Fludarabine and Targeted Busulfan Is Safe and Effective Conditioning Before Hematopoietic Stem Cell Transplantation in Adult Patients with Acute Lymphoblastic Leukemia in First Remission

• Published in: Blood 2011-11, Vol.118 (21), p.891-891
• Main Authors: Kunter, Ghada M, Perkins, Janelle, Perez, Lia, Pidala, Joseph, Field, Teresa, Tomblyn, Marcie, Fernandez, Hugo F., Anasetti, Claudio
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V118.21.891.891

Abstract 891 Chemotherapy for adult patients with acute lymphoblastic leukemia (ALL) is associated with high risk of relapse and an overall 2-year survival of 40 to 50%. Allogenic hematopoietic cell transplantation (HCT) in first complete remission (CR1) decreases the risk of relapse and improves outcome over chemotherapy for adult ALL pts, but non-relapse mortality (NRM) is a drawback especially in older patients. In the MRC UKALL XII/ECOG E2993 trial, the 2 year NRM of patient with an allogenic donor was 19% in standard risk patients and 36% in patients over 35 years or those with high risk leukemia. We tested safety and efficacy of a non-irradiation regimen consisting of fludarabine (FLU) and pharmacokinetically-targeted busulfan (BU) for adults with ALL in CR1. We report the outcomes of 42 consecutive patients with ALL in CR1, 21 positive for the Philadelphia chromosome (Ph+). All patients were in complete morphologic remission before HCT. The median age was 33 (range: 19–62) years, 19 were females and 23 males. Median time from diagnosis to HCT was 6 (range: 3–45) months. Thirty patients were treated to achieve an average daily BU area under the curve (AUC) of 5300 microM-min for 4 days, and 12 patients were treated on a clinical trial to achieve an average daily BU AUC of 6000 to 7500 microM-min for 4 days. Graft-versus-host disease (GVHD) prophylaxis was tacrolimus in all patients, in combination with either methotrexate (88%) or sirolimus (12%). Twenty (48%) patients received grafts from matched related donor, 16 (38%) from matched unrelated donor and 6 (14%) from a mismatched unrelated donor. The median follow-up of surviving patients is 2 (median 1.2–4.3) years. Overall survival at 2 years was 66% (95% CI 52%–81%) for all patients, 70% (95% CI 51%–88%) for Ph- and 63% (95% CI 41%–85%) for Ph+ patients (p=0.59). Overall survival did not differ by age, above or below 35 years (p=0.39). Disease-free survival at 2 years was 59% (95% CI 44%–74%) for all patients, 65% (95% CI 45%–84%) for Ph- and 52% (95% CI 28%–74%) for Ph+ pts (p=0.49). The cumulative incidence of relapse at 2-year was 27% (95% CI 16%–45%). The cumulative incidence of acute GVHD grades II–IV was 64% (95% CI 51%–81%) and grades III–IV GVHD was 25% (95% CI 13%–47%). The cumulative incidence of non-relapse mortality (NRM) was 5% (95% CI 1%–18%) at 100 days and 14% (95% CI 7%–30%) at 2 years. These data show that FLU with myeloablative doses of PK targeted BU is an effective alternative