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

Anita J. Kumar, Phyllis A. Gimotty, Joel Gelfand, Georgina Buck, Jacob M. Rowe, Anthony H. Goldstone, Adele Fielding, David I. Marks, Mark Litzow, Elisabeth M. Paietta, Hillard M. Lazarus, Martin S. Tallman, Selina M. Luger, Alison W. Loren

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1107-1112
Number of pages6
JournalAmerican Journal of Hematology
Volume91
Issue number11
DOIs
StatePublished - Nov 1 2016

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Philadelphia Chromosome
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Odds Ratio
Transplants
Drug Therapy
Disease-Free Survival
Survival
Induction Chemotherapy
Homologous Transplantation
Sex Ratio
Thrombocytopenia
Hospitalization
Stem Cells
Therapeutics
Logistic Models
Recurrence

ASJC Scopus subject areas

  • Hematology

Cite this

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. / Kumar, Anita J.; Gimotty, Phyllis A.; Gelfand, Joel; Buck, Georgina; Rowe, Jacob M.; Goldstone, Anthony H.; Fielding, Adele; Marks, David I.; Litzow, Mark; Paietta, Elisabeth M.; Lazarus, Hillard M.; Tallman, Martin S.; Luger, Selina M.; Loren, Alison W.

In: American Journal of Hematology, Vol. 91, No. 11, 01.11.2016, p. 1107-1112.

Research output: Contribution to journalArticle

Kumar, Anita J. ; Gimotty, Phyllis A. ; Gelfand, Joel ; Buck, Georgina ; Rowe, Jacob M. ; Goldstone, Anthony H. ; Fielding, Adele ; Marks, David I. ; Litzow, Mark ; Paietta, Elisabeth M. ; Lazarus, Hillard M. ; Tallman, Martin S. ; Luger, Selina M. ; Loren, Alison W. / 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. In: American Journal of Hematology. 2016 ; Vol. 91, No. 11. pp. 1107-1112.
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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.",
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