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Am J Hematol. 2016 Nov;91(11):1107-1112. doi: 10.1002/ajh.24497. Epub 2016 Aug 22.

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.

Author information

1
Division of Hematology/Oncology, Tufts University Medical Center, Boston, MA. akumar5@tuftsmedicalcenter.org.
2
Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
3
Department of Dermatology, University of Pennsylvania, Philadelphia, PA.
4
Clinical Trial Service Unit, Oxford, United Kingdom.
5
Rambam Medical Center, Haifa, Israel.
6
Eastern Cooperative Oncology Group, Brookline, MA.
7
North London Cancer Network, University College London Hospitals, London, United Kingdom.
8
Haematology, University College London, London, United Kingdom.
9
University Hospitals NHS Foundation Trust, Bristol, United Kingdom.
10
Mayo Clinic, Rochester, MN.
11
Cancer Center, The North Division of Montefiore Medical Center, Bronx, NY.
12
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH.
13
Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.
14
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.

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.

PMID:
27468137
PMCID:
PMC5073003
DOI:
10.1002/ajh.24497
[Indexed for MEDLINE]
Free PMC Article

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