Outcome of Relapsed Philadelphia Chromosome Positive Chronic Myeloid Leukemia (Ph+ CML) after Allogeneic Hematopoietic Cell Transplantation (HCT)

• Published in: Blood 2007-11, Vol.110 (11), p.3230-3230
• Main Authors: Heyn, Simone, Krahl, Rainer, Lange, Thoralf, Eisfeld, Ann-Kathrin, Niederwieser, Dietger, Al-Ali, Haifa K.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V110.11.3230.3230

In the imatinib era, HCT is mainly offered to patients (pts) with advanced disease or imatinib resistance. In this analysis, relapse incidence (RI) and the long-term efficacy of imatinib and immunomodulation for relapse after HCT for Ph+ CML were evaluated. Patients and Methods: From January 2000 to May 2006, 65 pts (38 m, 27 f; median age 41 (range 20–68) years) underwent HCT at the University of Leipzig. Median interval between diagnosis and HCT was 22 (2–264) months. Prior to HCT, 50 pts (77%) received imatinib for a median duration of 9 (range 1–54) months. Disease phase prior to imatinib was chronic phase (CP),n=25 (50%), accelerated phase (AP),n=18 (36%), blast phase (BP),n=7 (14%). HCT was performed because of resistance to imatinib, n=26 (BCR-ABL kinase domain (KD) mutations were found in 6 pts prior to HCT: F359V, G250E, Y253H, M315T, E255K, L248V. One patient had a K247R polymorphism), AP/BP prior to imatinib,n=14, or imatinib-intolerance/pts preference,n=10. HCT was performed in 15 (23%) pts (CP,n=12, AP,n=3) without prior imatinib. Conditioning consisted of 12 Gy TBI/cyclophosphamid 120 mg/kg in 44 (68%), and fludarabin 30 mg/m2/day for 3 days/2 Gy TBI in 21 (32%) pts. Donors were MRD, n=20; and MUD, n=45. After HCT, blood and marrow were examined at 3 months interval. A molecular relapse was diagnosed if two samples at least four weeks apart were BCR-ABL positive by reverse-transcriptase polymerase chain reaction (RT-PCR; sensitivity, approximately 1/106). In case of relapse, cyclosporine was tapered and withdrawn. Additionally, imatinib 400 mg/d was started. If a complete molecular remission (CMR) was achieved, imatinib was continued for another 12 months and then stopped. Results: Engraftment occurred in 61 (94%) pts. OS and TRM at 5 years were 70%, and 23% respectively. At a median time of 7 months after HCT, 31/48 (65%) relapsed [molecular,n=18 (58%), cytogenetic,n=4 (13%), hematological,n=9 (29%)]. Type of conditioning, and donor type had no influence on RI which tended to be higher in pts with imatinib prior to HCT (p=0.03). Incidence of chronic GvHD in pts without and those with relapse was 65% and 13% respectively (p