Case 1: First Bone Marrow Relapse of B-ALL/ Relapse Following HSCT

In the first scenario outlined in the review, a 12-year-old girl diagnosed with B-ALL 2 years ago experienced an isolated marrow relapse during maintenance therapy.

The authors recommended treatment with United Kingdom (UKALL) R3 reinduction regimen (dexamethasone, vincristine, mitoxantrone, pegaspargase, and intrathecal methotrexate) or another 4-drug reinduction regimen. As the risk of infection is high, she would be hospitalized until her count recovered and would be provided antibacterial, antifungal, and pneumocystis jirovecii prophylaxis.

If she has an M3 marrow (>25% marrow blasts), the CD22 antibody-drug conjugate inotuzumab and/or CAR T-cell therapy would be used. If she entered CR2 or has an M2 marrow (5-25% blasts), two 28-day cycles of blinatumomab would be administered, followed by HSCT in CR2 if she is MRD-negative. An HSCT would be considered if there is a readily available donor and if she is MRD-negative.

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But if this same patient relapses following HSCT (at 13 months), they recommended that she receive tisagenlecleucel, or enroll in a clinical trial that is evaluating other CAR T-cell therapies, given the limitations of a second HSCT. If her T-cell count is too low or T-cell collection not feasible for CAR T-cell therapy, chemotherapy would be administered to debulk the leukemia burden.

Case 1: Multiply Relapsed ALL

Assuming the scenario above eventually led to the patient receiving CD22-redirected CAR T cells on a clinical trial, attaining an MRD negative CR, but then having a marrow relapse while awaiting a second HSCT — what would the options be?

The authors noted that multiply relapsed ALL after HSCT and CAR T-cell therapy is very challenging to treat, and while potentially curative options may exist, assuming that she is healthy, it is also a situation in which focus could be directed at maximizing quality of life as opposed to a cure. That said, if her blasts remain CD22+, then inotuzumab can be used either as a single agent or as part of a chemotherapy regimen. Clinical or palliative therapy could also be considered, and if not already done, they recommended comprehensive genomic profiling to assess for potentially targetable alterations that could be matched to targeted therapy.

Case 2: First Extramedullary Relapse of B-ALL

The second patient described within the review was a 6-year-old boy who was diagnosed with B-ALL 15 months prior and had an asymptomatic isolated central nervous system (iCNS) relapse during maintenance therapy, with 10 white blood cells/microliter cerebral spinal fluid (CSF) with blasts on cytospin, and an MRD-negative bone marrow.

The authors recommended treatment with dexamethasone-based UKALL R3 reinduction combined with weekly triple intrathecal chemotherapy, which is generally considered to be superior to intrathecal methotrexate alone for patients presenting overt CNS leukemia. Placement of an Ommaya reservoir can be considered if the patient will be receiving frequent infusions of intrathecal chemotherapy. When remission is achieved following 3 blocks of intensive systemic reinduction therapy, the authors recommended HSCT with the best donor available, following a total body irradiation conditioning regimen with a CNS boost.

This article originally appeared on Hematology Advisor