Philadelphia chromosome positive childhood acute lymphoblastic leukemia: Clinical and cytogenetic characteristics and treatment outcome. A Pediatric Oncology Group study

Among 3,638 children with acute lymphoblastic leukemia (ALL) entered on Pediatric Oncology Group (POG) protocols between June 1981 and April 1989, successful cytogenetic studies were available for 2.519, 58 (2.3%) of which had the Philadelphia (Ph) chromosome detected. Features associated with the presence of the Ph chromosome were high leukocyte count (median. 33 × 10⁹/L), older age (median, 9.6 years), a higher proportion of French-American-British L2 morphology, and a lower frequency of mediastinal mass. Immunologic marker studies at diagnosis in 56 Ph⁺ cases identified early pre-B ALL in 42 cases 75%), pre-B-cell in 9 (16%), and T-cell in 5 (9%). This distribution is similar to that found in Ph^- ALL. Intensive multiagent chemotherapy induced complete remissions in only 78% of eligible Ph⁺ patients compared with 96% of those without an identified Ph chromosome (P < .001). Of 44 eligible Ph⁺ patients treated on POG frontline protocols for children with non-T, non-B-cell ALL, 27 have failed therapy, compared with 520 of 1,892 without an identified Ph chromosome (logrank P < .001). Ph⁺ ALL is an aggressive form of acute leukemia that frequently presents in older children with a high leukocyte count, FAB L2 morphology and a pseudodiploid karyotype, and becomes multidrug-resistant early. Thus, Ph⁺ cases require early identification to permit treatment with intensive induction regimens and experimental approaches such as bone marrow transplantation.