Allografting Myeloablative allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults: significant roles of total body irradiation and chronic graft-versus-host disease M Yanada 1 , T Naoe 1 , H Iida 2 , H Sakamaki 3 , T Sakura 4 , H Kanamori 5 , Y Kodera 6 , S Okamoto 7 , Y Kanda 8 , H Sao 2 , O Asai 9 , K Nakai 10 , A Maruta 11 , K Kishi 12 , T Furukawa 13 , Y Atsuta 1 , K Yamamoto 1 , J Tanaka 14 and S Takahashi 15 1 Nagoya University Graduate School of Medicine, Nagoya, Japan; 2 Meitetsu Hospital, Nagoya, Japan; 3 Tokyo Metropolitan Komagome Hospital, Tokyo, Japan; 4 Saiseikai Maebashi Hospital, Maebashi, Japan; 5 Yokohama City University Hospital, Yokohama, Japan; 6 Japanese Red Cross Nagoya First Hospital, Nagoya, Japan; 7 Keio University School of Medicine, Tokyo, Japan; 8 University of Tokyo Hospital, Tokyo, Japan; 9 Jikei University Hospital, Tokyo, Japan; 10 Kansai Medical University, Osaka, Japan; 11 Kanagawa Cancer Center, Yokohama, Japan; 12 Tokai University School of Medicine, Isehara, Japan; 13 Niigata University Medical & Dental Hospital, Niigata, Japan; 14 Hokkaido University Graduate School of Medicine, Sapporo, Japan; and 15 Institute of Medical Science, University of Tokyo, Tokyo, Japan Summary: Disease-free survival in Philadelphia chromosome-positive ALL (Ph þ ALL) is very poor, and allogeneic hemato- poietic stem cell transplantation (allo-HSCT) is currently considered the only procedure with curative potential. To identify factors affecting transplant outcome, we analyzed the data from 197 Ph þ ALL patients aged 16 years or older who had undergone allo-HSCT. The 5-year survival rates were 34% for patients in first complete remission (CR), 21% for those in second or subsequent CR, and 9% for those with active disease (Po0.0001). Multivariate analysis showed four pre-transplant factors as significantly associated with better survival: younger age, CR at the time of transplantation, conditioning with total body irradiation, and HLA-identical sibling donor (Po0.0001, Po0.0001, P ¼ 0.0301, P ¼ 0.0412, respectively). Severe acute GVHD increased the risk of treatment-related mortality (TRM) without diminishing the risk of relapse, whereas chronic GVHD reduced the risk of relapse without increasing the risk of TRM. Thus, patients who developed extensive chronic GVHD had better survivals (P ¼ 0.0217), and those who developed grade III–IV acute GVHD had worse survivals (P ¼ 0.0023) than did the others. Bone Marrow Transplantation (2005) 36, 867–872. doi:10.1038/sj.bmt.1705148; published online 22 August 2005 Keywords: stem cell transplantation; allogeneic; acute lymphoblastic leukemia; Philadelphia; total body irradia- tion; graft-versus-host disease Philadelphia chromosome (Ph), a t(9;22) reciprocal transloca- tion, is the most unfavorable prognostic marker for ALL, and has been detected in up to 30% of adult patients with ALL. Although conventional chemotherapy results in 50–80% of patients attaining complete remission (CR), long-term survi- val can rarely be achieved because of the extremely high relapse rate. 1–7 We and other investigators have recently reported promising results using chemo- therapy in combination with imatinib for Ph-positive ALL (Ph þ ALL), 8,9 but longer follow-up is needed to determine whether imatinib-containing therapy by itself can be curative. At present it is thought that allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for this disease. Several articles have dealt with the outcome for Ph þ ALL patients undergoing allo-HSCT, 10–22 but more detailed information is needed on a larger number of subjects. We therefore undertook a retrospective study involving 197 Ph þ ALL patients, using the registry data of the Japan Society of Hematopoietic Cell Transplantation (JSHCT). Patients and methods Patients A nationwide survey on HSCT has been conducted in Japan by the JSHCT. Registration is voluntary, and the number of transplants reported is around 2500 per year. Patients were eligible if they had been diagnosed as Ph þ ALL, were aged 16 years or older at the time of transplantation, and had undergone allo-HSCT between January 1991 and December 2001. None of them had been treated with imatinib mesylate. Those who had undergone a second or subsequent transplant, a nonmyeloablative stem cell transplant or a cord blood transplant were Received 12 May 2005; accepted 8 July 2005; published online 22 August 2005 Correspondence: Dr M Yanada, Department of Hematology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. E-mail: myanada@med.nagoya-u.ac.jp Bone Marrow Transplantation (2005) 36, 867–872 & 2005 Nature Publishing Group All rights reserved 0268-3369/05 $30.00 www.nature.com/bmt