CASE HISTORY
A 17-year-old female presented with epistaxis and bleeding gums in
February 2019. Complete blood cell count showed white blood cells
26.98×109/L,
hemoglobin 79g/L and platelets
12×109/L. A
differential count found 91% blasts. The diagnosis of B-ALL was
confirmed by bone marrow morphology and flow cytometry (FCM).
Cytogenetics was normal. No fusion genes or mutations were detected with
polymerase chain reaction and targeted next-generation sequencing.
Complete remission (CR) was not achieved after induction therapy with
the Hyper-CVAD regimen [7] (11.5% blasts in
morphology). After reinduction with idarubicin, pegasparagase and
dexamethasone, she achieved CR but measurable residual disease (MRD,
1.6%) was detected by FCM. This was followed by consolidation therapy,
including 1 cycle of high-dose methotrexate plus vincristine and
dexamethasone, and 1 cycle of high-dose cytarabine. To prevent central
nervous system infiltration, intrathecal chemotherapy with methotrexate
was used. However, MRD was consistently detected in bone marrow
specimens. Though she had no unfavorable genetic aberrations at
diagnosis, the persistence of MRD supported the risk classification of
high-risk group. As neither blinatumomab nor InO were approved for
marketing in China in 2019, she underwent haploidentical hematopoietic
stem cell transplantation (HSCT) from her father in August 2019 with a
positive MRD (1.47% MRD before HSCT). She did not suffer from acute or
chronic graft versus host disease (GVHD) and immunosupressors were
tapered off and stopped in 6-months post transplantation. Unfortunately,
a hematologic relapse was detected 23 months post-transplant (July
2021). She was then enrolled in a clinical trial (NCT04825496) and
received autologous anti-CD19 CART therapy (dose:
1×106/kg). At the day 28 evaluation after CAR T-cell
infusion, the patient achieved a MRD negative remission. She had grade 2
cytokine release syndrome and recovered with symptomatic treatment (Fig.
1A). The persistence of CAR T-cells was only detected within a month
following CART therapy (Fig. 1B). At the regular follow-up in August
2022, MRD-positive relapse was detected (FCM of 2.9% blasts with
CD10+CD19+CD20-CD22+CD38+ and morphology of 3% blasts). Expression of
CD22 was detected in 63.74% of the blasts. InO was selected for the
treatment of MRD. InO was applied 3 times: 0.8 mg/m2on day 1 and 0.5 mg/m2 on days 8 and 15.
Ursodeoxycholic acid was administered to prevent the development of
liver venoocclusive disease (VOD). She experienced only mild nausea.
Grade 1 neutropenia and grade 4 thrombocytopenia were observed, which
recovered with supportive care. At day 30 evaluation, no blasts were
detected in the BM smear. Surprisingly, the MRD by FCM decreased to
2.68×10-5 and CD22 expression was negative (Fig. 1C,
1D, 1E). No sinusoidal obstruction syndrome or other adverse effects
occurred. Currently, the patient is in remission until follow-up to
September 2023. Timeline of the treatments and responses are shown in
Fig. 1F.