title: Delays in postremission chemotherapy for Philadelphia chromosome negative acute lymphoblastic leukemia are associated with inferior outcomes in patients who undergo allogeneic transplant: An analysis from ECOG 2993/MRC UK ALLXII.
abstract: Adults with acute lymphoblastic leukemia (ALL) have a poorer prognosis than children due to a high risk of relapse. One explanation may be variable adherence to dose-intense chemotherapy. However, little is known about risk factors for delays in therapy and their impact on survival. We conducted an analysis of ECOG 2993/UKALLXII trial to study delays in postremission chemotherapy in adults with newly diagnosed ALL. Logistic regression was used to identify risk factors for a very long delay (VLD, >4 weeks) in start of intensification therapy. Cox regression was used to evaluate the impact of delays on overall survival (OS) and event-free survival (EFS). We evaluated 1076 Philadelphia chromosome negative (Ph-) patients who completed induction chemotherapy, achieved complete remission, and started intensification. Factors independently associated with VLD included duration of hospitalization (odds ratio [OR] = 1.2, P < 0.001) during Phase I; thrombocytopenia during Phase I (OR = 1.16, P = 0.004) or Phase II (OR 1.13, P = 0.001); chemotherapy dose reductions during Induction Phase I (OR = 1.72, P < 0.014); female sex (OR = 1.53, P = 0.010); Black (OR = 3.24, P = 0.003) and Asian (OR = 2.26, P = 0.021) race; and increasing age (OR = 1.31, P < 0.001). In multivariate Cox regression, patients who underwent allogeneic stem cell transplant (alloHCT) had significantly worse OS (HR 1.4, P = 0.03) and EFS (HR 1.4, P = 0.02) after experiencing a VLD compared to alloHCT patients who experienced ≤4 weeks delay. Specific populations (female, older, Black, and Asian patients) were more likely to experience delays in chemotherapy, as were those with significant toxicity during induction. VLDs in therapy negatively affected outcomes in patients undergoing allografting. Am. J. Hematol. 91:1107-1112, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Division of Hematology/Oncology, Tufts University Medical Center, Boston, MA. akumar5@tuftsmedicalcenter.org.
authors.forename: Anita J
authors.initials: AJ
authors.lastname: Kumar
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
authors.forename: Phyllis A
authors.initials: PA
authors.lastname: Gimotty
authors.affiliation: Department of Dermatology, University of Pennsylvania, Philadelphia, PA.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Gelfand
authors.affiliation: Clinical Trial Service Unit, Oxford, United Kingdom.
authors.forename: Georgina
authors.initials: G
authors.lastname: Buck
authors.affiliation: Rambam Medical Center, Haifa, Israel.|Eastern Cooperative Oncology Group, Brookline, MA.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.affiliation: North London Cancer Network, University College London Hospitals, London, United Kingdom.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Goldstone
authors.affiliation: Haematology, University College London, London, United Kingdom.
authors.forename: Adele
authors.initials: A
authors.lastname: Fielding
authors.affiliation: University Hospitals NHS Foundation Trust, Bristol, United Kingdom.
authors.forename: David I
authors.initials: DI
authors.lastname: Marks
authors.affiliation: Mayo Clinic, Rochester, MN.
authors.forename: Mark
authors.initials: M
authors.lastname: Litzow
authors.affiliation: Cancer Center, The North Division of Montefiore Medical Center, Bronx, NY.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Paietta
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH.
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.affiliation: Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
authors.forename: Selina M
authors.initials: SM
authors.lastname: Luger
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
authors.forename: Alison W
authors.initials: AW
authors.lastname: Loren
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality* / Q000628:therapy*; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents