Long-term remission of Philadelphia chromosome–positive acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation from matched sibling donors: a 20-year experience with the fractionated total body irradiation–etoposide regimen

Abstract

Allogeneic hematopoietic cell transplantation (HCT) is the only known curative modality for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ؉ ALL). Sixty-seven patients with HLA-matched sibling donors received fractionated total body irradiation (FTBI) and high-dose VP16, whereas 11 patients received FTBI/VP16/cyclophosphamide, and 1 patient received FTBI/VP16/busulfan. The median age was 36 years. At the time of HCT, 49 patients (62%) were in first complete remission (CR1) and 30 patients (38%) were beyond CR1 (> CR1). The median follow-up was 75 months (range, 14-245 months). The 10-year overall survival for the CR1 and beyond CR1 patients was 54% and 29% (P ‫؍‬ .01), respectively, and event-free survival was 48% and 26% (P ‫؍‬ .02), respectively. There was no significant difference in relapse incidence (28% vs 41%, P ‫؍‬ .28), but nonrelapse mortality was significantly higher in the beyond CR1 patients, (31% vs 54%, P ‫؍‬ .03, respectively). By univariate analysis, factors affecting event-free and overall survival were white blood cell count at diagnosis (< 30 ؋ 10 9 /L vs > 30 ؋ 10 9 /L) and disease status (CR1 vs > CR1)

Pre-transplant imatinib-based therapy improves the outcome of allogeneic hematopoietic stem cell transplantation for BCR–ABL-positive acute lymphoblastic leukemia

“…The City of Hope National Medical Center reported a favorable result from the use of a fractionated TBI-etoposide regimen in the treatment of Ph þ ALL. 26 However, in the comparative analysis, the clinical advantage of this approach seemed to be established mostly among patients transplanted in their second CR. 27 Moreover, this approach was commonly applied in our pre-imatinib cohort rather than in the imatinib cohort (22 and 4%, respectively).…”

A pathway-based gene signature correlates with therapeutic response in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

“…12 With the current standard of therapy being TKI and combination chemotherapy, 5-year OS in adult Ph þ ALL patients is approximately 30% or less. 24 SCT in first CR is potentially curative, 25,26 and TKI regimens have increased the number of patients who are able to proceed to transplant. However, morbidity and mortality associated with SCT also complicate its use, especially in elderly patients.…”

Genetic Studies in Acute Lymphoblastic Leukemia, from Diagnosis to Optimal Patient’s Treatment

“…Ph positivity is more often present in adult patients and the incidence increases with the age from 20% in 30 years to 39% in over 60 years (Moorman A.V., 2010). In these cases, targeted therapy using tyrosine kinase inhibitors such as imatinib or dasatinib is combined with chemotherapy both in young and elderly patients (Foa et al, 2011;Ravandi et al, 2010;Laport et al, 2008;Tanguy-Schmidt et al, 2009). These types of combined therapy give better results mostly if allogeneic bone marrow transplantation was performed in the first complete remission (Yanada et al, 2008).…”