Autologous Hemopoietic Stem Cell Transplantation in Severe RA

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J Rheumatol. 2004 Mar;31(3):482-8.

Autologous Hemopoietic Stem Cell Transplantation in Severe Rheumatoid

Arthritis: A Report from the EBMT and ABMTR.

Snowden JA, Passweg J, JJ, Milliken S, Cannell P, Van Laar J,

Verburg R, Szer J, K, Joske D, Rule S, Bingham SJ, Emery P, Burt

RK, Lowenthal RM, Durez P, McKendry RJ, Pavletic SZ, Espigado I,

Jantunen E, Kashyap A, Rabusin M, P, Bredeson C, Tyndall A.

Department of Rheumatology, Felix-Platter-Spital, University of Basel,

Basel, Switzerland.

OBJECTIVE: Since 1996, autologous hemopoietic stem cell transplantation

(HSCT) has been used to treat severe rheumatoid arthritis (RA). To date,

published reports have been individual cases or series containing small

numbers. This study combined the worldwide experience in a single

analysis. METHODS: The Autoimmune Disease Databases of the European

Group for Blood and Marrow Transplantation (EBMT) and the Autologous

Blood and Marrow Transplant Registry (ABMTR) were used to identify

patients with RA treated with autologous HSCT. Further information

relating to patient and treatment-specific variables was obtained by

questionnaire. RESULTS: Seventy-six patients were registered from 15

centers. Seventy-three patients had received autologous HSCT, and in 3

patients hematopoietic stem cells (HSC) were mobilized but not

transplanted. Transplanted patients (median age 42 yrs, 74% female, 86%

rheumatoid factor positive) had been previously treated with a mean of 5

(range 2-9) disease modifying antirheumatic drugs (DMARD). Significant

functional impairment was present, with a median Health Assessment

Questionnaire (HAQ) score of 1.4 (range 1.1-2.0) and Steinbrocker score

mean 2.39 (SD 0.58). The high dose treatment regimen was

cyclophosphamide (CYC) alone in the majority of patients, mostly 200

mg/kg (n = 62). Seven patients received anti-thymocyte globulin (ATG) in

addition to CYC, 2 patients busulfan and CYC (BuCYC), and one patient

CYC with total body irradiation and ATG. One patient received

fludarabine with ATG. Following treatment, one patient received bone

marrow but the rest received chemotherapy and/or granulocyte

colony-stimulating factor mobilized peripheral blood stem cells. The

harvest was unmanipulated in 28 patients, the rest receiving some form

of lymphocyte depletion, mostly through CD34+ selection. Median followup

was 16 months (range 3-55). Responses were measured using the American

College of Rheumatology (ACR) criteria. Forty-nine patients (67%)

achieved at least ACR 50% response at some point following transplant.

There was a significant reduction in the level of disability measured by

the HAQ (p < 0.005). Most patients restarted DMARD within 6 months for

persistent or recurrent disease activity, which provided disease control

in about half the cases. Response was significantly related to

seronegative RA (p = 0.02) but not to duration of disease, number of

previous DMARD, presence of HLA-DR4, or removal of lymphocytes from the

graft. There was no direct transplant related mortality, although one

patient, treated with the BuCYC regimen, died 5 months post-transplant

from infection and incidental non-small cell lung cancer.

CONCLUSION: Autologous HSCT is a relatively safe form of salvage

treatment in severe, resistant RA. In these open label studies

significant responses were achieved in most patients, with over 50%

achieving an ACR 50 or more response at 12 months. Although the

procedure is not curative, recurrent or persistent disease activity may

be subsequently controlled in some patients with DMARD. Clinical trials

are necessary to develop this approach in patients with aggressive

disease who have failed conventional treatment including anti-tumor

necrosis factor agents.

PMID: 14994391

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