Successful Bone-Marrow Transplantation for Infantile Malignant Osteopetrosis

Peter F. Coccia, William Krivit, Jaroslav Cervenka, Carlyle Clawson, John H. Kersey, Taehwan H. Kim, Mark E. Nesbit, Norma K.C. Ramsay, Phyllis I. Warkentin, Steven L. Teitelbaum, Arnold J. Kahn, David M. Brown

Research output: Contribution to journalArticlepeer-review

384 Scopus citations

Abstract

A five-month-old girl with autosomal-recessive osteopetrosis received a bone-marrow transplant from her five-year-old HLA-MLC-identical brother after preparation with cyclophosphamide and modified total-body irradiation. Engraftment was documented by chromosomal analysis. Anemia, thrombocytopenia, and leukoerythroblastosis corrected within 12 weeks of transplantation. Low serum calcium and elevated serum alkaline and acid phosphatase levels became normal. Serial x-ray studies revealed bony remodeling and new nonsclerotic bone formation. A pretransplantation bone biopsy revealed small marrow spaces, rare marrow elements, increased osteoclasts, and no bony resorption. After transplantation, osteoclasts were actively resorbing bone, and medullary cavities contained normal bone marrow. Fluorescent Y-body analysis after transplantation revealed donor (male) osteoclasts and recipient (female) osteoblasts. Monocyte bactericidal activity, markedly decreased before transplantation, became normal. Vision, hearing, growth, and development were progressively improving 16 months after transplantation. Allogeneic bone-marrow transplantation appears to be the treatment of choice in this fatal disorder. (N Engl J Med. 1980; 302:701–8.) Infantile malignant osteopetrosis (AlbersSchönberg syndrome, or marble bone disease) is a rare autosomal-recessive disorder characterized by dense, sclerotic, fragile, radiopaque bones and associated hematologic and neurologic abnormalities.1,2 Osteopetrosis is thought to result from dysfunction of osteoclasts, the multinucleated giant cells that resorb bone and mineralized cartilage.3,4 Defective bone resorption by osteoclasts, in the presence of normal bone formation by osteoblasts, results in the deposition of excessive mineralized osteoid and cartilage.5 Encroachment on bone-marrow spaces leads to extramedullary hematopoiesis6 and hypersplenism.7 The result is anemia, severe thrombocytopenia, leukoerythroblastosis, and progressive hepatosplenomegaly. Encroachment on cranial-nerve foramina leads to cranial-nerve palsies, optic atrophy.

Original languageEnglish
Pages (from-to)701-708
Number of pages8
JournalNew England Journal of Medicine
Volume302
Issue number13
DOIs
StatePublished - Mar 27 1980

Fingerprint

Dive into the research topics of 'Successful Bone-Marrow Transplantation for Infantile Malignant Osteopetrosis'. Together they form a unique fingerprint.

Cite this