title: Clinical and Radiologic Responses to Cladribine for the Treatment of Erdheim-Chester Disease.
abstract: OBJECTIVE
  While cladribine is best known for the treatment of hairy cell leukemia and other lymphoid cancers, it also has activity against myeloid neoplasms, such as Erdheim-Chester disease (ECD).
  
  
  OBJECTIVE
  To assess the efficacy of cladribine (2-chloro-2'-deoxyadenosine) in the treatment of ECD.
  
  
  METHODS
  This study was a single-institution retrospective medical record review from January 1, 1998, to April 6, 2016, at a tertiary academic medical center. In all eligible cases, the diagnosis of ECD was made using clinical criteria in conjunction with histopathologic findings.
  
  
  METHODS
  Cladribine therapy in first-line treatment or later.
  
  
  METHODS
  Two response criteria were used, clinical and radiological. For clinical response, the following criteria were used: complete response (complete resolution of symptoms attributed to ECD), partial response (partial resolution of symptoms attributed to ECD), stable disease (no change in symptoms attributed to ECD), and progressive disease (worsening of symptoms attributed to ECD). For radiological response, the following categories were used: complete response (complete resolution of proven or suspected lesion due to ECD), partial response (partial resolution of proven or suspected lesion due to ECD), stable disease (no significant change in proven or suspected lesion due to ECD for ≥3 months), and progressive disease (progression or worsening of proven or suspected lesion due to ECD).
  
  
  RESULTS
  A total of 63 adult patients with confirmed ECD were identified. Their median age at diagnosis of ECD was 54 years (age range, 18-80 years), and 67% (42 of 63) were male. Cladribine was the most commonly used chemotherapeutic agent and was administered in 21 of 63 patients (33%). Their median age at the time of cladribine therapy was 62 years (age range, 40-78 years). Cladribine was used as the first-line treatment in 9 patients and as later-line treatment in the remaining 12 patients. The median number of cycles of cladribine administered was 2.5 (range, 1-6). The overall clinical response rate was 52% (9 of 17) (6% [1 of 17] complete response and 46% [8 of 17] partial response), with 18% (3 of 17) stable disease and 30% (5 of 17) progressive disease. Among patients who responded to cladribine therapy, the median duration of clinical response was 9 months (range, 6-129 months), with ongoing response in 2 patients. The overall radiological response rate was 54% (8 of 15) (all partial response), with 26% (4 of 15) stable disease and 20% (2 of 15) progressive disease. Treatment-related adverse effects included 2 infectious complications (pneumonia and central line infection, both requiring hospitalization) and 2 hematologic adverse effects (grade 4 neutropenia and thrombocytopenia, and grade 3 neutropenia, both requiring therapy discontinuation).
  
  
  CONCLUSIONS
  Cladribine has moderate clinical efficacy in the treatment of ECD and can be considered a treatment option in cases without the BRAF V600E mutation. It is generally well tolerated and may result in a durable response.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Goyal
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Mithun V
authors.initials: MV
authors.lastname: Shah
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Call
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Litzow
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: William J
authors.initials: WJ
authors.lastname: Hogan
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Go
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017338:Cladribine / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D031249:Erdheim-Chester Disease / Q000000981:diagnostic imaging / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000072078:Positron Emission Tomography Computed Tomography; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D017338:Cladribine