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

Updated: Oct 23, 2019
  • Author: Karen Seiter, MD; Chief Editor: Koyamangalath Krishnan, MD, FRCP, FACP  more...
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Answer

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 x 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 that were 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) was approved in August 2012 by the FDA for treatment of Philadelphia chromosome–negative ALL patients in second or greater 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, was approved in December 2014 for Philadelphia chromosome–negative 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]

Inotuzumab is a CD22-directed antibody-drug conjugate approved for relapsed/refractory B-cell precursor ALL.


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