Risk classification at the time of diagnosis differentially affects the level of residual disease in children with B-precursor acute lymphoblastic leukemia after completion of therapy.

We have previously reported that children with B-precursor acute lymphoblastic leukemia (ALL) who remained in remission after successfully completing therapy had leukemia cells detectable by polymerase chain reaction (PCR) (N Engl J Med 1997;336(5):317-23). These patients were treated by an institutional protocol (P89-04) that lacked the post-remission intensification features of the contemporary Berlin-Frankfurt-Münster (BFM) based ALL protocols. In this report, we compared residual leukemia levels for patients on the P89-04 (n=15) and BFM-based Children's Cancer Group (CCG) studies (n=23) and for patients stratified according to risk group. Our goal was to establish which risk factors correlated with level of residual disease. Patients enrolled on the CCG protocols had lower levels of residual disease after completion of therapy than the P89-04 patients (P<0.019). Patients with high-risk disease also had lower levels of residual disease than patients with low risk disease (P<0.0001). Three-way analysis including time off treatment, risk group determined by features at presentation, and treatment protocol showed that risk group was the only significant independent variable (P<0.001).

Residual leukaemia after bone marrow transplant in children with acute lymphoblastic leukaemia after first haematological relapse or with poor initial presenting features.

Relapse is the major obstacle to cure for children with acute lymphoblastic leukaemia (ALL) after allogeneic bone marrow transplant (BMT). Development of salvage therapy for post-transplant relapse could be expedited by understanding the post-transplant behaviour of microscopically undetectable leukaemia and the ability to predict impending relapse. We have used a quantitative polymerase chain reaction method (sensitivity of 5.0 x 10-6) to measure residual leukaemia before the conditioning regimen, and at five time-points after transplantation. In total, 18 patients with ALL transplanted in first or second remission were studied for 1 year: For the first year post BMT, 12 remained in remission, four had haematological relapses, one had a cutaneous relapse, and one died of severe graft-versus-host disease. The post-engraftment levels of the leukaemia-specific immunoglobulin heavy (IgH) chain gene rearrangement for patients with haematological relapses were significantly different from those who remained in remission. The levels for the patients who remained in remission decreased with time, although there were occasional increases consistent with the known standard deviation of the measurement assay. In contrast, all clinical relapses were preceded by a rapid increase in levels. Both the rate of this increase and its timing were variable. These results suggest that residual leukaemia measurements can be used to direct post-transplant interventions and measure their effects.