Long-Term Treatment of Osteopetrosis with Recombinant Human Interferon Gamma

Key, L. Lyndon; Rodriguiz, Ramona M.; Willi, Steven M.; Wright, Nancy A.; Hatcher, Heather; Eyre, David R.; Curé, Joel K.; Griffin, Paul P.; Ries, William L.

doi:10.1056/nejm199506153322402

Cited by 258 publications

(145 citation statements)

References 18 publications

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“…22 In selected cases, surgical decompression of the optical nerve might be indicated to prevent further deterioration awaiting HSCT. 23 In some patients, calcitriol in high dosages 11 or interferon gamma 12 might slow the progression of the disease. Improvement of haematopoiesis can be achieved with prednisone.…”

Section: Discussionmentioning

confidence: 99%

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Long-term outcome of haematopoietic stem cell transplantation in autosomal recessive osteopetrosis: an EBMT report

Driessen

Gerritsen

Fischer

et al. 2003

Bone Marrow Transplant

163

130

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Summary:A retrospective analysis was made of 122 children who had received an allogeneic haematopoietic stem cell transplantation (HSCT) for autosomal recessive osteopetrosis between 1980 and 2001. The actuarial probabilities of 5 years disease free survival were 73% for recipients of a genotype HLA-identical HSCT (n ¼ 40), 43% for recipients of a phenotype HLA-identical or one HLAantigen mismatch graft from a related donor (n ¼ 21), 40% for recipients of a graft from a matched unrelated donor (n ¼ 20) and 24% for patients who received a graft from an HLA-haplotype-mismatch related donor (n ¼ 41). In the latter group, a trend towards improvement was achieved at the end of the study period (17% before 1994, 45% after 1994, P ¼ 0.11). Causes of death after HSCT were graft failure and early transplant-related complications. Severe visual impairment was present in 42% of the children before HSCT. Conservation of vision was better in children transplanted before the age of 3 months. Final height was related to height at the time of HSCT and better preserved in children transplanted early. Most children attended regular school or education for the visually handicapped. At present, HSCT is the only curative treatment for autosomal recessive osteopetrosis and should be offered as early as possible.

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Section: Discussionmentioning

confidence: 99%

“…10 Treatments with approaches other than HSCT such as corticosteroids, high doses of calcitriol (vitamin D 3 ) and interferon-g, have been disappointing. [11][12][13][14] We report the results of HSCT in 122 patients treated in Europe, Costa Rica and Saudi Arabia, including the follow-up of HSCT survivors from 1994.…”

mentioning

confidence: 99%

Long-term outcome of haematopoietic stem cell transplantation in autosomal recessive osteopetrosis: an EBMT report

Driessen

Gerritsen

Fischer

et al. 2003

Bone Marrow Transplant

163

130

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“…As a result of its numerous functions, recombinant human IFN-γ (rhIFN-γ) is finding increasing therapeutic applications. In the treatment of chronic granulomatous disease [6][7][8][9], and in severe malignant osteopetrosis [10,11], rhIFN-γ has clinically accepted beneficial effectiveness. Additionally, in the almost uniformly fatal progressive fibrosing lung disease, idiopathic pulmonary fibrosis (IPF), a recent metaanalysis has concluded that rhIFN-γ treatment is associated with reduced mortality [12].…”

Section: Introductionmentioning

confidence: 99%

Increased yield of high purity recombinant human interferon-γ utilizing reversed phase column chromatography

Reddy

Narala

et al. 2007

Protein Expression and Purification

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Increasing therapeutic applications for recombinant human interferon-γ (rhIFN-γ), an antiviral proinflammatory cytokine, has broadened interest in optimizing methods for its production and purification. We describe a reversed phase chromatography (RPC) procedure using Source-30 ™ matrix in the purification of rhIFN-γ from Escherichia coli that results in a higher yield than previously reported. The purified rhIFN-γ monomer from the RPC column is refolded in Tris buffer. Optimal refolding occurs at protein concentrations between 50-100 μg/ml. This method yields greater than 90% of the dimer form with a yield of 40 mg g −1 cell mass. Greater than 99% purity is achieved with further purification over a Superdex G-75 column to obtain specific activities of from 2 to 4 × 10 7 IU/mg protein as determined via cytopathic antiviral assay. The improved yield of rhIFN-γ in a simple chromatographic purification procedure promises to enhance the development and therapeutic application of this biologically potent molecule.

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“…Other neurological manifestations of osteopetrosis may include strabismus, facial paralysis, deafness, trigeminal nerve involvement and anosmia. 17 Most of these result from direct compression of cranial nerves and are most pronounced in patients with early disease onset. 20 Both of our patients only showed severe visual impairment with bilateral optic nerve subatrophy, which stabilized after BMT.…”

Section: Discussionmentioning

confidence: 99%

“…Each of these therapies, such as steroids, ␥ interferon, hydroxyvitamin D 3 alone or in combination, has produced limited and transient improvement. [14][15][16][17] The only curative therapy reported is allogeneic BMT. 18,19 During the last 15 years, almost 100 BMTs for osteopetrosis have been reported.…”

Section: Discussionmentioning

confidence: 99%

Long-term follow-up of two children with a variant of mild autosomal recessive osteopetrosis undergoing bone marrow transplantation

Dini

Floris

Garaventa

et al. 2000

Bone Marrow Transplant

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Summary:Malignant autosomal recessive (AR) osteopetrosis represents an absolute indication for bone marrow transplantation (BMT). Over the last 15 years, almost 100 BMTs for osteopetrosis have been reported. The median age at transplant of most patients is 4 months. Very few cases of mild AR osteopetrosis have been described. Here, we report the good outcome of two cases of mild AR osteopetrosis with a follow-up of 5 and 6 years, respectively, after an HLA-identical sibling transplant undergone at 5 and 12 years of age, respectively. At the time of BMT, severe visual impairment was present in both children. Bone biopsy demonstrated hypermineralization with virtual obliteration of the medullary spaces, rare microfoci of hematopoiesis and marked deficiency in osteoclastic activity. Successful engraftment was complicated by hypercalcemia, controlled by a combination of bisphosphonate, phosphate infusions, vigorous hydration and calcitonin. Following BMT, radiological and histological findings showed extensive bone resorption with marked augmentation of the osteoclasts in normalized marrow. No improvement was observed in visual acuity, despite complete remodeling of skeletal abnormalities. We conclude that allogeneic BMT is the only chance of curing mild AR osteopetrosis. Bone Marrow Transplantation (2000) 26, 219-224.

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Long-Term Treatment of Osteopetrosis with Recombinant Human Interferon Gamma

Abstract: Long-term therapy with interferon gamma in patients with osteopetrosis increases bone resorption and hematopoiesis and improves leukocyte function.

Cited by 258 publications

References 18 publications

Long-term outcome of haematopoietic stem cell transplantation in autosomal recessive osteopetrosis: an EBMT report

Long-term outcome of haematopoietic stem cell transplantation in autosomal recessive osteopetrosis: an EBMT report

Increased yield of high purity recombinant human interferon-γ utilizing reversed phase column chromatography

Long-term follow-up of two children with a variant of mild autosomal recessive osteopetrosis undergoing bone marrow transplantation

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