Treatment of lupus nephritis with total lymphoid irradiation. observations during a 12–79‐month followup

Strober, Samuel; Fariñas, M.C.; Field, Elizabeth H.; Solovera, J. J.; Kiberd, Bryce A.; Myers, Bryan D.; Hoppe, Richard T.

doi:10.1002/art.1780310705

Cited by 20 publications

(12 citation statements)

References 29 publications

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“…Hence, TLI/ATG with allogeneic HCT also represents a viable treatment option to improve or even cure autoimmune diseases by redirecting the malfunctioning immune system. 26,27 One distinguishing feature of TLI/ATG compared with other conditioning regimens is the greater variability in the levels of donor engraftment. Heavily pretreated cancer patients who receive unmanipulated mobilized peripheral blood grafts from HLAidentical donors, routinely achieve full donor chimerism.…”

Section: Treg Regulate Hsc Activitymentioning

confidence: 99%

Donor hematopoiesis in mice following total lymphoid irradiation requires host T-regulatory cells for durable engraftment

Müller

Poyser

Küpper

et al. 2014

Blood

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Section: Treg Regulate Hsc Activitymentioning

confidence: 99%

Donor hematopoiesis in mice following total lymphoid irradiation requires host T-regulatory cells for durable engraftment

Müller

Poyser

Küpper

et al. 2014

Blood

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“…Between 1979 and 1985, 10 patients with biopsy proven DPLN (World Health Organization, class IV) were consecutively subjected to TLI because of the development of a nephrotic syndrome that was refractory to corticosteroid therapy (9). All patients statisfied the criteria of the American Rheumatism Association for the diagnosis of SLE.…”

Section: Methodsmentioning

confidence: 99%

“…Fractions of irradiation were delivered sequentially to supra-(200 rad each) and subdiaphragmatic lymphoid tissues (150 rad each) over a 32-d period to a total dose of 2,000 rad, as described previously (7)(8)(9). The kidneys were shielded with lead so as to exclude -them from the fields subjected to irradiation.…”

Section: Methodsmentioning

confidence: 99%

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Outcome of the acute glomerular injury in proliferative lupus nephritis.

Chagnac¹,

Kiberd²,

Fariñas³

et al. 1989

J. Clin. Invest.

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Treatment with total lymphoid irradiation (TLI) and corticosteroids markedly reduced activity of systemic lupus erythematosis in 10 patients with diffuse proliferative lupus nephritis (DPLN) complicated by a nephrotic syndrome. Physiologic and morphometric techniques were used serially before, and 12 and 36 mo post-TLI to characterize the course of glomerular injury. Judged by a progressive reduction in the density of glomerular cells and immune deposits, glomerular inflammation subsided. A sustained reduction in the fractional clearance of albumin, IgG and uncharged dextrans of radius > 50 A, pointed to a parallel improvement in glomerular barrier size-selectivity. Corresponding changes in GFR were modest, however. A trend towards higher GFR at 12 mo was associated with a marked increase in the fraction of glomerular tuft area occupied by patent capillary loops as inflammatory changes receded. A late trend toward declining GFR beyond 12 mo was associated with progressive glomerulosclerosis, which affected 57% of all glomeruli globally by 36 mo post-TLI. Judged by a parallel increase in volume by 59%, remaining, patent glomeruli had undergone a process of adaptive enlargement. We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area.

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“…TLI has been shown to induce long‐term remission in several animal models of autoimmune disease, including adjuvant arthritis in rats and lupus‐like disease in NZB/NZW mice (1). There are published reports of experience in using TLI in the treatment of rheumatoid arthritis (RA) (1–3), multiple sclerosis (4), and systemic lupus erythematosus (SLE) (1, 3, 5–9). TLI has also been studied as an alternative agent to cytotoxic drug therapy for patients with refractory lupus nephritis (1, 3, 5–9).…”

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confidence: 99%

Long‐term followup of patients treated with total lymphoid irradiation for lupus nephritis

Genovese¹,

Uhrin²,

Blöch³

et al. 2002

Arthritis & Rheumatism

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Objective. To describe the long-term survival, renal condition, and morbidity outcomes in patients who received total lymphoid irradiation (TLI) for the treatment of lupus nephritis.Methods. Twenty-one patients with biopsy-proven, diffuse membranoproliferative glomerulonephritis and significant proteinuria of >2.5 grams/day received TLI from 1980 to 1987 at Stanford University Medical Center. All patients had previously failed to respond to treatment with high-dose corticosteroids or therapy with corticosteroids plus immunosuppressive agents (azathioprine, cyclophosphamide, or chlorambucil).Results. The mean duration of followup since TLI was 10.7 years. Fifteen of 21 patients (71%) remained alive at the time of this assessment. Nine of the 21 patients (43%) survived without developing end-stage renal disease (ESRD). The probability of long-term survival without ESRD and without need for additional immunosuppressive agents after TLI was 19% (4 of 21). Factors predicting renal failure at the time of TLI included elevated creatinine levels, increased interstitial fibrosis on renal biopsy, and increased fractional excretion of immunoglobulin and albumin. Malignancies were found in 4 patients, and opportunistic infections occurred in 7 patients.Conclusion. Overall, patients with lupus nephritis treated with TLI do not appear to have better 10-year survival with lower incidence of ESRD compared with patients in published series treated with conventional immunosuppressive therapies. However, in this series of patients, treatment with conventional immunosuppressive therapies had been unsuccessful and given the limited number of adverse events and the efficacy seen in some patients, TLI appears to be a reasonable therapeutic option for the treatment of severe lupus nephritis among patients who fail to respond under standard cytotoxic regimens.

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Treatment of lupus nephritis with total lymphoid irradiation. observations during a 12–79‐month followup

Cited by 20 publications

References 29 publications

Donor hematopoiesis in mice following total lymphoid irradiation requires host T-regulatory cells for durable engraftment

Donor hematopoiesis in mice following total lymphoid irradiation requires host T-regulatory cells for durable engraftment

Outcome of the acute glomerular injury in proliferative lupus nephritis.

Long‐term followup of patients treated with total lymphoid irradiation for lupus nephritis

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