How are relapses treated in acute lymphoblastic leukemia (ALL)?

Updated: Jul 02, 2021
  • Author: Karen Seiter, MD; Chief Editor: Matthew C Foster, MD  more...
  • Print


See the list below:

  • The prognosis for patients who experience relapse after front-line therapy is poor, with very few patients surviving long term. The best outcome is obtained if patients achieve a second remission and then proceed to allogeneic stem cell transplantation.

  • Patients who are in complete remission within 4 wk of starting therapy have a better prognosis. [27, 28, 29]

  • Most of the chemotherapy regimens used for front-line therapy of ALL can be used in the salvage setting; however, response rates are low and remission durations are short.

  • Tavernier et al reported the results of treatment of first relapse for patients entered on the LALA-94 trial [30] ; 187 patients (44%) achieved a second complete remission. The median disease-free survival was 5.2 mo, with a 5-y disease-free survival of 12%; factors predicting a better outcome after relapse were any transplant performed in second complete remission (CR), a first CR duration > 1y, and platelet level > 100 × 109/L at relapse. Risk groups defined at diagnosis and treatment received in first CR did not influence the outcome after relapse; best results were obtained in a subset of patients who were eligible for allogeneic stem cell transplantation.

  • In the second salvage setting, O'Brien et al noted that the complete remission rate was only 18% and the median survival was 3 mo. [31]  Prognostic factors associated with survival were duration of first complete remission, percentage of bone marrow blasts, platelet count, and albumin level.

  • Clofarabine is a purine nucleoside metabolic inhibitor approved for the treatment of pediatric patients aged 1-21 y with relapsed or refractory ALL after at least two prior regimens. In this patient population, the dosage is 52 mg/m2/day IV over 2 h for 5 d; adult patients are treated at a lower dose, no more than 40 mg/m2/day for 5 d. [32]

  • Nelarabine is approved for the treatment of patients with T-cell ALL and T-cell lymphoblastic lymphoma who have not responded to or have relapsed following treatment with at least two chemotherapeutic regimens. Recommended dose of nelarabine in adults is 1500 mg/m2 IV over 2h on days 1, 3, and 5 repeated every 21 d. [33]

  • Vincristine liposomal (Marqibo) is approved for treatment of Ph- ALL patients in second or subsequent relapse or whose disease has progressed following two or more antileukemia therapies; initial dosage regimen is 2.25 mg/m2 IV infusion over 1 h every 7 d. [34]

  • Blinatumomab, a bispecific T-cell engager (BiTE) antibody, is approved  for Ph- relapsed or refractory B-cell ALL; treatment cycles consist of 4 wk continuous IV infusion with at least a 2-wk treatment-free interval between cycles; a low dose is given for week 1 of the first cycle and then increased to 28 mcg/day for the remaining 3 weeks of cycle 1 and for subsequent cycles (up to five cycles total) [35, 36]

  • Blinatumomab was also granted accelerated approval for the treatment of CD19-positive B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) ≥ 0.1% in adults and children. Treatment course comprises 1 cycle for induction followed by up to 3 additional cycles for consolidation; each cycle consists of 28 days of continuous IV infusion followed by a 14-day treatment-free interval (total 42 days). [37]  In patients weighing < 45 kg, dosing is based on body surface area (BSA) and consists of a 15 mcg/m 2/day continuous IV infusion, not to exceed 28 mcg/day; patients weighing ≥ 45 kg receive a fixed-dose, 28 mcg/day continuous IV infusion.
  • Inotuzumab is a CD22-directed antibody-drug conjugate approved for relapsed/refractory B-cell precursor ALL. The total dose of inotuzumab is 1.8 mg/m² per 21-day cycle, administered as 3 divided doses: Day 1, 0.8 mg/m²; Days 8 and 15,: 0.5 mg/m². Cycles may be extended to 28 days, with a 7-day treatment-free interval starting on day 21, in patients with CR and/or to allow recovery from toxicity.

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!