Case 3: First Marrow Relapse of T-ALL
The third patient is an 8-year-old boy with T-ALL who suffered an isolated marrow relapse 17 months following his diagnosis. The patient’s initial treatment included a dexamethasone-based 4-drug induction regimen that was followed by augmented BFM-based chemotherapy with nelarabine, including intrathecal chemotherapy for CNS prophylaxis.
Relapses tend to occur earlier for T-ALL as compared with B-ALL, and most occur within 2 years of diagnosis. Survival following a relapse is poor, which is why HSCT is the preferred option for these patients, regardless of the site or timing of relapse. Reinduction chemotherapy is the recommended strategy, followed by HSCT with the best available donor as soon as an MRD-negative complete remission is attained. A standard reinduction approach for T-ALL has not yet been determined, and the superiority of 1 regimen over another has not been established. The authors recommended the UKALL R3 reinduction regimen, the same used for case 1, with hospitalization until white cell count recovery and antimicrobial prophylaxis.
Another potential reinduction regimen is nelarabine, cyclophosphamide, and etoposide (NECTAR), which has demonstrated CR2 rates of 44% in a phase 1 trial.
“The biggest question is whether CAR T cells or other immunotherapies can replace transplants,” said Dr Hunger. “These therapies are very active and effective and shouldn’t be reserved for people who have relapsed many times, and there are efforts now [to] move it earlier into the process.”
Studies are now being conducted with both children and adults to determine whether outcomes can be improved if immunotherapies are administered earlier in the process, as well as to newly diagnosed patients. “The good news is that we have great new drugs that are really remarkable, and provide many more opportunities than a decade ago, and the challenge is how and when to use them optimally,” Dr Hunger noted.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Hunger SP, Raetz E. How I treat relapsed acute lymphoblastic leukemia in the pediatric population. Blood. Published online June 26, 2020. doi:10.1182/blood.2019004043