PERIPHERAL BLAST COUNTS AT DIAGNOSIS OF LATE ISOLATED BONE-MARROW RELAPSE OF CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA PREDICT RESPONSE TO SALVAGE CHEMOTHERAPY AND OUTCOME

Purpose: In newly diagnosed childhood acute lymphoblastic leukemia (AL L), a high tumor burden indicates a poor prognosis, while no such link has been established yet after relapse. The impact of the absolute pe ripheral blast count (PBC) at the time of relapse on the response to s alvage chemotherapy after a late isolated bone marrow (BM) relapse is the subject of this prospective analysis. Patients and Methods: Since 1983, 260 children with a first isolated BM relapse of ALL that occurr ed 6 months or later after elective cessation of front-line therapy we re enrolled onto four consecutive multicenter trials of the Berlin-Fra nkfurt-Munster (BFM) Relapse Study Group. All patients received intens ive multiagent induction and consolidation chemotherapy for 6 months, followed by maintenance therapy with methotrexate (MTX) and thioguanin e for 2 years. Treatment of subclinical meningeal leukemia consisted o f high-dose intravenous MTX and intrathecally administered cytostatic drugs, which was augmented by cranial irradiation since 1988. Results: At the time relapse was diagnosed, PBC varied considerably among pati ents (median, 1,060/mu L; range, 0 to 106,800/mu L). Achievement of a second complete remission (CR) was not significantly different in chil dren without detectable circulating blasts at relapse (37 of 38) and t hose with moderate (1 to 9,999/mu L) PBC (165 of 171). In contrast, on ly 42 of 51 children with high PBC (greater than or equal to 10,000/mu L) achieved a second CR (P = .0015), At a median follow-vp time of 40 months, the 10-year event-free survival (EFS) probability was signifi cantly (P = .0001) higher in children without circulating blasts (.64) than in children with moderate PBC (.32) or high PBC (.10). There was a preponderance of boys in the group without detectable circulating b lasts, while the three PBC-defined groups did not differ with respect to frontline treatment, age at initial diagnosis, age at relapse, time off therapy, or salvage treatment protocol. On sequential univariate and multivariate analysis, only duration of first remission greater th an or equal to 48 months was an additional independent indicator of ad verse prognosis, while preventive cranial irradiation improved outcome independently of PBC. Conclusion: The absence of blasts on peripheral -blood smears at;the time of a first late isolated BM relapse of child hood ALL is associated with a favorable response and prognosis in chem otherapy-treated children, who should be regarded as ineligible for bo ne marrow transplantation (BMT) unless a second round of chemotherapy has failed to produce a response. (C) 1996 by American Society of Clin ical Oncology.