Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in the Imatinib-Era: High Survival Rate Following Allogeneic HSCT after Imatinib Failure: Results of the German CML Study IV

Abstract

Allogeneic HSCT remains an important option for patients with chronic myeloid leukemia (CML) who failed imatinib. Focus has been on second line tyrosine kinase inhibitors (TKI). Little is known on the outcome of HSCT for such patients. In July 2002, the German CML-Study Group activated a prospective randomized trial comparing different imatinib based strategies in chronic phase CML (CP). Elective early HSCT was considered for patients (pts) with EBMT score 0–1 for those with high disease risk, and after imatinib failure. By the end of July 2008, 1197 pts were randomized. In 80 (6,5 %) pts HSCT was documented. 52 pts were male (65%), 23 were high risk pts (28%) according to the Euro score. Median age at diagnosis was 37 years (yrs) (range 16–62), median time to HSCT was 12.6 months (mo, range 3.5–54 mo). EBMT score was 0–1 in 8 (10%), 2 in 10 (12%), 3–4 in 44 (55%) and 5 in 18 pts (23%). Median follow-up after HSCT was 19 mo (range 0–59). Cumulative response rates prior to HSCT were 68% for complete hematologic response, 23% for complete cytogenetic responses, and 9% for major molecular responses. Based on the indication for HSCT three groups were defined:early HSCT (n= 19, 23%; low EBMT score (n=9), high risk pts (n=7), patient request (n=3);HSCT after imatinib failure or intolerance in first CP (n=34, 43%) andHSCT in second CP or higher, accelerated phase or blast crisis (n=27, 34%).14 pts died, 10 deaths were transplantation related, 4 CML related. Two pts with a molecular relapse were successfully treated with donor lymphocyte infusion in combination with TKI. Overall survival rate at two yrs for group one was 87.8%, for group two 93.8%, and for group three 49.5%. By EBMT score, survival rates were 100% for risk score 0–2, 82.2% for risk score 3–4, and 43.5% for risk score 5. Data from this prospective controlled cohort study clearly show that HSCT remains an attractive and important rescue therapy for CML patients with imatinib failure or intolerance, particularly for those with a low EBMT risk score.HSCT in 1st CPearly HSCTHSCT for failure and intolerance in 1st CPTotalHSCT in advanced phasesN19345327Euro scorehigh68149intermediate312157low10142411% male63566078Median age (range)35 (16–56)38 (21–56)37 (16–56)37 (18–62)Median time to HSCT (Range) (months)8.5 (4.8–23.6)17,5 (5.0– 53.7)12.6 (4.8 53.7)12.0 (3.5–54.1)EBMT score0–15380254913–4926359>=501117Best responseCHR11/1828/3439/5214/26CCyR3/1710/3313/504/22MMR2/173/315/482/19Response at HSCTBC00024AP0003CP1934530HR1119300Ccyr2240MMR0000Transplant sourceSibling1010209Unrelated9243318Conditioning therapystandard14213517reduced3694other2796SourcePB13263922BM68145Dead22410TRM2246CML0004Probability of survival at 2 years after HSCT87.8%93.8%91.4%49.5%