Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Blood. 2016 Jul 28;128(4):504-7. doi: 10.1182/blood-2016-03-707562. Epub 2016 May 27.

Abstract

The impact of achieving complete molecular response (CMR) in Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) remains undefined. We evaluated the impact of CMR on outcomes among 85 patients with Ph(+) ALL who received first-line hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine plus a tyrosine kinase inhibitor, had minimal residual disease (MRD) assessments for BCR-ABL1 by quantitative polymerase chain reaction at complete remission (CR) and at 3-month time points, and did not undergo allogeneic stem cell transplantation (SCT). MRD status at 3 months had better discrimination for overall survival (OS; P = .005) and relapse-free survival (RFS; P = .002) than did MRD status at CR (P = .11 and P = .04, respectively). At 3 months, achievement of CMR vs response less than CMR was associated with longer median OS (127 vs 38 months, respectively; P = .009) and RFS (126 vs 18 months, respectively; P = .007). By multivariate analysis, only CMR at 3 months was prognostic for OS (hazard ratio, 0.42; 95% confidence interval, 0.21-0.82; P = .01). Patients with Ph(+) ALL who achieve CMR at 3 months have superior survival compared with those with lesser molecular responses and have excellent long-term outcomes even without SCT.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Fusion Proteins, bcr-abl / blood
  • Humans
  • Infant
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Neoplasm, Residual
  • Philadelphia Chromosome*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality*
  • Survival Rate
  • Vincristine / administration & dosage
  • Vincristine / adverse effects

Substances

  • BCR-ABL1 fusion protein, human
  • Cytarabine
  • Vincristine
  • Dexamethasone
  • Cyclophosphamide
  • Fusion Proteins, bcr-abl
  • Methotrexate