Plasma heparanase as a significant marker of treatment response in children with Hodgkin lymphoma: pilot study.
BACKGROUND
The aim of this pilot study was to determine heparanase plasma levels (HP) at diagnosis and at restaging in children diagnosed with Hodgkin lymphoma and to investigate whether this parameter provides prognostic information for response to treatment after induction therapy.


METHODS
HP levels of 19 pediatric patients (mean age: 10.3 years (y) (range, 4-18 y), 9 girls, 10 boys) with Hodgkin lymphoma were assayed at diagnosis and at restaging. HP levels were determined using an ELISA anti-human heparanase immunoassay kit. According to diagnosis, CAT scan and/or FDG/ PET-CT fusion were performed to assess response to treatment after 2-3 courses of chemotherapy. Two patients received VAMP protocol (1 stage IA, 1 stage IIA), 1 received AV-PC (nonbulky stage IIA), 4 received COPP/ABV (3 stage IIA bulky, 1 stage IIIA nonbulky), 4 received ABVE-PC (2 stage IIB, 1 stage IIA bulky, 1 stage IIIA bulky), 2 received ABVD (1 stage IIA bulky, 1 stage IIIA), and 6 received escalated BEACOPP (1 stage IIIB, 3 stage IVA, 2 stage IVB).


RESULTS
Changes in HP levels were found to correlate with response to treatment for most of the children. At diagnosis, average HP level was 1019 pg/mL (range, 141-5733 pg/mL), decreasing at restaging to 588 pg/mL (range, 62-3267 pg/mL) (p = .034). At diagnosis, the average HP of the 16 patients in CR or VGPR was 1104 pg/mL; it had decreased at restaging to 586 pg/mL (p = .032). At diagnosis, the average HP level for the 3 patients with TP or PR was 1704 pg/mL; it had increased to 1938 pg/mL at restaging (p = .166). Due to the small number of patients, no correlation was observed between HP levels at diagnosis, staging, or any other clinical prognostic factor.


CONCLUSIONS
Changes in plasma HP levels correlated with response to treatment for children diagnosed with Hodgkin lymphoma. This provides a rationale for exploring clinical interest in plasma heparanase measurements of a larger group, using the test for clinical trials of antiangiogenic therapies.
Ben Arush
Myriam Weyl
MW
Department of Pediatric Hematology Oncology, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel. m benarush@rambam.health.gov.il
Shafat
Itay
I
Shafat
I
I
Ben Barak
Ayelet
A
Shalom
Rachel Bar
RB
Vlodavsky
Israel
I
Vlodavsky
Eugene
E
Ilan
Neta
N
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005966:Glucuronidase / Q000097:blood*; D006689:Hodgkin Disease / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D010865:Pilot Projects; D000099175:Heparanase
D014408:Biomarkers, Tumor; D005966:Glucuronidase; D000099175:Heparanase