There are few studies of MRD in the CSF. In one study, MRD was documented in about one-half of children at diagnosis. In this study, CSF MRD was not found to be prognostic when intensive chemotherapy was given.
Although MRD is the most important prognostic factor in determining outcome, there are no data to conclusively show that modifying therapy based on MRD determination significantly improves outcome in newly diagnosed ALL.
Day 7 and day 14 bone marrow responses
Patients who have a rapid reduction in leukemia cells to less than 5% in their bone marrow within 7 or 14 days following initiation of multiagent chemotherapy have a more favorable prognosis than do patients who have slower clearance of leukemia cells from the bone marrow.
Peripheral blood response to steroid prophase
Patients with a reduction in peripheral blast count to less than 1,000/µL after a 7-day induction prophase with prednisone and one dose of intrathecal methotrexate (a good prednisone response) have a more favorable prognosis than do patients whose peripheral blast counts remain above 1,000/µL (a poor prednisone response). Poor prednisone response is observed in fewer than 10% of patients.[17,148] Treatment stratification for protocols of the Berlin-Frankfurt-Münster (BFM) clinical trials group is partially based on early response to the 7-day prednisone prophase (administered immediately prior to the initiation of multiagent remission induction).
Patients with no circulating blasts on day 7 have a better outcome than those patients whose circulating blast level is between 1 and 999/µL.[149,150]
Peripheral blood response to multiagent induction therapy
Patients with persistent circulating leukemia cells at 7 to 10 days after the initiation of multiagent chemotherapy are at increased risk of relapse compared with patients who have clearance of peripheral blasts within 1 week of therapy initiation. Rate of clearance of peripheral blasts has been found to be of prognostic significance in both T-cell and B-lineage ALL.
The vast majority of children with ALL achieve complete morphologic remission by the end of the first month of treatment. The presence of greater than 5% lymphoblasts at the end of the induction phase is observed in up to 5% of children with ALL. Patients at highest risk of induction failure have one or more of the following features:[153,154]
- T-cell phenotype (especially without a mediastinal mass).
- B-precursor ALL with very high presenting leukocyte counts.
- 11q23 rearrangement.
- Older age.
- Philadelphia chromosome.
In a large retrospective study, the OS of patients with induction failure was only 32%. However, there was significant clinical and biological heterogeneity. A relatively favorable outcome was observed in patients with B-precursor ALL between the ages of 1 and 5 years without adverse cytogenetics (MLL translocation or BCR-ABL). This group had a 10-year survival exceeding 50%, and SCT in first remission was not associated with a survival advantage compared with chemotherapy alone for this subset. Patients with the poorest outcomes (<20% 10-year survival) included those who were aged 14 to 18 years, or who had the Philadelphia chromosome or MLL rearrangement. B-cell ALL patients younger than 6 years and T-cell ALL patients (regardless of age) appeared to have better outcomes if treated with allogeneic SCT after achieving complete remission than those who received further treatment with chemotherapy alone.