Short-Term Efficacy and Safety of Haplo Hematopoietic Stem Cell Transplantation for Refractory and/or Relapsed Leukemia

BACKGROUND

Allogeneic hematopoietic stem cell transplantation is potentially curative and one of the most efficacious therapies for patients hematological malignancies. Yet, the relapse rate following allo-HSCT for refractory or relapsed (R/R) leukemia is still high even with high-intensity conditioning. The 1-year survival rate for R/R leukemia patients is less than 50%. How to optimize the conditioning regimen to reduce recurrence, improve prognosis and increase the rate of long-term survival has become a Major focus yetremains challenging. Thiotepa-based conditioning is an emerging radiation-free regimen. In this study, we analyzed a thiotepa-based conditioning regimen for allo-HSCT in patients with R/R leukemia.

OBJECTIVE

To evaluate the short-term efficacy and safety of haplo hematopoietic stem cell transplantation (haplo-HSCT) for R/R leukemia patients using a thiotepa-based conditioning regimen.

METHODS

We performed a retrospective analysis of 55 patients with R/R leukemia who received haplo-HSCT at the Beijing Lu Daopei Hospital between August 2019 and March 2022. Twenty-five of 55 (45%) patients received a conditioning regimen with busulfan/ cyclophosphamide (Bu/Cy) and the other 30 (55%) patients received total body irradiation/ cyclophosphamide (TBI/Cy). All patients also received thiotepa (5mg/kg, -3 days to -2 days) as part of their conditioning regimen. Overall survival (OS), disease-free survival (DFS), and transplant-related mortality (TRM) were evaluated.

RESULTS

A total of 55 patients were identified, 22 with acute myeloid leukemia, and 32 with acute lymphoblastic leukemia (22 with B-cell acute lymphoma and 10 with T acute lymphoma). There were 37 males and 18 females. The median age was 7 years (range: 0.7-58). The median follow-up time was 393 days (range: 41-669). Poor prognosis and stratification factors analyzed included high leukocyte onset in 17 (31%) patients, poor molecular genetic prognosis in 40 (73%) patients, and poor cytogenetic prognosis in 31 (56%) patients. There were 16 (29%) patients with central nervous system leukemia, 27 (49%) with extramedullary infiltration, 13 (24%) with a history of previous transplantation, and 21 (38%) with a history of immunotherapy. Seventeen (31%) patients required more than 2 courses to achieve complete remission. Disease status at time of transplantation was first complete remission (CR1) in 11 (20%) patients, ≥ CR2 in 27 (49%) patients, and no-remission（NR）in 17 (31%) patients. There were 29 (53%) patients in the middle-high risk group in the transplantation combined index score. The median concentration of mononuclear cells (MNCs) of the reinfused graft was 8.64 ×10⁸/kg (range: 3.49-26.7) and the CD34+ was 6.02 ×10⁶/kg (range: 2.98-17.86). The stem cell engraftment rate was 100%. Among patients who underwent an engraftment evaluation had leukocytes on +14 days (range: 9-24), neutrophils +15 days (range: 9-23), and platelets on +12 days (range: 7-60). The most common non-hematologic adverse reactions were gastrointestinal symptoms and oral mucositis. There was 1 case of grade III-IV infection, 2 cases of grade III hemorrhagic cystitis. No allergic or rash adverse reaction were observed. The infection rates of Epstein-Barr (EB) and cytomegalovirus (CMV) after transplantation were 9% and 56%, respectively. Ten (18%) patients had III-IV acute graft versus host disease (aGVHD) and 2 (4%) patients had extensive chronic graft versus host disease (cGVHD). Up to the cutoff date of June 30, 2022, 2 patients had hematological recurrence, 1 had residual recurrence, and 1 had molecular recurrence. A total of 11 (20%) patients died, including 9 who died of GVHD, 1 died of recurrence, and 1 of intracranial hemorrhage. Logical regression analysis showed that, every 1×10⁸/kg increase in MNCs was associated with a 0.49-fold increase in the risk of death [OR 95%CI 1.49(1.01-2.19)]. The OS rate was 80%, the DFS rate was 74.5%, and the transplant-related mortality (TRM) was 18%. There was no significant difference in OS (90.9%,82.4%,74.1%) and DFS (90.9%,82.4%,70.6%) among the CR1, ≥CR2, and NR subgroups (P>0.05).

CONCLUSION

Conditioning regimens that include thiotepa are feasible for patients with R/R leukemia. Additional patient outcomes analyses and prospective studies are needed to further explore how to optimize the process of evaluating patients for transplantation and conditioning regimens and reduce TRM.

No relevant conflicts of interest to declare.