Allogeneic Stem Cell Transplantation in High Risk ALL Patients: Influence of ALL Subtypes

In the German multicenter study group for Adult ALL (GMALL) high risk (HR) and very high risk (VHR) pts are candidates for allogeneic stem cell transplantation in CR1 from HLA matched siblings or unrelated donors. The risk factors are: VHR: Philadelphia chromosome positive ALL (Ph+ALL); HR of B-lineage ALL (HR-B): leukocytes > 30/nl at diagnosis and/or delayed CR > 3 weeks (other B) or pro B-ALL and of T-lineage ALL (HR-T): early-T-ALL and mature T-ALL. In addition standard risk pts were candidates for SCT in case of molecular failure or molecular relapse (SR-Mol). 106 high risk ALL pts in CR1 underwent allogeneic SCT between 1995 and 2012 at our center. Median age was 38 years (17 – 67). 70 pts were male, 36 female. 40/106 pts had Ph+ALL (VHR), 57/106 pts were HR pts (HR-B n = 32: pro-B-ALL n = 15, other B n = 17; HR-T n = 25: early T n = 17, mature T n = 4, thymic n = 4). 9/106 pts belonged to the SR-Mol group. Stem cell donors were matched related donors (MRD) in 42 pts and compatible unrelated donors in 64 pts. The conditioning regimen was 12 Gy TBI ± CY or VP16 in 86 pts, other n = 1, and in pts > 55 years 8 Gy TBI + FLU(n = 5) or FLU + BU (n = 14).

Results:

60/106 (57 %) pts with high risk ALL transplanted in CR1 are alive, 46/106 (43 %) pts are dead. The median follow-up of the surviving pts is 64 months (5 – 172). Causes of death were leukemia in 16/106 pts (15%) and transplant-related mortality (TRM) in 30/106 pts (28%). In Ph+ALL 19/40 pts (47 %) are alive in CR (CCR), 12/40 are dead due to TRM and 9/40 due to leukemia. In HR-B ALL 23/32 pts (71 %) are in CCR, 8/32 are dead due to TRM and 1/32 due to leukemia. In HR-T ALL 11/25 pts (44 %) are in CCR, 10/25 died due to TRM and 4/25 due to leukemia. In SR-Mol 7/9 pts (77 %) are in CCR, 2/9 died due to leukemia. Probability of survival (OS) for all pts at 96 months is 0.48, probability of disease free survival (DFS) at 96 months is 0.47, probability of TRM at 96 months is 0.34. OS was 0.5 for pts with myeloablative conditioning (MAC) (n = 86) and 0.38 for pts with RIC (n = 19), n.s. OS was different for the 4 risk groups: VHR 0.42, HR-B 0.67, HR-T 0.27, SR-Mol 0.74, but not sign. (0.09). DFS: VHR 0.42, HR-B 0.68, HR-T 0.24, SR-Mol 0.76 (0.04) and TRM: VHR 0.34, HR-B 0.26, HR-T 0.58, SR-Mol 0.0 (0.026). In HR-B OS was better for pro-B-ALL than other B-lineage (0.73.vs. 0.66, resp.). OS was lower in early-T-ALL (0.24). In mature T-ALL 3/4 pts are dead, in thymic ALL 1/4 pts.

Conclusion:

Long term survival and probably cure can be reached in high risk ALL pts after allogeneic stem cell transplantation in CR1. OS in HR-B pts is better than in HR-T-ALL due to lower relapse rate and lower TRM. If the quality of remission before allogeneic SCT could be improved in HR-T-ALL, has to be studied. Allogeneic SCT in SR-Mol show promising data, though in a small patient cohort. The results of Ph+ALL can be improved by thyrosine kinase inhibitors in induction chemotherapy, but was not given regularly in our pts. For all pts the TRM-rate due to GvHD and infection has to be improved.