Allogeneic BMT Ups 5-Year EFS in Ph-Negative ALL

ORLANDO-Allogeneicbone marrow transplant (BMT) significantlyreduced relapse rates andincreased event-free survival (EFS)rates, but not overall survival, inadults with Philadelphia chromosome(Ph)-negative acute lymphoblasticleukemia (ALL) in first completeremission.Jacob M. Rowe, MD, of RambamMedical Center, Haifa, Israel, reportedthe intent-to-treat analysis at the43rd Annual Meeting of the AmericanSociety of Hematology (abstract2009) on behalf of researchers in anongoing joint Medical ResearchCouncil/Eastern Cooperative OncologyGroup study (E2993).All patients in this protocol receivetwo phases of standard inductionchemotherapy. If the regimenproduces a complete response, patientsare assigned to allogeneic BMTif they have an HLA-matched siblingdonor and are age 50 or under.Other complete remission patientsare randomized to either standardconsolidation/maintenance therapyfor 2¹/₂ years or autologous BMT.All patients receive identical intensificationwith high-dose methotrexateprior to undergoing theirassigned or randomized therapy.Over 1,200 patients have beenregistered, 93% of whom achieved acomplete remission. The median ageis 30 years (range, 14 to 60 years).The induction death rate is 5%.Dr. Rowe's presentation wasAllogeneic BMT Ups5-Year EFS in Ph-Negative ALLbased on 173 Ph-negative patientsassigned to allogeneic BMT and 264Ph-negative patients who were randomized.Standard risk was definedas Ph-negative, age over 35 years,time to complete remission longerthan 4 weeks, and white blood cellcount below 30,000/μL for B lineagedisease and below 100,000/μLfor T lineage disease.

Overall survival was 44% at 5years and 35% at 7 years in the Phnegativepatients. "We have over 100patients already out past 5 years,"Dr. Rowe said.The 5-year event-free survival was54% in the Ph-negative patients whohad allogeneic BMT vs 34% for allrandomized Ph-negative patients (P= .04). The 5-year overall survivalwas 54% vs 43%, respectively (P =.4), and the 5-year relapse rate was23% vs 61% (P = .001), illustratingwhat Dr. Rowe described as "a verypotent graft-vs-leukemia effect forleukemia patients in first remission."Analysis by Risk Group
The most impressive differenceswere for standard-risk patients (seeTable). In this group, event-free survivalwas 67% with allogeneic BMTvs 44% for the randomized patients;overall survival was 69% vs 50%,respectively; and the relapse rate was15% vs 51%, respectively."For each risk subgroup, the allogeneicgroup appears to do betterthan the randomized cohort, butthese are small numbers," Dr. Rowesaid. In the best subgroup, overallsurvival was 80% for allogeneic BMTfor B lineage, standard-risk patientsvs 58% for similar patients in therandomized population."Even though we are dealing withrelatively small numbers, this is notablebecause there has been a persistentobjection to submitting standard-risk patients, particularT-lineage patients, to transplant, becausethey do well with standardtherapy," he said. "We agree thatthey do well, with a 60% overall survivalin the literature, but they appearto do even better with allogeneictransplant."He concluded that allogeneic BMT"can provide a potent antileukemia effectto all adult patients with ALL in firstcomplete remission. Despite increasedearly toxicity and a transplant-relatedmortality of 21%, allogeneic BMT providesfavorable long-term results."Overall Survival an Issue
The lack of significant differencein overall survival associated withallogeneic BMT for the patients as awhole sparked considerable discussion.One attendee said that sinceoverall survival was not changed forthe group as a whole, "why should Irecommend this very toxic procedureto a patient?"Dr. Rowe said that the reason wasthe greater chance of a cure at 5 years.He attributed the lack of significancein overall survival to study statisticians'use of log-rank tests, which hesaid "may not be the most appropriate,as this is an ongoing study."The study continues to accrue patients,predominantly to complete accrualto answer the "autologoustransplant vs chemotherapy question"in the randomized arm, Dr.Rowe said.