Adult Patients with Acute Lymphoblastic Leukemia (ALL) with Induction Failure or after Relapse: Cure By Allogeneic Stem Cell Transplantation (SCT), but High Risk of Relapse

In the German multicentre ALL studies, all patients (pts) with induction failure or after relapse are candidates for allogeneic SCT. We report here our single centre data on 57 pts. Median age was 28 years (18-57). ALL subtypes were: Ph+ ALL (n=8), B-lineage (pre B, B, pro B) (n=36), T lineage (pre T, mature T, thymic) (n=13). Before conditioning, 12/57 pts had induction failure, 31/57 pts were in CR2, 8/57 pts in 2. relapse, and 6/57 pts in CR3. Median duration of CR1 (n=45) was 21 months (2-107), CR2 (n=14) was 4 months (1-168). Pts with induction failure had at least GMALL, Induction I+II followed by 2 further protocols. Induction chemotherapy of relapse varied and consisted of the GMALL protocol, ALL relapse protocol, IdaFLAG, CLAEG, GIMEMA protocol, and local therapy of extramedullary leukemia. 27/37 pts transplanted in CR2 or CR3 reached CR after 1. chemotherapy, 7 after 2. chemotherapy, and 3 after 3. chemotherapy. Conditioning  regimen was myeloablative (12Gy TBI + Cy/ VP16) in 49 pts, reduced intensity conditioning (8Gy TBI or Flu+Bu+ATG) in 7 pts, and Treosulfan in 1 pt. Donors were matched unrelated donors (MUD) in 35 pts, HLA identical siblings in 21 pts, and a HLA-compatible child in 1 pt. GvHD prophylaxis was mainly CSA/MTX, since 2005 ATG was given in MUD additionally.

Results: 13/57 pts (23%) are alive in continuous CR (CCR). The median follow-up after allo-SCT for surviving pts is 155 months (5-222). 26/57 pts died due to relapse, 18/57 pts due to treatment-related mortality (TRM), mainly GvHD and/or infections. Probability of leukemia free survival (LFS) at 48 months is 25% for pts with induction failure, 30% for pts in CR2, 12% for pts in second relapse, and 33% for pts in CR3.

Conclusions: Adult ALL pts after 1. relapse can only be cured by allo-SCT, but the relapse rate is high. The same is true for ALL pts with induction failure/ primary refractory. Perspective in the GMALL studies is to transplant pts with molecular failure before hematologic relapse occurs. In patients with induction failure, up to now, allo-SCT is the only chance of cure. In B-lineage ALL, Blinatumomab may improve the results as bridging to allo-SCT.