The Effectiveness of Low-Dose Decitabine Following Infusion of Autologous Hematopoietic Stem Cells in Patients Experiencing Persistent Pancytopenia after CD19-CART
Authors: Guo Xutao , Zhang Yunxia , Lei Haohao , Wei Yongqiang , Wei Xiaolei , Wei Qi , Feng Ru 
Published: December 2024

Objectives: To evaluate the effectiveness of low-dose Decitabine in combination with autologous hematopoietic stem cell infusion for patients experiencing persistent pancytopenia after CD19-chimeric antigen receptor T (CAR-T) therapy.

Methods: Data from two adult patients with relapsed DLBCL and ongoing pancytopenia following CD19-CART therapy were analyzed.

Results: Both patients achieved hematopoietic reconstitution following treatment with low-dose Decitabine and autologous hematopoietic stem cell infusion. Secondary MDS was ruled out by bone marrow aspiration and biopsy, which revealed bone marrow characteristics consistent with aplastic anemia in both cases. Prior to this treatment, both patients had been administered glucocorticoids, G-CSF, erythrocyte promotion, TPO-RA and other drugs without successful recovery of blood cells. Patient 2 also received a transfusion of autologous hematopoietic stem cells 32 days after CART, but did not achieve blood cell recovery.

We used methylation-specific PCR to detect bone marrow samples from 2 patients and found that the DNA methylation level was significantly higher than that of CART patients with normal hematopoiesis. This indicates a potential epigenetic mechanism underlying the bone marrow failure in these patients. Considering the characteristics of bone marrow failure indicated by bone marrow biopsy, we are considering combining demethylation drugs with transfusions of autologous hematopoietic stem cells to address this clinical challenge.

The use of demethylation drugs aims to reverse the abnormal DNA methylation patterns in the bone marrow cells, potentially restoring their normal function and promoting hematopoiesis. Meanwhile, transfusions of autologous hematopoietic stem cells can provide a source of healthy blood-forming cells to replace the dysfunctional ones in the bone marrow.

The two patients were given a low dose of decitabine (5mg/m2, d1-5) followed by an infusion of autologous hematopoietic stem cells containing 4.6*106/kg and 5.2*106/ CD34-positive cells at 62 days and 84 days after CART, respectively. Neutrophil hematopoietic recovery took 21 and 35 days for the two patients, while erythrocyte recovery occurred in 48 and 53 days respectively; platelet recovery required 24 and 55 days for the two patients.

Conclusion: Low-dose decitabine following infusion of autologous hematopoietic stem cells is safe and effective in patients experiencing persistent pancytopenia after CD19-CART. This combined approach holds promise for improving outcomes in patients with bone marrow failure, but further research is needed to determine its efficacy and safety. Additionally, careful monitoring will be essential to assess treatment response and potential adverse effects. Overall, this strategy represents a novel therapeutic option for addressing the underlying molecular mechanisms contributing to bone marrow failure and has the potential to improve patient outcomes.