How are pediatric anaplastic (T-cell) LCLs treated?

Updated: Jun 14, 2018
  • Author: J Martin Johnston, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Answer

The therapy for anaplastic (T-cell) LCLs is somewhat controversial. Good results (event-free survival rates of 65-80%) have been reported with a number of protocols. Some were based on acute lymphoblastic leukemia (ALL) therapy, whereas others were similar or identical to those used to treat B-cell lymphomas.

The Berlin, Frankfurt, Muenster (BFM) group reported what may be the best results with treatment for Ki-1+ anaplastic LCLs. [75] The group administered a regimen for B-cell lymphomas that did not include local radiation therapy. Among 62 patients (none with bone marrow disease and 1 with CNS involvement), 4 did not achieve remission, 1 died from infection, and 7 had a relapse. At the time of the report, 50 patients remained in a continuous first episode of complete remission, and 56 were alive. The calculated event-free survival rate at 9 years was 83%.

Subsequent modifications have yielded the ALCL99 protocol as shown below and have further demonstrated that: (1) dosing methotrexate at 3 g/m2 over 4 hours appears to be at least as effective (and less toxic) when compared with a dose of 1 g/m2 over 24 hours with the addition of "triple" intrathecal chemotherapy and (2) the addition of vinblastine (both during chemotherapy and continuing weekly until 1 year from diagnosis) delayed but did not ultimately prevent relapses. [76, 77]

Table 7. Prephase Therapy for Ki-1+ Anaplastic LCLs According to the ALCL99 Protocol (Open Table in a new window)

Drug

Route

Dexamethasone

PO

Cyclophosphamide

IV

Methotrexate/Ara-C/prednisolone

IT

Ara-C = cytarabine; IT = intrathecal; IV = intravenous; PO = oral.

Table 8. Subsequent Therapy for Ki-1+ Anaplastic LCLs According to the ALCL99 Protocol (alternating cycles, repeated 3times each) (Open Table in a new window)

Cycle

Drug

Route

A

Dexamethasone

PO

Methotrexate with leucovorin rescue, ifosfamide, etoposide (VP-16), Ara-C

IV

B

Dexamethasone

PO

Methotrexate with leucovorin rescue, cyclophosphamide, doxorubicin

IV

Ara-C = cytarabine; IT = intrathecal; IV = intravenous; PO = oral.

Good results have been observed with the relatively uncomplicated APO regimen. In addition, a randomized study of children with LCL (including B-cell LCL and anaplastic LCL) showed no apparent advantage when intermediate-dose methotrexate and high-dose cytarabine were added to an APO backbone. [78]

A report from the SFOP described surprising efficacy for monotherapy with vinblastine for relapsing anaplastic LCL, even in patients who previously underwent myeloablative therapy with autologous bone marrow transplantation. [79]

The role of vinblastine in front-line therapy for anaplastic LCL was examined in a Children's Oncology Group protocol (A5941), which compared the standard APO regimen with an experimental therapy that included vinblastine. Myelosuppression was more significant than anticipated and the trial closed early; results have not been published.

The current Children's Oncology Group Phase 2 protocol for anaplastic LCLs uses the ALCL99 regimen (shown above) as a "backbone" and adds (in a randomized fashion) either brentuximab vedotin, an anti-CD30 monoclonal antibody, or crizotinib, a specific small-molecule inhibitor of the ALK pathway. [80]


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