UNASSIGNED: The central nervous system (CNS) is the most common site of extramedullary invasion in acute lymphoblastic leukemia (ALL), and involvement of the CNS is often associated with relapse, refractory disease, and poor prognosis. Chimeric antigen receptor-T (CAR-T) cell therapy, a promising modality in cancer immunotherapy, has demonstrated significant advantages in the treatment of hematological malignancies. However, due to associated adverse reactions such as nervous system toxicity, the safety and efficacy of CAR-T cell therapy in treating CNSL remains controversial, with limited reports available.
UNASSIGNED: Here, we present the case of a patient with confirmed B-ALL who experienced relapse in both bone marrow (BM) and cerebrospinal fluid (CSF) despite multiple cycles of chemotherapy and intrathecal injections. The infusion of autologous CD19 CAR-T cells resulted in complete remission (CR) in both BM and CSF for 40 days. However, the patient later experienced a relapse in the bone marrow. Subsequently, allogeneic CD19 CAR-T cells derived from her brother were infused, leading to another achievement of CR in BM. Significantly, only grade 1 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events were detected during the treatment period and showed improvement with symptomatic management. During subsequent follow-up, the patient achieved a disease-free survival of 5 months and was successfully bridged to hematopoietic stem cell transplantation.
UNASSIGNED: Our study provides support for the argument that CNS involvement should not be deemed an absolute contraindication to CAR-T cell therapy. With the implementation of suitable management and treatment strategies, CAR-T therapy can proficiently target tumor cells within the CNS. This treatment option may be particularly beneficial for relapsed or refractory patients, as well as those with central nervous system involvement who have shown limited response to conventional therapies. Additionally, CAR-T cell therapy may serve as a valuable bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in these patients.

UNASSIGNED: Refractory/relapsed acute myeloid leukemia (R/R AML) has unsatisfactory outcomes even after allogeneic hematopoietic stem cell transplantation. Long-term survival is mainly influenced by complete remission (CR) rates after induction therapies.
UNASSIGNED: To investigate CR/CR with incomplete hematologic recovery (CRi) rates and adverse events with a new induction therapy (bortezomib, homoharringtonine, and cytarabine [BHA]) for patients with R/R AML.
UNASSIGNED: We enrolled 21 patients with R/R AML (median age, 42 [range, 30-62] years), who received BHA for remission induction (bortezomib, 1.3 mg/m2/day on days 1 and 4; homoharringtonine, 4 mg/m2/day for 5 days, and cytarabine, 1.5 g/m2/day for 5 days). CR and adverse events were assessed.
UNASSIGNED: After one course of BHA, the CR/CRi and partial remission rates were 38.1% and 14.3%, respectively, with an overall response rate (ORR) of 52.4% in 21 patients. 9 of 21 patients harbored FLT3-ITD or FLT3-TKD mutations, and achieved either CR/CRi or ORR of 66.7% (P=0.03) by comparison with that in R/R AML without FLT3 mutation. After induction therapy, consolidation chemotherapy or allogeneic hematopoietic stem cell transplantation led to a one-year overall survival of 27.8% in all patients. One-year relapse-free survival was 50% in 8 patients who had achieved CR/CRi after one course of BHA. During induction, non-hematologic adverse events (grade 3/4) commonly were infection (90.5%), hypokalemia (14.4%), hypocalcemia (14.3%), and mucositis (9.5%). In patients achieving CR, the median time to neutrophil count >0.5×109/L and time to platelet count >20×109/L were 15 (13-17) days and 13 (13-18) days, respectively.
UNASSIGNED: BHA chemotherapy regimen was safe and tolerable to serve as an induction therapy for R/R AML, particularly with FLT3 mutation. The higher CR/CRi rate will give a clue to determine a potentialeffectiveness of BHA for AML patients carrying FLT3 mutation in a further investigation.
UNASSIGNED: https://www.chictr.org.cn/, identifier ChiCTR2000029841.

In recent decades, survival was significantly improved in B cell acute lymphoblastic leukemia (B-ALL) patients. But refractory and relapsed B-ALL still has aggressive clinical behavior and poor prognosis. Especially, the patients with central nervous system infiltration is very difficult to achieve complete remissions with routine treatment. Chimeric antigen receptor-modified T-cell therapy targeting CD-19 has shown to be a beneficial treatment approach in refractory and relapsed B cell acute lymphoblastic leukemia (r/r ALL). However, there are very few studies reporting to treatment of refractory and relapsed B cell ALL with central nervous system infiltration. Here, we reported one single case of a patient diagnosed with relapsed B cell ALL with CNS infiltration who was successfully treated by second generation CAR containing a co-stimulator CD28 or 4-1BB therapy. Long-term proliferation of CAR-T cells in peripheral blood and bone marrow was observed more than 18 months. After CAR-T treatment, the patient got toxicity of grade 1 cytokine release syndrome and achieved significantly 36 months event free survival of follow-up. It is suggested that CD-19 CAR containing CD28 or 4-1BB costimulatory may be an effective therapy in refractory and relapsed B cell ALL with central nervous system infiltration. Its toxicity is mild, and its safety is high. Clinical Trial Registration:ClinicalTrials.gov Identifier: NCT02349698.