NEW YORK (Reuters Health) Mar 22 - Patients with active rheumatoid arthritis have quantitative and qualitative abnormalities of bone marrow hematopoietic progenitor cells, and the bone marrow microenvironment is unable to support normal hematopoiesis, study results show.
The abnormalities are due, at least in part, to increased production of tumor necrosis factor alpha (TNF-alpha) by inflammatory cells within the bone marrow, according to Dr. Helen A. Papadaki, of University Hospital of Heraklion, Greece, and colleagues there and at St. George's Hospital Medical School in London.

Autologous stem cell transplantation is being explored as an alternative treatment for severe, refractory rheumatoid arthritis, the research group notes in the March 1st issue of Blood. However, few studies have examined whether the bone marrow stem cell compartment and the bone marrow stroma are damaged by the inflammatory process.

In 26 patients with active rheumatoid arthritis, the researchers found a "low number and increased apoptosis of CD34+ cells, defective clonogenic potential of bone marrow mononuclear and purified CD34+ cells, and low progenitor cell recovery in long-term bone marrow cultures," compared with 37 healthy controls.

They remark that hematopoiesis could not have been affected solely by drug-induced damage, because six of the 26 patients had never been exposed to cytotoxic agents or immune suppressants.

The hematologists also observed that the stromal layers of bone marrow did not support normal hematopoiesis in culture and produced abnormally high amounts of TNF-alpha. Treatment with an anti-TNF-alpha neutralizing antibody improved stromal cell function.

Dr. Papadaki told Reuters Health that according to accumulated data from four international organizations, more than 70 patients have undergone autologous stem cell transplantation as a treatment for rheumatoid arthritis. "Most patients have responded, sometimes dramatically, but it seems that there is a trend towards relapse," she said.

The current study "provides some evidence for potential difficulties in the transplantation since the hematopoietic progenitor or stromal cell abnormalities might impact on harvesting and engraftment potential of stem cells in these patients," Dr. Papadaki pointed out. "Indeed, there are data suggesting low yield of stem cells in the harvests from patients with rheumatoid arthritis undergoing autologous stem cell transplantation."

Blood 2002;99:1610-1619.

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