https://www.gastrojournal.org/article/0016-5085(86)90183-6/pdf

Randomized trial of chlorambucil for primary biliary cirrhosis.

https://www.amjmed.com/article/0002-9343(84)90753-8/pdf

Chlorambucil in the treatment of uveitis and meningoencephalitis of Behçet's disease

Of 32 patients with Behcet's disease, 21 had uveitis. The uveitis was seldom the initial manifestation of systemic disease, but once established, it tended to become chronic and bilateral, involving the anterior and posterior segments. Hypopyon was a relatively uncommon occurrence in this series. All patients with uveal inflammation had obvious cellular reactions within the vitreous body. Other posterior segment manifestations of the disease included localized retinal edema, macular edema, disc edema, retinal pigmentary changes, and accumulation of exudative material in the deep retina. One patient developed a necrotizing retinitis with deep retinal exudation and subsequent retinal detachment. Occlusions of retinal vessels were common. Neuro-ophthalmologic manifestations of Behcet's disease included cranial nerve palsies, a homonymous hemianopic field defect, and papillitis.

The Ocular Manifestations of Behçet's Disease

Aplastic anemia is a rare but usually fatal complication of gold salt therapy for rheumatoid arthritis. This report describes 3 patients who developed aplastic anemia while receiving gold salts, and a fourth patient who developed aplastic anemia after receiving gold and then cytotoxic agents. These patients failed to respond to conventional therapy for aplastic anemia and subsequently received bone marrow transplants from HLA-matched siblings. Engraftment occurred in all 4 patients. One patient is alive 2 years after transplantation, and 3 patients died of complications following transplantation.

Bone marrow transplantation in patients with gold-induced marrow aplasia.

We treated five patients with intractable sympathetic ophthalmia and six patients with severe Behcet9s disease by high-dose, short-term chlorambucil therapy. We used a total dose ranging from 306 mg to 4.2 g and a duration of therapy no longer than 36 weeks and in most cases less than 24 weeks. After termination of therapy all 11 patients had a sustained remission of their eye disease. Unless subretinal neovascularisation was present, all had a final visual acuity of 20/50 or better. Malignancy has not developed in any of our cases, with a follow-up ranging from 6 months to 12 years (mean, 4.5 years). Although 30- and 40-year follow-ups and larger numbers of patients may be necessary fully to realise the risks of chlorambucil, we believe that our high-dose, short-term regimen (Behcet9s disease: average duration, 23 weeks; average total dose 2.2 g; sympathetic ophthalmia: average duration, 11 weeks; total average dose, 0.9 g) may be safer than previously reported chlorambucil regimens of one to two years or longer. In addition we fulfilled our aim of discontinuing all concomitant systemic corticosteroids within a relatively short time (usually six to eight weeks).

https://bjo.bmj.com/content/bjophthalmol/74/6/353.full.pdf

High-dose short-term chlorambucil for intractable sympathetic ophthalmia and Behçet's disease.

Two cases of irreversible bone marrow failure are described, one with rheumatoid disease and one with systemic lupus erythematosus. Each case was associated with prior chlorambucil administration, effective in controlling the clinical manifestations (total dosage 398 and 1,764 mg respectively). The irreversibility of the bone marrow depression in the two cases presented stands in contrast to published assurances that chlorambucil-associated leukopenia is dose-related and readily reversible. The cases illustrate that chlorambucil therapy should not be continued after initial leukopenia, until peripheral counts or marrow cellularity has returned to normal. Titration of drug dosage and leukocyte count, as frequently employed with cyclophosphamide and other alkylating agents, must be presumed hazardous. Additional studies are needed to determine if irreversible bone marrow depression is dose-related or idiosyncratic.

W V Epstein

Papers

Irreversible bone marrow failure with chlorambucil.