of Texas Southwestern (O.S.), Dallas; NeuroRx (D.L.A.), McGill University, Montreal, Canada; Fred Hutchinson Cancer Research Center (G.E.G.), University of Washington (M.H.W., A.W., G.H.K.); and Swedish Hospital Medical Center (J.D.B.), Seattle, WA.
Paolo A
PA
Muraro
From the Colorado Blood Cancer Institute (R.A.N.), Denver; Baylor College of Medicine (G.J.H.), Houston, TX; Ohio State University (M.K.R., S.M.D.), Columbus; MD Anderson Cancer Research Center (U.P.), Houston, TX; Rho, Inc. (K.C.S.), Chapel Hill, NC; National Institute of Allergy and Infectious Diseases (L.M.G.), National Institutes of Health, Bethesda, MD; Division of Brain Sciences (P.A.M.), Imperial College London, UK; City of Hope National Medical Center (H.O.), Duarte, CA; Immune Tolerance Network (P.H.S.), University of California San Francisco; University of Texas Southwestern (O.S.), Dallas; NeuroRx (D.L.A.), McGill University, Montreal, Canada; Fred Hutchinson Cancer Research Center (G.E.G.), University of Washington (M.H.W., A.W., G.H.K.); and Swedish Hospital Medical Center (J.D.B.), Seattle, WA.
Harry
H
Openshaw
From the Colorado Blood Cancer Institute (R.A.N.), Denver; Baylor College of Medicine (G.J.H.), Houston, TX; Ohio State University (M.K.R., S.M.D.), Columbus; MD Anderson Cancer Research Center (U.P.), Houston, TX; Rho, Inc. (K.C.S.), Chapel Hill, NC; National Institute of Allergy and Infectious Diseases (L.M.G.), National Institutes of Health, Bethesda, MD; Division of Brain Sciences (P.A.M.), Imperial College London, UK; City of Hope National Medical Center (H.O.), Duarte, CA; Immune Tolerance Network (P.H.S.), University of California San Francisco; University of Texas Southwestern (O.S.), Dallas; NeuroRx (D.L.A.), McGill University, Montreal, Canada; Fred Hutchinson Cancer Research Center (G.E.G.), University of Washington (M.H.W., A.W., G.H.K.); and Swedish Hospital Medical Center (J.D.B.), Seattle, WA.
Peter H
PH
Sayre
From the Colorado Blood Cancer Institute (R.A.N.), Denver; Baylor College of Medicine (G.J.H.), Houston, TX; Ohio State University (M.K.R., S.M.D.), Columbus; MD Anderson Cancer Research Center (U.P.), Houston, TX; Rho, Inc. (K.C.S.), Chapel Hill, NC; National Institute of Allergy and Infectious Diseases (L.M.G.), National Institutes of Health, Bethesda, MD; Division of Brain Sciences (P.A.M.), Imperial College London, UK; City of Hope National Medical Center (H.O.), Duarte, CA; Immune Tolerance Network (P.H.S.), University of California San Francisco; University of Texas Southwestern (O.S.), Dallas; NeuroRx (D.L.A.), McGill University, Montreal, Canada; Fred Hutchinson Cancer Research Center (G.E.G.), University of Washington (M.H.W., A.W., G.H.K.); and Swedish Hospital Medical Center (J.D.B.), Seattle, WA.
Olaf
O
Stuve
From the Colorado Blood Cancer Institute (R.A.N.), Denver; Baylor College of Medicine (G.J.H.), Houston, TX; Ohio State University (M.K.R., S.M.D.), Columbus; MD Anderson Cancer Research Center (U.P.), Houston, TX; Rho, Inc. (K.C.S.), Chapel Hill, NC; National Institute of Allergy and Infectious Diseases (L.M.G.), National Institutes of Health, Bethesda, MD; Division of Brain Sciences (P.A.M.), Imperial College London, UK; City of Hope National Medical Center (H.O.), Duarte, CA; Immune Tolerance Network (P.H.S.), University of California San Francisco; University of Texas Southwestern (O.S.), Dallas; NeuroRx (D.L.A.), McGill University, Montreal, Canada; Fred Hutchinson Cancer Research Center (G.E.G.), University of Washington (M.H.W., A.W., G.H.K.); and Swedish Hospital Medical Center (J.D.B.), Seattle, WA.
Douglas L
DL
Arnold
From the Colorado Blood Cancer Institute (R.A.N.), Denver; Baylor College of Medicine (G.J.H.), Houston, TX; Ohio State University (M.K.R., S.M.D.), Columbus; MD Anderson Cancer Research Center (U.P.), Houston, TX; Rho, Inc. (K.C.S.), Chapel Hill, NC; National Institute of Allergy and Infectious Diseases (L.M.G.), National Institutes of Health, Bethesda, MD; Division of Brain Sciences (P.A.M.), Imperial College London, UK; City of Hope National Medical Center (H.O.), Duarte, CA; Immune Tolerance Network (P.H.S.), University of California San Francisco; University of Texas Southwestern (O.S.), Dallas; NeuroRx (D.L.A.), McGill University, Montreal, Canada; Fred Hutchinson Cancer Research Center (G.E.G.), University of Washington (M.H.W., A.W., G.H.K.); and Swedish Hospital Medical Center (J.D.B.), Seattle, WA.
Mark H
MH
Wener
From the Colorado Blood Cancer Institute (R.A.N.), Denver; Baylor College of Medicine (G.J.H.), Houston, TX; Ohio State University (M.K.R., S.M.D.), Columbus; MD Anderson Cancer Research Center (U.P.), Houston, TX; Rho, Inc. (K.C.S.), Chapel Hill, NC; National Institute of Allergy and Infectious Diseases (L.M.G.), National Institutes of Health, Bethesda, MD; Division of Brain Sciences (P.A.M.), Imperial College London, UK; City of Hope National Medical Center (H.O.), Duarte, CA; Immune Tolerance Network (P.H.S.), University of California San Francisco; University of Texas Southwestern (O.S.), Dallas; NeuroRx (D.L.A.), McGill University, Montreal, Canada; Fred Hutchinson Cancer Research Center (G.E.G.), University of Washington (M.H.W., A.W., G.H.K.); and Swedish Hospital Medical Center (J.D.B.), Seattle, WA.
George E
GE
Georges
From the Colorado Blood Cancer Institute (R.A.N.), Denver; Baylor College of Medicine (G.J.H.), Houston, TX; Ohio State University (M.K.R., S.M.D.), Columbus; MD Anderson Cancer Research Center (U.P.), Houston, TX; Rho, Inc. (K.C.S.), Chapel Hill, NC; National Institute of Allergy and Infectious Diseases (L.M.G.), National Institutes of Health, Bethesda, MD; Division of Brain Sciences (P.A.M.), Imperial College London, UK; City of Hope National Medical Center (H.O.), Duarte, CA; Immune Tolerance Network (P.H.S.), University of California San Francisco; University of Texas Southwestern (O.S.), Dallas; NeuroRx (D.L.A.), McGill University, Montreal, Canada; Fred Hutchinson Cancer Research Center (G.E.G.), University of Washington (M.H.W., A.W., G.H.K.); and Swedish Hospital Medical Center (J.D.B.), Seattle, WA.
Annette
A
Wundes
From the Colorado Blood Cancer Institute (R.A.N.), Denver; Baylor College of Medicine (G.J.H.), Houston, TX; Ohio State University (M.K.R., S.M.D.), Columbus; MD Anderson Cancer Research Center (U.P.), Houston, TX; Rho, Inc. (K.C.S.), Chapel Hill, NC; National Institute of Allergy and Infectious Diseases (L.M.G.), National Institutes of Health, Bethesda, MD; Division of Brain Sciences (P.A.M.), Imperial College London, UK; City of Hope National Medical Center (H.O.), Duarte, CA; Immune Tolerance Network (P.H.S.), University of California San Francisco; University of Texas Southwestern (O.S.), Dallas; NeuroRx (D.L.A.), McGill University, Montreal, Canada; Fred Hutchinson Cancer Research Center (G.E.G.), University of Washington (M.H.W., A.W., G.H.K.); and Swedish Hospital Medical Center (J.D.B.), Seattle, WA.
George H
GH
Kraft
From the Colorado Blood Cancer Institute (R.A.N.), Denver; Baylor College of Medicine (G.J.H.), Houston, TX; Ohio State University (M.K.R., S.M.D.), Columbus; MD Anderson Cancer Research Center (U.P.), Houston, TX; Rho, Inc. (K.C.S.), Chapel Hill, NC; National Institute of Allergy and Infectious Diseases (L.M.G.), National Institutes of Health, Bethesda, MD; Division of Brain Sciences (P.A.M.), Imperial College London, UK; City of Hope National Medical Center (H.O.), Duarte, CA; Immune Tolerance Network (P.H.S.), University of California San Francisco; University of Texas Southwestern (O.S.), Dallas; NeuroRx (D.L.A.), McGill University, Montreal, Canada; Fred Hutchinson Cancer Research Center (G.E.G.), University of Washington (M.H.W., A.W., G.H.K.); and Swedish Hospital Medical Center (J.D.B.), Seattle, WA.
James D
JD
Bowen
D000328:Adult; D004185:Disability Evaluation; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging / Q000628:therapy*; D014182:Transplantation, Autologous / Q000009:adverse effects; D016896:Treatment Outcome
D007166:Immunosuppressive Agents