Case Report Demonstrates Nuanced Decisions in Treating ALL Relapse With Skull Base Lesion

Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer, and it usually is curable. However, patients who experience relapse have lower odds of survival.

In a new case report, investigators outlined a particularly challenging case of ALL, in which a pediatric patient experienced a double relapse with a skull base lesion and leptomeningeal disease. The authors said the case offers insights into how a multidisciplinary approach can help manage difficult cases like these. The report was published in the Journal of Neurological Surgery Reports.¹

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The case involved an 11-year-old girl who had been diagnosed with standard-risk ALL at 18 months, completed 2 years of therapy, and had been in remission ever since. When she returned to the clinic 7 years later, she had left facial droop, mastoiditis/otitis, and swelling in her right elbow, the authors explained.

MRI revealed a large skull base lesion centered on the patient’s sphenoid bones and clivus, with extensive intracranial, nasopharyngeal, and left neck extension, the investigators said.

“The mass encapsulated the left VII and VIII cranial nerves, dorsally displacing the pons and medulla, and filling the left cavernous sinus,” the investigators noted.

A biopsy showed the tumor was not a new second malignancy, but rather relapsed precursor B-cell (pre-B) ALL. Analysis of cerebrospinal fluid from a lumbar puncture showed 15% blast-like cells with tissue flow from the tumor that was consistent with pre-B ALL, the authors said. The blasts were CD19-negative.

The patient was given chemotherapy with systemic mitoxantrone, dexamethasone, vincristine, and pegaspargase, along with weekly intrathecal methotrexate, cytarabine, and hydrocortisone.

Another lumbar puncture and bone marrow biopsy following induction chemotherapy showed no residual disease, the authors said.

“End of induction MRI brain scans, however, showed that while the intracranial lesion decreased significantly, there remained a residual mass centered on the left skull base, with mass effect on the brain stem,” the authors wrote.

At this point, the investigators evaluated a number of potential therapies, ultimately deciding on continued chemotherapy along with radiotherapy. They noted that surgery was highly risky given the particulars of the case, and the patient was ineligible for chimeric antigen receptor (CAR) T-cell therapy, since her blasts were not CD19 positive. The patient’s parents declined allogeneic hematopoietic stem cell transplantation.

The patient was given chemotherapy for 2 years, along with targeted radiation. The lesion at the skull base decreased remarkably over that time, the authors said, though the facial droop resisted. The patient’s tumor board decided to monitor the residual lesion and consider a biopsy and excision if it began regrowing.

“Unfortunately, 5 months after completing therapy, the patient presented to the hospital with worsening facial droop and neck pain,” Jung and colleagues said. “MRI scans showed the skull base lesion was stable, but there was a new finding of diffuse leptomeningeal enhancement.”

An initial lumbar puncture showed no blasts, but elevated cranial pressure, they said. However, a lumbar puncture a week later confirmed central nervous system (CNS) relapse.

As of the case report’s writing, the patient was receiving monthly intrathecal therapy of methotrexate, hydrocortisone, and cytarabine, along with a bone marrow biopsy every 2 months. The patient’s physicians have asked the family to consider bone marrow transplantation, and the physicians said that conversation is ongoing.

The authors emphasized that treating cases of relapsed ALL is challenging. A 2008 study examining survival rates after relapse found patients who relapsed within 18 months had particularly low rates of survival. However, it also found that factors such as age over 10 years, CNS involvement at diagnosis, male gender, and T-cell disease were significant negative predictors of postrelapse survival.²

Previous research has shown that high-dose chemotherapy and cranial radiation can be relatively successful in cases with late, isolated CNS relapse. However, long-term adverse effects, including neurocognitive impairment, are associated with radiation.

The authors of the case report wrote that these types of patients warrant careful management and an “intricate” decision-making process.

“Moving forward, we believe it is important to be able to identify patients at risk of relapsed CNS-ALL, as this would allow for swift clinical action to be taken before progression of disease,” they said.

They added that more targeted therapies for intracranial disease are also needed, and would also help to boost patient survival.

References:

1. Jung G, Buckner-Wolfson E, Tal A, et al. Nuanced management of a skull base tumor in the setting of relapsed acute lymphoblastic leukemia. J Neurol Surg Rep. 2024;85(2):e48-e52. doi:10.1055/a-2297-4265
2. Nguyen K, Devidas M, Cheng SC, et al. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children's Oncology Group study. Leukemia. 2008;22(12):2142-2150. doi:10.1038/leu.2008.251