Remission of a Relapsed T-ALL Patient with Central Nervous System Leukemia After CAR-T Therapy
This case involves a 16-year-old boy from Northeast China, whose journey with leukemia has been full of challenges since his diagnosis over a year ago.
On November 8, 2020, Dawei (a pseudonym) visited a local hospital due to facial stiffness, rash, and a crooked mouth. He was diagnosed with "acute lymphoblastic leukemia (T-cell type)." After one induction chemotherapy course, MRD (minimal residual disease) was negative, followed by regular chemotherapy. During this period, bone marrow puncture, lumbar puncture, and intrathecal injections showed no abnormalities.
On May 6, 2021, a lumbar puncture with intrathecal injection was performed, and cerebrospinal fluid (CSF) analysis confirmed "central nervous system leukemia." This was followed by two courses of regular chemotherapy. On June 1, a lumbar puncture with CSF analysis showed immature cells. Three additional lumbar punctures with intrathecal injections were administered, with the final CSF test showing no tumor cells.
On July 7, Dawei experienced vision loss in his right eye, reduced to light perception only. After one course of intensified chemotherapy, his right eye vision returned to normal.
On August 5, his right eye vision deteriorated again, leading to complete blindness, and his left eye became blurry. From August 10 to 13, he underwent whole-brain and spinal cord radiotherapy (TBI), which restored vision in his left eye, but the right eye remained blind. On August 16, an MRI scan of the brain showed slight improvement in the thickening of the right optic nerve and chiasm, with enhancement observed. No abnormal signals or enhancements were found in the brain parenchyma.
At this point, the family had prepared for a bone marrow transplant, awaiting only a bed in the transplant ward. Unfortunately, routine pre-transplant examinations revealed issues that made the transplant impossible.
On August 30, a bone marrow puncture was performed, revealing bone marrow MRD with abnormal immature T lymphocytes accounting for 61.1%. A lumbar puncture with intrathecal injection was also performed, showing CSF MRD with 127 total cells, of which abnormal immature T lymphocytes comprised 35.4%, indicating a complete relapse of leukemia.
On August 31, 2021, Dawei and his family arrived at Yanda Lu Daopei Hospital and were admitted to the second ward of the hematology department. Admission blood tests showed: WBC 132.91×10^9/L; peripheral blood differential (morphology): 76.0% blasts. Induction chemotherapy was administered for one course.
After reviewing Dawei's previous treatment, it was clear that his T-ALL was refractory/relapsed and that tumor cells had infiltrated the brain, affecting the optic nerve. The medical team led by Dr. Yang Junfang in the second hematology ward determined that Dawei met the criteria for enrollment in the CD7 CAR-T clinical trial.
On September 18, another examination was performed: peripheral blood differential (morphology) showed 11.0% blasts. Peripheral blood lymphocytes were collected for CD7 CAR-T cell culture on the same day, and the process went smoothly. After collection, chemotherapy was administered to prepare for CD7 CAR-T cell immunotherapy.
During chemotherapy, tumor cells proliferated rapidly. On October 6, the peripheral blood differential (morphology) showed 54.0% blasts, and the chemotherapy regimen was adjusted to reduce tumor burden. On October 8, a bone marrow cell morphology analysis showed 30.50% blasts; MRD indicated that 17.66% of cells were malignant immature T lymphocytes.
On October 9, CD7 CAR-T cells were reinfused. Following reinfusion, the patient experienced recurrent fever and gum pain. Despite enhanced anti-infection treatment, the fever was not well controlled, although the gum pain gradually subsided.
On the 11th day post-reinfusion, peripheral blood blasts increased to 54%; on the 12th day, a blood test showed white blood cells rising to 16×10^9/L. On the 14th day post-reinfusion, the patient developed severe CRS, including myocardial damage, liver and kidney dysfunction, hypoxemia, lower gastrointestinal bleeding, and convulsions. Aggressive symptomatic and supportive treatments, along with plasma exchange, gradually improved the function of the affected organs, stabilizing the patient's vital signs.
On October 27, the patient had 0-grade muscle strength in both lower limbs. On October 29 (21 days post-reinfusion), a bone marrow MRD test turned negative.
In a state of complete remission, Dawei strengthened his lower limb function with the help of nurses and family, gradually recovering muscle strength to 5 grades. On November 22, he was transferred to the transplant department to prepare for an allogeneic hematopoietic stem cell transplant.
