Leukemia (1999) 13, 2053–2058  1999 Stockton Press All rights reserved 0887-6924/99 $15.00 http://www.stockton-press.co.uk/leu Long-term follow-up of 23 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with allogeneic bone marrow transplant in first complete remission DS Snyder 1 , AP Nademanee 1 , MR O’Donnell 1 , PM Parker 1 , AS Stein 1 , K Margolin 1 , G Somlo 1 , A Molina 1 , R Spielberger 1 , A Kashyap 1 , H Fung 1 , ML Slovak 2 , A Dagis 3 , RS Negrin 4 , MD Amylon 5 , KG Blume 4 and SJ Forman 1 1 Department of Hematology/Bone Marrow Transplantation, 2 Division of Pathology, 3 Division of Information Sciences, City of Hope National Medical Center, Duarte, CA; 4 Departments of Medicine and 5 Pediatrics, Division of Bone Marrow Transplantation, Stanford University Medical Center, Stanford, CA, USA Between 1984 and 1997, 23 consecutive patients with Philadel- phia chromosome-positive acute lymphoblastic leukemia in first complete remission were treated with allogeneic bone mar- row transplants from HLA-matched siblings. All patients but one were conditioned with fractionated total body irradiation (1320 cGy) and high-dose etoposide (60 mg/kg). One patient received high-dose cyclophosphamide instead of etoposide, and another patient received both drugs. Nine patients died fol- lowing BMT, two from relapsed leukemia, and seven from trans- plant-related causes. The 3-year probabilities of disease-free survival and relapse are 65% and 12%, respectively. For patients transplanted after 1992, these probabilities are 81% (48–95%, 95% confidence interval) and 11% (2–50%), respect- ively. The relatively low relapse rate in this group of patients compared to published reports may reflect the enhanced anti- leukemic activity of etoposide in combination with FTBI com- pared to other conditioning regimens. The enhancement in overall survival for patients transplanted after 1992 may reflect improvements in supportive care, in particular, the prophylaxis of serious fungal and viral infections. Keywords: Philadelphia chromosome; ALL; allogeneic bone marrow transplantation; bcr-abl Introduction The Philadelphia chromosome (Ph) is found in 20–30% of adults and 3–5% of children with acute lymphoblastic leuke- mia (ALL). 1–3 Patients with Ph+ ALL have an extremely poor prognosis for long-term survival. 4 Although the ability to achi- eve a first complete remission (CR) is not significantly reduced in Ph+ ALL, the durability of these remissions with standard and intensified chemotherapy regimens is extremely limited. 5 Allogeneic bone marrow transplantation (BMT) has been util- ized as a post-induction therapy to try to improve disease-free survival (DFS) for these patients. 6 The IBMTR has reported a 38% disease-free survival rate for patients transplanted with Ph+ ALL in first CR. 7 The bcr-abl oncogene, which is the molecular counterpart of the Ph chromosome, is detected in two variant forms, either p190 or p210, by sensitive polymerase chain reaction (PCR) techniques. In adults with Ph+ ALL, the p190 form is detected in about 50% of cases, whereas in pediatric cases, the p190 is the dominant variant and is detected in about 90% of cases. 2,8 Generally, there are no significant differences in the biology or response to chemotherapy between p190+ vs p210+ ALL. 9 However, a recent report on allogeneic BMT for Ph+ ALL sug- gested that the expression of p190 bcr-abl after BMT was asso- Correspondence: DS Snyder, Department of Hematology/Bone Mar- row Transplantation, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA 91010, USA; Fax: (626)-301-8349 Received 19 April 1999; accepted 10 August 1999 ciated with a significantly increased risk of relapse compared to the expression of the p210 variant. 10 We have previously published our results for a group of 17 patients in first CR with a 2-year DFS of 46 ± 25%. 11 We now report the results for a larger group of 23 patients (including the original 17 patients) who have been followed for a median of 3 years (range 1.3–10.2 years). All patients but one were conditioned with fractionated total body irradiation (FTBI) and high-dose etoposide. Risk factors such as bcr-abl PCR results, cytogenetic findings in addition to the Ph chromosome, and year of transplant are reviewed. Patients and methods Patient characteristics The patient characteristics are presented in Table 1. There were 14 male and nine female patients ranging in age from 6 to 44 years (median 30 years). All patients were transplanted while in first CR. The patients were treated with a variety of induction chemotherapy regimens, using standard dosages and schedules, often at outside institutions before they were referred for BMT. For the majority of patients, a combination of vincristine (V), prednisone (P), daunorubicin (D), and L- asparaginase (L-asp) was used to induce a remission. Some patients received other drugs in combination such as cyclo- phosphamide (CY), cytosine arabinoside (Ara-C), and 6-mer- captopurine (6-MP). The 23 patients received the following combinations for induction chemotherapy: V/D/P in three; V/D/P/L-asp in nine; D/Ara-C/CY/6-MP/L-asp in two, Ara- C/idarubicin in one; other combinations of V/D (±Ara-C, CY) in eight. Two patients (UPN 893 and 1062) received high- dose Ara-C as part of the induction regimen. Eighteen of the 23 patients also received post-remission chemotherapy con- sisting of oral methotrexate, 6-MP, ± CY or Ara-C. The time from CR to BMT ranged from 20 to 163 days (median 76 days). The date of analysis was 1 April 1998. Cytogenetic analysis Cytogenetic studies on pretreatment and follow-up bone mar- row samples were performed using standard G-banding with trypsin-Giemsa or trypsin-Wright’s staining using the standard methods. Karyotypes were interpreted using International Sys- tem for Cytogenetic nomenclature (ISCN) criteria. 12 The pre- treatment cytogenetic data are presented in Table 2. Six patients were Ph+ as the sole abnormality at the time of diag- nosis and 13 patients had additional chromosomal abnormali- ties. For four patients the status of additional aberrations at