In 1993, we initiated an international trial in newly diagnosed adult (age 15–60 years) ALL patients. 1637 patients have been entered and data analyzed as of June 2004. All patients receive two induction phases of therapy and CNS prophylaxis (or therapy if CNS involved) as assessed by lumbar puncture for cytospin. Patients age ≤ 50 yr in CR1 who have a matched-related donor (MRD) undergo an allograft, and the remainder in CR1 are randomized either to an autograft or 4 cycles intensive consolidation and maintenance chemotherapy. Matched unrelated donor (MUD) allograft is an option in Philadelphia chromosome (Ph) positive patients. 46 (3%) patients had CNS leukemia at presentation. Median (range) age was 29 (16–56) years, and 5 were Ph+. Five patients never attained CR1 (3 died early during induction on days 4, 25 and 36). 41/46 (89%) patients attained CR1. 23 patients underwent transplant, 17 in CR1 (10 MRD, 2 MUD, and 5 autografts), while 3 MUD and 3 MRD allografts were performed for > CR1. 31/46 patients died, 12 of leukemia, 8 of infection, 3 of GVHD and 8 other causes. 12 patients died in remission due to infection (5), bleeding (2), GVHD (3), and visceral organ failure (2). 15 patients remain alive, one Ph+ in relapse at 58 mo and 14 (30%) Ph- remain in continuous CR at a median 67 (range: 2–133) mo after diagnosis. Treatments for these 15 long-term survivors were: MRD allograft (6 @ 45,53,63,67,98,120 mo), MUD allograft (1 @ 67 mo; performed in relapse), chemotherapy only (6 @ 2,55,87,98,125,133 mo) and autograft (1 @ 31 mo). In this study we noted a low incidence of CNS leukemia but we cannot exclude avoidance of enrollment due to suspected CNS involvement. Adult Ph- ALL patients with CNS leukemia at diagnosis can attain long-term disease-free survivorship using transplantation as well as conventional chemotherapy.
| Therapy (and status) | No. Pts | Survivors in CR (mo) |
|:-------------------------------------- | ------- | -------------------- |
| Induction death | 3 | |
| Died: no remission (resistant disease) | 2 | |
| MUD without remission | 1 | 67 |
| MUD in CR1 | 2 | |
| MUD post-relapse | 2 | |
| MRD in CR1 | 10 | 45,53,63,67,98,120 |
| MRD >CR1 | 3 | 58 (in relapse) |
| Auto (CR1) | 5 | 31 |
| Chemotherapy (CR1) | 18 | 2,55,87,98,125,133 |
| Total | 46 | |