Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Prolymphocytic Leukemia: Two Case Reports

PURPOSE Refractory and relapsed T-cell prolymphocytic leukemia (T-PLL) has a poor prognosis and effective treatment is still lacking. Our study explored the efficacy and safety of donor-derived CD7 chimeric antigen receptor (CAR) T-cell therapy for T-PLL.

PATIENT AND METHODS Case 1: A male patient (37 years old) was diagnosed with T-PLL due to elevated white blood cells (WBC 235×10⁹/L) and splenomegaly. After three courses of bendamustine, he failed to achieve complete remission (CR). The salvage therapy with anti-CD52 monoclonal antibody was not helpful. His disease was deteriorated with 67% lymphocytes in bone marrow (BM) and 77.74% abnormal phenotype T-lymphocytes detected by flow cytometry (FCM) with a phenotype positive for CD7^bri, CD2^dim, CD3, cCD3, CD5, CD8, CD45, CD99, TCRαβ, CD26^bri, CD52^bri, TCL1, TRBC1 (99.7%), CD4^partial. CAR T-cells which targeting CD7 antigen were manufactured using peripheral blood (PB) from his haploidentical donor. Splenic radiotherapy and FC regimen (fludarabine 30mg/m²·d day-5~-3; cyclophosphamide 300mg/m²·d day-5~-3) were given prior to CAR T cells infusion. He was then infused 0.5×10⁶/kg, 0.5×10⁶/kg, and 0.7×10⁶/kg of CAR T cells on day 0, day 5, and day 14 with informed consent. The vital signs, complete blood counts, cytokines, serum ferritin, CAR T-cell counts in PB, BM aspirate and MRD by FCM were monitored.

Case 2: A female patient (51 years old) was diagnosed with T-PLL due to elevated white blood cells, swollen face and splenomegaly. After multiple courses of treatment (Including cyclophosphamide, doxorubicin, vincristine, prednisone, anti-CD52 monoclonal antibody, fludarabine, mitoxantrone liposome, etoposide, chidamide, PI3K inhibitors and other drugs), she failed to achieve CR. Her disease was deteriorated with 98.91% abnormal phenotype T-lymphocytes in bone marrow detected by flow cytometry (FCM) with a phenotype positive for CD7^bri, CD5, CD2, CD3, CD4, CD8, cCD3. CAR T-cells targeting CD7 were manufactured using peripheral blood from her haploidentical donor. She received 1×10⁶/kg of CAR T cells on day 0 with informed consent. Splenic radiotherapy and FC regimen chemotherapy (fludarabine 30mg/m²·d day-5~-3; cyclophosphamide 300mg/m²·d day-5~-3) were given prior to CAR-T cell infusion. The vital signs, complete blood counts, cytokines, serum ferritin, CAR T-cell counts in PB, BM aspirate and MRD by FCM were monitored.

RESULTS Case 1: The patient developed fever on day 15 which peaked at 40.2°C, followed by hypoxia, hypotension, and pleural effusion. IL-6 and serum ferritin were elevated equally. The cytokine release syndrome (CRS) was assessed as grade 3. After tocilizumab, low-dose corticosteroids and vasopressor, the temperature returned to normal and the above symptoms improved. There was no immune effector cell-associated neurotoxicity syndrome (ICANS). CAR T cells expanded significantly in PB, up to 45.2% on day 19. The patient achieved CR with MRD negativity in BM by FCM on day 25. Then he underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from the same donor. Up to now, the patient has been in complete remission for 10 months after transplantation.

Case 2: The patient developed fever after infusion of CAR-T cells which peaked at 40°C on day 1, followed by hypoxia, hypotension and pleural effusion. IL-6 and serum ferritin were elevated equally. The CRS was assessed as grade 3. After low-dose corticosteroids and vasopressor, the temperature returned to normal and the above symptoms improved. There was no ICANS. CAR T cells expanded significantly in PB, up to 56.6% on day 10. The patient achieved CR with MRD negativity in BM by FCM on day 15. The patient developed grade 4 hematological toxicity after CAR T cells treatment. She died from hemoptysis due to pulmonary fungal infection while waiting for transplantation.

CONCLUSION Donor-derived CD7 CAR T cells are effective and safe for refractory and relapsed T-PLL. Bridging to allo-HSCT is a potential cure for the disease.

No relevant conflicts of interest to declare.