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Treatment of Childhood LCH

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Reactivation of single-system and multisystem LCH

Reactivation of LCH after complete response has been reported; usually occurring within the first 9 to 12 months after stopping treatment.[36] The percentage of patients with reactivations was 17.4% for single-site disease; 37% for single-system, multifocal disease; 46% for multisystem (nonrisk organ) disease; and 54% for patients with risk-organ involvement. Forty-three percent of reactivations were in bone, 11% in ears, 9% in skin, and 7% develop diabetes insipidus; a lower percentage of patients had lymph node, bone marrow, or risk-organ relapses.[36] The median time to reactivation was 12 to 15 months in nonrisk patients and 9 months in risk patients. One-third of patients had more than one reactivation varying from 9 to 14 months after the initial reactivation. Patients with reactivations were more likely to have long-term sequelae in the bones, diabetes insipidus, or other endocrine, ear, or lung problems.[36]

A comprehensive review of the DAL and Histiocyte Society clinical trials revealed a reactivation rate of 46% at 5 years for patients with multisystem LCH, with most reactivations occurring within 2 years of first remission. A second reactivation occurred in 44%, again within 2 years of the second remission. Involvement of the risk organs in these reactivations only occurred in those who were initially in the high-risk group (meaning they had liver, spleen, or bone marrow involvement at the time of original diagnosis).[20][Level of evidence: 3iiiDiii] Most reactivations, even in patients with high-risk disease who initially responded to therapy, were in bone, skin, or other nonrisk locations.

The percentage of reactivations in multisystem disease was identical in the Japanese trial, [25][Level of evidence: 1iiA] and the LCH-II trial [23] (45% and 46%, respectively). There was not a statistically significant difference in reactivations between the high-risk and low-risk groups. Both the DAL-HX and Japanese studies concluded that intensified treatment increased rapid response, particularly in young children and infants younger than 2 years, and together with rapid switch to salvage therapy for nonresponders, reduced mortality for patients with high-risk multisystem LCH.

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